Saturday, 28 October 2017

Mourinho one of the best managers in the world' - Pochettino denies bad blood with Man Utd boss*

Tottenham manager Mauricio Pochettino insists there is no rift between himself and Manchester United boss Jose Mourinho ahead of their weekend showdown.

United and Spurs are level on 20 points in the Premier League and sit as the closest challengers to leaders Manchester City on the eve of a keenly anticipated Old Trafford clash.

An extract from Pochettino's new book, published this week, detailed how the Argentinian was unimpressed by Mourinho hugging and talking with Eric Dier after last season's match at Old Trafford that United won 1-0.

Pochettino accused Mourinho of putting Dier "in a compromising position" but, speaking at a news conference ahead of Saturday's game, he insisted the affair had long since been put to bed.

"That is a thing that is in the past," said the Spurs boss, who will be without top scorer Harry Kane against United due to a hamstring injury.

"You can read in my book how he is, for me, one of the best managers in the world – admired like [Pep] Guardiola. I am not perfect, I am human too

Sushma Asks for πŸ”ŽProbe into Adoption of Murdered 3⃣-Yr-OldπŸ‡ΈSherin Mathews*

External Affairs Minister Sushma Swaraj has requested her cabinet colleague Maneka Gandhi for an investigation into the adoption of Sherin Mathews, the three-year-old Indian girl who died at her new home in the US earlier this month. Maneka Gandhi is the Women and Child Development Minister.

"I have requested Maneka Gandhi Minister for Women and Child Development for a thorough investigation into the adoption process of Baby Saraswati SherinMathews who has been killed by her foster father Wesley Mathews in United States," Ms Swaraj tweeted on Friday evening.

Sherin's adoptive father Wesley Mathews was charged on Monday with an injury to a child, a first-degree felony that carries a maximum punishment of 99 years in prison, the Texas police said. The body of Sherin was found in a culvert under a road. Activists in India have called for an immediate end to intercountry adoptions, which they say fail to protect children. "Intercountry adoptions have become a lucrative market where children are effectively sold," said activist Sujata Mody.

Kane out of Tottenham's Man Utd clash with hamstring strain*

Tottenham have confirmed that striker Harry Kane will miss the club's Premier League clash with Manchester United on Saturday.

Doubts over the 24-year-old's fitness first arose on Wednesday and those were realised following a scan, which showed minor damage to the forward's left hamstring.

Spurs are unwilling to risk the Premier League's top scorer for the Old Trafford date, aware that the injury could be made worse if he were to play too soon.

Kane has been an ever present for Pochettino in both the league and Europe this season, sitting out only a couple of EFL Cup fixtures, including the 3-2 defeat against West Ham in midweek.

"We cannot take a risk for tomorrow, we'll see after for Wednesday. But tomorrow, it is impossible," manager Mauricio Pochettino confirmed during his press conference.

Coutinho a doubt for Klopp's Wagner showdown*


Jurgen Klopp has doubts over the fitness of Philippe Coutinho as he prepares to take Liverpool into battle against a Huddersfield Town outfit managed by former colleague David Wagner.

The German duo worked together at Borussia Dortmund and both left for English soil in 2015, with Klopp heading to Anfield and Wagner taking the helm at a Terriers team then residing in the Championship.

He led the Yorkshire club to the Premier League last season, setting up Saturday's showdown with close friend Klopp, who could be without Coutinho as the Brazilian struggles with an adductor problem.

"It's not clear," said the Reds boss, who oversaw a 4-1 defeat at Tottenham last time out, when questioned on Coutinho's possible involvement. "Last week he had some back problems. During the week it settled with treatment. Now he has a problem with the abductor.

"We'll make the decision after training on Friday. He missed training yesterday, but that's all at the moment."

Conte blasts Chelsea player unrest rumours in fiery press conference*

Chelsea manager Antonio Conte has attacked rumours that his Premier League title champions have turned against him this season.

UK newspaper The Sun claimed that players had been texting former Chelsea No.2 Steve Holland to suggest that they no longer had a healthy relationship with Conte, although the story has been been pulled from its website.

Holland left his role in the summer to be England assistant coach working under Gareth Southgate and the reports had claimed that Chelsea players felt overworked in training in 2017-18. He is thought to have sent text messages to Conte and others at Chelsea to say that the story was untrue, while Conte publicly fumed at the rumours in Friday's press conference.

“Around us there is a lot of bullsh*t," he told reporters ahead of Chelsea's clash with Bournemouth on Saturday. "I see the past it happened the same with a lot of managers [at Chelsea].

"A lot of bullsh*t. They try to create problems between me, the club and the players. If someone is happy to continue to write this I answer very well in the past. I am answering very well about these different issues."

Football Manager 2018: Neymar, Messi & the most expensive players in the game


The beta for Football Manager 2018 went live on Thursday night, giving football fans their first chance to test out the newest version of the game and take charge of their favourite team.

Virtual managers will be looking to strengthen their teams as soon as they start up the game, but many of the world's biggest and best names may be a little out of their price range at the beginning.

Following his €222 million transfer from Barcelona to PSG, Brazil forward Neymar is the joint most expensive player in FM2018, with a market value of €95m. However, even if you do have that much to spend in your initial wage budget, it is unlikely that the Ligue 1 giants will be willing to sell their new superstar.

Here are the most expensive players:

🔰Neymar (PSG) - €95m

🔰Lionel Messi (Barcelona) - €95m

🔰Kevin de Bruyne (Man City) - €87m

🔰Gareth Bale (Real Madrid) - €84m

🔰Sergio Aguero (Man City) - €82m

🔰Robert Lewandowski (Bayern) - €82m

🔰Antoine Griezmann (Atletico) - €81m

🔰Isco (Real Madrid) - €78m

🔰Eden Hazard (Chelsea) - €78m

Jose Mourinho full of praise for Luke Shaw's comments on Mauricio Pochettino*


Manchester United manager Jose Mourinho has praised Luke Shaw's comments about reuniting with Mauricio Pochettino, saying the defender was just being honest.

Writing in the epilogue of Guillem Balague's new book, Brave New World: Inside Pochettino's Spurs, Shaw spoke glowingly about his former manager and said he would be keen on working under the Argentine once again.

Shaw had the most successful season of his career under Pochettino at St. Mary's before he left to join United and Mourinho was very understanding of his comments, describing them as the "perfect words".

When asked whether Shaw has any future at the club, he responded: "Why not? If you want to speak about his words - I would be very disappointed if his words were different. For me, they are the perfect words

"I'm always disappointed when a player has a new manager, the new manager becomes the best and the old manager becomes very bad.

"Football is full of examples of lack of character, Luke Shaw was just honest. The manager that helped him to come to the first team, the manager who brought him to the best point of his career."

Friday, 27 October 2017

DESIRE TO DO GOOD ALWAYS

⏰Friday of the Twenty-Ninth Week of Ordinary Time 1 (27 October 2017)

📖Rom 7:18-25a; Ps 119:66, 68, 76, 77, 93, 94 (R.v.68b); Luke 12:54-59

🎤DESIRE TO DO GOOD ALWAYS

Have you often found yourself falling prey to sin even when you desire strongly to do the right thing? That is often explained as concupiscence - what some people call human frailty, limitation or weakness. It is the orientation that drags man to move toward the bad which he wants to avoid. St. Paul, too, often complained about this (see Rom 7:18-25).

We know that some of us normally hide under that orientation to explain away our deep indulgence into sin. Before we join that crowd, it is important to note the difference between St. Paul in Rom 7:18-25 and the people that Jesus condemned as hypocrites in Luke 12:54-59 - the desire and effort to do good.

Even while it is true that we are bound by human limitations, we must always strive to live above boards. And then, remember that we have no power of our own. But with God on our side, we can do all things.

We therefore pray with the psalmist that he, the Lord, may teach us his statutes (cf. Ps 119:68) and help us to keep them at all times. Amen.

Have a lovely day spent in God's merciful love. Peace with you, through Christ our Lord, AMEN

Thursday, 26 October 2017

*Lazio to wear image πŸ“· of Anne Frank on shirts after fans' anti-Semitic slogans

On Sunday, during a leading football match in Europe, fans of Italian club Lazio posted stickers around Rome's Stadio Olimpico depicting Holocaust victim Anne Frank wearing the shirt of city rivals Roma alongside anti-Semitic slogans. 
The head of Rome's Jewish community, Ruth Dureghello, tweeted a picture of the stickers, writing: "This isn't the terraces, this isn't soccer, this isn't sport. Kick anti-Semitism out of the stadiums." 
Italian President Sergio Mattarella was widely reported to have called the case "alarming for our country," while Lazio players will wear an image of Frank on their shirts during the warm-up to Wednesday's Serie A match against Bologna.

In a statement on the club website, Lazio president Claudio Lotito said the move showed the team's commitment to fighting "all forms of racism and anti-Semitism." 
According to Italian newspaper Gazzetta dello Sport, Lotito has also promised that the club would organize an annual trip for 200 young fans to Auschwitz, where more than one million people were murdered in a Nazi concentration camp. 
Italian police is investigating Sunday's incident, and using the stadium's surveillance cameras, has identified 15 people, two of which are minors. All are possibly facing charges of incitement to racial hatred.

*Saudi πŸ‡ΈπŸ‡¦ Crown Prince πŸ‘‘ calls Qatar embargo a 'small issue' 😱*

Saudi Arabia's Crown Prince downplayed his country's months long dispute with Qatar in rare comments about the diplomatic and economic boycott.

"Qatar is a very, very, very small issue," Crown Prince Mohammed bin Salman said late Wednesday in a Reuters interview about the tiny gas-rich Gulf Arab country that has been the target of a major embargo since June.

"We're pursuing (the Yemen war) until we can be sure that nothing will happen there like Hezbollah again," bin Salman told Reuters, referring to the Iran-backed Lebanese Shia group.

Saudi Arabia, backed by a coalition of Arab states, launched a military operation in March 2015 against Iranian-backed Houthi rebels who toppled the internationally recognized leadership in Yemen.

I appeal to the parties to make the necessary concessions that can help paving the way for a long-lasting peace, and to the international community to ensure unity of purpose in supporting these much-needed initiatives," said UN envoy Ould Cheikh Ahmed.

*Twitter bans RT and Sputnik ads amid election interference fears

Twitter is banning two of Russia's biggest media outlets from buying advertising amid fears they attempted to interfere with the 2016 US election.

Twitter said the decision "was based on the retrospective work we've been doing around the 2016 US election and the US intelligence community's conclusion that both RT and Sputnik attempted to interfere with the election on behalf of the Russian government".

The statement, published on the social media platform's blog, continued: "We did not come to this decision lightly, and are taking this step now as part of our ongoing commitment to help protect the integrity of the user experience on Twitter."

The decision has provoked an angry response in Russia, with the country's foreign ministry accusing Twitter of bowing to pressure from the US intelligence services, saying the move was "another aggressive step" aimed at blocking Russian media in the US.

It added "retaliatory measures" would follow, according to RIA Novosti news agency [in Russian], Meanwhile, responding to the allegations, RT's deputy editor-in-chief Kirill Karnovich-Valua said the outlet "has never been involved in any illegal activity online, and that it never pursued an agenda of influencing the US election through any platforms".

*Ancient skull πŸ’€ may belong to earliest known tsunami 🌊 victim❗*

An ancient skull dating back more than 6,000 years may have belonged to the earliest known human victim of a tsunami, scientists say.

"The geological similarities between the sediments at the place where the skull was found and sediments laid down during the 1998 tsunami that hit this same coastline have made us realize that human populations in this area have been affected by these massive inundations for thousands of years."

"If we are right about how this person had died ... we have dramatic proof that living by the sea isn't always a life of beautiful golden sunsets and great surfing conditions," said its co-author John Terrell, Regenstein curator of Pacific anthropology at the Field Museum in Chicago.

Terrell, who has conducted extensive research in Papua New Guinea, also noted that the skull might help convince skeptics "that all of us on earth must take climate change and rising sea levels seriously."

"Many people in the world today face the threat of rising sea levels and (the) increasing numbers and power of climatic events, like tsunamis," added Marta Mirazon Lahr, from the Leverhulme Centre for Human Evolutionary Studies at the University of Cambridge, noting that almost 80% of the world's population today lives near the coast.

*At least 47 killed πŸ’ in Indonesia fireworks πŸŽ† factory explosion πŸ’₯*


At least 47 people were killed and dozens others injured in a fireworks factory explosion near the Indonesian capital of Jakarta on Thursday.

Regional police spokesman Argo Yuwono said 103 workers were believed to be in the building at the time of the blast and that 10 remained unaccounted for, according to CNN Indonesia, a CNN affiliate. Moreover

"We don't know, however, if those 10 workers were actually in the factory at the time, or whether they may have been ill and not come to work," he said. Officials said that a large explosion took place, followed by a smaller one, and that a fire then broke out, leaving some of the victims with burns.

The explosion occurred Thursday morning in Tangerang, a satellite city on Jakarta's western outskirts, where there are several industrial park.

The Kenyan πŸ‡°πŸ‡ͺ elections - what's happened so far?*

Kenya is holding a presidential election rerun because the Supreme Court nullified the results of the August 8 poll, which was won by President Uhuru Kenyatta. Opposition leader Raila Odinga, who got 45 percent of the vote last time round, has called for a boycott. President Kenyatta has urged voters to turn out, but also said those who wished not to vote were protected by the country's constitution.

The election re-run has been marred by isolated clashes and a boycott by the main opposition. A teenage boy was shot by police and later died amid clashes in the opposition stronghold of Kisumu, one of four counties hit by violence. The electoral commission said voting in those areas would be postponed until Saturday.

Tens of thousands of police and other security staff deployed to protect voters and polling stations, which closed at 17:00 local time (14:00 GMT). International observers have scaled down their missions for security reasons. The electoral commission has seven days to declare the results. 
After casting his vote in the town of Gatundu, Kenyatta had urged people to cast their ballots so the country could move on. "We're tired as a country of electioneering. It's time we moved forward," he said, adding that most of the country was "calm and peaceful".

More than 19 million Kenyans are registered to vote in the election rerun.

Juventus 4 SPAL 1: Bernardeschi, Dybala brilliance inspires champions to victory

Juventus kept the pressure on Serie A leaders Napoli with a 4-1 win over struggling SPAL at the Allianz Stadium on Wednesday.

Spectacular first-half goals from Federico Bernardeschi and Paulo Dybala set the champions on course for back-to-back league wins, before Gonzalo Higuain and Juan Cuadrado struck after the break.

Bernardeschi's stunning volley put Juve ahead early on and another fine free-kick from Dybala doubled the lead after only 22 minutes, as Massimiliano Allegri's side threatened a repeat of the goalscoring form they showed in the 6-2 thrashing of Udinese last time out.

SPAL recovered from their early jitters to make life more difficult but their heads dropped again when Higuain and Cuadrado scored in quick succession not long after the disallowed goal, and only a belated offside call denied the Argentina striker what would have been his 100th Serie A goal late on.

There was even a chance for Claudio Marchisio to make his first appearance since the opening-day win over Cagliari, the midfielder having recovered at last from a knee injury, as Juve cruised to the win that keeps them three points behind Napoli.

Juventus on best Serie A scoring pace in 65 years

Despite sitting just third in Serie A, Juventus are scoring at a rate not seen in the Italian top flight since the 1950s.

Juve's 4-1 win over SPAL on Wednesday saw the club hit their 31st goal of the season in just their 10th league game of the campaign.

The last time a Serie A side hit that many goals in their first 10 matches was when Juventus scored 32 during the 1951-52 season.

Paulo Dybala's ability to striker from distance has played a big part in the team's success to this point.

The 23-year-old leads all Serie A players with four goals from outside the box this season.

Juventus on best Serie A scoring pace in 65 years

Despite sitting just third in Serie A, Juventus are scoring at a rate not seen in the Italian top flight since the 1950s.

Juve's 4-1 win over SPAL on Wednesday saw the club hit their 31st goal of the season in just their 10th league game of the campaign.

The last time a Serie A side hit that many goals in their first 10 matches was when Juventus scored 32 during the 1951-52 season.

Paulo Dybala's ability to striker from distance has played a big part in the team's success to this point.

The 23-year-old leads all Serie A players with four goals from outside the box this season.

Tottenham 2 West Ham 3: Stunning comeback sees Hammers reach last eight

West Ham produced the most unlikely of second-half comebacks to beat Tottenham 3-2 at Wembley and book their place in the EFL Cup quarter-finals.

A dominant Spurs, without the rested Harry Kane, raced in to a two-goal half-time lead thanks to strikes from Moussa Sissoko and Dele Alli to seemingly leave Slaven Bilic's position hanging by a thread.

Bilic's players, though, produced a stirring second-half fightback, scoring three times in a stunning 15-minute spell to complete a remarkable turnaround.

Two quick-fire goals from Andre Ayew pulled the Hammers level before Angelo Ogbonna crashed a header in to seal a memorable win that provides their under-fire manager with a timely boost.

Bilic will now go into the Saturday's pivotal away clash with Crystal Palace full of confidence, while Tottenham will need to pick themselves up for a mouth-watering clash against Manchester United at Old Trafford, with one of their routes to silverware now gone.

*Spurs star Kane in doubt for Man United clash – Pochettino*

Tottenham manager Mauricio Pochettino revealed star Harry Kane is no certainty to face Manchester United on Saturday after missing the Carabao Cup midweek.

Kane, 24, sat out Tottenham's shock 3-2 loss to West Ham on Wednesday, having spearheaded Spurs against Real Madrid and Liverpool.

The Premier League's leading scorer - in pursuit of a third consecutive Golden Boot - was seemingly rested, though it appears there could have been more to Kane's absence at Wembley ahead of Tottenham's blockbuster trip to Old Trafford.

"We'll see, we'll see," Pochettino told beIN Sports when asked if Kane would face United after Spurs surrendered a 2-0 half-time lead against West Ham.

"We need to assess the team because we were forced to rotate for different reasons and we'll see what happens in the next few days."

Tottenham and United are level on 20 points after nine matches, five adrift of leaders Manchester City, though Jose Mourinho's men are second on goal difference.

*RB Leipzig 1 Bayern Munich 1 (aet, 4-5 pens): Ulreich denies Werner on night of spot-kick drama

There was penalty drama aplenty at the Red Bull Arena on Wednesday as Bayern Munich reached the last 16 of the DFB-Pokal thanks to a 5-4 shoot-out win over 10-man RB Leipzig.

After nine successful kicks, Timo Werner - who started on the bench - saw his weak penalty to the right saved low down by Sven Ulreich, who had come in for some criticism since replacing the injured Manuel Neuer as Bayern's number one.

The shoot-out followed a highly controversial 1-1 draw, which saw referee Felix Zwayer change his mind in awarding Leipzig a first-half penalty before giving the home side a soft spot-kick in the second period, either side of Naby Keita's dismissal for two cautions.

Emil Forsberg converted from 12 yards but Bayern were soon level through Thiago Alcantara and after the extra 30 minutes produced no further goals, the visitors kept their cool to join holders Borussia Dortmund in the draw.

Chelsea 2 Everton 1: Rudiger and Willian send spirited Toffees out

Chelsea 2 Everton 1: Rudiger and Willian send spirited Toffees out

Antonio Rudiger's header and Willian's stunning stoppage-time strike secured Chelsea a place in the EFL Cup quarter-finals as David Unsworth's first game in temporary charge of Everton ended in a 2-1 defeat.

Ronald Koeman's 16-month stint in charge of Everton was brought to a halt on Monday, following a humiliating 5-2 home defeat to Arsenal that left them 18th in Premier League.

However, a rejuvenated second-half display showed Everton's quality - with a moment of magic from Willian in the 92nd minute ensuring that Dominic Calvert-Lewin's effort soon after was a mere consolation.

Rudiger's superb 26th-minute effort, the defender's first goal for the Premier League champions, looked to have taken the spirit out of the Toffees, but Unsworth's side responded superbly and dominated in the second half - Willy Caballero pulling off a string of saves to preserve Chelsea's lead.

Ademola Lookman went close with a blistering strike against the bar just before Chelsea wrapped up the win late on.

Ultimately, though, it is now just two wins in 14 matches across all competitions for managerless Everton, who face fellow strugglers Leicester City next time out.

Pentagon: US airstrikes in Yemen kill 9 ISIS militants


The US military conducted two airstrikes targeting ISIS in Yemen on Wednesday, killing nine ISIS militants, according to US Central Command, which oversees US troops in the region. The two strikes hit ISIS vehicles and took place in al Bayda Governorate in Yemen. This is only the second time the US has targeted ISIS in Yemen with a series of strikes, suggesting US planners are increasingly concerned about the terror group's presence there.

Military strikes there have historically targeted al Qaeda in the Arabian Peninsula. "Ongoing US counter-terrorism operations against ISIS in the ungoverned spaces of Yemen continued today with two strikes, which killed nine terrorists," said US Army Maj. Josh Jacques, a Central Command spokesperson.

The first strike successfully targeted seven armed ISIS fighters travelling in a truck in a rural area of al Bayda. The second strike killed two armed ISIS fighters in a parked truck located about five miles to the west of the first site, Jacques said. In the last 10 days, US forces have successfully targeted and removed 60 ISIS terrorists from the battlefield in Yemen.

George HW Bush apologizes after actor accuses him of sexual assault


George HW Bush has reportedly apologized after an actor accused him of sexual assault.

Heather Lind, 34, alleged that the former US president “sexually assaulted” her when they posed for a photograph several years ago, according to a since deleted Instagram post. “He touched me from behind from his wheelchair with his wife Barbara Bush by his side. He told me a dirty joke,” she posted, according to the Mail Online.

A spokesman for the former president, who is 93, told the Mail Online: “President Bush would never – under any circumstance – intentionally cause anyone distress, and he most sincerely apologizes if his attempt at humour offended Ms Lind.”

In the Instagram post, Lind, who has starred in AMC’s 'Turn: Washington’s Spies', said the president touched her a second time and “Barbara rolled her eyes as if to say ‘not again’.”

“His security guard told me I shouldn’t have stood next to him for the photo,” Lind said

124 dead , nearly 1,200 infected with plague in Madagascar

 

A plague outbreak in Madagascar has infected 1,192 people since August, with 124 deaths, the United Nations Office for the Coordination of Humanitarian Affairs and Madagascar's National Bureau of Risk Management and Disaster reported on Monday.

Pneumonic plague is more virulent or damaging and is an advanced form characterized by a severe lung infection that can be transmitted from person to person via airborne droplets such as through coughing or sneezing, for example.

Charlotte Ndiaye, WHO representative in Madagascar, added that about half the deaths are occurring in the community, not health centers, according to government figures, which demonstrates that more work needs to be done to help people understand that treatment is available, and they need to go to health services as quickly as possible.

Plague is endemic to Madagascar, with an estimated 400 cases reported there every year, mostly the bubonic variety, but the current outbreak has affected more areas and started earlier than usual.

She explained WHO is working closely with Madagascar's airport authorities to ensure control measures -- such as temperature checks and medical teams -- are in place at airports and ports to prevent the spread of infection outside the country.

Honolulu first world city to ban texting while crossing road

Honolulu in Hawaii has become the first city in the world to ban people from looking at their phones or other digital devices while crossing roads. The law, passed in July in an attempt to reduce injuries and deaths that occur while people are distracted, came into force on Wednesday.

The Distracted Walking Law states that "no pedestrian shall cross a street or highway while viewing a mobile electronic device".

The National Safety Council in the US added "distracted walking" to a list of injury risks in 2015, the same year a study in the Journal of Safety Studies found that hundreds of American pedestrians a year were injured while engrossed in their phones.

Other countries have tried to find technological ways of dealing with the problem of "smartphone zombies", from , to but, crucially, are in the line of sight of someone looking at a telephone.

Pentagon: US airstrikes in Yemen kill 9 ISIS militants


The US military conducted two airstrikes targeting ISIS in Yemen on Wednesday, killing nine ISIS militants, according to US Central Command, which oversees US troops in the region. The two strikes hit ISIS vehicles and took place in al Bayda Governorate in Yemen. This is only the second time the US has targeted ISIS in Yemen with a series of strikes, suggesting US planners are increasingly concerned about the terror group's presence there.

Military strikes there have historically targeted al Qaeda in the Arabian Peninsula. "Ongoing US counter-terrorism operations against ISIS in the ungoverned spaces of Yemen continued today with two strikes, which killed nine terrorists," said US Army Maj. Josh Jacques, a Central Command spokesperson.

The first strike successfully targeted seven armed ISIS fighters travelling in a truck in a rural area of al Bayda. The second strike killed two armed ISIS fighters in a parked truck located about five miles to the west of the first site, Jacques said. In the last 10 days, US forces have successfully targeted and removed 60 ISIS terrorists from the battlefield in Yemen.

Kogi Govt Bans Unionism In State-Owned Tertiary Institutions*

Kogi State government has banned the activities of the Joint Action Committee (JAC) of Trade Unions of Tertiary Institutions and all forms of unionism in the state-owned tertiary institutions. The government made the announcement in a statement signed on Wednesday by the state governor, Yahaha Bello.

Institutions affected are Kogi State Polytechnic, Lokoja; Kogi State College of Education, Ankpa; Kogi State College of Education Technical, Kabba; College of Nursing and Midwifery, Obangede; College of Health Sciences and Technology, Idah; and Kogi State University Teaching Hospital, Anyigba.

The government said it respects the rights of all citizens to responsibly associate and pursue their welfare within the ambits of the Constitution of the Federal Republic of Nigeria, the laws of the state, the rights of other citizens and the general norms of a democratic society.

Nigerian Prison Inmates To Start Voting In 2019 - INEC*

Yes The Independent National Electoral Commission (INEC) has announced that it is making arrangements with the Nigerian Prisons Service to allow certain prisoners to vote in the forthcoming 2019 general elections. INEC Chairman Mahmood Yakubu said this on Tuesday in Abuja at a dialogue session involving over 70 civil society organizations in Nigeria.

This development is coming three years after a Federal High Court in Benin, Edo State ruled that prisoners in Nigeria have the right to vote in all elections conducted in every part of the country. Mr. Yakubu said that INEC is considering creating polling units in Nigerian prisons, clarifying that only “certain categories of prisoners” would be given the right to vote depending on the nature of the crimes committed.

“We have already engaged the Comptroller-General of Prisons and we have statistics on the number of prisoners nationwide and the number of inmates registered. We are looking at the possibility of creating polling units in the prisons and to enable some categories of prisoners to vote.

Guatemalan πŸ‡¬πŸ‡Ή first to be sentenced πŸ‘€ in US πŸ‡ΊπŸ‡Έ Fifa scandal*


A former Guatemalan judge who led his country's football federation has become the first person to be sentenced in a US investigation into corruption in Fifa. Hector Trujillo was sentenced to eight months in prison after pleading guilty to wire fraud and conspiracy.

He admitted to accepting almost $200,000 in bribes from a sports marketing company. Trujillo admitted offering media and marketing rights to Guatemala's World Cup qualifier matches in return for bribes.

The US investigation was first revealed in May 2015 and has seen federal prosecutors in New York indict around 40 sports and football executives linked to football in the Americas.

Jonathan’s loyalists responsible for Maina’s reinstatement – Presidency

The Presidency on Wednesday said some influential government officials loyal to the administration of former President Goodluck Jonathan were responsible for the reinstatement of the embattled former Chairman of the defunct Presidential Task Force on Pension Reforms, Mr Abdulrasheed Maina, into the service.

The Senior Special Assistant to the President on Media and Publicity, Garba Shehu, stated this in a statement made available to journalists. Shehu was reacting to a statement by the Peoples Democratic Party on the matter. He said the PDP had no moral right to level any accusations against the current government in respect to Maina.

“Some influential officials loyal to the previous government may have been the invisible hand in the latest scandal that saw the return of Maina to the public service, despite being on the EFCC’s wanted list,” the presidential spokesman said.

Nicki Minaj Channels Her Inner Goddess

Nicki Minaj Channels Her Inner Goddess
😡
"Celebrating 'The Greats' issue for the New York Times style magazine The Met Breuer in NYC. I'm told I'm the 3rd musician to be on the cover. Such a proud New Yorker tonight. Dress by Botegga Venetta. Shawl by Givenchy."

Love sin- cherish death

⏰Thursday of the Twenty-Ninth Week of Ordinary Time 1 (26 October 2017)

📖Rom 6:19-23; Ps 1:1-2, 3, 4 and 6 (R. Ps 40:5ab); Luke 12:49-53

🎤"THE WAGES OF SIN IS DEATH, BUT THE FREE GIFT OF GOD IS ETERNAL LIFE IN CHRIST" (Rom 6:23)

You see, out of laziness or wickedness, and in a bid to run away from our family responsibilities, many of us try to appeal to religion as a tool of division. Imagine a brother telling his siblings that he will not take care of them until they have embraced his religious orientation. Is that Christ-like? Even Christ himself embraced sinners.

So, what does Jesus mean when he says that he has come to bring division and not peace (Luke 12:49-53)? The answer must be seen more from the individual before going social. First, the division separates the old self which was rooted in sin and death from the new self which has embraced light and life.

The new self refuses to be associated again with its sinful past, which may include family or national beliefs. This refusal might attract resentment from families and nation. So, it is not the individual who is separating himself.

Instead of focusing on that social division, we are encouraged to yearn more for the internal division which is necessary for our salvation. St. Paul reminds us that the wages of sin is death. Christ has already separated us from that sin and death through his own death on the cross (cf. Rom 6:19-23).

It is important that we maintain this particular division so that we might remain on the track to eternal life. And may God grant us the grace to stay away from sin and embrace the free gift of eternal life which he gives us in Christ. Amen.

Have a spiritually focused and fulfilling day. Peace be with you.

Wednesday, 25 October 2017

Miracle subduer

Miracle miracle MIRACLE

"An eight-year-old child heard her parents talking about her little brother. All she knew was that he was very sick and they had no money left. They were moving to a smaller house because they could not afford to stay in the present house after paying the doctor's bills. Only a very costly surgery could save him now and there was no one to loan them the money.

When she heard her daddy say to her tearful mother with whispered desperation, 'Only a miracle can save him now', the little girl went to her bedroom and pulled her piggy bank from its hiding place in the closet. She poured all the change out on the floor and counted it carefully.

Clutching the precious piggy bank tightly, she slipped out the back door and made her way six blocks to the local drugstore. She took a quarter from her bank and placed it on the glass counter.

"And what do you want?" asked the pharmacist.

"It's for my little brother," the girl answered back. "He's really very sick and I want to buy a miracle."

"I beg your pardon?" said the pharmacist.

"His name is Andrew and he has something bad growing inside his head and my daddy says only a miracle can save him. So how much does a miracle cost?"

"We don't sell miracles here, child. I'm sorry," the pharmacist said, smiling sadly at the little girl.

"Listen, I have the money to pay for it. If it isn't enough, I can try and get some more. Just tell me how much it costs."

In the shop was a well-dressed customer. He stooped down and asked the little girl, "What kind of a miracle does you brother need?"

"I don't know," she replied with her eyes welling up. "He's really sick and mommy says he needs an operation. But my daddy can't pay for it, so I have brought my savings".

"How much do you have?" asked the man.

"One dollar and eleven cents; but I can try and get some more", she answered barely audibly.

"Well, what a coincidence," smiled the man, "A dollar and eleven cents - the exact price of a miracle for little brothers."

He took her money in one hand and held her hand with the other. He said, "Take me to where you live. I want to see your brother and meet your parents. Let's see if I have the kind of miracle you need." 

That well-dressed man was Dr Carlton Armstrong, a neurosurgeon. The operation was completed without charge and it wasn't long before Andrew was home again and doing well.

"That surgery," her mom whispered, "was a real miracle. I wonder how much it would have cost."

The little girl smiled. She knew exactly how much the miracle cost ... one dollar and eleven cents ... plus the faith of a little child.

Perseverance can make miracles happen! Miracle can come in various forms - as a doctor, as a lawyer, as a teacher, and many others..

A river cuts the rock not because of its power, but because of its consistency.

Never lose your hope; keep walking towards your vision."‎

Judge not

*AN INTERESTING READ*

A girl by name Fatima went to school in the neighbouring village where she wasn't known well.

For three weeks, she came to school late and every time the teacher punished her.

On the fourth week, Fatima didn't attend school at all and many thought she had *GIVEN UP* on school due to the everyday punishment.

However, Fatima reported again on fifth week and this time she came earlier than everybody.

When the teacher came to class, Fatima was punished for not attending school the previous week but the teacher was also kind enough to commend her for coming early that day, stating that the punishments had finally yielded some results.

Just then, Fatima asked if she could say something and the teacher gave her permission.

Then she started

_"I've been raised up by a single mother without a brother or a sister. Five weeks ago, my mother fell ill and was hospitalized. The three weeks I came late, I had to prepare something for her every morning and pass by the hospital to deliver the same. Unfortunately, mother passed away last week and that's the reason I didn't come to school. We buried her last Friday. Today I came early since I didn't have to prepare anything or even pass by the hospital. And now that she is gone, I will always be here early''_

As she sat down, no one in the whole class was able to hold their tears, the teacher was not spared either.

*Lesson:*

How many times do we judge others for things we know not ?

We ask questions like :

- When will you get married?
- When will you have kids ?
- When will you find a job ?
-When will you buy a car?
-When will you build a house?
etc....

Do we attempt to understand their situations or we just judge from the *case scenarios*

Some situations are not relative and what we think could be very far from the truth.

Don't assume you know what others go through or that people move in the same pace or direction as you

_*Life is far from that..*_

Just be kind enough to love one another as God has commanded, take time and kindly find out why your friend is not phoning, why your messages are not being replied promptly, why they are not coming to worship, why someone is missing in our midst as a colleague, friend, brother or sister even why someone is always late

Be kind, always......the position u are is not permanent someone was there before u and someone w b available when u leave d position. B nice to others.

🎀TO WHOM MUCH IS GIVEN, MUCH IS EXPECTED (Luke 12:48)

⏰Wednesday of the Twenty-Ninth Week of Ordinary Time 1 (25 October 2017)

📖Rom 6:12-18; Ps 124:1-3, 4-6, 7-8 (R.v.8a); Luke 12:39-48

🎤TO WHOM MUCH IS GIVEN, MUCH IS EXPECTED (Luke 12:48)

Yesterday, we pointed out about two challenges which Christ's coming into the world gives to us - to stay away from sin and to assist others to come to have a share in that salvation. These challenges are not optional to us as Christians. They are the only ways we can reciprocate the great love of God for us.

Again, we pointed out that the time to begin is now as tomorrow might be too late. Are you in the camp of those who always think they can 'enjoy' sin today and repent tomorrow? A stitch in time saves nine; be warned!

By the way, have you heard the Catholics talk about mortal and venial sins? We say that mortal sin is a serious offence against God which kills the soul and deserves hell while venial sin is ALSO an offence against God which DOES NOT kill the soul, but can lead to mortal sin. Venial sins are more easily pardoned than mortal sins.

"These Catholics don come again!" abi? Read Luke 12:45-48 and see for yourself whether that is Catholic invention.

And while doing that, also reflect on this: Assuming both the servant, who deserves to be punished with severe beatings, and the one who, deserves to be beaten lightly, dies at the same time, will our God of justice subject both of them to hell? If he does that, where would be the justification of paying each man according to his deed (Matt 16:27)? Now, does the doctrine of purgatory still sound unbiblical to you?

May God continue to give us the grace to stay away from all sins, whether mortal or venial, so that we may enjoy the opportunity that grace offers us (Rom 6:12-18) and so journey smoothly into eternal life. Amen.

Have a blessed day ahead. Peace be with you.

🎀"HERE I AM, LORD; I COME TO DO YOUR WILL" (Ps 40:8, 9)

⏰Tuesday of the Twenty-Ninth Week of Ordinary Time 1 (24 October 2017)

📖Rom 5:5, 12, 15b, 17-19, 20b-21; Ps 40:7-8a, 8b-9, 10, 17 (R.v.8a, 9a); Luke 12:35-38

🎤"HERE I AM, LORD; I COME TO DO YOUR WILL" (Ps 40:8, 9)

Are you encouraged by the account of our redemption which St. Paul gives us in Rom 5:12-21? St. Paul reminded us there that, through his coming, which we shall celebrate at Christmas in no distant time time, Jesus restored us back to life from death. That is a message of joy!

Nonetheless, that places two important challenges to us:
👉 We must work hard to stay away from sin, which initially placed us in that condition of death, so that we may remain alive in Christ.
👉 Now that we have been redeemed, we must assist Christ in working for the redemption of others. That is the challenge which St. Paul throws at the Romans, and indeed, to us today.

There is no gain waiting in order to begin another day. The Lord wants us to be on our toes doing good at all times so that he will meet us at it when he beckons on us to come to him (see Luke 12:35-38).

Are you ready to respond to him?

May God strengthen us always to do his will at all times. Amen.

Have a grace filled day ahead. Peace be with you.

Monday, 2 October 2017

SEMINAR PRESENTATION ON BCH 411 FRONTIERS IN BIOCHEMISTRY, MOLECULAR BIOLOGY AND BIOTECHNOLOGY TOPIC:THE ROLE OF GUT MICROBIOTA IN THE DEVELOPMENT OF DIABETES AND OBESITY. PRESENTED BY OBINWA MARY-ANN UKAMAKA REG NO: 2012474143 DEPARTMENT OF APPLIED BIOCHEMISTRY FACULTY OF BIOSCIENCES NNAMDI AZIKIWE UNIVERSITY,AWKA. SUPERVISOR: MR.NWAJIOBI JIDE DATE:DECEMBER, 2016 A ABSTRACT A recent growing number of evidences show that the increased prevalence of obesity and diabetes cannot be attributed to changes in the human genome, nutritional habits, or reduction in physical activity in our daily lives Gut microbiota may play an even an more important role in maintaining human health, as it function much like a “metabolic organ” influencing nutrient aquisition, energy homeostasis and, ultimately, the control of the body weight. Moreover, alterations in gut microbiota can lead to increase intestinal permeability, and metabolic endotoxemia which play a rolesss in the development of chronic low grade inflammatory state in the host that contributes to the development of obesity and diabetes. However the fact that gut microbiota can be modulated through dietary components highlights the importance to study how fatty acid, carbohydrates, probiotics, can influence gut microbiota composition and management of obesity. Gut microbiota seems to be an important and promising target in the prevention and treatment of obesity and its related metabolic disturbances. INTRODUCTION The epidemics of obesity and type 2 diabetes mellitus in the past 20 years have led to numerous investigations concerning the mechanisms that are responsible for the development of these diseases. The general view is that insulin resistance is an early alteration of type 2 diabetes mellitus and obesity, and both diseases are strongly influenced by genetics and environment. Moreover, studies in the past ten years have shown that low-grade inflammation has an important role in the molecular mechanism of insulin resistance in these diseases and more recently (within the past five years) a new component that has both genetic and environmental factors is also being studied: the gut microbiota. This way, a paradigm has been dismantled: microorganisms should no longer be associated with pathogenesis, since both bacteria and their eukaryote hosts benefit from their cooperative relationships. In humans, there are at least 100 trillion microbial cells, collectively called microbiota, distributed in complex and site-specific communities. As the genome of these bacteria—the microbiome—contains hundreds of genes that do not exist in the human genome, we can consider our symbionts as an important extra organ. This complex community—bacteria, eukaryotes, viruses and Archeae—in its majority cannot be cultured. The reasons for this limitation are unknown growth requirements of the bacteria, selectivity of the media that are used, stress imposed by the cultivation procedures, necessity of strictly anoxic conditions, and the difficulties on simulating the interactions of bacteria with other microbes and host cells. Thus, a new approach was introduced, culture-independent sequencing, which made detection of microbial genes and disease-associated patterns in our gut microbiota possible. The bacterial component of the microbiota has been intensively studied in the past few years, including high-investment studies such as the Human Microbiome Project and MetaHIT. Using this new approach made it possible to detect three dominating bacterial phyla in the human gastrointestinal tract: the gram-positive Firmicutes and Actinobacteria, and the gram-negative Bacteroidetes. Firmicutes is known as the largest bacterial phylum, comprehending 200 genera, which includes Lactobacillus, Mycoplasma, Bacillus, and Clostridium. In spite of Actinobacteria being also a dominant phylum, it is usually missed by RNA gene sequencing and can only be detected by fluorescent in situ hybridization. Although gut microbiota has been described as relatively stable concerning its composition until old age, this temporal consistency considers that numerous variables are being held constant. For example, dietary changes have been shown to have significant effects on the microbiota. Shifting mice to a high-fat, high-sugar ―Western‖ diet, from a low-fat, plant polysaccharide-rich diet, changed the microbiota within 24 hours . Likewise, shifting from a high-fat/low-fiber diet caused notable changes in the gut microbiota within a day. ORIGIN AND COMPOSITION OF GUT MICRIBIOTA The human body contains trillions of microorganisms that inhabit our bodies during and after birth.The gastrointestinal tract starts to be colonized during the delivery of the baby. During the first two years of life de microbiota is unstable and less diverse than in the adulthood, when the complexity and diver-sity is higher. 5 Many external factors influence the composition of the microbiota, especially the diet, the hygiene conditions and the use of antibiotics. 6ing the pregnancy, infant’s intestinal tract is free of mi-crobes until exposed to maternal vaginal microbes during normal birth. Infants born through Caesarian section are exposed to maternal skin bacteria altering their bacterial gut composition. Feeding represents another source of microorganisms where breast fed babies have different gut microbiota composition than formula fed babies(Tanaka et al.,2009). Introduction of solid food represents another shift in the composition of babies gut microbiota. After that, gut microbiota remains relatively unchanged until old age where the composition changes again. Adulthumans have more than 10 times the number of bacterial cells than the cells constituting the human body. Majority of microbiota in the GI tract are bacteria, nevertheless, viruses fungi and other microorganisms are still present. Even though, individuals have unique microbiota composition, gut microbiota is mainly members of four phyla (Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria) ,The distribution of microorganisms throughout the gastrointestinal tract is not homogenous. The stressful environment (gastric juice, bile, pancreatic juice, peri-stalsis) in the stomach and small intestine limits bacte-rial growth and the number of microorganisms.The large intestine contains the highest number of bacteria con-taining over 10 11 bacteria per gram of intestinal con-tent. The mouth contains 10 12 followed by the Ileum containing 10 8 –10 9 bacterial. On the other hand, the jejunum harbors 10 5 –10 6 while the stomach has the least number of bacteria 10 3 –10 4(Othman et al.,2016). The gut microbiota plays different roles that are important for the host. They exert a trophic effect in the intestinal epithelium, favoring the development of the microvilli, which in turn favors the absorption of nutri-ents. The influence of microbiota in innate and adaptive immune system maturation contributes to systemic and local immune homeostasis and immune tolerance for a variety of antigens. The modulation of the immune system activity can influence the intestinal barrier func-tion. The capacity to break down non-digested dietary molecules into metabolites such as short chain fatty acids (SCFS) and to synthesize vitamins demonstrates their importance to human nutrition. Even though we are still far from identifying, let alone characterizing all bacteria in our system, advancing molecular biology techniques such as next-generation sequencing has tremendously contributed to our understanding of the gut microbiota(Ji and Nielsen.,2015). The use of gnotobiological methods to breed mice in a sterile environment provided an invaluable tool to understand the role of infecting con-trolled bacterial cultures and defined bacterial strains into animals. Studying their effect through various genomic and proteomic tools. DIABETES AND GUT MICROBIOTA It’s becoming increasingly evident that gut microbiota is contributing to many human diseases including diabetes both type 1 and type 2. Type 1 diabetes (T1D) is an autoimmune disease that is caused by the destruction of pancreatic Ξ²-cells by the immune system. Even though T1D is mainly caused by genetic defect, epigenetic and environmental factors have been shown to play an im-portant role in this disease. Higher rates of T1D inci-dence have been reported in recent years that are not explained by genetic factors and have been attributed to changes in our lifestyle such diet, hygiene, and antibiotic usage that can directly affect microbiota. It has been shown that diabetes incidence in the germ free non-obese diabetic subjects or patients (NOD) was significantly increased which is in line with the observa-tion that the rates of T1D is higher in countries with stringent hygiene practices (Guiden et al.,2015). Similarly comparison of the gut microbiota composition between children with high genetic risk for T1D and their age mhealthy controls showed less diverse and less dynamic microbiota in the risk group. In the Diabetes Pre-vention and Prediction (DIPP) study it was shown that new-onset T1D subjects had different gut microbiota composition than controls(Murri et al., 2013).They showed that in the control group, mucin synthesis was induced by lactate- and butyrate-producing bacteria to maintain gut integrity while mucin synthesis was prevented by the non-butyrate-producing lactate-utilizing bacteria leading to Ξ²-cell autoimmunity and T1D (Othman et al.,2016). Recently, research has pointed out that the intestinal microbiome might be an important contributor for the development of type 2 diabetes (T2D). The use of genome-wide association studies (GWAS) has achieved many elucidations in this matter(Qin et al.,2013). characterized the gut microbiota of T2D patients and observed increase in membrane transport of sugars, branched-chain aminoacids transport, methane metabolism, xenobiotics degradation, and sulphate reduction. However, they observed decrease in the levels of butyrate biosynthesis, bacterial chemotaxis, flagellar assembly, vitamins and cofactors metabolism. This study has also shown that the gut environment of T2D individuals is one that stimulates bacterial defense mechanisms against oxidative stress and against drugs. (Andrea and Mario, 2013) GUT MICROBIOTA AND ITS ROLE IN ENERGY HOMEOSTASIS AND THE DEVELOPMENT OF OBESITY The metabolic activities of the gut microbiota have the end results of extracting calories from ingested dietary substances, helping to store those calories in host adipose tissue for later use, and providing energy and nutrients for microbial growth and proliferation. BΓ€ckhed et al 1 dem-onstrated that conventionally raised mice have a 40% higher body fat content and 47% higher gonadal fat con-tent than germ-free (GF) mice, despite lower food intake (Frazier et al 2011). However, it has been suggested that the main routes under influence of gut microbiota that could contribute to obesity develop-ment are provision of extra calories, increased lipopro-tein lipase (LPL) activity, lipogenesis, increased intestinal permeability, endotoxemia and endocannabi-noid (eCB) system (Blaut and Klaus, 2012).Gut microbiota contribute to energy metabolism through the production of SCFA that are produced by colonic fermentation which involves the anaerobic breakdown of dietary fiber, protein and peptides . The most important SCFA produced are acetate, propionate and butyrate. Acetate and propionate are mostly produced by Bacteriodetes phylum while butyrate is produced by the Firmicutes phylum (Othman et all 2016). These SCFA can provide additional calories when they are oxidized by the host, favoring the higher weight and fat gain observed in these animals. In addition, the binding of SCFA to G protein-coupled receptor (GPR) in the intestine induces the secretion of the hormone peptide YY (PYY). This hormone reduces intestinal transit time, increasing the time for nutrient absorption from the intestinal lumen. In fact, obese and overweight subjects presented higher concentration of SCFA in their feces in comparison to lean individuals (Bodoni et al, 2014). Low grade inflammation is a hallmark of obesity. Production of pro- inflammatory cytokines are coordinated via the Toll- like receptors and the master regulator of of key inflammation cascades the nuclear factor kappa(NF-kB) (Kim et al, 2012). The LPL (lipopolysaccharide) activity influences the accumulation of triglycerides in the adipose tissue. The microbiota can affect the activity of this enzyme by the influence on the expression of the protein fasting-induced adipose factor (FIAF). In the absence of microbiota (germ-free mice) it is observed higher expressin of FIAF. 16 On the other hand, the conventionalization of the germ-free animal causes inhibition of the expression of the FIAF and also stimulates body fat gain. It is suggested that FIAF is a circulating inhibitor of LPL activity. Thus, the inhibition of FIAF expression by the presence of microbiota allowus higher activity of LPL and accumulation of triglycerides in adipocytes (Backhad et al, 2004). Figure 2: Alteration in gut microbiota composition due to obesity is accompanied by changes in activation of enzymes and pathways which leads to and increased inflammatory state and energy harvest. AMPK: AMP- activated kinase, SCFA: Short chain fatty acids, LPL: Lipoprotein lipase, ACC: acetyl- CoA carboxylase, CPT1: Carnitine palmitoyltransferase. Source: Andrea and Mario., 2013 THE EFFECT OF GUT MICROBIOTA ON ENERGY METABOLISM The biological functions controlled by the intestinal flora are related to the effectiveness of energy harvest, by the bacteria, of the energy ingested but not digested by the host. Among the dietary compound escaping to the digestion occurring in the upper part of the human gastro-intestinal tract, the polysaccharides constitute the major source of nutrient for the bacteria. Part of these polysaccharides could be transformed into digestible substances such as sugars, or short chain carboxylic acids, providing energy substrates which can be used by the bacteria or the host. The control of body weight depends on mechanisms subtly controlled over time and a small daily excess, as low as 1% of the daily energy needs, can have important consequences in the long term on body weight and metabolism (Hill, 2015). Consequently, the gut microbiota of obese subjects changed according to the loss of body weight occurring after a hypocaloric diet. It was demonstrated that two groups of bacteria are dominant in the intestinal tract, Bacteroidetes and Firmicutes (Cani et al, 2008). The quantification and characterization of each dominant group of bacteria were carried out by measuring the concentration of the bacterial 16S rRNA. The number of Bacteroidetes bacteria depended on the weight loss whereas the Firmicutes bacteria group remained unchanged. Importantly, the bacterial lineage was constant one year after the dietary intervention for a given body weight, validating the bacterial signature of each individual. However, it could be related to the diet and in particular to the presence of dietary fibres (Cani et al, 2008). The gut bacteria from obese subjects are able to specifically increase the energy harvested from the diet, which provide an extra energy to the host. This conclusion was drawn from work showing that the axenic mice colonized with a conventional gut flora gain weight rapidly. The mechanisms of the apparent gain weight implied an increase in the intestinal glucose absorption, energy extraction from non-digestible food component (short chain fatty acids produced through the fermentation) and a concomitant higher glycemia and insulinemia, two key metabolic factors promoting lipogenesis. Thus an environmental factor such as gut microbiota regulates energy storage. The results, obtained both in rodents and human, suggest that obesity is associated with an altered composition of gut microbiota. However, this study did not demonstrate that the relative change in bacterial strains profile leads to different fates of body weight gain. This particularly original idea that the bacteria can contribute to the maintenance of the host body weight, is characterized by numerous paradoxes. It is not clear, however, whether the small increased of energy extraction can actually contribute to a meaningful body weight gain within a short period of time, as suggested in the gut flora transplantation studies. Moreover, other studies have clearly shown that a diet rich in non-digestible fibres decreases body weight, fat mass and the severity of diabetes (Cani et al, 2014). However these dietary fibres increase strains of bacteria able to digest these fibres and provide extra-energy for the host as they thus increase the total amount of bacteria in the colon (Kolida et al, 2013). This mechanism is not completely in accordance with the ‘‘energy harvesting theory’’ according to which the fermentation of non digestible polysaccharides would provide energy substrates for the host. In addition, it is difficult to conclude that small changes in energy ingestion (1–2%) can induce sufficient quick variation in weight (within two weeks) as observed in an American studies ( Backhed et aI, 2005). Importantly, the axenic mice colonized with the gut flora from normal mice ate more than their conventional mice counterparts; therefore, the body weight gain can also be dependent of the increased food intake. A last crucial point, which cannot depend only on the role played by the bacteria to harvest energy from nutrients escaping digestion in the upper part of the intestine, concerns a study showing that axenic mice are more resistant to diet-induced obesity. The authors maintained axenic or conventionalized mice on a high-fat/high-carbohydrates diet (western diet) and found that conventiona-lized animals fed the western diet gained significantly more weight and fat mass and had higher glycemia and insulinemia than the axenic mice. Strikingly, and opposite to the results previously observed in axenic mice fed a normal chow diet, the amount of western diet taken up by an axenic or a conventionalized mouse was similar and hence had similar fecal energy output. All those data suggest that a bacterially related factor is responsible for the development of diet-induced obesity and diabetes. GUT MICROBIOTA AND INFLAMMATION Obesity and type 2 diabetes are metabolic diseased characterized by a low grade inflammation (Wellen and Hotamisligil, 2011). In the models of high fat diet induced obesity, adipose depots express several inflammatory factors IL-1(interleukin-1), TNF-a (tumor necrosis factor-a) and IL-6 (interleukin-6) (Weisberg et al, 2010). These cytokines impaired insulin action and induce insulin resistance. For example, TNF-a phosphorylates serine residue substrate (IRS-1) from the insulin receptor leading its inactivation and it has been proposed that nutritional fatty acids trigger inflammatory response by acting via the toll-like receptor-4 (TLR4) signalling in the adipocytes and macrophages. It was shown that the capacity of fatty acids to induce inflammatory signalling following a high-fat diet feeding is blunted in the TLR4 knock out mice (Shi et al, 2014). TLR4 is the co-receptor for the lipopolysaccharides (LPS) constituent of the Gram negative bacteria. A triggering factor of the early development of metabolic diseases is the lipopolysaccharides, a molecule involved early in the cascade of inflammation. Furthermore, LPS is a strong inducer of inflammatory response and is involved in the release of several cytokines that are key factors triggering insulin resistance. The concept of dietary excess is more or less associated to high-fat feeding-induced inflammation. Experiment has shown that mice fed a high-fat diet for a short term period as two to four weeks exhibit a significant increase in plasma LPS. An endotoxemia that is characterized as a ‘‘metabolic endotoxemia’’, since, the LPS plasma concentrations were 10 to 50 times lower than those obtained during a septic shock. LPS is absorbed into intestinal capillaries to be transported by lipoproteins (i.e. chylomicrons). High-fat diet feeding changed gut microbiota in favour of an increase in the Gram negative to Gram positive. CD14 is a key molecule involved in the innate immune system is a multifunctional receptor constituted by a phosphatidyl inositol phosphate-anchored glycoprotein of 55 kDa expressed on the surface of monocytes, macrophages and neutrophils. CD14KO mice were hypersensitive to insulin even when fed a normal diet, suggesting that CD14 could be modulator of insulin sensitivity in physiological conditions. As a matter of fact, CD14KO mice resist high-fat diet and chronic LPS-induced metabolic disorders. Similarly hepatic steatosis, liver and adipose tissue inflammation and adipose tissue macrophages infiltration was totally blunted in the CD14KO mice fed a high-fat diet or bifidobacteria microflora Therefore high-fat feeding induced a low tone inflammation which originates from the intestinal absorption of the LPS. Thus data support the key idea that the gut microbiota can contribute to the pathophysiology of obesity and type 2 diabetes. High-fat feeding alters the intestinal microbiota composition were Bifidobacterium spp were reduced. Several studies have shown that this specific group of bacteria reduced the intestinal endotoxin levels and improved mucosal barrier function (Cani et al.,). The unique advantage of the prebiotic dietary fibres (oligofructose, [OFS])was used to specifically increase the gut bifidobacteria content of high fat diet treated mice. Among the different gut bacteria analysed, plasma LPS concentrations correlated negatively with Bifidobacterium spp. Together, these findings suggest that the gut microbiota contributes to the pathophysiological regulation of endotoxemia, and sets the tone of inflammation for the occurrence of diabetes/obesity. Thus, it would be useful to develop specific strategies for modifying gut microbiota to favour bifidobacteria growth and prevent the deleterious effect of high-fat diet-induced metabolic diseases (Cani et al.,2013). Figure 3: Signalling of LPs via NF-B and MAPK. ERK: extracellular signal related kinase, IL: Interleukin, IKB: Inhibitor of kappa B, IKK: IKB kinase, INOS: Inducible nitric oxide synthase, IRAK: Interleukin-1 receptor-associated kinase, JNK : c-jun NH2 –terminal kinase, LBP: Lipopolysaccharide binding protein, LPS: Lipopolysaccharide, MAPK: mitogen-activated protein kinase, MCP-1: monocyte chemotatic protein-1, MD-2: mycloid differentiation protein 2, MyD88: mycloid differentiation primary response gene 88, NF-KB: Nuclear factor Kappa B, NIK: NF-KB inducing kinase, TLR: toll-like receptor, TNF: tumor necrosis factor, TRAF6: TNF receptor-associated factor 6. Source: Boroni et al., 2014. MODULATION OF GUT MICROBIOTA The importance of gut microbiota in the mainte-nance of health has been receiving more attention worldwide. The homeostasis of gut microbiota depends on the characteristics of the host (age, gender, genetic factors) and the environment (stress, drugs, toxic agents, infections, diseases). However, the influ-ence of diet is also evident (Boroni Moreira et al., 2014). The conductance of future studies aiming to understand how changes in diet modulate gut microbiota composition is of great interest to help menu plannings that simulate the achievement of a favorable microbiota. Weight loss promotes changes in gut microbiota composition. .(Fleissner et al., 2015) The intake of specific dietary components (fatty acids, carbohydrates, micronutri-ents, prebiotics, probiotics) can result in changes in the composition of gut microbiota and modulate the expression of genes in the host, especially in organs as intestine, muscle, liver and adipose tissue (Boroni Moreira et al.2014,). The relevance of the use of prebiotics and probiotics in human’s obesity treatment is supported by few results obtained in interventional studies. However, animal models show potential beneficial effects. For example, genetically obese mice and mice fed with high-fat diet were given the prebiotic oligofructose. After the intervention it was observed a reduction in the circulatory levels of IL-18 and IL-1Ξ². These cytokines are considered as gut microbial related immunologic factors that drive the obesity development.(Vijay-Kumar et al. 2014,). Amongst probiotics, Lactobacillus plantaraum shows a potential to modulate negative effects of high-fat diets. High dietary fat intake increased body weight gain, white adipose tissue weight, mean adipocyte size and serum total cholesterol and leptin concentrations, and decreased serum adiponectin concentration in mice. The administration of L. plantaraum to mice significantly reduced the mean adipocyte size and tended to reduce the white adipose tissue weight and serum total cholesterol and leptin concentrations as compared with the vehicle-administered mice. Thus, it is suggested that gut microbiota is an important and promising target for the treatment of obesity (Takemura et al.,2014). CONCLUSION Conventional thoughts regarding caloric intake,energy expenditure,and the development of diabetes,obesity and obesity-related complication are being challenged by recent revelation regarding the role of the gut microbiota, not only does this symbiotic relationship result in vast differences in nutrient acquisition and energy homeostasis, but it appears that diet composition can rapidly induce important changes in the microbiota, which in turn, result in further metabolic consequences for the host organism. REFERENCE Backhed, F., Ding ,H., Wang, T., Hooper, L.V., Koh, G.Y., and Nagy, A. (2004). The gut microbiota as an environment factor in regulation of fat storage. Proc Natl Academic Science. 101(44):15718-15723. Backhed, F., Ley, R.E., Sonnenburg, J.L., Peterson, D.A., and Gordon, J.I. (2005). Host bacterial mutualism in human intestine. Journal of Science. 307(5717):1915-1920. Blaut, M., and Klaus, S. (2012). Intestinal microbiota and obesity. Handbook of pharmacology.209:251-273. Boroni, A.P., Fiche, T.T., Gouveia, c., and Cassia, R.C. (2014). Gut microbiota and the development of obesity. Journal of Nutricion Hospitalaria. 27(5):1408-1414. Cani, P.D., Bibiconi,R., Knauf, C.,Waget, A., Neyrinck, A.M., Delzenne, N.M., Burcelin, R. (2015).Changes in gut microbiota control metabolic endotoxomia-inducer inflammation in high fat diet-induced obesity and diabetes in mice. Diabetes.57:1470-1481. Cani, P.D., Delzenne, N.M., Amar, J., and Burcelin, R.(2013). Role of gut microbiota in the development of obesity and insulin resistance following high-fat diet feeding. Pathologie Biologie. 56:305-309. Cani, P.D., Dewever, C., and Delzenne, N.M. (2014). Inulin-type fructans modulate gastrointestinal peptides involved in appetite regulation. British Journal ofNutrition .92(3:)521-526. Fleissner,C.K., Huebel, N., El-Bary, M.M.A., Loh,G., Klaus,S., and Blaut, M. (2015). Absence of intestinal microbiota does not protect mice from diet-induced obesity. British Journal of Nutrition. 104 (6):919-929. Hill, J.O. (2015). Understanding and addressing the epidemic of obesity: an energy balance prespective. Endo Rev Dec.27(7):750-761. Ji, B., and Nielsen, J. (2015). From next generation sequencing to systematic modeling of the gut microbiome. Front Genetics. 6:219-220. Kim, S.J., Choi, Y.H., and Pack, T. (2014). Obesity activates Toll-like receptor-mediated proinflammatory signaling cascades in the adipose tissue. Journal of Nutritional Biochemistry. 32:11-122. Kolida, S., Saulnier, D.M., and Gibson, G.R.(2013). Gastrointestinal microflora:Probiotics. Advanced Applied Microbiology.59:187-219. Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J.K., Knight, R. (2012).Diversity,stability and resilience of the human gut microbiota. Nature.489:220-230. Murri, M., Leiva, I., Gomez-Zumaquero, J.M., Tinahones, F.J., Cardona, F., Soriguer, F., and Queipo-Ortuno, M.I.(2013). Gut microbiota in children with type ! diabetes differ from that in healthy children, a case study control study. BMC Med.11:46-47. Othman, A.B., Mazin, A.Z., Ibrahim, T., and Mohammed, A. (2016). The role of Gut Microbiota in the development of obesity and diabetes. Biomed. Central.15:108-112. Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan 1 Y, Shen D, et al. A metagenome-wide association study of gut microbiota in type2 diabetes. Nature. 2012;490:55-60. Rankinen, T., Zuberi, A., Chagnon, Y.C., Weisnagel, S. J., Argyropoulos, Walts, B., Perusse, and Bouchard, C. (2006).The human obesity gene map. Obesity.14:529-644. Shi, H., Kokoeva, M.V., Inouye,K., Tzameli, I, Yin, H., and Flier, J.S. (2014). TLR4 links innate immunity and fatty acid-induced insulin resistance. Journal of Clinical Investigation.116(11):3015-3025. Takemura, N., Okubo,T., and So/noyama, K.(2014). Lactobacillus plantarum strain reduces adipocyte sizein mice fed high-fat diet. Exp Biological Med.235(7):849-856. Tanaka, S., Kobayashi, T, Songjinda, P., Tatayema, A., Tsubouchi, M., Kiyohara, C., Shirakawa, T., and Nakajama, J.(2009). Influence of antibiotics exposure in the early postnatal period on the development of intestinal microbiota. FEMS Immunological Medical Microbiology.56:80-87. Vijay-Kumar, M., Aitken, J.D., Carvalho, F.A., Cullender, T.C., Mwangi, S., and Srinivasan, W.(2010). Metablic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5 Science.328:228-231. Weisberg, S.P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R.L., and Ferrante, A.W.(2010). Obesity is associated with macrophage accumulation in adipose tissue. Journal of Clinical Investigation.112(12):1796-1808. Zoetenda E.G and Vaughan E E. (2015). A microbial world within us. Journal of molecular microbiology. 59: 1639-1650 Qin. J, Li, R., Raes, J., Arumugam, M., Burgdorf, K, S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F. and Yamada, T. (2010). 464:39-65. Peterson, J, Garges, S, Giovanni, M, Mclnnes P, Wang L, Schloss J.A, Bonazzi V, wetterstrand K, A and Deal c. (2009). 19:2317-2323



                                                                    SEMINAR PRESENTATION
ON
BCH 411
FRONTIERS IN BIOCHEMISTRY, MOLECULAR BIOLOGY AND BIOTECHNOLOGY
TOPIC:THE ROLE OF GUT MICROBIOTA IN THE DEVELOPMENT OF DIABETES AND OBESITY.
PRESENTED BY
OBINWA MARY-ANN UKAMAKA
REG NO: 2012474143
DEPARTMENT OF APPLIED BIOCHEMISTRY
FACULTY OF BIOSCIENCES
NNAMDI AZIKIWE UNIVERSITY,AWKA.
SUPERVISOR: MR.NWAJIOBI JIDE
DATE:DECEMBER, 2016 A

ABSTRACT
A recent growing number of evidences show that the increased prevalence of obesity and diabetes cannot be attributed to changes in the human genome, nutritional habits, or reduction in physical activity in our daily lives Gut microbiota may play an even an more important role in maintaining human health, as it function much like a “metabolic organ” influencing nutrient aquisition, energy homeostasis and, ultimately, the control of the body weight. Moreover, alterations in gut microbiota can lead to increase intestinal permeability, and metabolic endotoxemia which play a rolesss in the development of chronic low grade inflammatory state in the host that contributes to the development of obesity and diabetes. However the fact that gut microbiota can be modulated through dietary components highlights the importance to study how fatty acid, carbohydrates, probiotics, can influence gut microbiota composition and management of obesity. Gut microbiota seems to be an important and promising target in the prevention and treatment of obesity and its related metabolic disturbances.      




INTRODUCTION
The epidemics of obesity and type 2 diabetes mellitus in the past 20 years have led to numerous investigations concerning the mechanisms that are responsible for the development of these diseases.
The general view is that insulin resistance is an early alteration of type 2 diabetes mellitus and obesity, and both diseases are strongly influenced by genetics and environment. Moreover, studies in the past ten years have shown that low-grade inflammation has an important role in the molecular mechanism of insulin resistance in these diseases and more recently (within the past five years) a new component that has both genetic and environmental factors is also being studied: the gut microbiota.
This way, a paradigm has been dismantled: microorganisms should no longer be associated with pathogenesis, since both bacteria and their eukaryote hosts benefit from their cooperative relationships. In humans, there are at least 100 trillion microbial cells, collectively called microbiota, distributed in complex and site-specific communities. As the genome of these bacteria—the microbiome—contains hundreds of genes that do not exist in the human genome, we can consider our symbionts as an important extra organ.
This complex community—bacteria, eukaryotes, viruses and Archeae—in its majority cannot be cultured. The reasons for this limitation are unknown growth requirements of the bacteria, selectivity of the media that are used, stress imposed by the cultivation procedures, necessity of strictly anoxic conditions, and the difficulties on simulating the interactions of bacteria with other microbes and host cells. Thus, a new approach was introduced, culture-independent sequencing, which made detection of microbial genes and disease-associated patterns in our gut microbiota  possible. The bacterial component of the microbiota has been intensively studied in the past few years, including high-investment studies such as the Human Microbiome Project and MetaHIT.
Using this new approach made it possible to detect three dominating bacterial phyla in the human gastrointestinal tract: the gram-positive Firmicutes and Actinobacteria, and the gram-negative Bacteroidetes. Firmicutes is known as the largest bacterial phylum, comprehending 200 genera, which includes Lactobacillus, Mycoplasma, Bacillus, and Clostridium. In spite of Actinobacteria being also a dominant phylum, it is usually missed by RNA gene sequencing and can only be detected by fluorescent in situ hybridization.
Although gut microbiota has been described as relatively stable concerning its composition until old age, this temporal consistency considers that numerous variables are being held constant.
For example, dietary changes have been shown to have significant effects on the microbiota. Shifting mice to a high-fat, high-sugar ―Western‖ diet, from a low-fat, plant polysaccharide-rich diet, changed the microbiota within 24 hours . Likewise, shifting from a high-fat/low-fiber diet caused notable changes in the gut microbiota within a day.













ORIGIN AND COMPOSITION OF GUT MICRIBIOTA
The human body contains trillions of microorganisms that inhabit our bodies during and after birth.The gastrointestinal tract starts to be colonized during the delivery of the baby. During the first two years of life de microbiota is unstable and less diverse than in the adulthood, when the complexity and diver-sity is higher. 5 Many external factors influence the composition of the microbiota, especially the diet, the hygiene conditions and the use of antibiotics. 6ing the pregnancy, infant’s intestinal tract is free of mi-crobes until exposed to maternal vaginal microbes during normal birth. Infants born through Caesarian section are exposed to maternal skin bacteria altering their bacterial gut composition. Feeding represents another source of microorganisms where breast fed babies have different gut microbiota composition than formula fed babies(Tanaka et al.,2009). Introduction of solid food represents another shift in the composition of babies gut microbiota.
After that, gut microbiota remains relatively unchanged until old age where the composition changes again. Adulthumans have more than 10 times the number of bacterial cells than the cells constituting the human body. Majority of microbiota in the GI tract are bacteria, nevertheless, viruses fungi and other microorganisms are still present. Even though, individuals have unique microbiota composition, gut microbiota is mainly members of four phyla (Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria) ,The distribution of microorganisms throughout the gastrointestinal tract is not homogenous. The stressful environment (gastric juice, bile, pancreatic juice, peri-stalsis) in the stomach and small intestine limits bacte-rial growth and the number of microorganisms.The large intestine contains the highest number of bacteria con-taining over 10 11 bacteria per gram of intestinal con-tent. The mouth contains 10 12 followed by the Ileum containing 10 8 –10 9 bacterial. On the other hand, the jejunum harbors 10 5 –10 6 while the stomach has the least number of bacteria 10 3 –10 4(Othman et al.,2016). The gut microbiota plays different roles that are important for the host. They exert a trophic effect in the intestinal epithelium, favoring the development of the microvilli, which in turn favors the absorption of nutri-ents. The influence of microbiota in innate and adaptive immune system maturation contributes to systemic and local immune homeostasis and immune tolerance for a variety of antigens. The modulation of the immune system activity can influence the intestinal barrier func-tion. The capacity to break down non-digested dietary molecules into metabolites such as short chain fatty acids (SCFS) and to synthesize vitamins demonstrates their importance to human nutrition.
Even though we are still far from identifying, let alone characterizing all bacteria in our system, advancing molecular biology techniques such as next-generation sequencing has tremendously contributed to our understanding of the gut microbiota(Ji and Nielsen.,2015). The use of gnotobiological methods to breed mice in a sterile environment provided an invaluable tool to understand the role of infecting con-trolled bacterial cultures and defined bacterial strains into animals. Studying their effect through various genomic and proteomic tools.










DIABETES AND GUT MICROBIOTA

It’s becoming increasingly evident that gut microbiota is contributing to many human diseases including diabetes both type 1 and type 2. Type 1 diabetes (T1D) is an autoimmune disease that is caused by the destruction of pancreatic Ξ²-cells by the immune system. Even though T1D is mainly caused by genetic defect, epigenetic and environmental factors have been shown to play an im-portant role in this disease. Higher rates of T1D inci-dence have been reported in recent years that are not explained by genetic factors and have been attributed to changes in our lifestyle such diet, hygiene, and antibiotic usage that can directly affect microbiota. It has been shown that diabetes incidence in the germ free non-obese diabetic subjects or patients (NOD) was significantly increased which is in line with the observa-tion that the rates of T1D is higher in countries with stringent hygiene practices (Guiden et al.,2015). Similarly comparison of the gut microbiota composition between children with high genetic risk for T1D and their age mhealthy controls showed less diverse and less dynamic microbiota in the risk group. In the Diabetes Pre-vention and Prediction (DIPP) study it was shown that new-onset T1D subjects had different gut microbiota composition than controls(Murri et al., 2013).They showed that in the control group, mucin synthesis was induced by lactate- and butyrate-producing bacteria to maintain gut integrity while mucin synthesis was prevented by the non-butyrate-producing lactate-utilizing bacteria leading to Ξ²-cell autoimmunity and T1D (Othman et al.,2016).

Recently, research has pointed out that the intestinal microbiome might be an important contributor for the development of type 2 diabetes (T2D). The use of genome-wide association studies (GWAS) has achieved many elucidations in this matter(Qin et al.,2013). characterized the gut microbiota of T2D patients and observed increase in membrane transport of sugars, branched-chain aminoacids transport, methane metabolism, xenobiotics degradation, and sulphate reduction. However, they observed decrease in the levels of butyrate biosynthesis, bacterial chemotaxis, flagellar assembly, vitamins and cofactors metabolism. This study has also shown that the gut environment of T2D individuals is one that stimulates bacterial defense mechanisms against oxidative stress and against drugs.
(Andrea and Mario, 2013)



GUT MICROBIOTA  AND ITS ROLE IN ENERGY  HOMEOSTASIS  AND THE DEVELOPMENT OF OBESITY
The metabolic activities of the gut microbiota have the end results of extracting calories from ingested dietary substances, helping to store those calories in host adipose tissue for later use, and providing energy and nutrients for microbial growth and proliferation. BΓ€ckhed et al 1 dem-onstrated that conventionally raised mice have a 40% higher body fat content and 47% higher gonadal fat con-tent than germ-free (GF) mice, despite lower food intake (Frazier et al 2011).
However, it has been suggested that the main routes under influence of gut microbiota that could contribute to obesity develop-ment are provision of extra calories, increased lipopro-tein lipase (LPL) activity, lipogenesis, increased intestinal permeability, endotoxemia and endocannabi-noid (eCB) system (Blaut and Klaus, 2012).Gut microbiota contribute to energy metabolism through the production of SCFA that are produced by colonic fermentation which involves the anaerobic breakdown of dietary fiber, protein and peptides . The most important SCFA produced are acetate, propionate and butyrate. Acetate and propionate are mostly produced by Bacteriodetes phylum while butyrate is produced by the Firmicutes phylum (Othman et all 2016). These SCFA can provide additional calories when they are oxidized by the host, favoring the higher weight and fat gain observed in these animals. In addition, the binding of SCFA to G protein-coupled receptor (GPR) in the intestine induces the secretion of the hormone peptide YY (PYY). This hormone reduces intestinal transit time, increasing the time for nutrient absorption from the intestinal lumen. In fact, obese and overweight subjects presented higher concentration of SCFA in their feces in comparison to lean individuals (Bodoni et al, 2014).
Low grade inflammation is a hallmark of obesity. Production of pro- inflammatory cytokines are coordinated via the Toll- like receptors and the master regulator of of key inflammation cascades the nuclear factor kappa(NF-kB) (Kim et al, 2012).
The LPL (lipopolysaccharide) activity influences the accumulation of triglycerides in the adipose tissue. The microbiota can affect the activity of this enzyme by the influence on the expression of the protein fasting-induced adipose factor (FIAF). In the absence of microbiota (germ-free mice) it is observed higher expressin of FIAF. 16 On the other hand, the conventionalization of the germ-free animal causes inhibition of the expression of the FIAF and also stimulates body fat gain. It is suggested that FIAF is a circulating inhibitor of LPL activity. Thus, the inhibition of FIAF expression by the presence of microbiota allowus higher activity of LPL and accumulation of triglycerides in adipocytes (Backhad et al, 2004).
Figure 2:  Alteration in gut microbiota composition due to obesity is accompanied by changes in activation of enzymes and pathways which leads to and increased inflammatory state and energy harvest.
AMPK: AMP- activated kinase, SCFA: Short chain fatty acids, LPL: Lipoprotein lipase, ACC: acetyl- CoA carboxylase, CPT1: Carnitine palmitoyltransferase.
Source: Andrea and Mario., 2013
THE EFFECT OF GUT MICROBIOTA ON ENERGY METABOLISM
The biological functions controlled by the intestinal flora are related to the effectiveness of energy harvest, by the bacteria, of the energy ingested but not digested by the host. Among the dietary compound escaping to the digestion occurring in the upper part of the human gastro-intestinal tract, the polysaccharides constitute the major source of nutrient for the bacteria. Part of these polysaccharides could be transformed into digestible substances such as sugars, or short chain carboxylic acids, providing energy substrates which can be used by the bacteria or the host. The control of body weight depends on mechanisms subtly controlled over time and a small daily excess, as low as 1% of the daily energy needs, can have important consequences in the long term on body weight and metabolism (Hill, 2015). Consequently, the gut microbiota of obese subjects changed according to the loss of body weight occurring after a hypocaloric diet. It was demonstrated that two groups of bacteria are dominant in the intestinal tract, Bacteroidetes and Firmicutes (Cani et al, 2008). The quantification and characterization of each dominant group of bacteria were carried out by measuring the concentration of the bacterial 16S rRNA. The number of Bacteroidetes bacteria depended on the weight loss whereas the Firmicutes bacteria group remained unchanged. Importantly, the bacterial lineage was constant one year after the dietary intervention for a given body weight, validating the bacterial signature of each individual. However, it could be related to the diet and in particular to the presence of dietary fibres (Cani et al, 2008).
 The gut bacteria from obese subjects are able to specifically increase the energy harvested from the diet, which provide an extra energy to the host. This conclusion was drawn from work showing that the axenic mice colonized with a conventional gut flora gain weight rapidly. The mechanisms of the apparent gain weight implied an increase in the intestinal glucose absorption, energy extraction from non-digestible food component (short chain fatty acids produced through the fermentation) and a concomitant higher glycemia and insulinemia, two key metabolic factors promoting lipogenesis. Thus an environmental factor such as gut microbiota regulates energy storage. The results, obtained both in rodents and human, suggest that obesity is associated with an altered composition of gut microbiota. However, this study did not demonstrate that the relative change in bacterial strains profile leads to different fates of body weight gain.
This particularly original idea that the bacteria can contribute to the maintenance of the host body weight, is characterized by numerous paradoxes. It is not clear, however, whether the small increased of energy extraction can actually contribute to a meaningful body weight gain within a short period of time, as suggested in the gut flora transplantation studies. Moreover, other studies have clearly shown that a diet rich in non-digestible fibres decreases body weight, fat mass and the severity of diabetes (Cani et al, 2014). However these dietary fibres increase strains of bacteria able to digest these fibres and provide extra-energy for the host as they thus increase the total amount of bacteria in the colon (Kolida et al, 2013). This mechanism is not completely in accordance with the ‘‘energy harvesting theory’’ according to which the fermentation of non digestible polysaccharides would provide energy substrates for the host.
In addition, it is difficult to conclude that small changes in energy ingestion (1–2%) can induce sufficient quick variation in weight (within two weeks) as observed in an American studies ( Backhed et aI, 2005). Importantly, the axenic mice colonized with the gut flora from normal mice ate more than their conventional mice counterparts; therefore, the body weight gain can also be dependent of the increased food intake. A last crucial point, which cannot depend only on the role played by the bacteria to harvest energy from nutrients escaping digestion in the upper part of the intestine, concerns a study showing that axenic mice are more resistant to diet-induced obesity. The authors maintained axenic or conventionalized mice on a high-fat/high-carbohydrates diet (western diet) and found that conventiona-lized animals fed the western diet gained significantly more weight and fat mass and had higher glycemia and insulinemia than the axenic mice. Strikingly, and opposite to the results previously observed in axenic mice fed a normal chow diet, the amount of western diet taken up by an axenic or a conventionalized mouse was similar and hence had similar fecal energy output. All those data suggest that a bacterially related factor is responsible for the development of diet-induced obesity and diabetes.
GUT MICROBIOTA AND INFLAMMATION

Obesity and type 2 diabetes are metabolic diseased characterized by a low grade inflammation (Wellen and Hotamisligil, 2011). In the models of high fat diet induced obesity, adipose depots express several inflammatory factors IL-1(interleukin-1), TNF-a (tumor necrosis factor-a) and IL-6 (interleukin-6) (Weisberg et al, 2010). These cytokines impaired insulin action and induce insulin resistance. For example, TNF-a phosphorylates serine residue substrate (IRS-1) from the insulin receptor leading its inactivation and it has been proposed that nutritional fatty acids trigger inflammatory response by acting via the toll-like receptor-4 (TLR4) signalling in the adipocytes and macrophages. It was shown that the capacity of fatty acids to induce inflammatory signalling following a high-fat diet feeding is blunted in the TLR4 knock out mice (Shi et al, 2014). TLR4 is the co-receptor for the lipopolysaccharides (LPS) constituent of the Gram negative bacteria.  A triggering factor of the early development of metabolic diseases is the lipopolysaccharides, a molecule involved early in the cascade of inflammation. Furthermore, LPS is a strong inducer of inflammatory response and is involved in the release of several cytokines that are key factors triggering insulin resistance. The concept of dietary excess is more or less associated to high-fat feeding-induced inflammation. Experiment has shown that mice fed a high-fat diet for a short term period as two to four weeks exhibit a significant increase in plasma LPS. An endotoxemia that is characterized as a ‘‘metabolic endotoxemia’’, since, the LPS plasma concentrations were 10 to 50 times lower than those obtained during a septic shock. LPS is absorbed into intestinal capillaries to be transported by lipoproteins (i.e. chylomicrons). High-fat diet feeding changed gut microbiota in favour of an increase in the Gram negative to Gram positive. CD14 is a key molecule involved in the innate immune system is a multifunctional receptor constituted by a phosphatidyl inositol phosphate-anchored glycoprotein of 55 kDa expressed on the surface of monocytes, macrophages and neutrophils.
CD14KO mice were hypersensitive to insulin even when fed a normal diet, suggesting that CD14 could be modulator of insulin sensitivity in physiological conditions. As a matter of fact, CD14KO mice resist high-fat diet and chronic LPS-induced metabolic disorders. Similarly hepatic steatosis, liver and adipose tissue inflammation and adipose tissue macrophages infiltration was totally blunted in the CD14KO mice fed a high-fat diet or bifidobacteria microflora
Therefore high-fat feeding induced a low tone inflammation which originates from the intestinal absorption of the LPS.
Thus data support the key idea that the gut microbiota can contribute to the pathophysiology of obesity and type 2 diabetes. High-fat feeding alters the intestinal microbiota composition were Bifidobacterium spp were reduced. Several studies have shown that this specific group of bacteria reduced the intestinal endotoxin levels and improved mucosal barrier function (Cani et al.,). The unique advantage of the prebiotic dietary fibres (oligofructose, [OFS])was used to specifically increase the gut bifidobacteria content of high fat diet treated mice. Among the different gut bacteria analysed, plasma LPS concentrations correlated negatively with Bifidobacterium spp. Together, these findings suggest that the gut microbiota contributes to the pathophysiological regulation of endotoxemia, and sets the tone of inflammation for the occurrence of diabetes/obesity. Thus, it would be useful to develop specific strategies for modifying gut microbiota to favour bifidobacteria growth and prevent the deleterious effect of high-fat diet-induced metabolic diseases (Cani et al.,2013).
Figure 3: Signalling of LPs via NF-B and MAPK. ERK: extracellular signal related kinase, IL: Interleukin, IKB: Inhibitor of kappa B, IKK: IKB kinase, INOS: Inducible nitric oxide synthase, IRAK: Interleukin-1 receptor-associated kinase, JNK : c-jun NH2 –terminal kinase, LBP: Lipopolysaccharide binding protein, LPS: Lipopolysaccharide, MAPK: mitogen-activated protein kinase, MCP-1: monocyte chemotatic protein-1, MD-2: mycloid differentiation protein 2, MyD88: mycloid differentiation  primary  response gene 88, NF-KB: Nuclear factor Kappa B, NIK: NF-KB inducing kinase, TLR: toll-like receptor, TNF: tumor necrosis factor, TRAF6: TNF receptor-associated factor 6.
Source: Boroni et al., 2014.


MODULATION OF GUT MICROBIOTA
The importance of gut microbiota in the mainte-nance of health has been receiving more attention worldwide. The homeostasis of gut microbiota  depends on the characteristics of the host (age, gender, genetic factors) and the environment (stress, drugs, toxic agents, infections, diseases). However, the influ-ence of diet is also evident (Boroni Moreira et al., 2014). The conductance of future studies aiming to understand how changes in diet modulate gut microbiota composition is of great interest to help menu plannings that simulate the achievement of a favorable microbiota.
Weight loss promotes changes in gut microbiota composition. .(Fleissner et al., 2015) The intake of specific dietary components (fatty acids, carbohydrates, micronutri-ents, prebiotics, probiotics) can result in changes in the composition of gut microbiota and modulate the expression of genes in the host, especially in organs as intestine, muscle, liver and adipose tissue (Boroni Moreira et al.2014,).
The relevance of the use of prebiotics and probiotics in human’s obesity treatment is supported by few results obtained in interventional studies. However, animal models show potential beneficial effects. For example, genetically obese mice and mice fed with high-fat diet were given the prebiotic oligofructose. After the intervention it was observed a reduction in the circulatory levels of IL-18 and IL-1Ξ². These cytokines are considered as gut microbial related immunologic factors that drive the obesity development.(Vijay-Kumar et al. 2014,).
Amongst probiotics, Lactobacillus plantaraum shows a potential to modulate negative effects of high-fat diets. High dietary fat intake increased body weight gain, white adipose tissue weight, mean adipocyte size and serum total cholesterol and leptin concentrations, and decreased serum adiponectin concentration in mice. The administration of L. plantaraum to mice significantly reduced the mean adipocyte size and tended to reduce the white adipose tissue weight and serum total cholesterol and leptin concentrations as compared with the vehicle-administered mice. Thus, it is suggested that gut
microbiota is an important and promising target for the treatment of obesity (Takemura et al.,2014).







CONCLUSION
Conventional thoughts regarding caloric intake,energy expenditure,and the development of diabetes,obesity and obesity-related complication are being challenged by recent revelation regarding the role of the gut microbiota,  not only does this symbiotic relationship result in vast differences in nutrient acquisition and energy homeostasis, but it appears that diet composition can rapidly induce important changes in the microbiota, which in turn, result in further metabolic consequences for the host organism.








REFERENCE

Backhed, F., Ding ,H., Wang, T., Hooper, L.V., Koh, G.Y., and Nagy, A. (2004). The gut microbiota as an environment factor in regulation of fat storage. Proc Natl Academic Science. 101(44):15718-15723.

Backhed, F., Ley, R.E., Sonnenburg, J.L., Peterson, D.A., and Gordon, J.I. (2005). Host bacterial mutualism in human intestine. Journal of Science. 307(5717):1915-1920.

Blaut, M., and Klaus, S. (2012). Intestinal microbiota and obesity. Handbook of pharmacology.209:251-273.

Boroni, A.P., Fiche, T.T., Gouveia, c., and Cassia, R.C. (2014). Gut microbiota and the development of obesity. Journal of Nutricion Hospitalaria. 27(5):1408-1414.
Cani, P.D., Bibiconi,R., Knauf, C.,Waget, A., Neyrinck, A.M., Delzenne, N.M., Burcelin, R. (2015).Changes in gut microbiota control metabolic endotoxomia-inducer inflammation in high fat diet-induced obesity and diabetes in mice. Diabetes.57:1470-1481.

Cani, P.D., Delzenne, N.M., Amar, J., and Burcelin, R.(2013). Role of gut microbiota in the development of obesity and insulin resistance following high-fat diet feeding. Pathologie Biologie. 56:305-309.

Cani, P.D., Dewever, C., and Delzenne, N.M. (2014). Inulin-type fructans modulate gastrointestinal peptides involved in appetite regulation. British Journal ofNutrition .92(3:)521-526.

Fleissner,C.K., Huebel, N., El-Bary, M.M.A., Loh,G., Klaus,S., and Blaut, M. (2015). Absence of intestinal microbiota does not protect mice from diet-induced obesity. British Journal of Nutrition. 104 (6):919-929.

Hill, J.O. (2015). Understanding and addressing the epidemic of obesity: an energy balance prespective. Endo Rev Dec.27(7):750-761.

Ji, B., and Nielsen, J. (2015). From next generation sequencing to systematic modeling of the gut microbiome. Front Genetics. 6:219-220.

Kim, S.J.,  Choi, Y.H., and Pack, T. (2014). Obesity activates Toll-like receptor-mediated proinflammatory signaling cascades in the adipose tissue. Journal of Nutritional Biochemistry. 32:11-122.

Kolida, S., Saulnier, D.M., and Gibson, G.R.(2013). Gastrointestinal microflora:Probiotics. Advanced Applied Microbiology.59:187-219.

Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J.K., Knight, R. (2012).Diversity,stability and resilience of the human gut microbiota. Nature.489:220-230.

Murri, M., Leiva, I., Gomez-Zumaquero, J.M., Tinahones, F.J., Cardona, F., Soriguer, F., and Queipo-Ortuno, M.I.(2013). Gut microbiota in children with type ! diabetes differ from that in healthy children, a case study control study. BMC Med.11:46-47.

Othman, A.B., Mazin, A.Z., Ibrahim, T., and  Mohammed, A. (2016). The role of Gut Microbiota in the development of obesity and diabetes. Biomed. Central.15:108-112.

Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan 1 Y, Shen D, et al. A metagenome-wide association study of gut microbiota in type2 diabetes. Nature. 2012;490:55-60.
Rankinen, T., Zuberi, A., Chagnon, Y.C., Weisnagel, S. J., Argyropoulos, Walts, B., Perusse, and Bouchard, C. (2006).The human obesity gene map. Obesity.14:529-644.

Shi, H., Kokoeva, M.V., Inouye,K., Tzameli,  I, Yin, H., and Flier, J.S. (2014). TLR4 links innate immunity and fatty acid-induced insulin resistance. Journal of Clinical Investigation.116(11):3015-3025.

Takemura, N., Okubo,T., and So/noyama, K.(2014). Lactobacillus plantarum strain reduces adipocyte sizein mice fed high-fat diet. Exp Biological Med.235(7):849-856.

Tanaka, S., Kobayashi, T, Songjinda, P., Tatayema, A., Tsubouchi, M., Kiyohara, C., Shirakawa, T., and Nakajama, J.(2009). Influence of antibiotics exposure in the early postnatal period on the development of intestinal microbiota. FEMS Immunological Medical Microbiology.56:80-87.

Vijay-Kumar, M., Aitken, J.D., Carvalho, F.A., Cullender, T.C., Mwangi, S., and Srinivasan, W.(2010). Metablic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5 Science.328:228-231.

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