Natural compound in vegetables helps fight fatty liver disease

New research shows how indole can reduce inflammation, fatty deposits

February 7, 2020

Science Daily/Texas A&M AgriLife Communications

A new study led by Texas A&M AgriLife Research scientists shows how a natural compound found in many well-known and widely consumed vegetables can also be used to fight fatty liver disease.

The study demonstrates how non-alcoholic fatty liver disease, or NAFLD, can be controlled by indole, a natural compound found in gut bacteria -- and in cruciferous vegetables such as cabbage, kale, cauliflower and Brussels sprouts. It also addresses how this natural compound may lead to new treatments or preventive measures for NAFLD.

The study was recently published in Hepatology.

"Based on this research, we believe healthy foods with high capacity for indole production are essential for preventing NAFLD and are beneficial for improving the health of those with it," said Chaodong Wu, M.D., Ph.D., a Texas A&M AgriLife Research Faculty Fellow and principal investigator for the study. "This is another example where altering the diet can help prevent or treat disease and improve the well-being of the individual."

About NAFLD and indole

NAFLD occurs when the liver becomes "marbled" with fat, sometimes due to unhealthy nutrition, such as excessive intake of saturated fats. If not properly addressed, this condition can lead to life-threatening liver disease, including cirrhosis or liver cancer.

Many diverse factors contribute to NAFLD. Fatty liver is seven to 10 times more common in people with obesity than in the general population. In addition, obesity causes inflammation in the body. Driving this inflammation are macrophages, types of white blood cells that normally battle infection. This inflammation exacerbates liver damage in those with liver disease.

Gut bacteria can also have an effect -- either positive or negative -- on the progression of fatty liver disease. These bacteria produce many different compounds, one of which is indole. This product of the amino acid tryptophan has been identified by clinical nutritionists and nutrition scientists as likely having preventive and therapeutic benefits to people with NAFLD.

The National Cancer Institute also notes the benefits of indole-3-carbinol found in cruciferous vegetables, including their anti-inflammatory and cancer-fighting properties.

A comprehensive and multi-level study on fatty liver disease

The present study examined the effect of indole concentrations on people, animal models and individual cells to help determine indole's effect on liver inflammation and its potential benefits to people with NAFLD. It investigated the extent to which indole alleviates non-alcoholic fatty liver disease, incorporating previous findings on gut bacteria, intestinal inflammation and liver inflammation. It also incorporated investigation into how indole improves fatty liver in animal models.

For the study, researchers investigated the effects of indole on individuals with fatty livers. As research collaborator Qifu Li, M.D., was also a physician at Chongqing Medical University in China, the team decided he should lead the clinical research using Chinese participants.

In 137 subjects, the research team discovered people with a higher body mass index tended to have lower levels of indole in their blood. Additionally, the indole levels in those who were clinically obese were significantly lower than those who were considered lean. And in those with lower indole levels, there was also a higher amount of fat deposition in the liver.

This result will likely extend to other ethnicities, Li noted, though ethnic background may have some influence on gut bacteria populations and the exact levels of metabolites.

To further determine the impact of indole, the research team used animal models fed a low-fat diet as a control and high-fat diet to simulate the effects of NAFLD.

"The comparisons of animal models fed a low-fat diet and high-fat diet gave us a better understanding of how indole is relevant to NAFLD," said Gianfranco Alpini, M.D., a study collaborator and former distinguished professor of Texas A&M Health Science Center, now the director of the Indiana Center for Liver Research.

Alpini said treatment of NAFLD-mimicking animal models with indole significantly decreased fat accumulation and inflammation in the liver.

The research team also studied how indole affected individual cells.

Shannon Glaser, M.D., a professor of Texas A&M Health Science Center, said that in addition to reducing the amount of fat in liver cells, indole also acts on cells in the intestine, which send out molecular signals that dampen inflammation.

"The link between the gut and the liver adds another layer of complexity to studies on non-alcoholic fatty liver disease, and future studies are very much needed to fully understand the role of indole," Glaser said.

Additional nutrition research needed

"Foods with a high capacity of indole production or medicines that mimic its effects may be new therapies for treatment of NAFLD," Wu said, adding prevention is another important aspect to consider.

"Preventing NAFLD's development and progression may depend on nutritional approaches to ensure that gut microbes allow indole and other metabolites to function effectively," he said. "Future research is needed to investigate how certain diets may be able to achieve this."

Wu said in future research he hopes to collaborate with food scientists and clinical nutritionists to examine what healthy foods can alter gut microbiota and increase indole production.

https://www.sciencedaily.com/releases/2020/02/200207123746.htm

Gut instincts: Researchers discover first clues on how gut health influences brain health

October 23, 2019

Science Daily/Weill Cornell Medicine

New cellular and molecular processes underlying communication between gut microbes and brain cells have been described for the first time by scientists at Weill Cornell Medicine and Cornell's Ithaca campus.

Over the last two decades, scientists have observed a clear link between autoimmune disorders and a variety of psychiatric conditions. For example, people with autoimmune disorders such as inflammatory bowel disease (IBD), psoriasis and multiple sclerosis may also have depleted gut microbiota and experience anxiety, depression and mood disorders. Genetic risks for autoimmune disorders and psychiatric disorders also appear to be closely related. But precisely how gut health affects brain health has been unknown.

"Our study provides new insight into the mechanisms of how the gut and brain communicate at the molecular level," said co-senior author Dr. David Artis, director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease, director of the Friedman Center for Nutrition and Inflammation and the Michael Kors Professor of Immunology at Weill Cornell Medicine. "No one yet has understood how IBD and other chronic gastrointestinal conditions influence behavior and mental health. Our study is the beginning of a new way to understand the whole picture."

For the study, published Oct. 23 in Nature, the researchers used mouse models to learn about the changes that occur in brain cells when gut microbiota are depleted. First author Dr. Coco Chu, a postdoctoral associate in the Jill Roberts Institute for Research in Inflammatory Bowel Disease, led a multidisciplinary team of investigators from several departments across Weill Cornell Medicine, Cornell's Ithaca campus, Boyce Thompson Institute, Broad Institute at MIT and Harvard, and Northwell Health with specialized expertise in behavior, advanced gene sequencing techniques and the analysis of small molecules within cells.

Mice treated with antibiotics to reduce their microbial populations, or that were bred to be germ-free, showed a significantly reduced ability to learn that a threatening danger was no longer present. To understand the molecular basis of this result, the scientists sequenced RNA in immune cells called microglia that reside in the brain and discovered that altered gene expression in these cells plays a role in remodeling how brain cells connect during learning processes. These changes were not found in microglia of healthy mice.

"Changes in gene expression in microglia could disrupt the pruning of synapses, the connections between brain cells, interfering with the normal formation of new connections that should occur through learning," said co-principal investigator Dr. Conor Liston, an associate professor of neuroscience in the Feil Family Brain & Mind Research Institute and an associate professor of psychiatry at Weill Cornell Medicine.

The team also looked into chemical changes in the brain of germ-free mice and found that concentrations of several metabolites associated with human neuropsychiatric disorders such as schizophrenia and autism were changed. "Brain chemistry essentially determines how we feel and respond to our environment, and evidence is building that chemicals derived from gut microbes play a major role," said Dr. Frank Schroeder, a professor at the Boyce Thompson Institute and in the Chemistry and Chemical Biology Department at Cornell Ithaca.

Next, the researchers tried to reverse the learning problems in the mice by restoring their gut microbiota at various ages from birth. "We were surprised that we could rescue learning deficits in germ-free mice, but only if we intervened right after birth, suggesting that gut microbiota signals are required very early in life," said Dr. Liston. "This was an interesting finding, given that many psychiatric conditions that are associated with autoimmune disease are associated with problems during early brain development."

"The gut-brain axis impacts every single human being, every day of their lives," said Dr. Artis. "We are beginning to understand more about how the gut influences diseases as diverse as autism, Parkinson's disease, post-traumatic stress disorder and depression. Our study provides a new piece of understanding of how the mechanisms operate."

"We don't know yet, but down the road, there is a potential for identifying promising targets that might be used as treatments for humans in the future," Dr. Liston said. "That's something we will need to test going forward."

https://www.sciencedaily.com/releases/2019/10/191023172106.htm

Scientists find psychiatric drugs affect gut contents

September 9, 2019

Science Daily/European College of Neuropsychopharmacology

Scientists have found that antidepressants and other psychiatric drugs can change the quantity and composition of gut bacteria in rats. These results raise questions about the specificity of psychoactive drug action, and if confirmed in humans whether psychiatrists might need to consider the effects on the body before prescribing. The research team is currently carrying out a large-scale human observational study which aims to answer the questions posed by these findings. This work is presented at the ECNP Conference in Copenhagen following part-publication in a peer-review journal (see Notes for Editors).

Scientists are increasingly finding that the microbiome -- the bacterial content of the digestive system -- has effects on other functions in the body, and vice versa. A group of Irish-based scientists has given 7 groups of rats (8 animals in each group) normal or slightly elevated levels of individual psychopharmaceuticals, including Lithium, valproate, and the antidepressants fluoxetine (Prozac) and escitalopram. After 4 weeks of treatment, the scientists examined the gut bacteria -- the microbiome -- to see what the effects the drugs had (see abstract for experimental details).

They found that some drugs consistently increased the number of certain bacteria in the gut. For example, lithium and valproate (both used for bipolar disorder) increased the numbers of Clostridium and other bacteria. In contrast, the (SSRI) antidepressants escitalopram and fluoxetine significantly inhibited growth of bacterial isolated strains such as E.coli.

Describing the work, lead researcher, Ms Sofia Cussotto (University College, Cork) said:

"We found that certain drugs, including the mood stabiliser lithium and the antidepressant fluoxetine, influenced the composition and richness of the gut microbiota. Although some psychotropic drugs have been previously investigated in in vitro settings, this is the first evidence in an animal model.

There are several implications of this work. First of all, some studies have shown that depressed or schizophrenic patients can have altered microbiota composition, therefore psychotropic drugs might work on intestinal microbes as part of their mechanisms of action. Of course, this has to be proved. Given that antidepressants, for example work on some people but not others, making an allowance for microbiome may change an individual's response to antidepressants. On the other hand, microbiome-targeting effects might be responsible for the side effects associated with these medications. All these hypotheses have to be tested in preclinical models and in humans, and this is our next step."

Commenting, Professor Serguei Fetissov from Rouen University, France said:

"These early data are intriguing, and worthy of further investigation. At the moment it would be premature to ascribe a direct role of gut bacteria in the action of antidepressant drugs until this work can be reproduced in humans, which is what the authors now hope to do. The composition of gut microbiota is very sensitive to the metabolic processes of the body and can change naturally, through drug-induced metabolic shifts in the brain and other organs. Some of the changes reported here, for example increased Christensenella, can be indeed beneficial, but overall significance of drug-induced changes of bacterial composition on the metabolic and mental health needs further research.

https://www.sciencedaily.com/releases/2019/09/190909095019.htm

Could eating garlic reduce aging-related memory problems?

April 8, 2019

Science Daily/Experimental Biology

Consuming garlic helps counteract age-related changes in gut bacteria associated with memory problems, according to a new study conducted with mice. The benefit comes from allyl sulfide, a compound in garlic known for its health benefits.

"Our findings suggest that dietary administration of garlic containing allyl sulfide could help maintain healthy gut microorganisms and improve cognitive health in the elderly," said Jyotirmaya Behera, PhD, who lead the research team with Neetu Tyagi, PhD, both from University of Louisville.

Behera will present the research at the American Physiological Society's annual meeting during the 2019 Experimental Biology meeting to be held April 6-9 in Orlando, Fla.

The gut contains trillions of microorganisms collectively referred to as the gut microbiota. Although many studies have shown the importance of these microorganisms in maintaining human health, less is known about health effects linked to gut microbiota changes that come with age.

"The diversity of the gut microbiota is diminished in elderly people, a life stage when neurodegenerative diseases such as Alzheimer's and Parkinson's develop and memory and cognitive abilities can decline," said Tyagi. "We want to better understand how changes in the gut microbiota relate to aging-associated cognitive decline."

For the study, the researchers gave oral allyl sulfide to mice that were 24 months old, which correlates to people between 56 and 69 years of age. They compared these mice with 4- and 24-month-old mice not receiving the dietary allyl sulfide supplement.

The researchers observed that the older mice receiving the garlic compound showed better long- and short-term memory and healthier gut bacteria than the older mice that didn't receive the treatment. Spatial memory was also impaired in the 24-month-old mice not receiving allyl sulfide.

Additional experiments revealed that reduced gene expression of neuronal-derived natriuretic factor (NDNF) in the brain was likely responsible for the cognitive decline. This gene was recently discovered by the University of Louisville researchers and is required for long-term and short-term memory consolidation.

The researchers found that mice receiving the garlic compound exhibited higher levels of NDNF gene expression. In addition, recombinant-NDNF protein therapy in the brain restored the cognitive abilities of the older mice that did not receive the garlic compound. The researchers also found that oral allyl sulfide administration produces hydrogen sulfide gas -- a messenger molecule that prevents intestinal inflammation -- in the gut lumen.

Overall, the new findings suggest that dietary allyl sulfide promotes memory consolidation by restoring gut bacteria. The researchers are continuing to conduct experiments aimed at better understanding the relationship between the gut microbiota and cognitive decline and are examining how garlic might be used as a treatment in the aging human population.

https://www.sciencedaily.com/releases/2019/04/190408091259.htm

Should you eat a low-gluten diet?

November 15, 2018

Science Daily/University of Copenhagen The Faculty of Health and Medical Sciences

When healthy people eat a low-gluten and fiber-rich diet compared with a high-gluten diet they experience less intestinal discomfort including less bloating which researchers show are due to changes of the composition and function of gut bacteria. The new study also shows a modest weight loss following low-gluten dieting. The researchers attribute the impact of diet on healthy adults more to change in composition of dietary fibers than gluten itself.

An increasing number of people choose a low-gluten diet, even though they are not allergic to the dietary substance. This trend has sparked public debate about whether or not low-gluten diets are recommendable for people without allergies. Now, researchers from University of Copenhagen among others have looked into just that.

In an intervention study of healthy Danish adults, reported today in Nature Communications, an international team of scientists shows that a low-gluten but fibre-rich diet changes the community of gut bacteria and decreases gastrointestinal discomfort such as bloating and is linked to a modest weight loss. The changes in intestinal comfort and body weight relate to changes in gut bacteria composition and function.

"We demonstrate that, in comparison with a high-gluten diet, a low-gluten, fibre-rich diet induces changes in the structure and function of the complex intestinal ecosystem of bacteria, reduces hydrogen exhalation, and leads to improvements in self-reported bloating. Moreover, we observed a modest weight loss, likely due to increased body combustion triggered by the altered gut bacterial functions," explains the leading principal investigator of the trial, Professor Oluf Pedersen, Novo Nordisk Foundation Center for Basic Metabolic Research at University of Copenhagen.

Change in dietary fibre composition seems to be the cause

The researchers undertook a randomised, controlled, cross-over trial involving 60 middle-aged healthy Danish adults with two eight week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day).

The two diets were balanced in number of calories and nutrients including the same amount of dietary fibres. However, the composition of fibres differed markedly between the two diets.

Based on their observations of altered food fermentation patterns of the gut bacteria, the researchers conclude that the effects of low-gluten dieting in healthy people may not be primarily due to reduced intake of gluten itself but rather to a change in dietary fibre composition by reducing fibres from wheat and rye and replacing them with fibres from vegetables, brown rice, corn, oat and quinoa.

No basis for change of diet recommendation yet

A low-gluten diet has previously been proposed to diminish gastrointestinal symptoms in patients with inflammatory bowel diseases and irritable bowel syndrome, disorders which occur in up to 20 percent of the general Western population.

The present study suggests that even some healthy individuals may prefer a low-gluten diet to combat intestinal discomfort or excess body weight.

"More long-term studies are definitely needed before any public health advice can be given to the general population. Especially, because we find dietary fibres -- not the absence of gluten alone -- to be the primary cause of the changes in intestinal discomfort and body weight. By now we think that our study is a wake-up call to the food industry. Gluten-free may not necessarily be the healthy choice many people think it is.

Most gluten-free food items available on the market today are massively deprived of dietary fibers and natural nutritional ingredients. Therefore, there is an obvious need for availability of fibre-enriched, nutritionally high-quality gluten-free food items which are fresh or minimally processed to consumers who prefer a low-gluten diet. Such initiatives may turn out to be key for alleviating gastro-intestinal discomfort and in addition to help facilitating weight control in the general population via modification of the gut microbiota," concludes senior lead investigator, Professor Oluf Pedersen.

https://www.sciencedaily.com/releases/2018/11/181115115340.htm

Anti-inflammatory protein promotes healthy gut bacteria to curb obesity

New approach to weight loss and diabetes prevention published

September 19, 2018

Science Daily/University of North Carolina Health Care

Scientists have discovered that the anti-inflammatory protein NLRP12 normally helps protect mice against obesity and insulin resistance when they are fed a high-fat diet. The researchers also reported that the NLRP12 gene is underactive in people who are obese, making it a potential therapeutic target for treating obesity and diabetes, both of which are risk factors for cardiovascular disease and other serious conditions.

The study, published in Cell Host & Microbe, showed that NLRP12's anti-inflammatory effect promotes the growth of a "good" family of gut-dwelling bacteria, called Lachnospiraceae, that produce small molecules butyrate and propionate, which in turn promote gut health and protect mice against obesity and insulin resistance.

"Obesity is influenced by inflammation, not just by overeating and lack of exercise, and this study suggests that reducing inflammation promotes 'good' bacteria that can help maintain a healthy weight," said study senior author Jenny P-Y Ting, PhD, a William R. Kenan, Jr. Distinguished Professor of Genetics. "In mice, we showed that NLRP12 reduces inflammation in the gut and in adipose fat tissues. Although a direct causal effect is difficult to show in humans, our collaborators did help us show there are reduced expression levels of NLRP12 in individuals who are considered obese."

In humans, NLRP12 is produced by several types of immune cells and appears to function as a brake on excessive inflammation. Ting and colleagues in recent years have published studies showing that mice lacking the NLRP12 gene are highly susceptible to excessive inflammation, including experimental colon inflammation (colitis) and associated colon cancer.

In recent years, researchers have found evidence that inflammation in the gut and in where fat is deposited promotes obesity. About 40 percent of adults and 20 percent of children and teens age 2 to 19 in the United States are considered obese, according to recent government estimates. Being obese or even overweight can lead to a host of other conditions, including heart disease, stroke, cancers, and diabetes. Ting and colleagues in this study therefore sought to determine whether mice lacking the NLRP12 gene are more susceptible to obesity. The findings showed that they are.

The scientists fed mice that lacked the NLRP12 gene (NLRP12-knockout mice) and ordinary mice a high-fat diet for several months. The NLRP12-knockout mice ate and drank no more than their healthy cousins but accumulated significantly more fat and became heavier. The knockout mice also showed signs of insulin resistance, which involves a reduced ability to clear glucose from the bloodstream and tends to follow the development of obesity.

The absence of NLRP12 in these mice led to increased signs of inflammation in the gut and in fat deposits, but it wasn't clear how this led to extra weight gain until the researchers moved the animals from one facility to another. Following standard safety protocols to prevent disease spread, the researchers dosed the mice with antibiotics before the move.

"We noticed that the mice treated with antibiotics gained less weight than the mice that stayed in the old facility," said study co-first author Agnieszka Truax, PhD, a postdoctoral researcher in the Ting lab during the study. "That led us to suspect that gut bacteria were involved in promoting obesity."

Further tests showed that when NLRP12-knockout mice were kept in a bacteria-free condition, the mice did not gain weight because there were no bacteria. The deficiency of NLRP12 didn't matter as much. This suggested that "bad" bacteria had been driving the excess weight gain during a high-fat diet.

Remarkably, the knockout mice were also protected from excess weight gain when they were co-housed with control mice, hinting that "good" bacteria from the control mice were getting into them and helping to protect them.

Scientists have known that high-fat diets, as compared to low-fat diets, tend to reduce the diversity of bacterial species in the gut by suppressing some species and allowing a few others to proliferate abnormally. The UNC researchers confirmed this in their high-fat-eating mice, and they observed that the loss of bacterial diversity was much worse in the Nlrp12-knockout mice.

The experiments suggested that inflammation caused by a high-fat diet and worsened by the absence of NLRP12 was a major cause of this shift. Killing off rival bacterial species allowed a sharp rise in the levels of a bacterial family called Erysipelotrichaceae. These microbes became more prominent as gut inflammation worsened and exacerbated the weight-gain from a high-fat diet when put into the guts of otherwise germ-free mice.

By contrast, the Lachnospiraceae family of bacteria, which tended to die off in mice fed a high-fat diet, appeared to be highly beneficial. The researchers fed Lachnospiraceae to NLRP12-knockout mice prior to and during three weeks of high-fat eating and found that these "good" bacteria reduced gut inflammation, eliminated the hegemony of harmful Erysipelotrichaceae, and promoted more bacterial diversity. The Lachnospiraceae also significantly protected the animals against obesity and associated insulin-resistance.

"All the inflammatory and metabolic changes we had seen in the NLRP12-knockout mice during a high-fat diet were essentially reversed when we re-supplied Lachnospiraceae," Truax said.

Lachnospiraceae contain enzymes that convert carbs and fiber into small molecules called short-chain fatty acids (SCFAs). The scientists observed that two in particular, butyrate and propionate, appeared in significantly greater abundance when Lachnospiracea levels rose. Butyrate and propionate are known to have anti-inflammatory properties that promote gut health. The UNC team fed these SCFAs to the NLRP12-knockout mice and found that SCFAs protected the animals from the absence of NLRP12 just as well as the Lachnospiraceae had done.

Butyrate, propionate, and other SCFAs are already widely available as health supplements. But are these results in mice relevant to humans? A further test suggested that they are. Collaborating scientists Mihai Netea, MD, PhD, and Rinke Stienstra, PhD, from Radboud University Medical Center in the Netherlands examined fat cells from obese human patients and observed that the higher the measure of obesity -- the body-mass index -- the lower the activity of the NLRP12 gene tended to be.

Thus, treating people with "good" bacteria or the beneficial SCFAs they produce might one day be a relatively inexpensive strategy to combat obesity as well as diabetes and other obesity-driven conditions. Ting and colleagues plan to continue their investigations in that direction.

https://www.sciencedaily.com/releases/2018/09/180919133616.htm

Young children's oral bacteria may predict obesity

September 19, 2018

Science Daily/Penn State

Weight gain during early childhood is related to the composition of oral bacteria of two-year-old children, suggesting this understudied aspect of a children's collection of microorganisms could serve as an early indicator for childhood obesity.

Weight gain trajectories in early childhood are related to the composition of oral bacteria of two-year-old children, suggesting that this understudied aspect of a child's microbiota -- the collection of microorganisms, including beneficial bacteria, residing in the mouth -- could serve as an early indicator for childhood obesity. A study describing the results appears September 19 in the journal Scientific Reports.

"One in three children in the United States is overweight or obese," said Kateryna Makova, Pentz Professor of Biology and senior author of the paper. "If we can find early indicators of obesity in young children, we can help parents and physicians take preventive measures."

The study is part of a larger project with researchers and clinicians at the Penn State Milton S. Hershey Medical Center called INSIGHT, led by Ian Paul, professor of pediatrics at the Medical Center, and Leann Birch, professor of foods and nutrition at the University of Georgia. The INSIGHT trial includes nearly 300 children and tests whether a responsive parenting intervention during a child's early life can prevent the development of obesity. It is also designed to identify biological and social risk factors for obesity.

"In this study, we show that a child's oral microbiota at two years of age is related to their weight gain over their first two years after birth," said Makova.

The human digestive tract is filled with a diverse array of microorganisms, including beneficial bacteria, that help ensure proper digestion and support the immune system. This "microbiota" shifts as a person's diet changes and can vary greatly among individuals. Variation in gut microbiota has been linked to obesity in some adults and adolescents, but the potential relationship between oral microbiota and weight gain in children had not been explored prior to this study.

"The oral microbiota is usually studied in relation to periodontal disease, and periodontal disease has in some cases been linked to obesity," said Sarah Craig, a postdoctoral scholar in biology at Penn State and first author of the paper. "Here, we explored any potential direct associations between the oral microbiota and child weight gain. Rather than simply noting whether a child was overweight at the age of two, we used growth curves from their first two years after birth, which provides a more complete picture of how the child is growing. This approach is highly innovative for a study of this kind, and gives greater statistical power to detect relationships."

Among 226 children from central Pennsylvania, the oral microbiota of those with rapid infant weight gain -- a strong risk factor for childhood obesity -- was less diverse, meaning it contained fewer groups of bacteria. These children also had a higher ratio of Firmicutes to Bacteroidetes, two of the most common bacteria groups found in the human microbiota.

"A healthy person usually has a lot of different bacteria within their gut microbiota," said Craig. "This high diversity helps protect against inflammation or harmful bacteria and is important for the stability of digestion in the face of changes to diet or environment. There's also a certain balance of these two common bacteria groups, Firmicutes and Bacteroidetes, that tends to work best under normal healthy conditions, and disruptions to that balance could lead to dysregulation in digestion."

Lower diversity and higher Firmicutes to Bacteroidetes (F:B) ratio in gut microbiota are sometimes observed as a characteristic of adults and adolescents with obesity. However, the researchers did not see a relationship of weight gain with either of these measures in gut microbiota of two-year-olds, suggesting that the gut microbiota may not be completely established at two years of age and may still be undergoing many changes.

"There are usually dramatic changes to an individual's microbiota as they develop during early childhood," said Makova. "Our results suggest that signatures of obesity may be established earlier in oral microbiota than in gut microbiota. If we can confirm this in other groups of children outside of Pennsylvania, we may be able to develop a test of oral microbiota that could be used in clinical care to identify children who are at risk for developing obesity. This is particularly exciting because oral samples are easier to obtain than those from the gut, which require fecal samples."

Interestingly, weight gain in children was also related to diversity of their mother's oral microbiota. This could reflect a genetic predisposition of the mother and child to having a similar microbiota, or the mother and child having a similar diet and environment.

"It could be a simple explanation like a shared diet or genetics, but it might also be related to obesity," said Makova. "We don't know for sure yet, but if there is an oral microbiome signature linked to the dynamics of weight gain in early childhood, there is a particular urgency to understand it. Now we are using additional techniques to look at specific species of bacteria -- rather than larger taxonomic groups of bacteria -- in both the mothers and children to see whether specific bacteria species influence weight gain and the risk of obesity."

https://www.sciencedaily.com/releases/2018/09/180919083508.htm

Switching to hunter-gatherer lifestyle may increase diversity in children's gut microbes

August 29, 2018

Science Daily/American Society for Microbiology

Immersing city dwellers in the traditional lifestyle and diet of a rainforest village for two weeks increases the diversity of the visiting children's -- but not the adults' -- gut microbiota. In a small pilot study, researchers show that the immersion visit did little to shift the adults' skin, oral, nasal and fecal microbiota.

An international team of researchers has shown that immersing city dwellers in the traditional lifestyle and diet of a rainforest village for two weeks increases the diversity of the visiting children's -- but not the adults' -- gut microbiota. In a small pilot study published this week in mSphere®, an open-access journal of the American Society for Microbiology, the team shows that the immersion visit did little to shift the adults' skin, oral, nasal and fecal microbiota.

"We wanted to look at the question of whether microbiota change during a drastic, radical change of diet and lifestyle," says Maria Gloria Dominguez-Bello, a microbial ecologist at Rutgers University in New Brunswick, New Jersey who led the study with microbiologist Monica Contreras from the Venezuelan Institute of Scientific Research. "In this village, there was no market economy, no bodega, no Coca-Cola -- so this represented a radical shift in diet from a high percentage of processed foods in urban places to zero processed foods and an all-natural diet."

Dominguez-Bello, along with researchers from New York University and two Venezuelan institutes, took advantage of a visit planned by five, city-dwelling adult visitors -- and two of their children -- to live among an indigenous Yekwana village in the Bolivar State of Venezuela for 16 days. The village has a hunter-gatherer-gardener lifestyle and diet.

Typical fare includes cassava (a starchy, high-fiber tuber), corn, various wild fruits, including plantains, pineapples, and berries, fish, and small amounts of game meat and eggs gathered from wild birds. Visitors had two meals a day that consisted of soup with a bit of fish or meat. The rest of their diet consisted of "all-day snacking on cassava with fruit" says Dominguez-Bello. The visitors also bathed in the river without soap and followed the natural circadian rhythms of their hosts.

"The diet contains very little animal protein and it's very, very high in fiber and very low in fat," compared to Western diets, says Dominguez-Bello.

While it is known that people with traditional diets have higher gut microbiota diversity compared to those with urban diets, it was unknown if urban dwellers could shift the diversity of their microbiota higher simply by following a traditional lifestyle and diet. In the gut, a high diversity of microbes is considered a sign of good health.

Traditional people eat diets rich in unprocessed plant material, which are much more chemically complex compared to processed foods. The smorgasbord of chemicals acts as fuel for a higher variety of microbes. Traditional people use less antimicrobial medicines and compounds in daily life, which might also contribute to their increased gut microbe diversity.

During the 16-day visit, the researchers collected samples from the visitors' skin, mouth, nose, and from a fecal swab. Age-matched samples were also collected from villagers. The samples were sequenced and compared.

Surprisingly, none of the adult visitors' microbiota shifted significantly during the visit, while the two children's gut microbiota trended toward a higher number of total microbial species present. Although these results were not statistically significant and in just two subjects, the researchers saw this as interesting nonetheless, given the children's ages of 4 and 7.

Up to now, it was thought that children's gut microbiota become stable and more 'adult-like' by the time they reach 3 years of age. "This indicates that the window for maturing your microbiome may not be 3 years of age, but longer," says Dominguez-Bello. Her team plans to do a larger study with 12 children participating in an "immersion summer camp" to a traditional village.

Because the children's gut microbiota exhibited more plasticity, these results raise an interesting possibility that urban children who eat a more traditional, high-fiber, low-fat and low-processed diet early in life might cultivate a more diverse set of gut microbes. Conversely, adults may have a limited response due to their low microbiome plasticity.

Dominguez-Bello was not terribly surprised that the adults' gut and other microbiota changed so little: "If you take traditional people and bring them to New York, give them antibiotics and McDonald's to eat everyday, it's not surprising that they lose diversity," she says. "But if, as an urban dweller, you've already lost that gut microbe diversity and you move to a high-diversity diet, maybe you cannot 'bloom' diversity because you simply don't have those microbes present anymore."

https://www.sciencedaily.com/releases/2018/08/180829133429.htm

Endurance exercise training has beneficial effects on gut microbiota composition

October 15, 2018

Science Daily/University of Jyväskylä - Jyväskylän yliopisto

According to recent research, endurance exercise training beneficially modifies gut microbiota composition. After six weeks of training, potentially inflammation causing microbes (Proteobacteria) decreased and microbes that are linked to enhanced metabolism (Akkermansia) increased.

Even though there was no significant drop in the weight of the subjects, exercise had other beneficial health effects, says Academy of Finland research fellow Satu Pekkala from the Faculty of Sport and Health Sciences of the University of Jyväskylä.

"We found that phospholipids and cholesterol in VLDL particles decreased in response to exercise. These changes are beneficial for cardiometabolic health because VLDL transports lipids from the liver to peripheral tissues, converts into 'bad' LDL cholesterol in the circulation, and thus has detrimental cardiovascular effects."

Exercise training also decreased Vascular adhesion protein-1 activity, which can have beneficial anti-inflammatory effects especially on vasculature, though the underlying mechanisms could not be determined in this study.

Whether Akkermansia mediates the health benefits of exercise is under further investigation

A few other cross-sectional studies have shown that microbes belonging to the Akkermansia genus are more abundant among physically active subjects than they are among inactive ones. Akkermansia has been a target of intense research recently, and some researchers believe that it may prevent obesity and diabetes.

"However, more studies are needed to prove that Akkermansia might mediate some of the health benefits of exercise," Pekkala says.

In addition to the composition of the gut microbiota, changes in their genes, that is, in their functionality, were studied.

"The abundance of the functional genes did not change much, which was perhaps to be expected because the diet did not change during training," Pekkala points out. "If the training period had been longer, greater effects probably would have been seen."

The research team made an exercise intervention for overweight women, which was completed by 17 subjects. Over a six-week period, previously sedentary women participated in three training sessions per week with a bicycle ergometer. The training intensity was controlled with heart rate. During the study, other lifestyle factors, including diet, were not changed in order to ensure that the effects of exercise could be observed. The research was carried out as a collaboration between the Faculty of Sport and Health Sciences of the University of Jyväskylä, University of Turku and the Spanish nonprofit research and healthcare organization FISABIO.

https://www.sciencedaily.com/releases/2018/10/181015105451.htm