Age and Aging Have Critical Effects on the Gut Microbiome

Researchers at Cedars-Sinai have found that aging produces significant changes in the microbiome of the human small intestine distinct from those caused by medications or illness burden. The findings have been published in the journal Cell Reports.

“By teasing out the microbial changes that occur in the small bowel with age, medication use and diseases, we hope to identify unique components of the microbial community to target for therapeutics and interventions that could promote healthy aging,” said Ruchi Mathur, MD, the study’s principal investigator.

Research exploring the gut microbiome, and its impact on health, has relied predominantly on fecal samples, which do not represent the entire gut, according to Mathur. In their study, investigators from Cedars-Sinai’s Medically Associated Science and Technology (MAST) Program analyzed samples from the small intestine–which is over 20 feet in length and has the surface area of a tennis court–for examination of the microbiome and its relationship with aging.

“This study is the first of its kind to examine the microbial composition of the small intestine of subjects 18 years of age to 80. We now know that certain microbial populations are influenced more by medications, while others are more affected by certain diseases. We have identified specific microbes that appear to be only influenced by the chronological age of the person,” said Mathur, an endocrinologist and director of the Diabetes Outpatient Treatment & Education Center.

The 21st century has been referred to as the “era of the gut microbiome” as scientists turn considerable attention to the role trillions of gut bacteria, fungi and viruses may play in human health and disease. The microbiome is the name given to the genes that live in these cells. Studies have suggested that disturbances in the constellations of the microbial universe may lead to critical illnesses, including gastroenterological diseases, diabetes, obesity, and some neurological disorders.

While researchers know that microbial diversity in stool decreases with age, Cedars-Sinai investigators identified bacteria in the small bowel they refer to as “disruptors” that increase and could be troublesome.

“Coliforms are normal residents of the intestine. We found that when these rod-shaped microbes become too abundant in the small bowel–as they do as we get older–they exert a negative influence on the rest of the microbial population. They are like weeds in a garden,” said study co-author Gabriela Leite, PhD.

Investigators also found that as people age, the bacteria in the small intestine change from microbes that prefer oxygen to those that can survive with less oxygen, something they hope to understand as the research continues.

“Our goal is to identify and fingerprint the small intestinal microbial patterns of human health and disease. Given the important role the small bowel plays in absorption of nutrients, changes in the microbiome in this location of the gut may have a greater impact on human health, and warrants further study,” said Mark Pimentel, MD, director of the MAST program and a co-author of the study.

Source: Cedars Sinai

Study: A Fermented-food Diet Increases Microbiome Diversity and Lowers Inflammation

A diet rich in fermented foods enhances the diversity of gut microbes and decreases molecular signs of inflammation, according to researchers at the Stanford School of Medicine.

In a clinical trial, 36 healthy adults were randomly assigned to a 10-week diet that included either fermented or high-fiber foods. The two diets resulted in different effects on the gut microbiome and the immune system.

Eating foods such as yogurt, kefir, fermented cottage cheese, kimchi and other fermented vegetables, vegetable brine drinks, and kombucha tea led to an increase in overall microbial diversity, with stronger effects from larger servings. “This is a stunning finding,” said Justin Sonnenburg, PhD, an associate professor of microbiology and immunology. “It provides one of the first examples of how a simple change in diet can reproducibly remodel the microbiota across a cohort of healthy adults.”

In addition, four types of immune cells showed less activation in the fermented-food group. The levels of 19 inflammatory proteins measured in blood samples also decreased. One of these proteins, interleukin 6, has been linked to conditions such as rheumatoid arthritis, Type 2 diabetes and chronic stress.

“Microbiota-targeted diets can change immune status, providing a promising avenue for decreasing inflammation in healthy adults,” said Christopher Gardner, PhD, the Rehnborg Farquhar Professor and director of nutrition studies at the Stanford Prevention Research Center. “This finding was consistent across all participants in the study who were assigned to the higher fermented food group.”

Microbe diversity stable in fiber-rich diet

By contrast, none of these 19 inflammatory proteins decreased in participants assigned to a high-fiber diet rich in legumes, seeds, whole grains, nuts, vegetables and fruits. On average, the diversity of their gut microbes also remained stable. “We expected high fiber to have a more universally beneficial effect and increase microbiota diversity,” said Erica Sonnenburg, PhD, a senior research scientist in basic life sciences, microbiology and immunology. “The data suggest that increased fiber intake alone over a short time period is insufficient to increase microbiota diversity.”

The study published online in Cell. Justin and Erica Sonnenburg and Christopher Gardner are co-senior authors. The lead authors are Hannah Wastyk, a PhD student in bioengineering, and former postdoctoral scholar Gabriela Fragiadakis, PhD, who is now an assistant professor of medicine at UC-San Francisco.

A wide body of evidence has demonstrated that diet shapes the gut microbiome, which can affect the immune system and overall health. According to Gardner, low microbiome diversity has been linked to obesity and diabetes.

“We wanted to conduct a proof-of-concept study that could test whether microbiota-targeted food could be an avenue for combatting the overwhelming rise in chronic inflammatory diseases,” Gardner said.

The researchers focused on fiber and fermented foods due to previous reports of their potential health benefits. While high-fiber diets have been associated with lower rates of mortality, the consumption of fermented foods can help with weight maintenance and may decrease the risk of diabetes, cancer and cardiovascular disease.

The researchers analyzed blood and stool samples collected during a three-week pre-trial period, the 10 weeks of the diet, and a four-week period after the diet when the participants ate as they chose.

The findings paint a nuanced picture of the influence of diet on gut microbes and immune status. On one hand, those who increased their consumption of fermented foods showed similar effects on their microbiome diversity and inflammatory markers, consistent with prior research showing that short-term changes in diet can rapidly alter the gut microbiome. On the other hand, the limited change in the microbiome within the high-fiber group dovetails with the researchers’ previous reports of a general resilience of the human microbiome over short time periods.

Designing a suite of dietary and microbial strategies

The results also showed that greater fiber intake led to more carbohydrates in stool samples, pointing to incomplete fiber degradation by gut microbes. These findings are consistent with other research suggesting that the microbiome of people living in the industrialized world is depleted of fiber-degrading microbes.

“It is possible that a longer intervention would have allowed for the microbiota to adequately adapt to the increase in fiber consumption,” Erica Sonnenburg said. “Alternatively, the deliberate introduction of fiber-consuming microbes may be required to increase the microbiota’s capacity to break down the carbohydrates.”

In addition to exploring these possibilities, the researchers plan to conduct studies in mice to investigate the molecular mechanisms by which diets alter the microbiome and reduce inflammatory proteins. They also aim to test whether high-fiber and fermented foods synergize to influence the microbiome and immune system of humans. Another goal is to examine whether the consumption of fermented food decreases inflammation or improves other health markers in patients with immunological and metabolic diseases, and in pregnant women and older individuals.

“There are many more ways to target the microbiome with food and supplements, and we hope to continue to investigate how different diets, probiotics and prebiotics impact the microbiome and health in different groups,” Justin Sonnenburg said.

Source: Stanford Medicine

Are You Eating Foods That Harm Your ‘Microbiome’?

Amy Norton wrote . . . . . . . . .

People who eat plenty of vegetables, fish and fiber may have more inflammation-fighting bacteria in their guts, but fast-food lovers may be feeding inflammatory microbes.

That’s the conclusion of a new study that looked at people’s diet habits and the makeup of their gut “microbiome.”

The term refers to the vast collection of bacteria and other microbes that naturally dwell in the gut. Studies in recent years have been revealing just how important those bugs are to the body’s normal processes — from metabolism and nutrient synthesis to immune defenses and brain function.

In the new study, researchers found that people who ate diets rich in plant-based foods and fish — akin to the famous Mediterranean diet — had an advantage: More collections of gut bacteria that can temper inflammation.

On the other hand, people who favored meat, processed foods and sugar tended to have clusters of gut microbes that are pro-inflammatory.

Many studies have tied Mediterranean-style eating and plant-rich diets to lower risks of various diseases.

The researchers said the new findings add to evidence that effects on the gut microbiome are one reason why.

“Our study provides support for the idea that the gut microbiome could be one link between diet and disease risk,” said senior researcher Dr. Rinse Weersma, a gastroenterologist and professor at the University of Groningen in the Netherlands.

His team found that people who ate more vegetables, fruit, fatty fish, nuts and fiber-rich grains generally had higher concentrations of bacteria that churn out short-chain fatty acids.

Short-chain fatty acids are produced when gut bacteria ferment non-digestible fiber, and they are anti-inflammatory, Weersma explained.

On the opposite end of the spectrum was the “fast-food cluster,” where people had a high intake of meat, french fries, soda and processed snack foods.

They were in double-trouble, according to Weersma: Owing to a lack of dietary fiber, they had fewer bacteria that produce short-chain fatty acids. They also showed a greater abundance of pro-inflammatory gut microbes.

Many factors influence the balance of bacteria in any one person’s gut microbiome, including genes, age, health conditions, medication use (particularly antibiotics) and stress, experts say.

“But I would say diet is the number one factor for adults,” said Dr. Emeran Mayer, a professor at the University of California, Los Angeles School of Medicine.

Mayer, who was not involved in the study, is author of the forthcoming book “The Gut-Immune Connection.”

He said he generally recommends a largely plant-based diet, choosing the particular foods based on individuals’ needs. Diet is the way to go, rather than taking probiotic supplements, Mayer said.

“There’s no way to get around the biology. You can’t eat a bad diet then take a probiotic,” he said. “You have to make a fundamental shift in your diet and overall lifestyle.”

Unfortunately, Mayer added, processed foods and other unhealthy choices are often cheaper, which makes it hard for lower-income people to eat healthfully.

“That’s a real problem,” he said.

The new findings — published online recently in the journal Gut — are based on more than 1,400 Dutch adults who answered questions on their diet habits and gave stool samples for a gut-microbe analysis. Some were generally healthy, while others had digestive disorders, including ulcerative colitis and Crohn’s disease.

Overall, the study found consistent links between fish and food from plants and anti-inflammatory gut microbes, including in people with digestive conditions.

Dr. Andrew Chan is a gastroenterologist at Massachusetts General Hospital in Boston and professor at Harvard Medical School.

Chan said evidence is growing that the gut microbiome is one important link between diet and disease risks.

But it’s likely that inflammation is only one part of the story, according to Chan.

Researchers are just beginning to understand the many roles of the gut microbiome, which some view as an organ unto itself, he noted. Much more work is needed to characterize how the microbiome might influence human health, and define what a “healthy” one is, Chan added.

For now, Weersma said these findings support current recommendations to eat more “whole” plant foods and fewer processed ones.

Chan agreed, but added that, ultimately, research into the gut microbiome could move experts away from one-size-fits-all advice. It’s becoming possible to individualize diets based on how a person, and his or her gut microbiome, respond to food, he said.

Source: HealthDay

Gut Microbiome Implicated in Healthy Aging and Longevity

The gut microbiome is an integral component of the body, but its importance in the human aging process is unclear. ISB researchers and their collaborators have identified distinct signatures in the gut microbiome that are associated with either healthy or unhealthy aging trajectories, which in turn predict survival in a population of older individuals. The work was just published in the journal Nature Metabolism.

The research team analyzed gut microbiome, phenotypic and clinical data from over 9,000 people – between the ages of 18 and 101 years old – across three independent cohorts. The team focused, in particular, on longitudinal data from a cohort of over 900 community-dwelling older individuals (78-98 years old), allowing them to track health and survival outcomes.

The data showed that gut microbiomes became increasingly unique (i.e. increasingly divergent from others) as individuals aged, starting in mid-to-late adulthood, which corresponded with a steady decline in the abundance of core bacterial genera (e.g. Bacteroides) that tend to be shared across humans.

Strikingly, while microbiomes became increasingly unique to each individual in healthy aging, the metabolic functions the microbiomes were carrying out shared common traits. This gut uniqueness signature was highly correlated with several microbially-derived metabolites in blood plasma, including one – tryptophan-derived indole – that has previously been shown to extend lifespan in mice. Blood levels of another metabolite – phenylacetylglutamine – showed the strongest association with uniqueness, and prior work has shown that this metabolite is indeed highly elevated in the blood of centenarians.

“This uniqueness signature can predict patient survival in the latest decades of life,” said ISB Research Scientist Dr. Tomasz Wilmanski, who led the study. Healthy individuals around 80 years of age showed continued microbial drift toward a unique compositional state, but this drift was absent in less healthy individuals.

“Interestingly, this uniqueness pattern appears to start in mid-life – 40-50 years old – and is associated with a clear blood metabolomic signature, suggesting that these microbiome changes may not simply be diagnostic of healthy aging, but that they may also contribute directly to health as we age,” Wilmanski said. For example, indoles are known to reduce inflammation in the gut, and chronic inflammation is thought to be a major driver in the progression of aging-related morbidities.

“Prior results in microbiome-aging research appear inconsistent, with some reports showing a decline in core gut genera in centenarian populations, while others show relative stability of the microbiome up until the onset of aging-related declines in health,” said microbiome specialist Dr. Sean Gibbons, co-corresponding author of the paper. “Our work, which is the first to incorporate a detailed analysis of health and survival, may resolve these inconsistencies. Specifically, we show two distinct aging trajectories: 1) a decline in core microbes and an accompanying rise in uniqueness in healthier individuals, consistent with prior results in community-dwelling centenarians, and 2) the maintenance of core microbes in less healthy individuals.”

This analysis highlights the fact that the adult gut microbiome continues to develop with advanced age in healthy individuals, but not in unhealthy ones, and that microbiome compositions associated with health in early-to-mid adulthood may not be compatible with health in late adulthood.

“This is exciting work that we think will have major clinical implications for monitoring and modifying gut microbiome health throughout a person’s life,” said ISB Professor Dr. Nathan Price, co-corresponding author of the paper.

This research project was conducted by ISB and collaborators from Oregon Health and Science University, University of California San Diego, University of Pittsburgh, University of California Davis, Lifestyle Medicine Institute, and University of Washington. It was supported in part by a Catalyst Award in Healthy Longevity from the National Academy of Medicine, and the Longevity Consortium of the National Institute on Aging.

Source: ISB

An Avocado a Day Keeps Your Gut Microbes Happy

Marianne Stein wrote . . . . . . . . .

Eating avocado as part of your daily diet can help improve gut health, a new study from University of Illinois shows. Avocados are a healthy food that is high in dietary fiber and monounsaturated fat. However, it was not clear how avocados impact the microbes in the gastrointestinal system or “gut.”

“We know eating avocados helps you feel full and reduces blood cholesterol concentration, but we did not know how it influences the gut microbes, and the metabolites the microbes produce,” says Sharon Thompson, graduate student in the Division of Nutritional Sciences at U of I and lead author on the paper, published in the Journal of Nutrition.

The researchers found that people who ate avocado every day as part of a meal had a greater abundance of gut microbes that break down fiber and produce metabolites that support gut health. They also had greater microbial diversity compared to people who did not receive the avocado meals in the study.

“Microbial metabolites are compounds the microbes produce that influence health,” Thompson says. “Avocado consumption reduced bile acids and increased short chain fatty acids. These changes correlate with beneficial health outcomes.”

The study included 163 adults between 25 and 45 years of age with overweight or obesity – defined as a BMI of at least 25 kg/m2 – but otherwise healthy. They received one meal per day to consume as a replacement for either breakfast, lunch, or dinner. One group consumed an avocado with each meal, while the control group consumed a similar meal but without the avocado. The participants provided blood, urine, and fecal samples throughout the 12-week study. They also reported how much of the provided meals they consumed, and every four weeks recorded everything they ate.

While other research on avocado consumption has focused on weight loss, participants in this study were not advised to restrict or change what they ate. Instead they consumed their normal diets with the exception of replacing one meal per day with the meal the researchers provided.

The purpose of this study was to explore the effects of avocado consumption on the gastrointestinal microbiota, says Hannah Holscher, assistant professor of nutrition in the Department of Food Science and Human Nutrition at U of I and senior author of the study.

“Our goal was to test the hypothesis that the fats and the fiber in avocados positively affect the gut microbiota. We also wanted to explore the relationships between gut microbes and health outcomes,” Holscher says.

Avocados are rich in fat; however, the researchers found that while the avocado group consumed slightly more calories than the control group, slightly more fat was excreted in their stool.

“Greater fat excretion means the research participants were absorbing less energy from the foods that they were eating. This was likely because of reductions in bile acids, which are molecules our digestion system secretes that allow us to absorb fat. We found that the amount of bile acids in stool was lower and the amount of fat in the stool was higher in the avocado group,” Holscher explains.

Different types of fats have differential effects on the microbiome. The fats in avocados are monounsaturated, which are heart-healthy fats.

Soluble fiber content is also very important, Holscher notes. A medium avocado provides around 12 grams of fiber, which goes a long way toward meeting the recommended amount of 28 to 34 grams of fiber per day.

“Less than 5% of Americans eat enough fiber. Most people consume around 12 to 16 grams of fiber per day. Thus, incorporating avocados in your diet can help get you closer to meeting the fiber recommendation,” she notes.

Eating fiber isn’t just good for us; it’s important for the microbiome, too, Holscher states. “We can’t break down dietary fibers, but certain gut microbes can. When we consume dietary fiber, it’s a win-win for gut microbes and for us.”

Holscher’s research lab specializes in dietary modulation of the microbiome and its connections to health. “Just like we think about heart-healthy meals, we need to also be thinking about gut healthy meals and how to feed the microbiota,” she explains.

Avocado is an energy-dense food, but it is also nutrient dense, and it contains important micronutrients that Americans don’t eat enough of, like potassium and fiber.

“It’s just a really nicely packaged fruit that contains nutrients that are important for health. Our work shows we can add benefits to gut health to that list,” Holscher says.

Source: The University of Illinois