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This article from the Tufts University Gerald J . and Dorothy R. Friedman School of Nutrition Science and Policy, published in the February 2022 Tufts University Health and Nutrition Letter sums up the benefits of maintaining a healthy gut biome.
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This community of bacteria, fungi, viruses, and parasites is known as the microbiota. “Previous estimates have suggested that there could be ten times as many microbial cells in our body as human cells,” says Naisi Zhao, MHS, DrPH, a research assistant professor at Tufts University School of Medicine Department of Public Health & Community Medicine. The collective genomes of the microbiota are called the microbiome. “Each of us has about 23,000 human genes, and around three million bacterial genes,” says Zhao.
“The gut microbiota starts
to establish a stable population early in life,” Zhao explains. “These ‘new
microbial friends’ interact with the young immune system in the gut and are
established as a typical adultlike gut microbiota by about age three. If a
bacterial strain is not a part of your gut microbiota by age three, we’re not
yet sure if it will be able to colonize in your gut, no matter how beneficial
it is.”
These microorganisms, found mostly in the lower part of the intestines, help digest food, synthesize a variety of vitamins and hormones, and produce metabolites that influence our health.
Microbiome and Health. “We know the gut microbiome plays a fundamental
role in multiple aspects of human health,” says Eran Segal, PhD, a professor at
the Weizmann Institute of Science who heads a multi disciplinary team applying
computational and systems biology to the microbiome, “including obesity, cardiovascular
disease, inflammatory diseases, metabolic diseases, non-alcoholic fatty liver
disease, cancer, aging, and neurodegenerative disorders.” Unfortunately, we
have yet to figure out exactly how these interactions play out. “The complexity
of people’s habitual diets, the difficulty of disentangling the impact of
dietary intake from other lifestyle variables, and the personalized nature of
the
microbiome make this a very
difficult topic to study,” says José Ordovás, a professor at the Friedman
School and senior scientist and leader of the Nutrition and Genomics Team at the
Human Nutrition Research Center on Aging (HNRCA).
We do know our diet and
other environmental factors can encourage the growth of some bacteria and
discourage others. “We’re shaping this microbial ecosystem as we eat,” says
Zhao. “Any undigested food becomes available to our gut bacteria. They feed on
nutrients from our leftovers and grow.” What we eat determines which microbes get
to flourish, the ‘good,’ or the ‘bad.’ Nourishing the right microbes can
benefit our health.
Some of the vitamins
produced by our gut microbiota are absorbed into our bloodstreams, just like
those we get directly from foods. Other compounds our microbiota make when they
break down our undigested food can impact our health in ways we are just
beginning to understand. “Some of these byproducts, called metabolites, have physiological effects,” says Meng Wang, PhD, a postdoctoral
fellow at the Friedman School conducting research on microbiome metabolites.
For example, the short chain fatty acids produced when gut bacteria digest
dietary fiber are used as an energy source and may play a role in regulating
blood pressure. “Some metabolites, however, can be harmful,” says Wang.
Zhao suggests we think of
humans as superorganisms. “It’s not just our own cells that play a role in our
health, it’s us plus our microbiome,” she says. “It’s this relationship scientists
are hard at work trying to understand.”
Let’s take a look at what
we know about how a few common health problems may be impacted by the gut
microbiome:
➧➧ Systemic Inflammation: Low-grade inflammation throughout the body plays a role in
cardiovascular disease and other health problems. Research has suggested a link
between gut bacteria and this systemic inflammation. “A certain type of
bacteria, called gram-negative, has molecules called lipopolysaccharides (LPS)
sticking out of their outer membranes,” says Zhao. “If you have a large population
of gram-negative bacteria, these LPS molecules can induce a strong immune reaction
that triggers low-grade inflammation.” In one early study, LPS molecules
injected into healthy animals caused them to develop low-grade inflammation and
insulin resistance. While this animal study does not prove the same thing happens
in humans, it suggests gut bacteria might play a role in systemic inflammation
as well as weight and blood sugar control. “Molecules our gut bacteria generate
could enter our bloodstream, where they likely cause some kind of reaction,”
says Zhao.
➧➧ Obesity: “Microbiome
links to obesity have attracted a lot of interest,” says Ordovás, “although
results in human studies
have varied.” In 2006, scientists transplanted microbiota from genetically obese
mice or normal lean mice into germ-free mice (raised to harbor no microbes at
all). Although they were all fed the same chow diet, those with the microbiota from
obese mice became fatter compared to those who had received transplants from
normal weight mice.
In a case study in China, a
morbidly obese individual was fed a high fiber diet to encourage the growth of “good”
bacteria. “The individual lost a significant amount of weight and had a lot of
really positive health changes,” says Zhao, who was close to the study. “Genetic
sequencing of his stool found a specific bacteria strain in very high abundance
before the diet had been reduced to almost undetectable levels after the
intervention period.” While this is just one individual, this particular study helped
to address the “chicken/egg” problem that accompanies a lot of nutrition
research: does changing the microbiota lead to improved health outcomes, or
does better health change the microbiome? “In this case study, the bacterial
strain from the obese individual’s microbiota was isolated and inoculated into
germ-free
mice,” Zhao explains. The
mice experienced changes related to fat burning and fat storage and they
developed systemic inflammation and insulin resistance. “This finding points to
causation: the pre-diet microbiome was negatively impacting health and weight,”
says Zhao.
These fascinating studies
do not prove the microbiome causes obesity in humans, nor that fecal
transplants can decrease body weight. In fact, the few human studies available
have been negative.
➧➧Muscle: There is a growing body of research in animal models suggesting the
gut microbiome influences muscle, including mass, strength, and aerobic endurance
capacity, but there’s not much data in humans. “A small number of studies have
looked at the differences in gut microbiome composition between highly fit and
lesser fit individuals,” says Michael Lustgarten, PhD, a scientist on the Nutrition,
Exercise Physiology, and Sarcopenia Team at the HNRCA, “and two randomized controlled
trials have demonstrated that exercise training improved muscle function in
conjunction with changes in microbiome composition in older adults, but we don’t
yet know if the microbiome on its own can impact muscle-related measures in
people.”
Any affect that the
microbiome has on muscle would likely be due to metabolites such as the short
chain fatty acids that are produced when bacteria digest soluble fiber. “Most
people in the U.S. don’t consume the recommended 20 to 30 grams of fiber a day,”
says Lustgarten, “and they certainly don’t get enough soluble fiber from foods
like fruits, vegetables, legumes, and whole grains.” Older adults are even less
likely to meet their fiber needs, and they are particularly at risk for loss of
muscle mass and infiltration of fat into muscle.
➧➧ Cardiovascular Disease: The output of some gut microbes may play a role in increasing risk
for cardiovascular disease (CVD). The most studied example of this possible
connection is a molecule called TMAO (trimethylamine N-oxide). When we ingest
phosphatidyl choline (found in a variety of animal
products) and carnitine
(almost exclusively from red meat), gut microbes turn these nutrients into a
molecule called TMA, which is then absorbed and converted in the liver to TMAO.
High levels of TMAO in the blood are associated with increased risk for
cardiovascular disease. Studies have demonstrated TMAO can promote atherosclerosis,
thrombosis (blood clot formation), and hyperglycemia (high blood sugar) in
animal models. “There seems to be an association,” says Wang, “but evidence
from human studies has not been sufficient to establish a causal relationship
between TMAO and cardiovascular disease.”
“The possibility that TMAO
influences cardiovascular health would help explain the association between red
meat intake and CVD,” Wang suggests. “We know red meat intake is associated with
increased CVD risk, but we don’t fully understand the mechanism behind the
connection. While it’s just a hypothesis at this time, it could be that gut
microbes metabolizing the carnitine in red meat leads to increased TMAO, which
increases CVD risk.”
Two randomized controlled trials recently showed that TMAO levels in the body rose in people at high cardiometabolic risk after they consumed foods rich in omega-3 fatty acids (found in fish) and whole-grain cereals, both of which are associated with lower CVD risk. This finding casts doubt on the usefulness of TMAO as a universally valid biomarker of cardiometabolic risk. More research is needed.
Other possible links between diet, the microbiome, and cardiometabolic health are being explored. Ordovás and his colleagues recently published a study that shows a strong link between the gut microbiome and markers of cardiometabolic health like blood pressure, triglyceride levels, total cholesterol, HDL (good) cholesterol, LDL (bad) cholesterol, and blood sugar levels. This study, called Personalised Responses to Dietary Composition Trial (PREDICT 1), included more than 1,000 participants in the U.K. and the U.S. who spent a day in the lab eating specific meals and being tested to determine their individual responses. Participants also carefully tracked dietary intake, took blood tests, gave stool samples for gut microbiome analysis, and underwent continuous glucose monitoring for two weeks. The researchers mapped out what affect foods had on the composition of the microbiome. They found a panel of 15 bacterial strains all consistently associated with markers of good health and 15 consistently associated with markers of poor health. “These same microbes were also associated with certain dietary intake,” says Ordovás. In other words, a healthy dietary pattern was associated with higher levels of specific species of bacteria, and people with more of these species were likely to have lower blood pressure, better blood sugar control, and other important measures of health. Less healthy dietary intake was associated with higher levels of other bacteria species, and the presence of these species was associated with markers of poor cardiometabolic health.
Having a greater variety of
bacteria in the gut was also found to be beneficial. “The richer the diversity
of species in the gut, the less likely participants were to have high BMI, fatty
liver, or high levels of visceral fat,” says Ordovás, “and the more likely they
were to have higher HDL (good) cholesterol levels.” This study is the first to
identify microbial signatures that are related to both diet and metabolic
health. “These results will help us begin to use the gut microbiome as a
biomarker for cardiometabolic risk,” says Ordovás.
Shaping Your Microbiome.
“Diet is probably the most
powerful force shaping our gut microbiota,” says Zhao. “We are feeding
ourselves and the bacteria in our gut with every meal we eat.” If we can
understand the health impacts of different gut microbes and learn what they
like to eat, we should be able to improve our health by manipulating our
microbiome. “The gut microbiota is an ecosystem,” says Zhao. “If we can make
sure the good bacteria are provided with nutrients to grow and flourish, they
will help keep the bad ones in check.” Research has shown that, in general, plant-based
diets are associated with greater microbial diversity than animal-based diets, and
higher diversity is associated with better health outcomes. Not all plant-based
foods are equally health-promoting, however.
Dietary fiber is very important.
The best way to get fiber is to eat plants—fruits, vegetables, nuts/seeds,
beans/lentils, and whole grains. “Most ‘good’ bacteria living in our gut feed
on fiber,” says Zhao. “We cannot digest fiber, so it provides the microbes with
plenty to eat.”
In the PREDICT 1 study, healthier plant-based
foods (like spinach, seeds, tomatoes, and broccoli) were more strongly associated
with positive microbial strains than less healthy plant-based foods (for
example, juices, sweetened beverages, and refined grains). The same was true
for animal-based foods: foods generally considered to be healthy (for example
fish and eggs) correlated with “good” bacterial strains, while less healthy
choices (like meat pies, bacon, and dairy desserts) correlated more strongly
with the presence of “bad” strains. In another recent study, intake of plant-
and fiber-rich dietary choices was associated with a greater variety of gut microbes,
which, as explained above, is considered beneficial.
Fermented foods also
nourish gut microbiota. A recently published study found that a 10-week diet
rich in fermented foods like yogurt, kefir (a yogurt drink), miso, tempeh,
kambucha tea, and kimchi (Korean fermented cabbage) and other fermented
vegetables enhanced the diversity of gut microbes. Participants on the high
fermented foods diet also had lower levels of inflammatory proteins in their
blood. (Do watch out for high levels of sodium or added sugars in some fermented
foods.)
“It’s challenging to disentangle
the independent associations of single foods with microbial species,” says
Ordovás, “but a diversity of healthy foods, including plenty of healthy
plant-based foods, is proving to be important.”
Looking to the Future. While the research discussed above is promising,
it is still speculative at this time. “Looking at the microbiome should capture
different aspects of disease than the blood tests and screenings we currently
use,” says Segal. “A combination of methods could lead to earlier and more
robust disease detection. However, it must be stressed that very few microbiome-based
markers predictive of disease onset and progression have been found to date,
and none are currently used by healthcare systems. Discovery of microbiome-based
risk factors is a promising research area, but it is still in its infancy.”
Zhao agrees. “We hope the microbiome can someday be used to personalize nutrition,”
she says. “We’d ideally be able to take a stool sample before and after a diet
as a way to measure how that diet has impacted the individual’s health. We’re
not quite there yet, but that’s the goal we’re working towards.”
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