We already knew that top athletes’ microbiota differs from that of sedentary people, and that intense physical activity has a significant impact on the gut flora. 

But how does more moderate physical activity affect our health? Moreover, is the impact the same regardless of weight?

Several hundred volunteers enrolled

To answer these questions, researchers from Canada and European research institutes recruited 350 men and women aged between 38 and 65 and divided them into two groups: one made up of volunteers of normal weight (BMI (sidenote: Body Mass Index (BMI) Body Mass Index (BMI) assesses the corpulence of an individual by estimating the body fat mass calculated by a ratio between weight ((kg) and height squared (m2). https://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmicalc.htm https://www.euro.who.int/en/health-topics/disease-prevention/nutrition/a-healthy-lifestyle/body-mass-index-bmi ) between 18.5 and 25) and the other of overweight people only (BMI between 25 and 30, i.e., not obese).

The scientists asked them what types of physical activity they performed on a daily basis: rather light (walking, washing up, cooking, etc.), moderate (brisk walking, gardening, cycling, badminton, etc.), or intense (heavy work, running, weight training, basketball, football, etc.).

They also recorded the number of hours devoted to these activities for each participant (less than 2.5 hours, between 2.5 and 8 hours, or more than 8 hours).

Lastly, the researchers collected stools from all participants in order to analyze their gut microbiota.

Health benefits for all, but more comprehensive benefits in slim people

The results showed that improvements in the diversity and richness of the microbiota are linked more to total hours of physical activity than to the intensity of that activity. Regardless of your weight, at least 2.5 hours of physical activity a week is enough to benefit your gut.

Despite this, only the normal-weight volunteers (BMI < 25) saw changes in bacterial composition. The more time these volunteers devoted to physical activity, the richer their microbiota became in:

• Actinobacteria, a group of bacteria known for multiple benefits to cardiometabolic health, e.g., lower cholesterol, the production of acetate – a short-chain fatty acid (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. )   –, the digestion of complex carbohydrates such as resistant starch;
• Collinsella, bacteria belonging to the Actinobacteria family, which protect against gut permeability and produce butyrate, another SCFA with anti-inflammatory properties.

Impact also depends on gender

Another finding was that in normal weight men, as well as overweight women, the greater the grip strength, the higher the abundance of Faecalibacterium prausnitzii, bacteria known for their anti-inflammatory properties and effects countering dysbiosis (sidenote: Dysbiosis Generally defined as an alteration in the composition and function of the microbiota caused by a combination of environmental and individual-specific factors. Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232.   ) .

BMI and gender therefore play a role in how physical activity impacts the microbiota. This is another major advance in our understanding of how the gut-muscle axis works.

Though not as high-profile as space dog Laika, astronaut mice have taken part in a major Nasa research program.

The aim was to evaluate the effects of microgravity on bone homeostasis, with the ultimate goal of finding ways to mitigate the consequences of extended space travel. Spaceflight is associated with altered bone formation and increased bone resorption.

Recent studies have established a link between changes in the gut microbiota and bone diseases such as osteoporosis via effects on the immune system, endocrine regulation, vitamin and nutrient deficiencies, and energy metabolism through short-chain fatty acids (SCFAs). To better understand the mechanisms involved in bone health, the Rodent Research 5 mission assessed the influence of microgravity on the gut and oral microbiota of 20 female mice that spent 4.5 weeks (10 rodents) or 9 weeks (10 rodents) in the International Space Station (ISS). This is the equivalent of several years in space for Neil Armstrong, since human life expectancy is 30 to 40 times longer than that of these small rodents.

Effects of extended space travel

After 4.5 weeks in space, the rodents’ microbiota remained broadly similar in terms of diversity to that of 20 control rodents who stayed behind on Earth under identical conditions, except for microgravity. However, a more prolonged stay in the ISS (9 weeks) saw increased gut microbiota diversity, with a higher relative abundance of Firmicutes and a lower relative abundance of Bacteroidetes. More specifically, a longer stay in space led to an enrichment in Lactobacillus murinus (from the Firmicutes phylum) and Dorea sp. compared to the mice who had a 4.5-week stay. 
Moreover, compared with the rodents who remained on Earth, those that spent 9 weeks in space had enriched metabolic pathways associated with the production of lactic, malic and butyric acids, as well as glutathione and amino acids such as leucine and isoleucine.

Links with bone density

These metabolites are linked to bone mineral density in rodents. For example, glutathione promotes the survival of osteoblast precursors and thus bone regeneration, while leucine and isoleucine, two branched-chain amino acids, are actively imported into osteoblasts during chondrogenesis. 
From here it is only a short step to deducing that the microbiota and bodies of the mice are trying to compensate for bone loss during periods of microgravity. However, the researchers refuse to take this step until their hypotheses have been clearly confirmed by mechanistic studies. Nevertheless, the implications may be far-reaching: the identification of potential treatments, such as probiotic bacteria to help maintain bone health, may be beneficial to the health of astronauts in space, as well as that of ordinary earthlings suffering from osteopenia or osteoporosis.

Anorexia nervosa is an eating disorder that affects 1% of the population, with 95% of cases occurring in women. It is characterized by distortions of body image and obsessions with weight loss, leading to a drastic voluntary restriction of food intake.

This in turn leads to emaciation and health complications that can sometimes result in death. The causes of anorexia nervosa remain poorly understood, and its management is complicated, resulting in remission in less than half of cases. Previous studies involving a small number of patients had already associated a gut microbiota imbalance (dysbiosis) with the disorder. Does gut dysbiosis promote the development of the disease?

Profoundly disturbed gut microbiota in anorexic women

Researchers analyzed stool and blood samples taken from 77 women suffering from anorexia nervosa and 70 healthy women of the same age. They compared gut microbiota composition and blood metabolites (sidenote: Metabolites Small molecules produced during cellular or bacterial metabolism. For example, short-chain fatty acids are metabolites produced by intestinal microbiota during fermentation of non-digestible complex carbohydrates (fibers, etc.). Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25.  Lamichhane S, Sen P, Dickens AM, et al An overview of metabolomics data analysis: current tools and future perspectives. Comprehensive analytical chemistry. 2018 ; 82: 387-413 ) between the two groups, and indeed found differences. For example, the gut microbiota of the women suffering from anorexia nervosa contained fewer bacteria from the genus Roseburia, which are considered beneficial to health. In addition, the greater the abundance of bacteria from the genus Clostridium, the more severe the anorexic symptoms, suggesting that these species are involved in the regulation of eating behavior.

Gut microbiota contributes to eating disorders

The researchers then transplanted fecal samples from women suffering from anorexia nervosa to germ-free (sidenote: Germ-free mice mice that have no microbes at all, raised in sterile conditions. )  mice. After three weeks of a 30% reduction in food intake (to mimic the eating behaviors of anorexic patients), the mice given fecal samples from anorexia nervosa patients had lost more weight and took longer to return to normal weight than the “control” mice. A functional analysis of the bacteria present in the mice’s feces then confirmed the role of the gut microbiota in controlling eating behavior.

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Anorexia nervosa (AN) affects 1% of the population and about 95% of cases occur in women. The disorder is associated with high morbidity and mortality, and treatment leads to remission in less than half of cases. The causes of AN remain unknown but are thought to include both genetic and environmental factors. By influencing the regulation of appetite, behavior, and emotions via the “gut-brain axis”, the gut microbiota and its metabolites may play a role in the disease. Small-scale studies have already demonstrated dysbiosis of the gut microbiota in patients of the disease.

Profoundly disturbed gut microbiota in women suffering from anorexia

A team from the University of Copenhagen in Denmark used shotgun sequencing of fecal samples and serum metabolome profiling to collect data from 77 female AN patients, then compared the results with data taken from 70 healthy women of the same age. The researchers found that the gut microbiota composition of the women suffering from AN differed from that of the healthy women. In particular, there were reduced levels of the bacterial species Roseburia intestinalis and R. inulinivorans, which are involved in the digestion of plant polysaccharides and are beneficial to health.

In addition, Clostridium species were positively correlated with eating disorders and mental health, suggesting they play a role in the regulation of eating behavior and neuropsychiatric symptoms. Lastly, the gut microbiota of these patients presented higher viral diversity and richness, particularly for Lactococcus phages. 
The serum metabolome of AN patients also showed significant differences from that of healthy women. The researchers observed an increase in several bile acids, including indole-3-propionic acid, a metabolite associated with the secretion of glucagon-like peptide 1, which stimulates satiety and slows gastric emptying. Causal inference analyses by the team suggest that bacterial metabolites mediate some of the effects of gut dysbiosis on eating disorders.

Reduced weight gain and altered energy metabolism in mice

The researchers then took germ-free (sidenote: Germ-free mice mice that have no microbes at all, raised in sterile conditions. ) emice on a calorie-restricted diet and gave them a fecal microbiota transplant from either the AN women or the healthy women (control mice). After three weeks of a 30% reduction in food intake (to mimic the eating behaviors of anorexia patients), the mice given fecal samples from the AN women had a greater initial weight loss and slower weight regain than the control mice. Furthermore, there was a higher expression of appetite suppressor genes in the hypothalamus of the AN-transplanted mice and of thermogenesis-related genes in their adipose tissue.

Cosmic radiation, sleep disturbance, loss of bone density... space travel is no easy ride. If we hope to one day wake up fresh and ready to go the day after our arrival on Mars, we’ll need to understand how space affects our body and how to mitigate these effects. This is the goal of the NASA-led Rodent Research 5 mission, which studies changes in the bone structure of rodents sent to the International Space Station (ISS) for several weeks. The first results are surprising: the digestive microbiota seems to adapt to microgravity, with modifications that limit bone loss.

Microbiota influenced by space

Mice that spent nine weeks of their short lives on the ISS (the equivalent of several years for an astronaut) returned to Earth with a more diversified microbiota and whose composition had evolved. Certain bacterial species became more abundant, particularly Lactobacillus murinus and Dorea sp., which seem capable of producing molecules known to promote bone regeneration.

^{Sources (sidenote: Johnston CB, Dagar M. Osteoporosis in Older Adults. Med Clin North Am. 2020 Sep;104(5):873-884 )}

Indeed, it is a mistake to think that bone becomes a “dead” tissue once growth is complete and adulthood reached. On the contrary, bone tissue is constantly being remodeled through a balanced and continuous process of destruction and rebuilding.  However, this balance can break down in the event of illness such as osteoporosis, or during space travel, since the absence of gravity disrupts the process. However, Lactobacillus murinus and Dorea sp. appear to activate when their mouse host is weightless in space, producing molecules that promote bone regeneration. In fact, some of these compounds are more abundant in the blood of rodents that travel in space.

Implications for both astronauts and osteoporosis

In other words, it is as if the mice’s gut microbiota helps their bodies to compensate for the bone loss associated with microgravity in space. However, despite the appeal of this hypothesis, it needs to be validated before any conclusions can be drawn from it in relation to microbiota and bone health. The implications for treatment may be far-reaching: the identification of probiotic bacteria involved in maintaining bone density might not only help astronauts stay healthier in space, it may also benefit many terrestrial patients suffering from bone diseases such as osteoporosis (sidenote: Osteoporosis Osteoporosis is a "skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture". NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy, March 7-29, 2000: highlights of the conference. South Med J. 2001 Jun;94(6):569-73. ) .

The microbiota is made up of billions of microorganisms (bacteria, viruses, fungi, etc.) that live in symbiosis with our body. We do not only have a gut microbiota, but also a skin microbiota, a mouth and lung microbiota, a urinary and vaginal microbiota, etc. All of them make an essential contribution to our health. But is everyone currently aware of the role of microbiota? Do they know how to look after their microbiota? Are they suffering from health problems that they associate with the microbiota? What role do healthcare professionals presently play in informing patients?

About the Microbiota Institute 

The Biocodex Microbiota Institute is an international hub of knowledge that aims to foster better health by spreading information about human microbiota. To do so, the Institute addresses both healthcare professionals and the general public to raise awareness about the central role of this little-known organ.

BMI-23.36

The microbiota is made up of billions of microorganisms (bacteria, viruses, fungi, etc.) that live in symbiosis with our body. We do not only have a gut microbiota, but also a skin microbiota, a mouth and lung microbiota, a urinary and vaginal microbiota, etc. All of them make an essential contribution to our health. But is everyone currently aware of the role of microbiota? Do they know how to look after their microbiota? Are they suffering from health problems that they associate with the microbiota? What role do healthcare professionals presently play in informing patients?

About the Microbiota Institute

The Biocodex Microbiota Institute is an international hub of knowledge that aims to foster better health by spreading information about human microbiota. To do so, the Institute addresses both healthcare professionals and the general public to raise awareness about the central role of this little-known organ.

BMI-23.36

Less diversity, fewer beneficial micro-organisms, and more opportunistic pathogens: we know that with advancing age, the gut microbiota changes. But what about centenarians, who have managed to live longer, escaping a raft of chronic diseases and infections? To investigate the relationship between the gut microbiota and longevity, researchers at a Chinese research institute compared the gut microbiota of 1,575 individuals aged between 20 and 117, all living in Guangxi province in China, including 314 young adults (20-44 years), 277 adults (45-65 years), 386 seniors (66-85 years), 301 nonagenarians (90-99 years), and 297 centenarians (100-117 years). The results of this new study on the microbiota’s aging process were published in Nature Aging.

Centenarians with the microbiota of a 20-year-old

The bottom line: species diversity in the gut microbiota declines with age, reaching its lowest level in seniors aged 66-85 years. Surprisingly, however, it increases again in nonagenarians and centenarians, with the latter having the richest flora, on a par with younger individuals. However, the researchers believe that longevity is linked not so much to species diversity as to evenness in the relative abundances of the various species.
Other signs of youthfulness and good health in the microbiota of centenarians are an increased presence of potentially beneficial Bacteroidetes compared to seniors and nonagenarians and a reduced presence of potentially pathogenic bacteria, notably those that cause inflammation.

Particularity that grows stronger from age 100

Since these initial results suggest that a specific signature may characterize the gut microbiota of centenarians, the researchers went on to conduct a longitudinal study of gut microbial alterations in 45 of the 297 centenarians, from whom a second stool sample was collected 1.5 years later on average. They found the gut microbiota of the centenarians to be characterized by greater evenness in the relative abundance of species, a decrease in inter-individual variation, and stability of the Bacteroidetes population. The evenness of abundances at the start of the study correlated with the stability of the centenarians’ gut microbiota over the 1.5 years, suggesting that this balance of species may protect the gut flora from disruption and aging.

According to the researchers, centenarians show specific microbiota profiles, including an inter-species balance that is not only high for their age but continues to grow, and a stable abundance of Bacteroidetes. Despite their years, their gut flora remains very similar to that of young adults.

Some say that growing old is a state of mind. However, a new study by Chinese researchers suggests that the secret to a long and healthy life is to be found in the bellies of those who live to a hundred years or more. To be more precise, the answers can be found in their gut microbiota, i.e. the microbial communities made up of billions of bacteria, viruses, fungi – including yeasts – and parasites that live in the warmth of the digestive system.

Their flora rival that of 20-44-year-olds

There’s no avoiding it: the diversity of our microbiota diminishes with age. However, centenarians are the exception to this rule, since their gut microbiota stays unusually rich for their age. Indeed, it is even richer than that of 44-65-year-olds and 66-85-year-olds. So, while centenarians (sidenote: Centenaire  live to the age of 100 or more. ) and supercentenarians (sidenote: Supercentenaire Supercentenarians live to the age of 110 or more. )  have lived for more than a hundred years, they have the microbiota of young adults.

Another peculiarity of centenarians’ microbiota is the strong presence of bacteria from the phylum Bacteroidetes (sidenote: Bacteroïdetes Bacteroidetes are one of the gut microbiota’s four major bacterial groups (phyla), together with Actinobacteria, Firmicutes, and Proteobacteria. One of the most common Bacteroidetes in the gut flora is the genus Bacteroides. Zafar H, Saier MH Jr. Gut Bacteroides species in health and disease. Gut Microbes. 2021 Jan-Dec;13(1):1-20. )  compared to seniors aged 66-85 and nonagenarians. However, these beneficial bacteria are usually only found in people under the age of 40 and from this point tend to diminish in favor of other bacteria not always beneficial to our health. At the same time, the flora of centenarians is relatively low in potentially pathogenic bacteria. More beneficial bacteria, less harmful bacteria: is this the magic potion centenarians use to keep illness at bay? Perhaps. In any case, numerous specific characteristics seem to serve as signatures for their exceptional longevity and healthy aging.

Longevity, a question of balance

One last particularity identified by the researchers was that the gut microbiota of centenarians is very balanced in terms of species distribution, with no single bacterium taking the lion’s share to the detriment of others. Rather than declining over time, this relative uniformity in the abundance of the various bacterial species – already incredible when you’ve seen a hundred years – instead seems to consolidate. It may even ensure the stability over time of centenarians’ gut flora and its continued richness in Bacteroidetes. Could this be the key to a long and healthy life?

The nasal microbiota’s involvement in allergic rhinitis had long been suspected. But what is an allergy? An allergy is a chronic disease caused by an exaggerated reaction of immune system cells to normally harmless foreign substances in our body, such as animal hair, food, or pollen.

Studies have already shown reduced nasal microbiota diversity in those who suffer from allergies, which is linked to antibody production typical of the condition. But which bacterial genera or species are responsible for this nasal dysbiosis? And what role do they play in allergy-related respiratory diseases? Researchers decided to compare in detail the nasal microbiota of 55 people suffering from allergic rhinitis with that of 105 healthy individuals. They were on to the right scent, with enlightening results.

Streptococcus salivarius makes itself at home in the nostrils of allergy sufferers

The researchers were able to confirm reduced microbial diversity in the subjects with allergic rhinitis compared to the healthy controls. The Streptococcus genus made all the difference, particularly the Streptococcus salivarius species, which was highly abundant in the allergic patients. In contrast, Staphylococcus epidermidis, a species considered beneficial to the nasal microbiota, dominated in the healthy subjects. However, S. salivarius is regularly found in the mouth and throat. It is even considered probiotic and therefore good for our health, since it produces antimicrobial substances known as bacteriocins. So, are they present in the noses of allergy sufferers to fight harmful germs? No, because when the researchers put the allergy patients’ S. salivarius into contact with bacteria known to colonize the nose, they found that it secreted only small quantities of bacteriocins.

Sticky and inflammatory... can allergies be relieved by dislodging this bacterium from the nose?

To better understand the role of S. salivarius, the researchers transferred these bacteria from the allergic patients to mice, together with Alternaria alternata, an allergen which causes allergic rhinitis, over three days. The sensitized mice reacted by secreting several inflammatory proteins. What’s more, when S. salivarius from allergy patients and S. epidermidis from healthy subjects were brought into contact with mouse nasal mucosa cells, only S. salivarius stimulated inflammation and a biochemical cascade associated with allergic reactions. The gene for mucin-5AC, a “sticky” substance that protects mucous membranes, was also overexpressed, a sign of respiratory hyperreactivity. Lastly, unlike S. epidermidis, S. salivarius adhered more strongly to mucous cells when exposed to the allergen, unless the mice were genetically modified not to produce this mucin. This adhesion increases contact between the bacterium’s pro-inflammatory substances and inflammation receptors in the nasal mucosa.