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.

How do you explain that only two sweeteners have an effect on blood sugar levels (saccharin and sucralose) while the four sweeteners tested had an impact on the composition and functions of the gut microbiota?

The use of sweeteners can be suggested in people with metabolic diseases to help them reduce their calorie intake, lose weight and improve their metabolic risk [4]. However, over time, concerns have emerged due to the fact that sweeteners do not have a neutral effect [5, 6]. In 2014, the authors of this publication had already shown that mice consuming high doses of aspartame, saccharin and sucralose developed glucose intolerance due to disturbances in the gut microbiota [7]. In this new research, they have gone one step further by carrying out a well-conducted clinical study in humans. In 120 healthy participants, the researchers assessed the effects on glucose tolerance of sucralose, saccharin, stevia and aspartame administered for 14 days (5 study arms, 20 participants per group and one control group). Sweeteners were used at levels lower than the recommended daily intake. The ingestion of sucrose and sucralose aggravated glucose tolerance, while aspartame and stevia had a neutral effect. These sweeteners had distinct effects on the composition of the oral and faecal microbiota and on key functions (such as purine and pyrimidine metabolism, glycolysis, and amino-acid metabolism). The most significant effect was observed with sucralose. Microbiota transfer studies (human to mouse) have established the causality of effects. Animals colonised with samples from sweetener-supplemented subjects showed varying degrees of altered glucose tolerance. The chemical composition of sweeteners appears to influence the microbiota; however, the precise mechanism by which they exert these variable effects on the host through changes in the faecal microbiota requires further detailed study. More specifically, sucralose, saccharin and stevia are partially metabolised in the upper digestive tract and only a tiny proportion reaches the colon.

Does this mean you recommend that your patients should not use non-nutritive sweeteners, since they may not be physiologically inert?

In my clinical practice, we do not systematically suggest patients use sweeteners, as there is no evidence that they are an effective weight-loss tool. Although, in patients who are unable to lose their sweet tooth, we prefer suggesting the use of natural sweeteners such as steviol glucoside, which can be used on a short-term and reasonable basis. However, the above discussed results highlight the need for a rigorous assessment of the short- and longterm impact of the available sweeteners on human health before deciding whether or not to recommend their continued use as an aid to reducing metabolic risks.

IDIOPATHIC URETHRITIS IN MEN: NEW INFECTIOUS ETIOLOGIES?

^{Plummer EL, Ratten LK, Vodstrcil LA, et al. The urethral microbiota of men with and without idiopathic urethritis. mBio 2022; 13: e0221322.}

Some Australian researchers sought to determine which infectious agents, apart from those already known, might contribute to non-gonococcal urethritis in men, taking into account their sexual practices and the biological sex of their partner. For this, they conducted a case study including 199 men, 96 of whom had symptoms of idiopathic urethritis and 103 of whom did not, who served as controls. The median age of participants was 31 years, 73 had had a sexual relationship with a man in the month prior to inclusion (classified as MSM), and the remainder were classified as MSW. For all of them, the researchers had samples of urinary and urethral microbiota available for sequencing analysis. Their results revealed that Haemophilus influenzae, which naturally colonizes nasopharyngeal microbiota, was more abundant in MSM participants with idiopathic urethritis. In addition, H. influenzae was clearly associated with clinical features such as urethral burning, dysuria and purulent discharge. The researchers believe having oral sex without a condom could be the main mode of contamination by this bacterium. They observed more of the genus Corynebacterium in affected MSW, which they found surprising since it is considered commensal in male genital microbiota. The scientists conclude that some specific species of Corynebacterium may become pathogenic when present in abundance. There were also more Ureaplasma, Staphylococcus haemolyticus, Streptococcus pyogenes, Escherichia and Streptococcus pneumoniae in the urinary and urethral microbiota of symptomatic subjects, so they may all promote urethritis. Possible infectious causes of non-gonococcal urethritis, previously described as idiopathic, have thus been discovered. If these results are confirmed by other studies, doctors may eventually be able to offer their patients more targeted treatments.