The microbiota and its powerful effects through the ages

“It’s still a largely descriptive science,” notes Lipkin. The only certainty: certain microbes are associated with certain conditions.

That caveat aside, Lipkin is eager to know where microbiota science will lead. He hopes that within five to ten years scientists will understand how the microbiota influences the body, and that human clinical trials will have begun to show the effect of altered microbiota on our health. that the science of the microbiota “will have become mechanical and testable, asserts W. Ian Lipkin, then it will become real. »

ADOLESCENCE

In developed countries, the vast majority of teenagers are prone to pimples. For them, it seems that there is an “acne microbiota”. Many teenagers have particularly welcoming skin for two varieties of Cutibacterium acnes (formerly called Propionibacterium acnes) closely linked to acne.

Despite having the word “acne” in its name, most strains of this bacterium are either harmless or beneficial in keeping pathogenic microbes away. C. acnes is the main component of the normal microbiota of the face and neck. But a harmful variety of C. acnes can pose a problem. It’s one of the triggers for acne, says Amanda Nelson, a researcher at Pennsylvania State University School of Medicine.

Researchers at Washington University School of Medicine in Saint Louis studied the microbiota of acne. They discovered that the only treatment providing lasting remission, isotretinoin, works in part by modifying the microbiota of the skin. It reduces the number of bacteria C. acnes while increasing the diversity of the skin microbiota.

Knowing this, scientists could attempt to design microbial treatments with the same effect. But, they hope, safer treatments than isotretinoin – which can cause birth defects if taken during pregnancy.

Among these possible new remedies are what researchers at the University of Washington call “prebiotic fertilizers” (that is, microbes that establish the conditions for a healthy skin microbiota to develop) and “selective weed killers”. (which eliminate harmful strains of C. acnes, but spare beneficial strains). They add that one could also introduce probiotics into the mix – oral or topical supplements containing doses of beneficial strains of Cutibacterium.

ADULTHOOD

What if your physical exercises benefited you more just by transferring microbes from an athlete’s large intestine into your own? Every day for two weeks, Harvard scientists took stool samples from fifteen Boston Marathon runners. They started a week before the race and stopped a week after. Then they compared them with stool samples taken for two weeks from a control group of ten non-runners. A few days after the marathon, the bacteria Veillonella atypicala were much more numerous in the saddles of runners than in those of non-runners.

“It was kind of a revelation, because of the unique metabolism of Veillonella, of which lactate is the preferred energy source,” says Aleksandar Kostic, of the Joslin Diabetes Center and Harvard Medical School. Muscles generate lactate during intense exercise. “It made us think: what if Veillonella metabolize muscle-derived lactate in athletes? And, if that were the case, inoculations of Veillonella could they help non-athletes improve their performance?

The researchers extracted Veillonella stool from a runner to inoculate sixteen mice with normal microbiota and after screening for pathogens. They placed the mice on tiny treadmills and made them run until they were exhausted. They did the same with sixteen control mice, inoculating them with another bacterium, not linked to lactate metabolism.

The mice carrying Veillonella ran 13% longer than control mice. Conclusion of the researchers: the role of the microbiota may be crucial in physical performance.

The experiment offers “a very subtle example of how a symbiosis occurs, believes Aleksandar Kostic. These kinds of relationships, I think, underlie most relationships between humans and microbes. Ultimately, it is this sort of mutualistic relationship that occurs. »

The microbiota can also explain certain less positive phenomena – notably mental states such as anxiety and depression. In 2016, scientists from University College Cork (Ireland) published an article proving the link between microbiota and depression.

To do this, they had transplanted stool from depressed humans into rats. Twenty-eight rodents were divided into two groups. The rats in the experimental group received fecal transplants from a mixture of preparations from three severely depressed men. The control rats received transplants of a mixture of excrement from three healthy men.

It turned out that the fecal transplants from the depressed men also depressed the rats in the first group. Compared to control rats, they showed a loss of interest in pleasurable activities and increased anxiety. There is a long way from the rat to the human being, admit the scientists. But they say their work supports the thesis that the microbiota of the large intestine may play a role in the development of depression. And that targeting these microorganisms could one day help treat depression and other mood disorders.

OLD AGE

The microbiota is both constant and in permanent evolution. Your unique microbiological profile is pretty much established by the age of 4. Only significant changes (changing your diet or exercise habits, moving house, spending less time outdoors, taking antibiotics or certain other medications) can really alter it.

At the same time, the microbiota is constantly evolving, varying minimally with each meal. Throughout adulthood, it changes in such a predictable course that your age can be estimated just by looking at your gut flora.

As the Hong Kong-based start-up Insilico Medicine recently demonstrated, artificial intelligence makes it possible to read this “microbiotic clock of aging”. Its researchers collected information on the microbiota of 1165 inhabitants of Europe, Asia and North America, from open access datasets. About a third of the samples came from people between the ages of 20 and 40, a third from people in their 40s and 50s, and a third from people between 60 and 90 years old.

The scientists integrated microbiota data from 90% of the subjects, classified by age, into a machine learning program. Then they applied the models found by artificial intelligence to the other 10% of microbiota, unclassified. They wanted to see if they could thus determine the age of the initial hosts of these microbiota. The “microbiotic aging clock” delivered answers accurate to within four years.

What does this tell us about the physical changes that occur with age – in particular, the weakening of immunity, systemic inflammation and the fragility of our bodies? At the Babraham Institute in Cambridge, researchers tried to find out by using faecal transplants. Knowing that the immune system works less well with age, they wondered if transplanting feces from young mice into old mice would have a restorative effect.

Prior to transplantation, the clusters of follicles (or Peyer’s patches) lining the small intestine of old mice showed a significant drop in immune response. When these mice received fecal transplants from young mice, their Peyer’s patch immune response was that of younger subjects. It appears, the scientists concluded, that the slowing of the immune response observed in aged mice is reversible. We can “rescue” it by inoculating young mice with intestinal microbes. In view of these results, one wonders if a dose of “young” stools could be the secret to a healthier old age.

Fecal transplantation is a common practice in animal microbiota research. It is also one of the main clinical interventions being studied in humans. It would introduce into our intestines microbes capable of fighting a wide range of diseases. And this is not just speculation.

Fecal transplantation has been used for about ten years to treat recurrent infection in Clostridium difficile, antibiotic resistant, which causes a serious and potentially fatal intestinal infection. Between 12,000 and 15,000 stool transplants are performed each year under medical supervision in this country alone, according to Colleen Kelly of Brown University, co-director of the National Registry of Fecal Microbiota Transplants in the United States.

In general, the results are good. But, last June, the Food and Drug Administration (FDA) reported that a patient had died of an infection following a transplant. This was done with stool that had not been adequately screened for drug-resistant bacteria.

Besides fecal transplants, scientists are considering other methods to manipulate our microbiota. In particular, they are studying the use of prebiotics and probiotics, as well as changes in diet or physical exercise likely to modify the composition of the microbial cocktails present in the large intestine.

But even the most ardent proponents of microbiotics admit that drawing conclusions about the link between microbiota and human health is difficult, and advise against rushing to design treatments.

“Faecal transplantation and the use of microbiota for therapeutic purposes are generating a lot of enthusiasm,” observes Paul Wilmes, of the University of Luxembourg, noting that companies are working on new probiotics aimed at “restoring a microbiota, so that it is in balance with its host”. That’s great on paper (by the way, Wilmes knows the environmental value of ecological restoration), but a little premature.

“Before we can do this properly and rationally, he advocates, we need to understand what a healthy microbiota really consists of and what functions microbiota confer on the human host. I don’t think we’re there yet. »

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