Fecal transplants may reverse some of the effects of aging

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Research in anti-aging medicine is going well. Some scientists are focusing on our diet, while others are trying to genetically “reprogram” mature cells back to the pluripotent stage. But other approaches are much more surprising, such as those tested by researchers at the Quadram Institute and the University of East Anglia: Their method involves transplanting fecal microbiota from young subjects into the bodies of older subjects. Tested on mice, the approach seems to be paying off.

It is now known and proven that the intestinal flora plays an important role in the development of the fetus and in our state of health throughout life. This set of microorganisms contribute to various digestive, metabolic, immune and neurological functions. Therefore, the slightest imbalance in the microbiota can be the cause of many diseases; therefore, it is now the subject of much research aimed at developing new therapies.

From a certain age, an imbalance of the gut microbiota is associated with inflammation, a decline in tissue function and an increased susceptibility to age-related chronic diseases, including neurodegenerative dementias. Based on this observation, researchers set out to determine whether manipulation of the gut microbiota could influence the development of key co-morbidities associated with aging, particularly inflammation affecting the brain and retina. The results of their research reveal a new way to reverse some of the effects of aging.

Inflammation linked to increased intestinal permeability

Most diseases are associated with changes in the types and behavior of bacteria, viruses, fungi and other microbes that make up an individual’s gut microbiota. Some of these changes inevitably occur with age and have a negative effect on metabolism and immunity. From this imbalance arise several conditions, which in the past have been termed “age-related”, such as inflammatory bowel disease, cardiovascular, autoimmune, metabolic and neurodegenerative disorders.

The tissues of the central nervous system and eye, which exhibit a high susceptibility to metabolic dysregulation, are particularly vulnerable to microbiota imbalances. The gastrointestinal epithelial barrier, which must maintain rapid cell turnover and integrity in the face of constant exposure to environmental influences, also becomes particularly sensitive with age.

To better understand the deleterious effects of changes in microbiota composition in the elderly, scientists from the Quadram Institute, Norwich, conducted the following experiment: Via fecal microbiota transplantation, they swapped the gut microbiota of mice (18 and 24 months of age) ) with those of healthy young mice (3 months old), and vice versa. They then examined the induced changes in the microbiota composition and metabolic potential of the rodents.

Graphic summary of the experiment. The researchers found that the microbiota of young mice caused reduced microglial cell activity and minimal intestinal permeability. © A. Parker et al.

The team first found that fecal microbiota transplantation effectively transferred microbiota composition profiles and associated metabolic pathways. They then found that the transfer of the “aged” microbiota to young mice led to a loss of the integrity of the gut epithelial barrier, allowing bacterial products to enter the bloodstream — causing a response from the system. and inflammation in the brain and eyes.

A decrease associated with lipid and vitamin metabolism

Chronic age-related inflammation, a phenomenon called “inflammation,” has been linked to the activation of specific immune cells in the brain (microglial cells, macrophages in the central nervous system). However, the researchers found that these cells were overactive in young mice that had received transplants of senescent microbiota. Likewise, these young mice had relatively high levels of C3 proteins in their eyes, an increase of which contributes to retinal degeneration.

The experiment also showed that the harmful changes seen in the gut, brain and eyes in old mice could be reversed by transplanting fecal microbiota from young mice. † Several pro-inflammatory cytokines increased in aged mice were reduced after transplantation of young microbiota ‘, the researchers note in their article. It remained to identify precisely the organisms of the microbiota that contribute to the reduction of inflammation.

The microbiota of young mice is enriched with bacteria previously associated with good health (in both mice and humans); these are bacteria of the type BifidobacteriaAkkermansiaceae and Eubacteria† The researchers therefore analyzed the products that these bacteria make by breaking down food. They found that microbiota transplantation caused significant changes in lipid and vitamin metabolism (their proportional abundance in old mice transplanted with microbiota from young donors increased, and vice versa). This could explain the observed changes in eye and brain cells.

Our findings provide new evidence of important links between gut microbes and healthy aging of body tissues and organs. We hope that our findings will ultimately contribute to the understanding of how we can manipulate our diet and gut bacteria to maximize good health in old age. said Aimée Parker, a researcher at the Quadram Institute and lead author of the study.

However, the researchers point out that direct extrapolation of their results to humans would be premature until studies in the elderly have been conducted. A facility dedicated to microbiota replacement therapy is currently being built at the Quadram Institute to facilitate such trials.

Source: A. Parker et al., Microbiome

Learn more about the gut microbiota with the documentary Microbiota, new organ », available on our VOD channel Trust my science TV

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