Fecal transplants reverse the hallmarks of aging

Summary: Transplantation of fecal microbiota from young mice to older mice reversed hallmark signs of aging in the gut, brain, and eyes. Transplanting faecal microbiota from older mice to younger mice had the opposite effect, inducing inflammation in the brain and depleting a key protein associated with healthy vision.

Source: University of East Anglia

In the search for eternal youth, poop transplants may seem like an unlikely way to reverse the aging process.

However, scientists from the Quadram Institute and the University of East Anglia have provided evidence from mouse research that transplanting faecal microbiota from young to old mice can reverse the signs of aging in the human body. gut, eyes and brain.

In the reverse experiment, microbes from aged mice induced inflammation in the brains of young recipients and depleted a key protein needed for normal vision.

These results show that gut microbes play a role in regulating some of the adverse effects of aging and open up the possibility of gut microbe-based therapies to combat decline later in life.

Professor Simon Carding, from UEA’s Norwich Medical School and Head of the Gut Microbes and Health Research Program at the Quadram Institute, said: “This groundbreaking study provides tantalizing evidence of the direct involvement of Gut microbes in aging and functional brain decline. function and vision and offers a potential solution in the form of gut microbe replacement therapy.

The population of microbes we carry in our gut, collectively called the gut microbiota, has been known for some time to be linked to health. Most illnesses are associated with changes in the types and behavior of bacteria, viruses, fungi and other microbes in an individual’s gut.

Some of these changes in the composition of the microbiota occur with age, negatively affecting metabolism and immunity, and this has been associated with age-related disorders including inflammatory bowel disease, as well as to cardiovascular, autoimmune, metabolic and neurodegenerative disorders.

To better understand the effects of these microbiota changes in the elderly, scientists at the Quadram Institute transferred gut microbes from elderly mice to healthy young mice, and vice versa. They then looked at how this affected inflammatory features of aging in the gut, brain and eyes, which suffer functional decline later in life.

The study, published in the journal Microbiotafound that the microbiota of former donors led to a loss of integrity of the intestinal mucosa, allowing bacterial products to pass into the circulation, leading to the triggering of the immune system and inflammation of the brain and eyes.

Chronic age-related inflammation, known as inflammaging, has been associated with the activation of specific immune cells found in the brain. These cells were also overactivated in young mice that received aged microbiome transplants.

In the eye, the team also found that specific proteins associated with retinal degeneration were elevated in young mice receiving microbiota from former donors.

In aged mice, these damaging gut, eye and brain changes could be reversed by transplanting gut microbiota from young mice.

In ongoing studies, the team is now working to understand how long these positive effects can last, and to identify the beneficial components of the young donor’s microbiota and their impact on organs away from the gut.

The microbiota of young mice and old mice that received young microbiota transplants became enriched with beneficial bacteria that were previously associated with good health in mice and humans.

It shows an elderly woman sitting on a park bench
In the reverse experiment, microbes from aged mice induced inflammation in the brains of young recipients and depleted a key protein needed for normal vision. Image is in public domain

The researchers also analyzed the products that these bacteria make by breaking down elements of our diet. This revealed significant changes in lipid (fat) and vitamin metabolism, which may be related to changes seen in inflammatory cells in the eye and brain.

Similar pathways exist in humans, and the human gut microbiota also changes significantly later in life, but the researchers caution against directly extrapolating their findings to humans until studies similar in the elderly man can be achieved.

A new facility for Microbiota Replacement Therapy (MRT), also known as Fecal Microbiota Transplantation (FMT) is being built at the Quadram Institute that will facilitate these trials, as well as other trials for conditions related to the microbiota.

The study’s lead author, Dr Aimee Parker of the Quadram Institute, said: “We were thrilled to find that by altering the gut microbiota of older adults, we could rescue indicators of decline associated with age commonly seen in degenerative conditions of the eye and brain.

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This shows the metathalamic structures in the brain

“Our results provide more evidence of the important links between microbes in the gut and the healthy aging of body tissues and organs. We hope that our findings will ultimately contribute to understanding how we can manipulate our diet and gut bacteria to maximize good health later in life.

About this microbiome and current aging research

Author: Press office
Source: University of East Anglia
Contact: Press Office – University of East Anglia
Image: Image is in public domain

Original research: Access closed.
Transfer of fecal microbiota between young and old mice reverses aging characteristics of the gut, eyes and brainby Aimée Parker et al. Microbiota


Abstract

Transfer of fecal microbiota between young and old mice reverses aging characteristics of the gut, eyes and brain

Background

Altered composition of the gut microbiota later in life is associated with inflammation, declining tissue function, and increased susceptibility to chronic age-related diseases, including neurodegenerative dementias. Here, we tested the hypothesis that manipulation of the gut microbiota influences the development of major comorbidities associated with aging and, in particular, inflammation affecting the brain and retina.

Methods

Using faecal microbiota transplantation, we exchanged the gut microbiota of young (3 months), old (18 months), and old (24 months) mice. Full metagenomic sequencing and metabolomics were used to develop a custom analysis workflow to analyze changes in gut microbiota composition and metabolic potential. The effects of age and microbiota transfer on the gut barrier, retina and brain were assessed using protein assays, immunohistology and behavioral tests.

Results

We show that microbiota composition profiles and key species enriched in young or old mice are successfully transferred by FMT between young and old mice and that FMT modulates the resulting metabolic pathway profiles. Transferring microbiota from aged donors into young mice accelerates age-associated central nervous system (CNS) inflammation, retinal inflammation and cytokine signaling and promotes loss of key functional proteins in the eye, effects that coincide with increased permeability of the intestinal barrier. Conversely, these harmful effects can be reversed by the transfer of microbiota from young donors.

conclusion

These results demonstrate that aging gut microbiota drives detrimental changes in the gut-brain and gut-retina axes, suggesting that microbial modulation may have therapeutic benefit in preventing inflammation-related tissue decline later in life. .

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