Summary: Transplanting fecal microbiota from young mice into older mice reversed key markers of aging in the gut, brain, and eye. In contrast, transferring microbes from aged animals into young mice triggered brain inflammation and reduced a protein important for normal vision.
Source: University of East Anglia
Fecal microbiota transplantation (FMT) — sometimes dismissed as unlikely medicine — shows promise for reversing some age-related decline in mice.
Researchers at the Quadram Institute and the University of East Anglia report that swapping gut microbiota between young and aged mice shifts inflammatory and functional markers across the gut–brain and gut–retina axes. Young-to-old microbiota transfers restored markers of gut barrier integrity and reduced inflammation in the brain and retina. Conversely, aged-to-young transfers drove inflammation and depletion of proteins linked to retinal health.
These experiments add to growing evidence that the gut microbiota plays an active role in healthy aging and in the onset of age-associated disorders. They also suggest microbiota-based therapies could potentially slow or reverse tissue decline in later life.
Prof Simon Carding of UEA’s Norwich Medical School and head of the Gut Microbes and Health Research Program at the Quadram Institute commented: “This ground-breaking study provides tantalizing evidence for the direct involvement of gut microbes in aging and the functional decline of brain function and vision and offers a potential solution in the form of gut microbe replacement therapy.”
The gut microbiota — the complex community of bacteria, viruses, fungi and other microorganisms that live in the digestive tract — is already known to influence metabolism, immunity, and disease risk. Composition and function of the gut microbiome change with age, and those shifts have been linked to conditions such as inflammatory bowel disease, cardiovascular disease, metabolic disorders, autoimmune disease, and neurodegeneration.
To test whether age-related microbiota changes drive tissue decline, the team performed reciprocal fecal microbiota transplants between young (3 months), old (18 months), and aged (24 months) mice. They then assessed barrier function in the intestine, inflammatory status in the brain and retina, and changes in microbial composition and metabolism.
Published in the journal Microbiome, the study used whole metagenomic sequencing and metabolomics to characterize transferred communities and their metabolic outputs. The researchers report that aged donor microbiota caused increased intestinal permeability in young recipients, allowing bacterial products to enter the circulation and trigger immune activation and inflammation in distant tissues such as the brain and eye.
Markers of age-associated chronic inflammation — often called “inflammaging” — were elevated after aged-to-young transfers. Specific immune cells in the central nervous system were over-activated, and proteins associated with retinal degeneration increased in young mice receiving aged microbiota. Conversely, transplanting microbiota from young donors into old mice reversed these negative changes: gut integrity improved, inflammation markers fell, and retinal proteins linked to decline were reduced.
Microbiome profiles from young donors and from aged mice that received young microbiota were enriched with bacterial species previously associated with health in both mice and humans. Metabolomic analysis revealed shifts in lipid and vitamin metabolism linked to these microbial changes, offering plausible biochemical pathways that could influence immune cells in the eye and brain.
The authors caution that mouse models do not directly equal human biology, but many of the implicated metabolic and inflammatory pathways are conserved across species. To enable human testing, a new Microbiota Replacement Therapy (MRT) facility — also known as an FMT center — is being established at the Quadram Institute to support clinical trials and research into microbiota-driven conditions.
Lead author Dr. Aimée Parker of the Quadram Institute said: “We were excited to find that by changing the gut microbiota of elderly individuals, we could rescue indicators of age-associated decline commonly seen in degenerative conditions of the eye and brain. Our results provide more evidence of the important links between microbes in the gut and healthy aging of tissues and organs around the body. We hope that our findings will contribute ultimately to understanding how we can manipulate our diet and our gut bacteria to maximize good health in later life.”
Ongoing work aims to determine how long beneficial effects persist after microbiota transfer and to identify the specific bacterial species, metabolites, or combinations that drive improvements in distant organs. Such discoveries could guide targeted therapies to support healthy aging, reduce inflammaging, and protect vision and cognitive function.
About this microbiome and aging research news
Author: Press Office
Source: University of East Anglia
Contact: Press Office – University of East Anglia
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Original Research: Closed access.
“Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain” by Aimée Parker et al. Microbiome
Abstract
Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain
Background
Changes in intestinal microbiota composition during aging are linked to chronic low-grade inflammation (inflammaging), reduced tissue function, and greater vulnerability to age-related diseases, including neurodegenerative conditions. This study tested whether deliberately altering the gut microbiota can influence inflammation and functional decline in the brain and retina.
Methods
Researchers performed fecal microbiota transplantation between young (3 months), old (18 months), and aged (24 months) mice. They applied whole metagenomic shotgun sequencing and metabolomics to map microbiota composition and metabolic potential after transfer. The study evaluated gut barrier integrity, retinal and brain inflammation, and behavior using protein assays, immunohistology, and functional testing.
Results
Microbiota composition and key species characteristic of young or aged donors were successfully transferred by FMT, with corresponding shifts in metabolic pathways. Aged donor microbiota accelerated central nervous system inflammation, retinal inflammation, and cytokine signaling in young recipients and was associated with loss of important retinal proteins and increased intestinal permeability. Transfers of young donor microbiota into aged recipients reversed these detrimental effects.
Conclusions
The findings indicate that the aging gut microbiota actively drives harmful changes along the gut–brain and gut–retina axes. Modulating the microbiota may therefore offer therapeutic potential to prevent or reverse inflammation-related tissue decline in later life.