Promising study: Improving longevity via microbiome transplant in mice

The gut microbiome, composed of bacteria, viruses, fungi, protozoa, and other organisms, contributes to and is influenced by aging. In addition, these microorganisms play a significant role in the development and maintenance of host immunity, and their disturbance and changes (due to aging and other causes) lead to cardiovascular, metabolic, neurodegenerative, and autoimmune disorders.

One of the most vulnerable organs to aging is the brain. Evidence suggests that the gut microbiome is connected with the brain through the "gut-brain axis". Sufficient amount of studies has indicated that gut microbiota is one of the key players in brain health. As an extension of the central nervous system, the eyes are also vulnerable to stressors and the effects resulting from the aging process.

Preclinical studies have shown that the transfer of gut microbiome from aged to young animals resulted in decreased lifespan and increased risk of developing age-related conditions and vice versa. The epithelial and mucosal cell integrity is compromised with aging, leading to increased permeability to antigens circulating in the body. Together with reduced immune function and immunosenescence, the latter results in inflammaging (elevated systemic inflammation resulting from the aging process).

To investigate the effects of age-related change in gut microbiota composition on inflammaging and its impact on the gut, brain, and retina, Parker et al. initiated a study on a murine model. The investigators divided the mice into three groups based on age, including young (3 months), old (18 months), and aged (24 months). Using fecal microbiota transplant, they compared the effects of transferring microbiota between mice from different age groups to those receiving it from the same age group. Control groups received antibiotics or phosphate-buffered saline gavage.

Results revealed that the microbiota transfer from aged donors to young mice leads to inflammation, loss of integrity of the intestinal barrier epithelium, and elevated systemic markers of inflammaging. Moreover, there was an upregulation of inflammation in the brain and retina. In other words, it accelerated age-related decline in function. On the contrary, microbiota transfer from young to old mice resulted in opposite effects.

The authors concluded that age-associated alterations in the murine gut microbiota affect the stability of the intestinal epithelium, resulting in systemic inflammation. However, they highlighted that these changes could be reversed by replacing younger donor microbiota. The investigators mentioned the need for further research to better understand the long-term benefits that aged individuals could receive from the transfer of microbiota from younger donors. The results of this preclinical study provide a foundation that could potentially be translated to humans, but this step requires further investigation and validation.

Source: Parker A, Romano S, Ansorge R, Aboelnour A, Le Gall G, Savva GM, Pontifex MG, Telatin A, Baker D, Jones E, Vauzour D. Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain. Microbiome. 2022 Dec;10(1):1-25.

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