Fecal Microbiota Transplantation from Old Mice to Younger Adult Mice Accelerates Aging

The composition of the gut microbiome changes with age to favor inflammatory microbial species at the expense of those producing useful metabolites. Fecal microbiota transplantation is a way to permanently alter the composition of the gut microbiome, moving that of the recipient much closer to that of the donor. A number of studies in mice and other species have demonstrated that transplantation from young to old produces improved health and greater longevity, while transplantation from old to young has the opposite effect, as in the study noted here. While fecal microbiota transplantation is used in human medicine, only a few small studies have assessed outcomes in older people receiving material from young donors. The size of the effect in animal studies is promising, and thus we might hope that future studies demonstrate meaningful benefits in human patients.

The gut microbiota communicates with the homeostatic systems (nervous, immune, and endocrine). As we age, there is an increase in oxidative stress, which can deteriorate these systems, the microbiota, and the communication between them. It has been suggested that the microbiota influence the aging process, though its specific effects remain unclear. This study aimed to assess the impact of transferring microbiota from old to adult mice on behavioral, immune, and redox parameters, as well as their rate of aging and longevity.

Adult female mice were divided into three groups (N = 10/group): old microbiota (received 200 μL of old mice feces resuspended in PBS/3 days week/2 weeks, after a previous intestinal lavage with polyethylene glycol), adult microbiota (received adult mouse feces following the same procedure), and control (no manipulation). Feces were collected after treatment for microbiota and short-chain fatty acid analyses. After microbiota transfer, behavioral tests were performed, and peritoneal leukocytes were extracted to analyze immune and redox parameters, and to quantify biological age. These parameters were re-evaluated in old age, and the animals' longevity was recorded.

The results showed that old microbiota group was characterized by the increase of Akkermansia, Anaerostipes, Dubosiella, and Ruminococcus, among others. In addition, the group displayed elevated levels of anxiety, impaired immune function, and increased oxidative-inflammatory stress, effects that continued into old age. These changes translated into higher biological age and lower longevity. In conclusion, microbiota transfer from old to adult mice disrupts neuroimmune homeostasis, increases oxidative-inflammatory stress and accelerates aging process, reducing longevity.

Link: https://doi.org/10.1016/j.mad.2026.112177

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