Fecal microbiota transplantation restores any effects of antibiotic use on skeletal muscle strength and contractility

Antibiotic use is widespread and often unavoidable to treat certain infections. Unfortunately, antibiotics are nonselective and also impact the gut microbiome, leading to bacterial depletion often resulting in dysbiosis. Gut dysbiosis is linked to several diseases and with the emergence of the gut-muscle axis has also been linked to skeletal muscle weakness, lack of adaptation to exercise training and muscle atrophy. Therefore, the goal of this work was to determine the time course required for recovery of lean mass and muscle function following gut microbiome depletion. Methods. Male Balb/c mice underwent a gut cleansing protocol at 13-weeks of age including 5 days of an antibiotic (AB) cocktail (ampicillin (1g/L), metronidazole (1g/L), neomycin (1g/L), and vancomycin (0.5g/L)) in sterile drinking water with 2% sucrose followed by a single dose of PEG gavaged 4 hours prior to the first fecal transplant which was derived from control untreated mice. Fecal microbiota transfers were performed every 3 days until 4 total transfers has been completed. Body composition and forelimb grip strength was measured before and after AB, and each week thereafter until in situ muscle contractility measurements at 6 weeks post AB. At 4-5 weeks post AB, mice were placed in metabolic cages. Results. During the AB treatment period, food intake was not different between control (CON) and AB; however, water intake and body weight were reduced days 2-5. Body composition on day 5 of AB treatment indicated that the decrease in body weight was due entirely to loss of lean mass, as fat mass was unchanged from pre-measurements. Grip strength was also lower after AB treatment, however when normalized to BW or lean mass, grip strength was not different between groups indicating the loss in lean mass was directly responsible for the loss in muscle strength following AB use. By 3 weeks post AB use, percent lean mass was not different between CON and AB, however absolute grip strength remained lower and did not match CON until 4 weeks post AB cessation. A compensatory increase in fat mass was observed during the first 3 weeks after AB use. By 4 weeks post AB use, lean mass, fat mass, grip strength and BW were not different between CON and AB. No differences in whole body metabolism were evident at week 4-5 post AB treatment, however ambulation during the dark cycle was lower in AB treated mice. Accordingly, 6 weeks after cessation of antibiotic use, triceps surae weight, force production and fatigue resistance were not different between CON and AB. Conclusion. It takes at least 4 weeks with repeated fecal microbiota transplantation for mice to recover body mass, grip strength and lean mass following gut microbiome depletion. This work indicates that antibiotic use led to significant loss of lean mass and grip strength, while fat mass and food intake were maintained. These were transient effects that fecal microbiota transplantation and adequate recovery time can normalize. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.