Exercise-acclimated microbiota improves skeletal muscle metabolism via circulating bile acid deconjugation
Wataru Aoi,
Ryo Inoue,
Katsura Mizushima,
Akira Honda,
Marie Björnholm,
Tomohisa Takagi,
Yuji Naito
Affiliations
Wataru Aoi
Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto 6068522, Japan; Corresponding author
Ryo Inoue
Laboratory of Animal Science, Department of Applied Biological Sciences, Faculty of Agriculture, Setsunan University, Osaka 5730101, Japan
Katsura Mizushima
Department of Human Immunology and Nutrition Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan
Akira Honda
Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Ibaraki 3000395, Japan
Marie Björnholm
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 17176, Sweden
Tomohisa Takagi
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan; Department for Medical Innovation and Translational Medical Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan
Yuji Naito
Department of Human Immunology and Nutrition Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 6028566, Japan
Summary: Habitual exercise alters the intestinal microbiota composition, which may mediate its systemic benefits. We examined whether transplanting fecal microbiota from trained mice improved skeletal muscle metabolism in high-fat diet (HFD)-fed mice. Fecal samples from sedentary and exercise-trained mice were gavage-fed to germ-free mice. After receiving fecal samples from trained donor mice for 1 week, recipient mice had elevated levels of AMP-activated protein kinase (AMPK) and insulin growth factor-1 in skeletal muscle. In plasma, bile acid (BA) deconjugation was found to be promoted in recipients transplanted with feces from trained donor mice; free-form BAs also induced more AMPK signaling and glucose uptake than tauro-conjugated BAs. The transplantation of exercise-acclimated fecal microbiota improved glucose tolerance after 8 weeks of HFD administration. Intestinal microbiota may mediate exercise-induced metabolic improvements in mice by modifying circulating BAs. Our findings provide insights into the prevention and treatment of metabolic diseases.