Pyruvate Might Bridge Gut Microbiota and Muscle Health in Aging Mice After Chronic High Dose of Leucine Supplementation

Yuxiao Liao; Dan Li; Xiaolei Zhou; Zhao Peng; Zitong Meng; Rui Liu; Wei Yang

doi:10.3389/fmed.2021.755803

Pyruvate Might Bridge Gut Microbiota and Muscle Health in Aging Mice After Chronic High Dose of Leucine Supplementation

Front Med (Lausanne). 2021 Nov 22:8:755803. doi: 10.3389/fmed.2021.755803. eCollection 2021.

Authors

Yuxiao Liao^{1

2}, Dan Li^{1

2}, Xiaolei Zhou^{1

2}, Zhao Peng^{1

2}, Zitong Meng^{1

2}, Rui Liu³, Wei Yang^{1

2}

Affiliations

¹ Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Nutrition and Food Hygiene and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Preventive Medicine, School of Medicine, Jianghan University, Wuhan, China.

Abstract

Background: The previous studies demonstrated that there might be complex and close relationships among leucine supplementation, gut microbiota, and muscle health, which still needs further investigation. Aims: This study aimed to explore the associations of gut microbiota with muscle health after leucine intake. Methods: In this study, 19-month-old male C57BL/6j mice (n = 12/group) were supplemented with ultrapure water, low dose of leucine (500 mg/kg·d), and high dose of leucine (1,250 mg/kg·d) for 12 weeks by oral gavage. The mice fecal samples in each group before and after supplementation were collected for baseline and endpoint gut microbiota analysis by using 16S rDNA amplicon sequencing. Meanwhile, ultrasound measurement, H&E staining, myofiber cross-sectional area (CSA) measurement, and western blotting were performed in the quadriceps subsequently. The pyruvate levels were detected in feces. Results: Improvement in muscle of histology and ultrasonography were observed after both low and high dose of leucine supplementation. High dose of leucine supplementation could promote skeletal muscle health in aging mice via regulating AMPKα/SIRT1/PGC-1α. The richness and diversities of microbiota as well as enriched metabolic pathways were altered after leucine supplementation. Firmicutes-Bacteroidetes ratio was significantly decreased in high-leucine group. Moreover, pyruvate fermentation to propanoate I were negatively associated with differential species and the pyruvate levels were significantly increased in feces after high dose of leucine supplementation. Conclusions: Chronic high dose of leucine supplementation changed gut microbiota composition and increased pyruvate levels in the feces, which possibly provides a novel direction for promoting muscle health in aging mice.

Keywords: aging mice; gut microbiota; leucine; muscle health; pyruvate.