# PGC-1 alpha overexpression in the skeletal muscle results in a metabolically active microbiome which is independent of redox signaling

## TL;DR

This study shows that overexpressing PGC-1 alpha in skeletal muscle changes the gut microbiome in ways that are not linked to redox signaling.

## Contribution

The study reveals a novel link between mitochondrial activity and the microbiome that operates independently of redox signaling.

## Key findings

- PGC-1α overexpression increases basal levels in skeletal muscle and colon.
- Microbial composition shifts in PGC-1α overexpressing mice, possibly to handle increased metabolism.
- Exercise training differently affects the microbiome in PGC-1α overexpressing and wild-type mice.

## Abstract

In this study, we investigated the potential relationship between the mitochondrial network and the microbiome using wild-type and skeletal muscle-specific PGC-1α (Pparg coactivator 1 alpha) overexpressing mice, both with and without exercise training. Basal PGC-1α levels were significantly higher in the skeletal muscle (J Physiol Biochem 80:329–335, 2024. 10.1007/s13105-024-01006-1) and, notably, in the colon, which is anatomically proximal to the microbiome. However, no significant changes were observed in cell signaling or mitochondria-related proteins within the colon. On the other hand, mitochondrial H₂O₂ production in the colon decreased in the PGC-1α overexpressing group. The relative abundance of several bacterial taxa differed between wild-type and PGC-1α overexpressing groups at baseline condition, indicating a shift in the microbiome milieu probably to cope with the increased metabolism, enhanced short-chain fatty acid utilization, and improved endurance capacity. Ten weeks of exercise training differentially modulated the host microbiome in PGC-1α overexpressing and wild-type mice, facilitating adaptations to a broad range of exercise-induced challenges. The results of this study provide new insights into the possible cross-talk between mitochondria and the microbiome.

The online version contains supplementary material available at 10.1038/s41598-025-05594-w.