Thigh muscle mass is associated with circulating valeric acid in healthy male volunteers

Short-chain fatty acids (SCFAs) are circulating metabolites generated by gut microbiota. Recently, a link between age-related muscle loss and gut microbiota has been described, and SCFAs could play a mediating role in this relationship. Acetic, propionic, and butyric acid are the abundant forms and are considered to have health benefits, less is known about valeric and caproic acid. In a cross-sectional study including 155 healthy volunteers, we investigated the relationship between muscle area, as well as intramuscular adipose tissue measured by magnet resonance imaging and circulating SCFAs. SCFAs and additional parameters were measured from serum and sport activities recorded by means of a questionnaire. We found a significant positive association between valeric acid (VA) levels and the thigh cross-sectional muscle area in males. This relationship was independent of age, BMI and weekly training times and was not observed in females. No associations between other SCFAs and the thigh muscle cross-sectional area were observed. To our knowledge, this is the first human study demonstrating a significant relationship between thigh muscle mass and VA, supporting the thesis of the “gut–muscle axis” with VA as a possible interacting player, on the one hand, affected by sex differences, on the other.