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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The author(s) received no specific funding for this work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: . This study was approved by the local Ethics Committee of the Medical University Graz (approval num-ber: EK-Nr. 29-585 ex 16/17). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All relevant data are within the manuscript and its Supporting Information files. * CA : caproic acid (C6) FFA : free fatty acids GC-EI/MS : gas chromatograph-electron impact-mass spectrometer IMAT : intramuscular adipose tissue MA : muscle area MRI : magnet resonance imaging MTBE : methyl tert-butyl ether SCFA : short-chain fatty acids SMA : spinal muscular atrophy SMN : survival motoneuron VA : valeric acid (C5)