Fermented Foods May Support Muscle Health Through the Gut-Muscle Axis

Skeletal muscle makes up roughly 40% of body mass. It is a primary site of glucose disposal, amino acid storage, and metabolic regulation. Age-related loss of muscle mass and function, culminating in sarcopenia, is linked to frailty, metabolic dysfunction, cognitive decline, loss of independence, and higher mortality. Dietary protein and exercise remain the foundations of prevention. This review in Communications Biology asks whether the gut microbiome adds a third lever through the gut-muscle axis (GMA), and whether fermented protein foods (FPFs) are a distinctive way to engage it.

The authors (Farsi, Cotter, and O'Sullivan) define FPFs as fermented foods in which protein is a substantial share of energy and contributes essential amino acids. Examples include yogurt, kefir, cheese, tempeh, and newer fermented pea, fava, wheat, or oat proteins. Fermentation, particularly by lactic acid bacteria, cleaves proteins into peptides and free amino acids. This can change digestibility, amino acid release kinetics, and bioactive peptide content, while also delivering live microbes and metabolites. The review has three aims: map mechanisms, evaluate human evidence, and identify research gaps.

Four mechanistic domains are described. First, microbial metabolites: short-chain fatty acids signal via FFA2/GPR43 and FFA3/GPR41, and in preclinical diabetic models butyrate activated PI3K/Akt through FFA2, boosting mTORC1 activity and attenuating atrophy. Butyrate also inhibits histone deacetylases, potentially remodeling muscle gene expression. Secondary bile acids act through TGR5, which is abundant in skeletal muscle, and indole derivatives act through the aryl hydrocarbon receptor. Veillonella atypica converted lactate to propionate and improved treadmill performance in mice.

Second, barrier and immune signaling: a leaky gut allows lipopolysaccharide into circulation, activating TLR4–NF-κB and raising TNF-α, IL-6, and IL-1β, which can impair insulin signaling and PI3K/Akt/mTOR-driven protein synthesis. Third, endocrine signaling: germ-free animals show reduced IGF-1 and impaired muscle development, and antibiotic disruption has reduced muscle mass in preclinical models. The authors caution that the microbiome is not the primary regulator of systemic IGF-1. Branched-chain fatty acids from microbial BCAA breakdown can amplify GLP-1 secretion, but a direct anabolic effect of GLP-1 on muscle is unproven.

Fourth, nutrient handling: microbial balance between branched-chain amino acid producers (such as Prevotella copri) and degraders may determine whether amino acid availability supports anabolism or promotes insulin resistance. Protein fermentation in a low-fiber environment can also generate p-cresol, ammonia, and hydrogen sulfide, which are linked to barrier damage and inflammation. In one cited example, Roseburia inulinivorans was lower in older adults, correlated with strength, and improved grip strength and muscle fiber size in mice.

The key conclusion is a gap between plausible mechanisms and human proof. Emerging human studies suggest favorable effects on metabolic regulation, inflammation, and gut ecology. Direct evidence that FPFs change muscle protein synthesis, mass, or function remains limited, and interventions and outcomes are highly heterogeneous. Most mechanistic data come from animals, and human trials mostly rely on systemic biomarkers. The authors call for studies with multi-omics, comprehensive microbiome profiling, and direct muscle phenotyping, comparing FPFs against conventional protein and probiotics.