Recent scientific evidence suggests that traits energy and fatigue are two unique unipolar moods with distinct mental and physical components. This exploratory study investigated the correlation between mental energy (ME), mental fatigue (MF), physical energy (PE), physical fatigue (PF), and the gut microbiome. The four moods were assessed by survey, and the gut microbiome and metabolome were determined from 16 S rRNA analysis and untargeted metabolomics analysis, respectively. Twenty subjects who were 31 ± 5 y, physically active, and not obese (26.4 ± 4.4 kg/m²) participated. Bacteroidetes (45%), the most prominent phyla, was only negatively correlated with PF. The second most predominant and butyrate-producing phyla, Firmicutes (43%), had members that correlated with each trait. However, the bacteria Anaerostipes was positively correlated with ME (0.048, p = 0.032) and negatively with MF (−0.532, p = 0.016) and PF (−0.448, p = 0.048), respectively. Diet influences the gut microbiota composition, and only one food group, processed meat, was correlated with the four moods—positively with MF (0.538, p = 0.014) and PF (0.513, p = 0.021) and negatively with ME (−0.790, p < 0.001) and PE (−0.478, p = 0.021). Only the Firmicutes genus Holdemania was correlated with processed meat (r = 0.488, p = 0.029). Distinct metabolic profiles were observed, yet these profiles were not significantly correlated with the traits. Study findings suggest that energy and fatigue are unique traits that could be defined by distinct bacterial communities not driven by diet. Larger studies are needed to confirm these exploratory findings.

Muscle builders frequently consume protein supplements, but little is known about their effect on the gut microbiota. This study compared the gut microbiome and metabolome of self-identified muscle builders who did or did not report consuming a protein supplement. Twenty-two participants (14 males and 8 females) consumed a protein supplement (PS), and seventeen participants (12 males and 5 females) did not (No PS). Participants provided a fecal sample and completed a 24-h food recall (ASA24). The PS group consumed significantly more protein (118 ± 12 g No PS vs. 169 ± 18 g PS, p = 0.02). Fecal metabolome and microbiome were analyzed by using untargeted metabolomics and 16S rRNA gene sequencing, respectively. Metabolomic analysis identified distinct metabolic profiles driven by allantoin (VIP score = 2.85, PS 2.3-fold higher), a catabolic product of uric acid. High-protein diets contain large quantities of purines, which gut microbes degrade to uric acid and then allantoin. The bacteria order Lactobacillales was higher in the PS group (22.6 ± 49 No PS vs. 136.5 ± 38.1, PS (p = 0.007)), and this bacteria family facilitates purine absorption and uric acid decomposition. Bacterial genes associated with nucleotide metabolism pathways (p < 0.001) were more highly expressed in the No PS group. Both fecal metagenomic and metabolomic analyses revealed that the PS group’s higher protein intake impacted nitrogen metabolism, specifically altering nucleotide degradation.

Diet is one of the primary determinants of gut microbiota composition and its metabolic output. That output is emerging as a critical determinant of systemic health and has been linked to most physiological systems in the body, yet its relationship to skeletal muscle physiology has only recently received attention. Evidence from experimental, observational, and clinical studies supports the existence of a gut–muscle axis, in which microbial composition and metabolic activity in the gut, influenced by diet, affect muscle metabolism, strength, function, and physical performance. Fiber, protein intake, probiotics, prebiotics, synbiotics, and fermented foods are examples of dietary constituents that transiently alter the gut microbiota, producing key metabolic mediators including short-chain fatty acids (SCFA), microbially generated amino acid products, and metabolites implicated in systemic inflammation and gut barrier integrity, alongside endocrine crosstalk involving myokines and hormones (e.g., cortisol and testosterone). Human studies consistently associate higher microbial diversity and enrichment of SCFA-producing taxa with improved muscle-related outcomes, while age-related dysbiosis has been linked to sarcopenia and functional decline. This narrative review summarizes current evidence of the gut–muscle axis and highlights potential mechanisms linking gut microbial composition to skeletal muscle function. Future advances in personalized nutrition may offer novel opportunities to preserve muscle health and functional capacity throughout aging.