Spore Powder of Paecilomyces hepiali Shapes Gut Microbiota to Relieve Exercise-Induced Fatigue in Mice

Paecilomyces hepiali, a fungal strain isolated from natural Ophiocordyceps sinensis, contains similar pharmacologically active components, has been used widely as a substitute of O. sinensis in functional food and medicine. However, the components and anti-fatigue effects of P.hepiali spores and their mechanisms of action are largely unknown. Here, we compared the chemical composition in P.hepiali spore (HPS) and mycelium (HPM) by liquid chromatography with tandem mass spectrometry analysis. We found 85 metabolites with significant differences, and HPS contains more L-Malic acid, Oxalacetic acid, Fructose-1,6-bisphosphate, and L-Arginine than HPM. Then we evaluated their anti-fatigue effects and regulatory effects on the gut microbiota in mice. The forced swimming time (SW) was only significantly increased in HPS groups: the high and low dose of the HPS group was 101% and 72% longer than the control group, respectively. Both HPS and HPM treatment decreased lactic acid, blood urea nitrogen, creatine kinase while increased lactate dehydrogenase (LDH) levels in the blood. Moreover, mice treated with HPS and HPM showed less skeletal muscle fiber spacing and breakage. The relative abundance of Alistips, Eubacterium, Bacterium, Parasutterella, and Olsenella in the gut microbiota of the HPS group was higher than that in the HPM group through 16S rRNA gene sequencing analysis. These changes may be related to the regulation of nucleotide, amino acid, and carbohydrate metabolism. Correlation analysis between the gut microbiota and fatigue-related indicators suggested that Alistips, Clostridium, Akkermansia, Olsenella, and Lactobacillus were positively correlated with the SW and LDH content. Our findings demonstrated that HPS has beneficial anti-fatigue effects by regulating gut microbiota.