Limosilactobacillus reuteri CCFM1388 Enhances Exercise Endurance by Modulating Intestinal Bile Acid Metabolism and Cholesterol Absorption

ABSTRACT Although probiotics have been shown to enhance physical endurance, the underlying mechanisms remain unclear. This study investigates the effects of Limosilactobacillus reuteri Culture Collection of Food Microorganisms (CCFM)1388 on exercise endurance and its regulatory role in gut microbiota and host metabolism. A treadmill fatigue model in mice demonstrated that CCFM1388 significantly improved exercise endurance by modulating testosterone biosynthesis. CCFM1388 altered gut bacterial genera involved in bile acid metabolism, leading to changes in deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) levels. These bile acids downregulated Niemann–Pick C1‐Like 1 (NPC1L1) , reducing intestinal cholesterol absorption and increasing low‐density lipoprotein cholesterol (LDL‐C) levels, a precursor for testosterone synthesis. A randomized, placebo‐controlled clinical trial further revealed that CCFM1388 supplementation significantly enhanced thigh muscle strength of rehabilitation inpatients undergoing exercise therapy, compared to those in the placebo group, accompanied by increased LDL‐C and high‐density lipoprotein cholesterol (HDL‐C) levels, although no significant changes in testosterone were observed. These findings highlight the potential of CCFM1388 in improving exercise performance by modulating cholesterol metabolism, suggesting its nutritional relevance in enhancing physical endurance and muscle function.