Project description:Enhancing exercise endurance holds significant practical implications for boosting the physical fitness of the general population to address daily challenges and improving the physical capabilities and quality of life of patients with relevant diseases. Polysaccharides from Gynostemma pentaphyllum Makino (GPMP) have been shown to increase the expression of slow muscle fibers in muscles. However, the underlying mechanism remains to be further investigated. Previous research has indicated that alterations in the gut microbiota are closely intertwined with the improvement of muscle endurance. In this study, we demonstrate that GPMP enriches B. acidifaciens in the murine gut, showing a notable association with muscle endurance. Subsequently, we identified that succinic acid, a key metabolite of B. acidifaciens, can effectively enhance the exercise endurance of mice and the antioxidant capacity of their muscles, protecting the muscles from damage induced by strenuous exercise. Specifically, succinic acid enters the circulatory system and acts upon skeletal muscles, activating the non-canonical Wnt signaling pathway. This activation leads to an increase in slow muscle fibers and an elevation of the oxidative phosphorylation level in muscle tissues, ultimately contributing to the improvement of exercise endurance. Moreover, we observed similar increases in B. acidifaciens and succinic acid in the feces and sera of endurance athletes. Overall, these findings uncover that GPMP modulates the body's exercise endurance through specific gut microbiota and their metabolites, thereby establishing a regulatory mechanism of host exercise endurance by gut microbiota.
Project description:It is increasingly recognised that the gastrointestinal microbiota plays a critical role in human health and promising evidence is accumulating that with dietary strategies, of prebiotic intervention, microbiota imbalances can be corrected and host health improved. Several prebiotics are widely used commercially in foods including inulin, fructo-oligosaccharides, galacto-oligosaccharides and resistant starches and there is convincing evidence, in particular for galacto-oligosaccharides, that prebiotics can modulate the microbiota and promote the growth of bifidobacteria in the intestinal tract of infants and adults. In this study we describe the identification and functional characterisation of the genetic loci responsible for the transport and metabolism of purified galacto-oligosaccharides (PGOS) by our model bifidobacterial strain, B. breve UCC2003. We further demonstrate that the extracellular endogalactanase specified by several B. breve strains, including B. breve UCC2003, is essential for metabolism of PGOS components with a long retention time and high degree of polymerisation. These PGOS components are transported into the bifidobacterial cell via various ABC transport systems and sugar permeases where they are further metabolised to galactose and glucose monomers that feed into the bifid shunt. This research described here advances our understanding of GOS metabolism by bifidobacteria and for the future there is great potential for exploiting bifidobacterial beta-galactosidase to create targeted prebiotics that can enrich for selected Bifiobacteria sp. and other beneficial microbes among the gut microbiota.
Project description:The factors that govern the retention and abundance of specific microbial lineages within a developing intestinal microbiota remain poorly defined. Human milk oligosaccharides consumed by nursing infnats pass undigested to the distal gut where they may be consumed by microbes. We investigated the transcriptional response of Bacterides fragilis, a prominent gut resident, to the presence of HMOs. In vitro transcriptional profiles of Bacteroides fragilis obtained from biological duplicate cultures taken at middle log phase in minimal media glucose (MM-Glu) and in minimal media with human milk oligosaccharides (MM-HMO).
Project description:Endurance exercise has a dramatic impact on the functionality of mitochondria and on the composition of intestinal microbiome, but the mechanisms regulating the crosstalk between these two components are still largely unknown. Here, we sampled 20 elite horses before and after an endurance race and used blood transcriptome, blood metabolome and fecal microbiome to describe the microbiota-mitochondria inter-talk. A subset of mitochondria-related differentially expressed genes involved in pathways such as energy metabolism, oxidative stress and inflammation was discovered and then shown to be associated with butyrate-producing bacteria of the Lachnospiraceae family, especially Eubacterium. The mechanisms involved were not fully understood, but through the action of their metabolites likely acted on PPARδ, the FRX-CREB axis and their downstream targets to delay the onset of hypoglycemia, inflammation and extend running time. Our results also suggested that circulating free fatty acids may act not merely as fuel but drive mitochondrial inflammatory responses triggered by the translocation of gut bacterial polysaccharides following endurance. Targeting the gut-mitochondria axis appears therefore as a potential strategy to enhance athletic performance.
Project description:<p>Enhancing exercise endurance holds significant practical implications for boosting the physical fitness of the general population to address daily challenges and improving the physical capabilities and quality of life of patients with relevant diseases. Polysaccharides from Gynostemma pentaphyllum Makino (GPMP) have been shown to increase the expression of slow muscle fibers in muscles. However, the underlying mechanism remains to be further investigated. Previous research has indicated that alterations in the gut microbiota are closely intertwined with the improvement of muscle endurance. In this study, we demonstrate that GPMP enriches B. acidifaciens in the murine gut, showing a notable association with muscle endurance. Subsequently, we identified that succinic acid, a key metabolite of B. acidifaciens, can effectively enhance the exercise endurance of mice and the antioxidant capacity of their muscles, protecting the muscles from damage induced by strenuous exercise. Specifically, succinic acid enters the circulatory system and acts upon skeletal muscles, activating the non-canonical Wnt signaling pathway. This activation leads to an increase in slow muscle fibers and an elevation of the oxidative phosphorylation level in muscle tissues, ultimately contributing to the improvement of exercise endurance. Moreover, we observed similar increases in B. acidifaciens and succinic acid in the feces and sera of endurance athletes. Overall, these findings uncover that GPMP modulates the body's exercise endurance through specific gut microbiota and their metabolites, thereby establishing a regulatory mechanism of host exercise endurance by gut microbiota.</p>
Project description:Lean nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a distinct clinical phenotype with limited evidence for effective non-pharmacological interventions and unclear mechanistic pathways. Aerobic exercise is recommended for NAFLD management, yet its effects and underlying gut microbiota–mediated mechanisms in lean NAFLD remain insufficiently characterized. This study is based on a randomized controlled trial (ClinicalTrials.gov identifier: NCT04882644) in which 100 adults with lean NAFLD were randomly assigned to a 3-month aerobic exercise intervention or usual care. 63 paired fecal samples were collected at baseline and after intervention. Gut microbiota profiles were generated using 16S rRNA gene sequencing. The dataset includes processed taxonomic abundance tables derived from fecal samples collected before and after the intervention. These data were used to characterize exercise-induced alterations in gut microbial diversity, composition, and functional potential, and to explore interindividual heterogeneity in microbiota responses to aerobic exercise in lean NAFLD. The microbiome data deposited in this series support integrative analyses with clinical phenotypes and circulating metabolomic profiles, aiming to elucidate gut microbiota–associated mechanisms underlying the metabolic benefits of aerobic exercise in lean NAFLD.
Project description:Lean nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a distinct clinical phenotype with limited evidence for effective non-pharmacological interventions and unclear mechanistic pathways. Aerobic exercise is recommended for NAFLD management; however, its effects and the gut microbiota–associated mechanisms in lean NAFLD remain incompletely understood. This dataset was generated from a randomized controlled trial (ClinicalTrials.gov identifier: NCT04882644). Participants assigned to the aerobic exercise intervention group provided fecal samples at baseline and after the 3-month intervention. A total of 33 paired fecal samples were included in this dataset. Gut microbiota profiles were generated using shotgun metagenomic sequencing. The dataset includes processed and de-identified species-level relative abundance tables derived from fecal samples collected before and after the intervention. These data were used to characterize exercise-induced alterations in gut microbial composition and interindividual variability in microbiota responses to aerobic exercise in lean NAFLD. The data support integrative analyses with clinical phenotypes and circulating metabolomic profiles to explore gut microbiota–associated mechanisms underlying the metabolic benefits of aerobic exercise.
Project description:Rationale: Physical exercise is essential for skeletal integrity and bone health. The gut microbiome, as a pivotal modulator of overall physiologic states, is closely associated with skeletal homeostasis and bone metabolism. However, the potential role of intestinal microbiota in the exercise-mediated bone gain remains unclear. Methods: We conducted microbiota depletion and fecal microbiota transplantation (FMT) in ovariectomy (OVX) mice and aged mice to investigate whether the transfer of gut ecological traits could confer the exercise-induced bone protective effects. The study analyzed the gut microbiota and metabolic profiles via 16S rRNA gene sequencing and LC-MS untargeted metabolomics to identify key microbial communities and metabolites responsible for bone protection. Transcriptome sequencing and RNA interference were employed to explore the molecular mechanisms. Results: We found that gut microbiota depletion hindered the osteogenic benefits of exercise, and FMT from exercised osteoporotic mice effectively mitigated osteopenia. Comprehensive profiling of the microbiome and metabolome revealed that the exercise-matched FMT reshaped intestinal microecology and metabolic landscape. Notably, alterations in bile acid metabolism, specifically the enrichment of taurine and ursodeoxycholic acid, mediated the protective effects on bone mass. Mechanistically, FMT from exercised mice activated the apelin signaling pathway and restored the bone-fat balance in recipient MSCs. Conclusion: Our study underscored the important role of the microbiota-metabolic axis in the exercise-mediated bone gain, heralding a potential breakthrough in the treatment of osteoporosis.
Project description:The factors that govern the retention and abundance of specific microbial lineages within a developing intestinal microbiota remain poorly defined. Human milk oligosaccharides consumed by nursing infnats pass undigested to the distal gut where they may be consumed by microbes. We investigated the transcriptional response of Bacterides fragilis, a prominent gut resident, to the presence of HMOs.