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Integrating Metagenomics and Metabolomics to Study the Gut Microbiome and Host Relationships in Sports Across Different Energy Systems

ABSTRACT: This study explores the role of the gut microbiome in modulating host metabolism among Colombian athletes, comparing elite weightlifters (n = 16) and cyclists (n = 13) through integrative omics analysis. Fecal and plasma samples collected one month before an international event underwent metagenomic, metabolomic, and lipidomic profiling. Metagenomic analysis using bioBakery tools identified significant microbial pathways, including L-arginine biosynthesis III and fatty acid biosynthesis initiation (Figure 1). Key metabolic pathways were enriched in both athlete groups, such as phenylalanine, tyrosine, and tryptophan biosynthesis, arginine biosynthesis, and folate biosynthesis. Plasma metabolomics and lipidomics revealed distinct metabolic profiles and a separation between athlete types through multivariate models, with lipid-related pathways such as lipid droplet formation and glycolipid synthesis driving the differences. Notably, elevated carnitine, amino acid, and glycerolipid levels in weightlifters suggest energy system-specific metabolic adaptations. These findings underscore the complex relationship between gut microbiota composition and metabolic responses tailored to athletic demands, laying groundwork for personalized strategies to optimize performance. This research highlights the potential for targeted modulation of gut microbiota as a basis for tailored interventions to support specific energy demands in athletic disciplines.

INSTRUMENT(S): 6545 Q-TOF LC/MS

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Viviana Aya

PROVIDER: MSV000096474 | MassIVE | Wed Nov 20 13:43:00 GMT 2024

REPOSITORIES: MassIVE

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Project description:<p>Emerging evidence that the gut microbiota may contribute in important ways to human health and disease has led us and others to hypothesize that both symbiotic and pathological relationships between gut microbes and their host may be key contributors to obesity and the metabolic complications of obesity. Our "Thrifty Microbiome Hypothesis" poses that gut microbiota play a key role in human energy homeostasis. Specifically, constituents of the gut microbial community may introduce a survival advantage to its host in times of nutrient scarcity, promoting positive energy balance by increasing efficiency of nutrient absorption and improving metabolic efficiency and energy storage. However, in the presence of excess nutrients, fat accretion and obesity may result, and in genetically predisposed individuals, increased fat mass may result in preferential abdominal obesity, ectopic fat deposition (liver, muscle), and metabolic complications of obesity (insulin resistance, hypertension, hyperlipidemia). Furthermore, in the presence of excess nutrients, a pathological transition of the gut microbial community may occur, causing leakage of bacterial products into the intestinal lymphatics and portal circulation, thereby inducing an inflammatory state, further aggravating metabolic syndrome traits and accelerating atherosclerosis. This pathological transition and the extent to which antimicrobial leakage occurs and causes inflammatory and other maladaptive sequelae of obesity may also be influenced by host factors, including genetics. In the proposed study, we will directly test the Thrifty Microbiome Hypothesis by performing detailed genomic and functional assessment of gut microbial communities in intensively phenotyped and genotyped human subjects before and after intentional manipulation of the gut microbiome. To address these hypotheses, five specific aims are proposed: (1) enroll three age- and sex-matched groups from the Old Order Amish: (i) 50 obese subjects (BMI > 30 kg/m2) with metabolic syndrome, (ii) 50 obese subjects (BMI > 30 kg/m2) without metabolic syndrome, and (iii) 50 non-obese subjects (BMI < 25 kg/m2) without metabolic syndrome and characterize the architecture of the gut microbiota from the subjects enrolled in this study by high-throughput sequencing of 16S rRNA genes; (2) characterize the gene content (metagenome) to assess the metabolic potential of the gut microbiota in 75 subjects to determine whether particular genes or pathways are correlated with disease phenotype; (3) characterize the transcriptome in 75 subjects to determine whether differences in gene expression in the gut microbiota are correlated with disease phenotype, (4) determine the effect of manipulation of the gut microbiota with antibiotics on energy homeostasis, inflammation markers, and metabolic syndrome traits in 50 obese subjects with metabolic syndrome and (5) study the relationship between gut microbiota and metabolic and cardiovascular disease traits, weight change, and host genomics in 1,000 Amish already characterized for these traits and in whom 500K Affymetrix SNP chips have already been completed. These studies will provide our deepest understanding to date of the role of gut microbes in terms of 'who's there?', 'what are they doing?', and 'how are they influencing host energy homeostasis, obesity and its metabolic complications? PUBLIC HEALTH RELEVANCE: This study aims to unravel the contribution of the bacteria that normally inhabit the human gastrointestinal tract to the development of obesity, and its more severe metabolic consequences including cardiovascular disease, insulin resistance and Type II diabetes. We will take a multidisciplinary approach to study changes in the structure and function of gut microbial communities in three sets of Old Order Amish patients from Lancaster, Pennsylvania: obese patients, obese patients with metabolic syndrome and non-obese individuals. The Old Order Amish are a genetically closed homogeneous Caucasian population of Central European ancestry ideal for genetic studies. These works have the potential to provide new mechanistic insights into the role of gut microflora in obesity and metabolic syndrome, a disease that is responsible for significant morbidity in the adult population, and may ultimately lead to novel approaches for prevention and treatment of this disorder.</p>

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Integrating Metagenomics and Metabolomics to Study the Gut Microbiome and Host Relationships in Sports Across Different Energy Systems

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