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<p>The gut microbiome plays a critical role in human health through its influence on numerous physiological functions such as metabolism and immunity, with disruptions in microbial communities increasingly linked to metabolic disorders. In a large-scale cohort study in Japan, we investigated the association between gut microbiome profiles and metabolic health. Using 16S rRNA gene sequencing, four-enterotype clustering revealed that the <i>Bacteroides</i> 2 (B2) enterotype was associated with lower alpha-diversity and increased risk of metabolic diseases, particularly obesity (OR = 1.51) and hypertension (OR = 1.49). Refined seven-enterotype clustering further stratified the <i>Ruminococcus</i>, <i>Prevotella</i>, and <i>Bacteroides</i> enterotypes into distinct subtypes, uncovering a novel high-risk <i>Prevotella</i> 2 (P2) enterotype associated with nearly two-fold increased risk of obesity and diabetes mellitus. The B2 and P2 enterotypes were characterized by reduced abundance of beneficial short-chain fatty acid (SCFA) producers (<i>Faecalibacterium</i>, <i>Anaerostipes</i>) and enrichment of opportunistic pathogens (<i>Fusobacterium</i> and <i>Veillonella</i> for B2, <i>Megamonas</i> and <i>Megasphaera</i> for P2). Microbial metabolic influence network analysis revealed enterotype-specific interaction patterns, with R1, R2, and P1 enterotypes demonstrating cooperative production of SCFAs and other metabolites, while B enterotypes displayed synergy in the production of a range of sugar compounds. These findings underscore the utility of refined enterotype clustering as a powerful tool to reveal previously unrecognized gut microbial patterns linked to metabolic risk. By identifying B2 and the newly characterized P2 enterotypes as high-risk microbial profiles, this study opens new avenues for microbiome-based stratification and early intervention in metabolic disease management.</p>

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Bacteroides- and Prevotella-enriched gut microbial clusters associate with metabolic risks

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月21日

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  • Yi Rou Bah,
  • Kairi Baba,
  • Dayang Nurul Asyiqin Binte Mustafa,
  • Satoshi Watanabe,
  • Aya K. Takeda,
  • Tomoya Yamashita,
  • Kazuyuki Kasahara

摘要

The gut microbiome plays a critical role in human health through its influence on numerous physiological functions such as metabolism and immunity, with disruptions in microbial communities increasingly linked to metabolic disorders. In a large-scale cohort study in Japan, we investigated the association between gut microbiome profiles and metabolic health. Using 16S rRNA gene sequencing, four-enterotype clustering revealed that the Bacteroides 2 (B2) enterotype was associated with lower alpha-diversity and increased risk of metabolic diseases, particularly obesity (OR = 1.51) and hypertension (OR = 1.49). Refined seven-enterotype clustering further stratified the Ruminococcus, Prevotella, and Bacteroides enterotypes into distinct subtypes, uncovering a novel high-risk Prevotella 2 (P2) enterotype associated with nearly two-fold increased risk of obesity and diabetes mellitus. The B2 and P2 enterotypes were characterized by reduced abundance of beneficial short-chain fatty acid (SCFA) producers (Faecalibacterium, Anaerostipes) and enrichment of opportunistic pathogens (Fusobacterium and Veillonella for B2, Megamonas and Megasphaera for P2). Microbial metabolic influence network analysis revealed enterotype-specific interaction patterns, with R1, R2, and P1 enterotypes demonstrating cooperative production of SCFAs and other metabolites, while B enterotypes displayed synergy in the production of a range of sugar compounds. These findings underscore the utility of refined enterotype clustering as a powerful tool to reveal previously unrecognized gut microbial patterns linked to metabolic risk. By identifying B2 and the newly characterized P2 enterotypes as high-risk microbial profiles, this study opens new avenues for microbiome-based stratification and early intervention in metabolic disease management.