Kim Hanseul, Nelson Paul, Nzabarushimana Etienne, Shen Jiaxian, Jensen Jordan, Bhosle Amrisha, Li Chengchen, Lee Nawon, Everett Christine, Berdy Brittany, Frongillo Giana, Livny Jonathan, Hu Frank B, Simon Tracey G, McIver Lauren, Franzosa Eric A, Chan Andrew T, Hayete Boris, Thompson Kelsey N, Huttenhower Curtis, Nguyen Long H
Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA, USA.
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Nat Metab. 2025 Jul 2. doi: 10.1038/s42255-025-01318-6.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition linked to obesity and the metabolic syndrome, yet its transkingdom connections have been under-investigated. We performed high-resolution multi-omic profiling-including stool metagenomes, metatranscriptomes and metabolomes-in 211 MASLD cases and 502 controls from a cohort of female nurses. Here we show that MASLD is associated with shifts in 66 gut bacterial species, including widespread enrichment of oral-typical microbes, and transkingdom dysbiosis involving not only bacterial but also viral taxa. Streptococcus spp. are more abundant in non-lean versus lean MASLD, the latter being a paradoxical subtype of a disease typically associated with increased adiposity. These microbial changes correspond with shifts in transcripts and metabolites, including increases in polyamines and acylcarnitines and reductions in secondary bile acids. We highlight gut viral perturbations in MASLD, showing that expansions of bacteriophage targeting oral-typical bacteria correspond to expansions of their bacterial hosts in the gut. We provide a comprehensive resource for understanding MASLD and highlight transkingdom multi-omic microbial shifts as potential contributors to its aetiopathogenesis.
代谢功能障碍相关脂肪性肝病（MASLD）是一种与肥胖和代谢综合征相关的常见疾病，但其跨领域联系尚未得到充分研究。我们对来自一组女性护士的211例MASLD病例和502例对照进行了高分辨率多组学分析，包括粪便宏基因组、宏转录组和代谢组。我们发现，MASLD与66种肠道细菌种类的变化有关，包括口腔典型微生物的广泛富集，以及不仅涉及细菌而且涉及病毒类群的跨领域生态失调。在非瘦型与瘦型MASLD中，链球菌属更为丰富，后者是一种通常与肥胖增加相关疾病的矛盾亚型。这些微生物变化与转录本和代谢物的变化相对应，包括多胺和酰基肉碱增加以及次级胆汁酸减少。我们强调了MASLD中肠道病毒的扰动，表明靶向口腔典型细菌的噬菌体扩增与其在肠道中的细菌宿主扩增相对应。我们提供了一个全面的资源来理解MASLD，并强调跨领域多组学微生物变化是其发病机制的潜在促成因素。
