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Nat Metab., 02 July 2025 | https://doi.org/10.1038/s42255-025-01318-6
Multi-omic analysis reveals transkingdom gut dysbiosis in metabolic dysfunction-associated steatotic liver disease
Hanseul Kim 1 2 3, Paul Nelson 4, Etienne Nzabarushimana 1 2 3, Jiaxian Shen 1 2 3, Jordan Jensen 1, Amrisha Bhosle 1 5, Chengchen Li 6, Nawon Lee 2, Christine Everett 6 7, Brittany Berdy 5, Giana Frongillo 5, Jonathan Livny 5, Frank B Hu 7 8, Tracey G Simon 2 3, Lauren McIver 1 6, Eric A Franzosa 1 5 6, Andrew T Chan 2 3, Boris Hayete 4, Kelsey N Thompson 1 5 6, Curtis Huttenhower 1 5 6 9 *, Long H Nguyen 1 2 3 5 6 *
1Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA, USA.
2Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
3Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
4Empress Therapeutics, Cambridge, MA, USA.
5Broad Institute of MIT and Harvard, Cambridge, MA, USA.
6The Harvard Chan Microbiome in Public Health Center, Harvard TH Chan School of Public Health, Boston, MA, USA.
7Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
8Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
2Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
3Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
4Empress Therapeutics, Cambridge, MA, USA.
5Broad Institute of MIT and Harvard, Cambridge, MA, USA.
6The Harvard Chan Microbiome in Public Health Center, Harvard TH Chan School of Public Health, Boston, MA, USA.
7Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
8Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
9Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, MA, USA
*Corresponding authors: correspondence to Curtis Huttenhower or Long H Nguyen
Abstract
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.
논문정보
- Research article
- 2025년 07월 (BRIC 등록일 2025-07-04)
- 국외 연구진
- 의약학 > 응용의학
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