Gut Phageome in Mexican Americans: A Population at High Risk for Metabolic Dysfunction-Associated Steatotic Liver Disease and Diabetes

Authors

Suet-Ying Kwan
Caroline M Sabotta
Lorenzo R Cruz
Matthew C Wong
Nadim J Ajami
Joseph B McCormick
Susan P Fisher-Hoch
Laura Beretta

Publication Date

9-17-2024

Journal

mSystems

Abstract

Mexican Americans are disproportionally affected by metabolic dysfunction-associated steatotic liver disease (MASLD), which often co-occurs with diabetes. Despite extensive evidence on the causative role of the gut microbiome in MASLD, studies determining the involvement of the gut phageome are scarce. In this cross-sectional study, we characterized the gut phageome in Mexican Americans of South Texas by stool shotgun metagenomic sequencing of 340 subjects, concurrently screened for liver steatosis by transient elastography. Inter-individual variations in the phageome were associated with gender, country of birth, diabetes, and liver steatosis. The phage signatures for diabetes and liver steatosis were subsequently determined. Enrichment of Inoviridae was associated with both diabetes and liver steatosis. Diabetes was further associated with the enrichment of predominantly temperate Escherichia phages, some of which possessed virulence factors. Liver steatosis was associated with the depletion of Lactococcus phages r1t and BK5-T, and enrichment of the globally prevalent Crassvirales phages, including members of genus cluster IX (Burzaovirus coli, Burzaovirus faecalis) and VI (Kahnovirus oralis). The Lactococcus phages showed strong correlations and co-occurrence with Lactococcus lactis, while the Crassvirales phages, B. coli, B. faecalis, and UAG-readthrough crAss clade correlated and co-occurred with Prevotella copri. In conclusion, we identified the gut phageome signatures for two closely linked metabolic diseases with significant global burden. These phage signatures may have utility in risk modeling and disease prevention in this high-risk population, and identification of potential bacterial targets for phage therapy.

IMPORTANCE

Phages influence human health and disease by shaping the gut bacterial community. Using stool samples from a high-risk Mexican American population, we provide insights into the gut phageome changes associated with diabetes and liver steatosis, two closely linked metabolic diseases with significant global burden. Common to both diseases was an enrichment of Inoviridae, a group of phages that infect bacterial hosts chronically without lysis, allowing them to significantly influence bacterial growth, virulence, motility, biofilm formation, and horizontal gene transfer. Diabetes was additionally associated with the enrichment of Escherichia coli-infecting phages, some of which contained virulence factors. Liver steatosis was additionally associated with the depletion of Lactococcus lactis-infecting phages, and enrichment of Crassvirales phages, a group of virulent phages with high global prevalence and persistence across generations. These phageome signatures may have utility in risk modeling, as well as identify potential bacterial targets for phage therapy.

Keywords

Humans, Male, Female, Gastrointestinal Microbiome, Bacteriophages, Middle Aged, Virome, Mexican Americans, Fatty Liver, Cross-Sectional Studies, Adult, Diabetes Mellitus, Feces, Aged, metagenomics, healthcare disparities, gut phageome, liver steatosis, diabetes mellitus

Comments

This article has been corrected. See mSystems. 2024 Oct 18;9(11):e01297-24.

DOI

10.1128/msystems.00434-24

PMID

39166873

PMCID

PMC11406975

PubMedCentral® Posted Date

8-21-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes