Alterations in the Gut Virome in Obesity and Type 2 Diabetes Mellitus.

BACKGROUND & AIMS Obesity and type 2 diabetes mellitus (T2DM) are associated with changes in the gut bacterial composition, but little is known about the role of the viral community (virome) in disease development. This study aims to characterize the gut virome alterations in obese subjects with or without T2DM. METHODS 128 obese subjects (Body Mass Index (BMI) ≥28Kg/m2) and 101 lean controls (BMI ≥ 18.5 and < 23 Kg/m2) were recruited from two regions in China (Hong Kong: HK; Kunming: KM). Fecal virome and bacteriome were profiled by shotgun metagenomic sequencing. Gut virome, bacteriome and viral-bacterial correlations were compared between obese subjects and lean controls. RESULTS Obese subjects especially those with T2DM (ObT2) had a decreased gut viral richness and diversity compared with lean controls in the HK cohort (p < .05), while no significant differences were observed in the KM cohort. Eleven viruses, including Escherichia phage, Geobacillus phage and Lactobacillus phage were enriched in obese subjects (q < .1). Besides, seventeen differentially abundant viruses were identified between ObT2 and lean controls (q < .1). Further ecological analysis revealed that intensive trans-kingdom correlations between viruses and bacteria observed in lean controls were significantly decreased in ObT2 subjects (p < .001). CONCLUSIONS Obesity is characterized by altered viral taxonomic composition and weakened viral-bacterial correlations compared with lean controls. Accompanied with T2DM may aggravate the obesity-associated virus signatures, signifying that gut virome may play an important role in the development of obesity and T2DM. Geographic factors also contributed to the variations of gut virome in obesity and T2DM.