Alterations in the gut virome are associated with type 2 diabetes and diabetic nephropathy

ABSTRACT

Although changes in gut microbiome have been associated with the development of T2D and its complications, the role of the gut virome remains largely unknown. Here, we characterized the gut virome alterations in T2D and its complications diabetic nephropathy (DN) by metagenomic sequencing of fecal viral-like particles. Compared with controls, T2D subjects, especially those with DN, had significantly lower viral richness and diversity. 81 viral species were identified to be significantly altered in T2D subjects, including a decrease in some phages (e.g. Flavobacterium phage and Cellulophaga phaga). DN subjects were depleted of 12 viral species, including Bacteroides phage, Anoxybacillus virus and Brevibacillus phage, and enriched in 2 phages (Shigella phage and Xylella phage). Multiple viral functions, particularly those of phage lysing host bacteria, were markedly reduced in T2D and DN. Strong viral-bacterial interactions in healthy controls were disrupted in both T2D and DN. Moreover, the combined use of gut viral and bacterial markers achieved a powerful diagnostic performance for T2D and DN, with AUC of 99.03% and 98.19%, respectively. Our results suggest that T2D and its complication DN are characterized by a significant decrease in gut viral diversity, changes in specific virus species, loss of multiple viral functions, and disruption of viral-bacterial correlations. The combined gut viral and bacterial markers have diagnostic potential for T2D and DN.

KEYWORDS:

• Type 2 diabetes
• gut virome
• metagenomics
• microbiota
• biomarker

Data availability statement

The data that support the findings of this study are openly available in the National Center for Biotechnology Information through BioProject number PRJNA891875 https://www.ncbi.nlm.nih.gov/.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplemental material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2226925.

Additional information

Funding

The work was supported by the Key Research and Development Program of Sichuan Province of China [2022YFS0434], the National Key Research and Development Program of China [2017YFC1703900 and 2019YFC1712302], and the Sichuan Provincial Scientific and Technological Innovation Seedling Project [2022036].