Dataset Information

Whole gut virome analysis of 476 Japanese revealed a link between phage and autoimmune disease.

ABSTRACT:

Objective

The relationship between autoimmune diseases and the gut microbiome has been intensively studied, and several autoimmunity-associated bacterial taxa have been identified. However, much less is known about the roles of the gut virome in autoimmune diseases.

Methods

Here, we performed a whole gut virome analysis based on the shotgun sequencing of 476 Japanese which included patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis and healthy control subjects.

Results

Our case-control comparison of the viral abundance revealed that crAss-like phages, which are one of the main components of a healthy gut virome, significantly decreased in the gut of the patients with autoimmune disease, specifically the patients with RA and SLE. In addition, Podoviridae significantly decreased in the gut of the patients with SLE. To understand how these viruses affected the bacteriome, we performed a quantitative virus-bacterium association analysis and clustered regularly interspaced short palindromic repeat-based virus-bacterium interaction analysis. We identified a symbiosis between Podoviridae and Faecalibacterium. In addition, multiple bacterial targets of crAss-like phages were identified (eg, Ruminococcus spp).

Conclusion

Our data suggest that the gut virome can affect our body either directly or via bacteria. Our analyses have elucidated a previously missing part of the autoimmunity-associated gut microbiome and presented new candidates that contribute to the development of autoimmune diseases.

SUBMITTER: Tomofuji Y

PROVIDER: S-EPMC8761997 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) are the most frequent chronic autoimmune diseases worldwide. Several autoimmune endocrine and non-endocrine disorders tend to occur together. T1D and AITD often cluster in individuals and families, seen in the formation of autoimmune polyendocrinopathy (AP). The close relationship between these two diseases is largely explained by sharing a common genetic background. The HLA antigens DQ2 (DQA1*0501-DQB1*0201) and DQ8 (DQA1*0301-DQB1*0302), tightly linked with DR3 and DR4, are the major common genetic predisposition. Moreover, functional single nucleotide polymorphisms (or rare variants) of various genes, such as the cytotoxic T-lymphocyte- associated antigen (CTLA4), the protein tyrosine phosphatase non-receptor type 22 (PTPN22), the interleukin-2 Receptor (IL2Ra), the Vitamin D receptor (VDR), and the tumor-necrosis-factor-α (TNF) that are involved in immune regulation have been identified to confer susceptibility to both T1D and AITD. Other genes including cluster of differentiation 40 (CD40), the forkhead box P3 (FOXP3), the MHC Class I Polypeptide-Related Sequence A (MICA), insulin variable number of tandem repeats (INS-VNTR), the C-Type Lectin Domain Containing 16A (CLEC16A), the Erb-B2 Receptor Tyrosine Kinase 3 (ERBB3) gene, the interferon-induced helicase C domain-containing protein 1 (IFIH1), and various cytokine genes are also under suspicion to increase susceptibility to T1D and AITD. Further, BTB domain and CNC homolog 2 (BACH2), C-C motif chemokine receptor 5 (CCR5), SH2B adaptor protein 3 (SH2B3), and Rac family small GTPase 2 (RAC2) are found to be associated with T1D and AITD by various independent genome wide association studies and overlap in our list, indicating a strong common genetic link for T1D and AITD. As several susceptibility genes and environmental factors contribute to the disease aetiology of both T1D and AITD and/or AP subtype III variant (T1D+AITD) simultaneously, all patients with T1D should be screened for AITD, and vice versa.