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Researchers from Osaka University Graduate School of Medicine identify a previously unknown link between the viral component of the gut microbiome and autoimmune diseases

Figure1 : Schematic illustration of the study design　

Autoimmune diseases are conditions where your immune system mistakenly attacks your body. We know from previous research that the composition of the gut microbiome, the billions of microorganisms living in the human digestive system, is linked to the development of autoimmune diseases. However, the contribution of the gut virome – the viruses living in our gastrointestinal tract – in autoimmune diseases is unknown.

In a study recently published in Annals of the Rheumatic Diseases, researchers from Osaka University Graduate School of Medicine have shown that in people suffering from autoimmune diseases, the composition of the gut virome is compromised.

Autoimmune diseases cause significant chronic morbidity and disability worldwide. They include rheumatoid arthritis, which is most common in older adults, and systemic lupus erythematosus, which is relatively prevalent among young women. The human gastrointestinal tract contains diverse populations of bacteria, fungi, viruses, and other microorganisms collectively called the gut microbiome. It is now widely recognised that the gut microbiome markedly influences our health via the immune and metabolic systems.

Although they make up a large proportion of the gut microbiome, the contribution of viruses to the effects on health has been far less studied than that of the bacterial component of the gut microbiome because of the technical difficulty of studying these tiny entities. The most predominant component of the gut virome are bacteriophages, viruses that infect bacteria and can alter their physiological function. The Osaka team aimed to investigate the role of bacteriophages in the gut microbiome of individuals with autoimmune diseases in order to reveal a potential link.

The researchers analysed the gut virome of 476 Japanese individuals, including 111 patients with rheumatoid arthritis, 47 patients with systemic lupus erythematosus, 29 patients with multiple sclerosis, and 289 healthy control volunteers. They constructed a new analytic pipeline to recover viral sequences from whole-metagenome shotgun sequencing data. This enabled them to quantify the abundance of the viruses that reside within the gut environment, providing an invaluable tool to study viruses, which  are otherwise difficult or impossible to analyse.

“Our case–control comparison of viral abundance revealed that crAss-like phages, which are one of the main components of a healthy gut virome, were significantly less abundant in the gut of the patients with autoimmune disease, particularly in patients with rheumatoid arthritis and systemic lupus erythematosus,” says Yoshihiko Tomofuji, lead author of the study.

The investigators went on to use CRISPR-based analysis to study possible bacterial targets of crAss-like phages. They observed that the virus called Podoviridae, which has a symbiotic relationship to the bacteria Faecalibacterium, significantly decreased in the gut of the patients with systemic lupus erythematosus. “These analyses have revealed a previously missing part of the autoimmunity-associated gut microbiome and presented new candidates that contribute to the development of autoimmune diseases,” explains Yukinori Okada, senior author of the study.

From a therapeutic perspective, understanding the composition of the gut virome of individuals with autoimmune diseases is important because it allows the development of targeted therapies to keep the microbiome, and potentially the disease, under control.

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The article “Whole gut virome analysis of 476 Japanese revealed a link between phage and autoimmune disease” was published in Annals of the Rheumatic Diseases at DOI: https://doi.org/10.1136/annrheumdis-2021-221267

Summary: The gut microbiome, the billions of bacteria and viruses living in the human digestive system, is now considered an “organ,” given its importance for human health. Researchers from Osaka University Graduate School of Medicine showed that individuals suffering from rheumatoid arthritis and systemic lupus erythematosus have a significantly compromised gut microbiome, specifically the viral component. Knowing what is altered in these diseases is important to develop therapeutic strategies that could keep them under control.

Tweet 1: Just a phage going through you? Delving into the weird world of the gut virome
Tweet 2: When is viral content the opposite of inflammatory? When it’s in your gut

Primary Keyword: Health and Medicine
Additional Keywords: Gut microbiota, Viruses, Bacteriophages, Autoimmunity, Rheumatoid Arthritis, Lupus

Method of Research: Data/statistical analysis

Subject of Research: People

Title: “Whole gut virome analysis of 476 Japanese revealed a link between phage and autoimmune disease”
Journal: Annals of the Rheumatic Diseases
Authors: Yoshihiko Tomofuji, Toshihiro Kishikawa, Yuichi Maeda, Kotaro Ogawa, Takuro Nii, Tatsusada Okuno, Eri Oguro-Igashira, Makoto Kinoshita, Kenichi Yamamoto, Kyuto Sonehara, Mayu Yagita, Akiko Hosokawa, Daisuke Motooka, Yuki Matsumoto, Hidetoshi Matsuoka, Maiko Yoshimura, Shiro Ohshima, Shota Nakamura, Hidenori Inohara, Hideki Mochizuki, Kiyoshi Takeda, Atsushi Kumanogoh Yukinori Okada
DOI: 10.1136/annrheumdis-2021-221267
Funded by: Japan Society for the Promotion of Science, Japan Agency for Medical Research and Development, Japan Science and Technology Agency, Takeda Science Foundation