Gut Microbe and Gene Candidates Nominated for Inflammatory Myopathies

A multi-omics study published in AMB Express has nominated a candidate gut microbe and a candidate risk gene for idiopathic inflammatory myopathies, a group of autoimmune muscle diseases. By integrating Mendelian randomization, database screening, molecular docking and in vitro experiments, the researchers computationally identified Lachnoclostridium as a candidate risk microbe and ENO1 as a candidate risk gene, while emphasizing that the findings are hypothesis-generating and require further experimental validation.

The gut microbiota has emerged as a potential therapeutic target in autoimmune diseases, but its role in inflammatory myopathies has remained unclear. This type of analysis suggests associations rather than proving causation, and the authors frame their results as computational nominations of candidates rather than established disease mechanisms.

Beyond the microbe-gene pairing, the analysis suggested that Lachnoclostridium and Fusobacterium nucleatum may exhibit potential interactions within the gut microbial community. Such ecological relationships could matter for how microbial communities influence the host, although the study did not demonstrate that these interactions occur in patients with inflammatory myopathies.

To connect the nominated gene to muscle biology, the team turned to structural predictions. Molecular docking and molecular dynamics simulations predicted a binding affinity between ENO1 and FBP. These simulations model how molecules interact at the atomic level but do not by themselves establish activity in living tissue.

The most direct experimental evidence came from cell culture. In vitro, ENO1 knockdown in C2C12 myotubes, a mouse muscle cell line differentiated into muscle fibers, significantly attenuated the secretion of CXCL10 and CCL2 following interferon-gamma stimulation, with a reported p value below 0.01. Both chemokines are critical for immune cell recruitment, meaning they help guide immune cells into inflamed tissue.

This result suggests that ENO1 may positively regulate interferon-gamma-induced chemokine secretion in muscle cells. Because the experiment used a mouse myotube line rather than human muscle, and because knockdown removes a gene rather than reproducing disease, the finding supports a plausible mechanism but does not confirm one in patients.

Adding an immune dimension, immune infiltration analysis suggested a positive correlation between ENO1 expression and the infiltration of CD8-positive T cells and macrophages in patient muscle tissue. Correlation, however, cannot show whether ENO1 expression drives immune infiltration or the reverse.

Taken together, the study proposes a potential microbe-gene-immune axis in inflammatory myopathies: a gut microbial candidate, a gene whose expression links to chemokine secretion from muscle cells, and immune cell infiltration in affected tissue. The authors are explicit that this chain is a hypothesis to be tested, not a validated pathway.

For patients and clinicians, the practical implications remain distant. None of the results establish Lachnoclostridium as a cause of disease, ENO1 as a drug target, or any microbiome-based therapy. What the work provides is a shortlist of testable candidates and a set of measurable links, from genetic association through structural prediction to cell-level chemokine signaling, that future studies in patient cohorts and human muscle models can now examine directly.

Subject of Research: Candidate gut microbiota and risk genes in idiopathic inflammatory myopathies identified through multi-omics screening

Article Title: Multi-omics screening and identification of candidate gut microbiota and risk genes in idiopathic inflammatory myopathies

Article References: Wu, R., Qi, Y., Zhang, J., & Jiang, X. (2026). Multi-omics screening and identification of candidate gut microbiota and risk genes in idiopathic inflammatory myopathies. AMB Express. https://doi.org/10.1186/s13568-026-02114-5

Image Credits: AI Generated

DOI: 10.1186/s13568-026-02114-5

Keywords: gut microbiota, idiopathic inflammatory myopathies, Mendelian randomization, ENO1, Lachnoclostridium, CXCL10, CCL2, molecular docking, immune infiltration, autoimmune disease, myotubes, interferon-gamma