Neutralization of IL-1α ameliorates Crohn’s disease-like ileitis by functional alterations of the gut microbiome

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Significance Here we demonstrate that IL-1α neutralization reduces the severity of disease in a mouse model of Crohn’s disease. Unexpectedly, IL-1α neutralization exerts its antiinflammatory effects by modulating the gut microbial ecosystem, and corrected the mucosal dysbiosis. Although studies report that the gut microbiome affects cytokine production, few have shown that specific neutralization of a pivotal cytokine such as IL-1α alters the composition and function of the gut microbiome. The study demonstrates a predictive relationship between IL-1α neutralization and abundance of specific bacterial species. The findings have translational significance, since IL-1α treatment prevented DSS-induced mucosal dysbiosis and preserved immunological homeostasis. These preclinical findings support the therapeutic potential of IL-1α neutralization in patients with IBD.

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