Engineering commensal Lachnospiraceae for programmable therapeutic delivery in the mouse gut.

Engineered native Coprococcus Lachnospiraceae programmed to secrete IL-22 in the mouse gut improved glucose homeostasis and attenuated hepatic steatosis in a metabolic dysfunction-associated steatotic liver disease model.

• Why it matters: Many prevalent gut taxa are genetically intractable, limiting persistent, programmable therapeutic delivery; Lachnospiraceae are common and linked to intestinal and metabolic health.
• What they did: The study built a modular engineering toolkit for Lachnospiraceae, enabling constitutive or inducible expression, chromosomal integration, and secretion, then used it to program IL-22 secretion by gut native Coprococcus in mice.
• The result: IL-22-secreting Coprococcus in the mouse intestinal tract induced epithelial defence transcriptional programmes and, in metabolic dysfunction-associated steatotic liver disease, improved glucose homeostasis, reduced systemic endotoxemia, and attenuated hepatic steatosis.

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