Gut Commensal Barnesiella Intestinihominis Ameliorates Hyperglycemia and Liver Metabolic Disorders.

Summary

Across two human cohorts, Barnesiella intestinihominis was depleted in T2D. Oral live B. intestinihominis or its metabolite acetate improved hyperglycemia and hepatic metabolic dysfunction in HFD/STZ and db/db mice by increasing FGF21 via HDAC9 inhibition and H3K27 acetylation at the FGF21 promoter. The prebiotic puerarin promoted B. intestinihominis growth and replicated metabolic benefits.

Key Findings

• B. intestinihominis abundance is reduced in feces of T2D patients across two independent centers.
• Oral live B. intestinihominis improves hyperglycemia and liver metabolic disorders in HFD/STZ and db/db mice.
• Acetate elevates FGF21 by inhibiting HDAC9 and increasing H3K27 acetylation at the FGF21 promoter.
• Puerarin promotes B. intestinihominis growth and improves metabolic phenotypes in a microbiota-dependent manner.

Clinical Implications

Supports development of B. intestinihominis as a probiotic or puerarin as a prebiotic to augment endogenous FGF21 and improve glycemia and NAFLD-like features; suggests monitoring FGF21 and short-chain fatty acids as pharmacodynamic biomarkers.

Limitations

• Human interventional data are lacking; efficacy and safety of live B. intestinihominis in patients remain untested
• Sample sizes and detailed cohort characteristics are not specified in the abstract

Future Directions

Conduct phase 1/2 trials of B. intestinihominis and puerarin in T2D with FGF21/acetate biomarker readouts; define colonization dynamics, dosing, and long-term hepatic and cardiometabolic outcomes.