Bile acid receptor Tgr5 prevents macrophage hyperinflammation during bacterial sepsis through metabolic and epigenetic silencing.

Summary

The study demonstrates that the bile acid receptor TGR5 is induced in macrophages during stimulation and prevents hyperinflammatory responses in bacterial sepsis via metabolic and epigenetic silencing mechanisms. This positions TGR5 signaling as a tractable immunometabolic target to temper dysregulated innate immunity in sepsis.

Key Findings

• TGR5 expression is upregulated in macrophages upon stimulation and constrains hyperinflammation in bacterial sepsis.
• Macrophage hyperactivation is suppressed through metabolic and epigenetic silencing mechanisms downstream of TGR5.
• The findings support TGR5 as a targetable node to rebalance innate immunity during sepsis.

Clinical Implications

Pharmacologic activation of TGR5 could modulate macrophage responses in sepsis, potentially reducing cytokine-driven organ injury while aligning with bile acid and metabolic pathways.

Limitations

• Abstract provides limited methodological and outcome details; full experimental breadth not visible.
• Translational applicability and dosing strategies for TGR5 modulation in humans remain to be determined.

Future Directions

Test selective TGR5 agonists in clinically relevant sepsis models; delineate epigenetic modifiers downstream of TGR5; assess interactions with bile acid pools and microbiome in sepsis.