Christensenella tenuis inhibits gut-derived endotoxins to alleviate metabolic disorders

This study is reported by the team of Professor Shuang-jiang Liu from Shandong University. The study reveals that the gut probiotic Christensenella tenuis significantly alleviates endotoxemia and metabolic disorders in a diet-induced obesity (DIO) mouse model by modulating gut bile acids (BAs) metabolism and suppressing lipopolysaccharide (LPS) translocation across the gut barrier.

LPS-induced endotoxemia is a key pathogenic factor in obesity, diabetes, and other metabolic diseases. Although previous studies have shown that probiotics can reduce circulating LPS levels, the underlying mechanism remains poorly understood. In this study, Professor Liu’s team systematically demonstrated that C. tenuis improves host metabolism via a distinct “BAs-LPS” interaction.

The researchers discovered that treatment with C. tenuis significantly improved glucose and lipid metabolism, reduced inflammation, and lowered LPS levels in the blood and liver of DIO mice. Further research has revealed that C. tenuis alleviated endotoxemia and metabolic disorders in DIO mice by inhibiting the LPS-TLR4 signaling pathway and modulating downstream metabolism. Moreover, omics analysis revealed increased levels of BAs after C. tenuis treatment, while in vitro experiments confirmed that C. tenuis hydrolyzed conjugated BAs into free BAs via bile salt hydrolase (BSH) activity. Further molecular dynamics simulations showed that these free bile acids form non-membrane-permeable complexes with LPS, effectively preventing LPS from translocating into the bloodstream.

The study also employed isothermal titration calorimetry to confirm direct binding between free BAs and LPS. The interaction was shown to be primarily enthalpy-driven, consistent with computational simulation results. Notably, oral administration of free BAs alone also reduced plasma LPS levels in DIO mice, further validating the universality and physiological relevance of the mechanism.

The paper’s co–first authors are Dr. Yu Jiang, Dr. Minzhi Jiang (postdoctoral fellow), and Dr. Jingyi Zhu. The corresponding authors are Professor Shuang-jiang Liu, Professor Chang Liu, and Associate Researcher Dr. Xukai Jiang of the State Key Laboratory of Microbiology, Shandong University. This work deepens the understanding of how probiotics modulate intestinal barrier integrity and systemic metabolism and offers a promising new direction for developing gut-targeted interventions against metabolic diseases.

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