Lactobacillus casei Alleviated the Abnormal Increase of Cholestasis-Related Liver Indices During Tuberculosis Treatment: A Post Hoc Analysis of Randomized Controlled Trial

Scope Probiotics are promising in mitigating drug-induced liver injury in animal experiments. However, the clinical evidence is absent. The objective is to investigate the effect of adjunctive Lactobacillus casei on tuberculosis-drug-induced liver injury. Methods and results A post hoc analysis is conducted for a previous randomized controlled trial. The trial is registered at the Chinese Clinical Trial Registry (No. ChiCTR-IOR-17013210). Four hundred twenty nine patients are allocated to receive standard tuberculosis therapy alone (control group), or together with 1 x 10(10) colony-forming units (CFU) per day (low-dose group), or 2 x 10(10) CFU per day of L. casei (high-dose group) during tuberculosis treatment. The L. casei supplementation significantly reduced the incidence of the abnormal increase of cholestasis-related liver indices including alkaline phosphatase (p = 0.024) and bilirubin (p = 0.013). Plasma lipopolysaccharide (p = 0.02), intestinal permeability biomarkers including zonula occludens-1 (p = 0.001) and intestinal fatty acid binding protein (p = 0.002) are significantly reduced. The gut microbiota composition is dramatically altered with a reduction of Bacteroidetes (p < 0.001) and a corresponding increase of Actinobacteria (p < 0.001) and Firmicutes (p = 0.003). Conclusions L. casei supplementation is beneficial for suppressing abnormally elevated cholestasis-related liver indices during tuberculosis treatment, which may be related to its modification on blood lipopolysaccharide, intestinal barrier function, and gut microbiota.

Automated summary

The study showed that adjunctive L. casei supplementation significantly reduced the incidence of abnormal increase in cholestasis-related liver indices during tuberculosis treatment. This beneficial effect may be attributed to its modification of blood lipopolysaccharide, intestinal barrier function, and gut microbiota.