Lactobacillus casei alleviated the abnormal increase of cholestasis-related liver indices during tuberculosis treatment: a post hoc analysis of randomized controlled trial.

Abstract

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 × 1010 colony-forming units (CFU) per day (low-dose group), or 2 × 1010 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.

Keywords: drug-induced liver injury; gut microbiota; intestinal barrier function; probiotics; randomized controlled trial; tuberculosis.