Lactobacillus casei modulates inflammatory cytokines and metabolites during tuberculosis treatment: A post hoc randomized controlled trial.

Abstract

BACKGROUND AND OBJECTIVES Inflammatory cytokines and metabolic abnormalities are common in patients with tuberculosis. Observational studies have indicated that probiotics modulate inflammatory cytokines and metabolites; however, clinical evidence of the effect of probiotics on patients with tuberculosis is lacking. This study investigated the effects of Lactobacillus casei on inflammatory cytokines and metabolites during tuberculosis treatment. METHODS AND STUDY DESIGN A randomized controlled trial was conducted. A total of 47 inpatients were included and randomly assigned to receive standard antituberculosis therapy only (control group) or that treatment together with 1 × 1010 colony-forming units per day of Lactobacillus casei (low-dose group) or 2 × 1010 colony-forming units per day of Lactobacillus casei (high-dose group) for 4 weeks of intensive treatment during hospitalization. Plasma samples were analyzed for inflammatory cytokines and metabolomics with ELISA kits and ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry. RESULTS Daily Lactobacillus casei supplementation of up to 2 × 1010 colony-forming units significantly lowered the concentrations of tumor necrosis factor-α, interleukin-6, interleukin-10, and interleukin-12 (p=0.007, p=0.042, p=0.002, p<0.001, respectively) in patients with tuberculosis. Compared with the control and low-dose groups, the plasma metabolites of phosphatidylserine, maresin 1, phosphatidylcholine, L-saccharopine, and pyridoxamine were significantly upregulated, and N-acetylmethionine, L-tryptophan, phosphatidylethanolamine, and phenylalanine were downregulated in the high-dose group. Strong correlations were observed between metabolites and inflammatory cytokines. CONCLUSIONS Lactobacillus casei supplementation during the intensive phase of tuberculosis treatment can significantly modulate inflammatory cytokines and metabolites. Decreased inflammatory cytokines may be related to metabolite changes.