Lactobacillus casei Improve Anti-Tuberculosis Drugs-Induced Intestinal Adverse Reactions in Rat by Modulating Gut Microbiota and Short-Chain Fatty Acids

Abstract

The adverse effects of anti-tuberculosis (TB) drugs in the intestines were related to alteration of the intestinal microbiota. However, there was less information about microbial metabolism on the adverse reactions. This study aimed to explore whether Lactobacillus casei could regulate gut microbiota or short-chain fatty acids (SCFAs) disorders to protect intestinal adverse reactions induced by isoniazid (H) and rifampicin (R). Male Wistar rats were given low and high doses of Lactobacillus casei two hours before daily administration of anti-TB drugs. After 42 days, colon tissue and blood were collected for analysis. The feces at two-week and six-week were collected to analyze the microbial composition and the content of SCFAs in colon contents was determined. Supplementation of Lactobacillus casei increased the proportion of intestinal goblet cells induced by H and R (p < 0.05). In addition, HR also reduced the level of mucin-2 (p < 0.05), and supplementation of Lactobacillus casei restored. After two weeks of HR intervention, a decrease in OTUs, diversity index, the abundance of Bacteroides, Akkermansia, and Blautia, and an increase of the abundance of Lacetospiraceae NK4A136 group and Rumencoccus UCG-005, were observed compared with the control group (p all < 0.05). These indices in Lactobacillus casei intervention groups were similar to the HR group. Six-week intervention resulted in a dramatic reduction of Lacetospiraceae NK4A136 group, butyric acid, valeric acid and hexanoic acid, while an increase of Bacteroides and Blautia (p all < 0.05). Pretreatment with Lactobacillus casei significantly increased the content of hexanoic acid compared with HR group (p < 0.05). Lactobacillus casei might prevent intestinal injury induced by anti-tuberculosis drugs by regulating gut microbiota and SCFAs metabolism.

Regulation of Gut Microflora by Lactobacillus casei Zhang Attenuates Liver Injury in Mice Caused by Anti-Tuberculosis Drugs

“…Notably, Lc intervention reversed inflammatory responses in the colon and upregulated tight junction protein expression. The results further demonstrated that Lc could alleviate intestinal inflammation by enhancing the intestinal barrier, as evidenced by a previous rat study [32]. In this study, anti-tuberculosis drugs reduced the Chao 1 index in mice, but Lc could not recover it.…”

Role of Gut Microecology in the Pathogenesis of Drug-Induced Liver Injury and Emerging Therapeutic Strategies

“…It was found that INH treatment led to a reduction in the intestinal flora of mice like Bacteroides , Campylobacter , and Lactobacillus genus, which had shown significant beneficial immunomodulatory features [ 113 ]. At the same time, Akkermansia muciniphila are also known for its probiotic potential and illustrate the key function of intestinal barrier protection and systemic inflammation inhibition [ 114 , 115 ]. It was also confirmed that the abundance of Akkermansia muciniphila bacterium was restricted and decreased during liver injury in rats caused by anti-tuberculosis drugs, while the levels of mRNA and protein of tumor necrosis factor alpha and interleukin 6 were reduced in rats supplemented with A. muc.…”

Impact of the gut-lung axis on tuberculosis susceptibility and progression

“…Lacticaseibacillus rhamnosus isolated from the vagina of healthy women, inhibited Mtb growth in culture medium and showed intracellular killing activity against drug sensitive and resistant strains of Mtb in a murine macrophage cell line without cytotoxicity ( Rahim et al, 2022 ). A murine experiment involving the intragastric administration of Lactobacillus casei indicated a protective role for probiotics against the gut-based adverse reactions of isoniazid and rifampicin through modulation of SCFAs ( Li Y. et al, 2022 ). This was consistent with a larger randomized open label dose–response clinical trial of Lactobacillus casei that found reduced anti-TB associated gastrointestinal adverse effects ( Lin et al, 2020 ).…”