Lactobacillus casei Strain Shirota Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Increasing Taurine-Conjugated Bile Acids and Inhibiting NF-κB Signaling via Stabilization of IκBα

Abstract

Inflammatory bowel disease (IBD) is a chronic progressive intestinal inflammatory disease, characterized by an altered gut microbiota composition and accompanying alterations in circulatory bile acids. Increasing evidence supports the beneficial effect of probiotics intake on health. Introduction of probiotics to the intestines can modulate gut microbiota composition and in turn regulate the host immune system and modify the inflammatory response. Probiotics can also improve intestinal barrier function and exhibit a positive impact on host physiological and pathological conditions via gut microbiota-derived metabolites. Previous studies have demonstrated that Lactobacillus casei strain Shirota (LcS) treatment could inhibit clinical manifestation of colitis in dextran sulfate sodium (DSS)-induced mice, however, the underlying mechanisms remain unknown. In this study, we employed the DSS-induced acute colitis mouse model to investigate the anti-inflammatory effects of LcS and related mechanisms. Administration of LcS ameliorated the severity of DSS-induced colitis and enhanced intestinal integrity via induction of mucin-2 and occludin expression in colons. Fecal microbiota analysis showed that LcS increased the relative abundance of beneficial bacterial species in colitic mice, whereas the relative abundance of pathobionts was reduced. Additionally, LcS treatment modulated circulating bile acid profiles in colitic mice. In mice treated with LcS, we identified increased levels of primary taurine-conjugated bile acids, including taurocholic acid (TCA) and taurochenodeoxycholic acid (TCDCA). LcS treatment also increased the levels of secondary taurine-conjugated bile acids, including taurodeoxycholic acid (TDCA) and tauroursodeoxycholic acid (TUDCA). Moreover, LcS treatment exhibited a suppressive effect on the hydroxylated primary bile acids α-muricholic acid (α-MCA) and β-muricholic acid (β-MCA). We further demonstrated that LcS treatment suppressed the expression of pro-inflammatory mediators interferon-gamma (IFN-γ) and nitric oxide (NO), and increased the expression of the anti-inflammatory mediator interleukin-10 (IL-10) in colon tissues, potentially as a result of altered bile acid profiles. Mechanistically, we showed that LcS treatment suppressed the activation of nuclear factor-kappa B (NF-κB) signaling via stabilization of inhibitor of NF-κB alpha (IκBα). Altogether, we have demonstrated the therapeutic effects of LcS in DSS-induced colitis, providing new insights into its effect on bile acid metabolism and the related anti-inflammatory mechanisms. Our findings provide support for the application of LcS in the treatment of IBD.

Combination of Lactobacillus plantarum improves the effects of tacrolimus on colitis in a mouse model

“…Based on our previous research proposing that tacrolimus plus gut microbiota achieved an increased allograft survival rate ( Zhang et al., 2018 ), this study confirmed that the combination of tacrolimus and Lactobacillus strains played a positive role in colitis. Since we observed that the colonic contents were inadequate for the detection of two-omics, especially in the condition of colitis, the cecal content was used following the protocol as previous studies ( Wong et al., 2022 ). There are certain limitations to do this since the most representative alterations in the gut microbiome are in the area where inflammation occurs.…”

“…Theoretically, an improved composition of the gut microbiome and bile acid metabolism might help explain the mechanism of amelioration after combination therapy. A recent study has shown that one strain from Lactobacillus casei ameliorated DSS-induced colitis in mice by increasing taurine-conjugated bile acids, and the activation of FXR by the increased TCDCA might exhibit anti-inflammatory effects ( Wong et al., 2022 ). This possibly resulted from the activation of FXR shifting the polarization of macrophages toward the anti-inflammatory M2 phenotype, which promoted IL-10 secretion and inhibited IFN-γ production ( Fiorucci et al., 2018 ).…”

Disturbances of the Gut Microbiota and Microbiota-Derived Metabolites in Inflammatory Bowel Disease

“…Probiotics can restore abnormal BA metabolism in IBD patients. The administration of Shirota strain of Lactobacillus casei could significantly ameliorate the severity of DSS-induced colitis by restoring the composition of the gut microbiota and circulating bile acid profiles in colitic mice [ 102 ].…”

Bile acids as inflammatory mediators and modulators of intestinal permeability

“…et al. showed that increasing the amount of taurine conjugated bile acids through Lactobacillus case strain Shirota (LcS) mediated increases led to improvement in DSS induced colitis ( 111 ). Specifically, improvement in colon length, improvement in histological architecture, and decreases in CD45 expression in the colons of these mice as compared to untreated mice with DSS colitis.…”