Clostridium tyrobutyricum Protects against LPS-Induced Colonic Inflammation via IL-22 Signaling in Mice

Abstract

This study aimed to investigate the effects of Clostridium tyrobutyricum (C. tyrobutyricum) on colonic immunity and the role of IL-22 in the protective function of C. tyrobutyricum. Mice were supplemented with 108 CFU/mL C. tyrobutyricum daily for 20 days, followed by injecting with LPS for 24 h. In vivo interference of IL-22 via injecting with an adeno-associated virus was conducted to elucidate the role of IL-22 in C. tyrobutyricum attenuating colonic inflammation. The results showed that C. tyrobutyricum decreased the mRNA expression of IL-6 and IL-1β. C. tyrobutyricum enhanced the mRNA expression of IL-22 and the expression of MUC2 in the colon. The in vivo interference results showed that C. tyrobutyricum enhanced the mRNA expression of IL-6 and IL-1β while decreased the expression of MUC2 after knocking down IL-22. The flow cytometric analysis showed that C. tyrobutyricum decreased the proportions of macrophages, DCs, and mast cells and effectively regulated the proportion of Th17 cells, indicating that C. tyrobutyricum may stimulate the expression of IL-22 via regulating Th17 cells. Our study concluded that C. tyrobutyricum protected against LPS-induced colonic barrier dysfunction and inflammation via IL-22 signaling, suggesting that C. tyrobutyricum could be a potential probiotic in regulating colonic health.

A Potential Probiotic for Diarrhea: Clostridium tyrobutyricum Protects Against LPS-Induced Epithelial Dysfunction via IL-22 Produced By Th17 Cells in the Ileum

“…Strangely, LPS stimulation decreased the mRNA expression of IL-6 and proportions of immune cells like macrophages and DCs in the ileum after knocking down IL-22. Some similar results were also observed in the colon (13). Unlike the earlier study in which IL-22 level in the intestine is enhanced in response to LPS (64), herein, the expression of IL-22 in the ileum was decreased in response to LPS.…”

A Potential Prophylactic Probiotic for Inflammatory Bowel Disease: The Overall Investigation of Clostridium tyrobutyricum ATCC25755 Attenuates LPS‐Induced Inflammation via Regulating Intestinal Immune Cells

“…These results were similar in the colon, in which Ct treatment alone enhanced the proportions of macrophages in the colon. [ 30 ] However, unlike the study described before, [ 18 ] although supplementation with Ct alone activated the function of macrophages, Ct blocked the activation of macrophages in the duodenum in response to LPS, indicated that Ct alleviated inflammation by inhibiting the excessive activation of macrophages but not depending on IL‐10 production via intestinal macrophages in the duodenum. The mast cells are regarded as effector cells in acute allergic responses to food, bacteria, and pathogens.…”

“…Unlike the phenomenon observed in the small intestine, our previous study showed that Ct treatment alone decreased the DCs numbers in the colon, although no differences were observed in mice treated with LPS and Ct plus LPS, in response to LPS, pre-treatment with Ct stimulated the differentiation of T cell subsets in the colon. [30] Interestingly, we found that the role of Ct in regulating immune cells varied dramatically in the intestinal sections. These significant differences may rely on the anatomical and physiological distinctions among the duodenum, jejunum, and ileum.…”

“…[ 31–33 ] In response to LPS, Ct could dramatically inhibit the function of mast cells in the duodenum and ileum, while no differences were observed in the jejunum in this study and colon in our previous study. [ 30 ] Strangely, we found that supplementation with Ct alone greatly enhanced the mast cells proportions in the ileum, guiding us to hypothesize whether Ct was a bacterial allergen in the ileum to activate mast cells. The effects of Ct on the function of mast cells and their feedback to the gut microbiota and immune system need to be revealed in the future.…”

“…Unlike the phenomenon observed in the small intestine, our previous study showed that Ct treatment alone decreased the DCs numbers in the colon, although no differences were observed in mice treated with LPS and Ct plus LPS, in response to LPS, pre‐treatment with Ct stimulated the differentiation of T cell subsets in the colon. [ 30 ]…”