Lactobacillus rhamnosus MN‐431 Metabolic Tryptophan Alleviates Complementary Food‐Induced Diarrhea through PXR–NF‐κB Pathway and AHR–Th17 Cell Response Pathways

Scope Lactobacillus rhamnosus MN‐431 tryptophan broth culture (MN‐431 TBC) can prevent complementary food‐induced diarrhea (CFID). However, it is not clear whether this effect is related to indole derivatives. Methods and results In this study, the anti‐CFID effects of different components in MN‐431 TBC including MN‐431 cells, unfermented tryptophan broth, and supernatant of MN‐431 TBC (MN‐431 TBS) are investigated. Only MN‐431 TBS can significantly prevent CFID, indicating that indole derivatives produced by MN‐431 can exert antidiarrheal effects. Intestinal morphological analysis reveals that MN‐431 TBS can increase the number of goblet cells, height of ileal villi, and length of rectal glands while also increasing the expression of ZO‐1 in colon. Furthermore, HPLC analysis reveals the indole derivatives in MN‐431 TBS are IAld and skatole. Cell experiments demonstrate that MN‐431 TBS promotes the transcription of aryl hydrocarbon receptor (AHR) and pregnane X receptor (PXR), comparable to the synergistic effect of IAld and skatole. MN‐431 TBS can activate AHR and reduces the concentrations of Th17 cell‐inflammatory factors IL‐17A and IL‐21 in intestine and IL‐17F, IL‐21, and IL‐22 in serum. MN‐431 TBS can also activate PXR and reduces the concentrations of TNF‐α and IL‐6 in intestine and serum. Conclusion MN‐431 TBS, containing IAld and skatole, can exert anti‐CFID effects through the AHR–Th17 and PXR–NF‐κB pathways.