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

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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.

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