LMWP (S3-3) from the Larvae of Musca domestica Alleviate D-IBS by Adjusting the Gut Microbiota.

Diarrhea-based Irritable Bowel Syndrome (D-IBS) and diarrhea are both associated with ecological imbalance of the gut microbiota. Low Molecular Weight Peptides (LMWP) from the larvae of Musca domestica have been shown to be effective in the treatment of diarrhea and regulation of gut microbiota. Meanwhile, the single polypeptide S3-3 was successfully isolated and identified from LMWP in our previous studies. It remains unclear exactly whether and how LMWP (S3-3) alleviate D-IBS through regulating gut microbiota. We evaluated the gut microbiota and pharmacology to determine the regulation of gut microbiota structure and the alleviating effect on D-IBS through LMWP (S3-3). The rates of loose stools, abdominal withdrawal reflex (AWR) and intestinal tract motility results revealed that LMWP (S3-3) from the larvae of Musca domestica had a regulating effect against diarrhea, visceral hypersensitivity and gastrointestinal (GI) dysfunction in D-IBS model mice. Additionally, 16S rRNA gene sequencing was utilized to examine the gut microbiota, which suggests that LMWP induce structural changes in the gut microbiota and alter the levels of the following gut microbiota: Bacteroidetes, Proteobacteria and Verrucomicrobia. LMWP putatively functioned through regulating 5-HT, SERT, 5-HT2AR, 5-HT3AR and 5-HT4R according to the results of ELISA, qRT-PCR and IHC. The findings of this study will contribute to further understanding how LMWP (S3-3) attenuate the effects of D-IBS on diarrhea, visceral hypersensitivity and GI dysfunction.