Graphical AbstractHighlights d FMT from resistant to susceptible piglets prevents earlyweaning stress-induced diarrhea d Lactobacillus gasseri LA39 and Lactobacillus frumenti confer diarrhea resistance d Diarrhea resistance is mediated by the bacterial secretory circular peptide gassericin A d Gassericin A binding to KRT19 on the membrane of intestinal epithelial cells is essential SUMMARY Alternatives to antibiotics for preventing diarrhea in early-weaned farm animals are sorely needed. CM piglets (a native Chinese breed) are more resistant to early-weaning stress-induced diarrhea than the commercial crossbred LY piglets. Transferring fecal microbiota, but not saline, from healthy CM into LY piglets by oral administration prior to early weaning conferred diarrhea resistance. By comparing the relative abundance of intestinal microbiota in saline and microbiota transferred LY piglets, we identified and validated Lactobacillus gasseri LA39 and Lactobacillus frumenti as two bacterial species that mediate diarrhea resistance. Diarrhea resistance depended on the bacterial secretory circular peptide gassericin A, a bacteriocin. The binding of gassericin A to Keratin 19 (KRT19) on the plasma membrane of intestinal epithelial cells was essential for enhancement of fluid absorption and decreased secretion. These findings suggest the use of L. gasseri LA39 and L. frumenti as antibiotic alternatives for preventing diarrhea in mammals.
Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease, the occurrence of which has been increasing worldwide. Research in recent years has found that the level of lysozyme in the feces and blood of UC patients is abnormally elevated, and the bacterial product after the action of lysozyme can be used as an agonist to recognize different cell pattern receptors, thus regulating the process of intestinal inflammation. Berberine (BBR), as a clinical anti-diarrhea and anti-inflammatory drug, has been used in China for hundreds of years. In this study, results showed that BBR can significantly inhibit the expression and secretion of lysozyme in mice. Therefore, we try to investigate the mechanism behind it and elucidate the new anti-inflammatory mechanism of BBR. In vitro, lipopolysaccharide (LPS) was used to establish an inflammatory cell model, and transcriptomic was used to analyze the differentially expressed genes (DEGs) between the LPS group and the LPS + BBR treatment group. In vivo, dextran sulfate sodium salt (DSS) was used to establish a UC mice model, and histologic section and immunofluorescence trails were used to estimate the effect of BBR on UC mice and the expression of lysozyme in Paneth cells. Research results showed that BBR can inhibit the expression and secretion of lysozyme by promoting autophagy via the AMPK/MTOR/ULK1 pathway, and BBR promotes the maturation and expression of lysosomes. Accordingly, we conclude that inhibiting the expression and secretion of intestinal lysozyme is a new anti-inflammatory mechanism of BBR.
Background Intestinal surface epithelial cells (IECs) have long been considered an effective barrier for maintaining water and electrolyte balance and participating in the absorption of nutrients. When intestinal inflammation occurs, IECs tend to malfunction. Berberine (BBR) is an isoquinoline alkaloid found as the major alkaloid in many medicinal plants, which has been clinically used in China to treat gastrointestinal pathogenic bacterial infection, especially bacteria-induced diarrhea and inflammation. Methods We treated rat intestinal epithelial cells IEC-18 with lipopolysaccharide to establish an in vitro model of epithelial cell inflammation and used berberine to treat the cells in order to explore the anti-inflammatory mechanism of berberine. We then used transcriptome data to find the differentially expressed genes (DEGs) in each group, and analyzed DEGs by GO, KEGG, WGCNA and IPATH to find the functions and pathways enriched by DEGs. Finally, we used q-pcr to vertify our transcriptome dates. Results We found DEGs between LPS and LPS+BBR groups are enriched in DNA replication, cell cycle, apoptosis, leukocyte migration, NF-κB and Ap-1pathway. The results showed berberine can restrict DNA replication, inhibits cell cycle and promote apoptosis. It can also inhibit the traditional inflammatory pathways such as NF-κB, Ap-1 and the expression of various chemokines to prevent the migration of leukocyte. Conclusion According to our transcriptomics dates, berberine can exert anti-inflammatory effect by regulating a variety of cellular physiological activities like cell cycle, apoptosis, inflammation pathways and leukocyte migration.
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