Abstract
Abstract Background Diet and gut microbiota alteration are considered as the most important environmental factors triggering inflammatory bowel disease. Phytosterols are rich in edible oils, and can be oxidized to oxyphytosterols during high-temperature cooking. Previous studies have indicated that oxyphytosterols exposure exerted potential adverse effects in cell and animal models. It remains unknown whether oxyphytosterols could promote colonic inflammation. 7-ketositosterol has the highest proportion in oxyphytosterols. Methods The fried and baked foods intake was collected and compared in IBD patients and healthy individuals. 7-ketositosterol was synthesized from β-sitosterol and impacts of 7-ketositosterol on intestinal inflammation was evaluated in colitis mice models. 16S rRNA and transcriptome sequencing were carried out. Furthermore, fecal microbiota transplantation was carried out to evaluate the effect of gut microbiota. Protein interaction of Staphylococcus lentus and PDLIM3 was explored by co-immunoprecipitation. Results The fried and baked foods intake in IBD patients was much more than that of healthy individuals, with higher exposure to oxyphytosterols. 7-ketositosterol (KS) aggravated mice colitis. KS increased the abundance of Actinobacteria (p=0.023). Meanwhile, the abundance of potential pathogens such as Staphylococcus (p=0.004) and Corynebacterium_1 (p=0.003) were increased in KS group, while the abundance of short chain fatty acids producing bacteria were decreased. Transcriptome data showed KS increased the expression of PDLIM3 (p=0.004). PDLIM3 expression was demonstrated to increase in intestinal epithelial cells, and the expression tendency of p-p38 and p-p65 was consistent with PDLIM3. In addition, KS did not exacerbate DSS induced colitis after antibiotic cocktails treatment, and PDLIM3 expression decreased in parallel. The gut microbiota from KS also aggravated DSS induced colitis in antibiotic treated mice. Proteins from Staphylococcus lentus could interact with PDZ domain and promote PDLIM3 expression. Conclusion 7-ketositosterol in high temperature heating oils such as fried foods could aggravate colitis by modulation of gut microbiota. Gut microbiota interacted with PDZ domain, promoted PDLIM3 expression and then activated p38MAPK/NF-κB signaling pathway.
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