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BACKGROUND: Inflammatory bowel disease (IBD) is a multifactorial immune disorder characterized by chronic relapsing inflammation in the intestine. Gut microbiome dysbiosis is an important factor that contributes to the development of IBD. The intake of natural bioactive compounds from the diet has been linked to the regulation of the gut microbiota balance, which further exerts beneficial effects. However, the potential mechanisms through which the microbiome exerts its effects are largely unknown. In the present study, we aimed to evaluate the effects of the gut microbiome regulated by CiLi (Rosa roxburghii Tratt.) friut, especially its polyphenols, on dextran sulfate sodium (DSS)-induced colitis. Moreover, the mechanisms through which the gut microbiome is involved in lipid metabolism and immune cell activities in colitis have been explored. RESULTS: Our results revealed that pretreatment with CiLi juice, especially its bioactive polyphenol CL_PP, for 3 weeks alleviated dextran sulfate sodium (DSS)-induced colitis and maintained intestinal barrier integrity. Moreover, CL_PP reduced inflammation and oxidative stress in colon tissue and enriched fecal short-chain fatty acids. Importantly, it significantly regulated the gut microbiome diversity and abundance of beneficial bacteria, such as Clostridia_UCG-014, f_Muribaculaceae and Ileibacterium_valens, and decreased the abundance of harmful bacteria, such as Escherichia-Shigella and Romboutsia. Multiomics data revealed that CL-PP upregulated bioactive lipid metabolites, especially polyunsaturated fatty acids, including resolvin D2, prostaglandin A1 and glycerophosphocholine, as well as related genes, such as Pltp, Alox15 and Pld4. Additionally, it downregulated the oxidative stress-related metabolite oxidized glutathione and the gene Gpx3, as well as immune cell markers, such as CD8 and CD68. Network analysis revealed strong correlations among the gut microbiota, lipid metabolites, oxidative stress, and immunity. Furthermore, fecal microbiota transplantation (FMT) experiments confirmed that the fecal microbiota from CL_PP-treated mice had an anti-colitis effect and regulated the genes and metabolites mentioned above, while these effects were almost abolished in antibiotic-treated mice, indicating that the gut microbiota plays a critical role in alleviating colitis via lipid metabolites and immune cell regulation. CONCLUSION: This study provides the first data showing that oral CiLi polyphenols improve the inflammatory response in a colitis model by regulating the gut microbiota-lipid mediator-immune cell axis, suggesting new insights into CL_PP as a potential modulator of gut microbiome dysbiosis for the prevention/treatment of inflammation-related colitis.

China Agricultural University

Analytical Chemistry in Food Science

Creative Commons Attribution 4.0 International

Sample collection Five-week-old male C57BL/6J mice were purchased from Beijing Vital River Laboratory Animal Science and Technology Co. (Beijing, China) and kept in a standard facility for specific pathogen-free animals with a light and dark cycle of 12 h. Animal experiments were conducted in accordance with the protocols approved by the Animal Care and Ethics Committee of China Agricultural University (No. AW32602202-4-2). Treatment of DSS-induced colitis mice with CL_PP CL_PP (100 mg/kg) were orally administered for 4 weeks, and 2.5% DSS was added to the drinking water for 7 days to induce acute colitis during the last week. Body weight and DAI were measured daily during the DSS treatment. Blood was collected from the eyeball in EDTA anticoagulant tubes and centrifuged to obtain plasma. Treatment of antibiotic-treated mice with CL_PP The mice were given a mixture of antibiotic cocktail (100 mg/L neomycin, 50 mg/L streptomycin, 100 mg/L penicillin, 50 mg/L vancomycin and 100 mg/L metronidazole) in drinking water during the whole experiment. After 2 weeks, the mice were divided into two groups, and CL_PP or PBS was orally administered every day for 3 weeks. Colitis was induced by treatment with 2.5% DSS in the drinking water for 7 days. Treatment of DSS-induced colitis mice with CL_PP_FMT Mice were divided into 4 groups (the PBS, PBS_FMT, CL_PP, and CL_PP_FMT groups). The two groups (the PBS_FMT and CL_PP_FMT groups) were treated with the antibiotic cocktail mentioned above for 2 weeks. The feces of mice in the PBS and CL_PP groups were collected, and the homogenate was diluted, filtered through a 70 μm filter and subsequently subjected to FMT. The final concentration was 50 mg of feces/mL. After 2 weeks of fecal treatment, 2.5% DSS solution was added to the drinking water of the mice in the PBS_FMT group and CL_PP_FMT group to induce colitis.

China Agricultural University

Analytical Chemistry in Food Science

Creative Commons Attribution 4.0 International