Biometabolites of Citrus unshiu Peel Enhance Intestinal Permeability and Alter Gut Commensal Bacteria

• Published in: Nutrients Vol. 15; no. 2; p. 319
• Main Authors: Lee, Se-Hui, Seo, Dongju, Lee, Kang-Hee, Park, So-Jung, Park, Sun, Kim, Hyeyun, Kim, Taekyung, Joo, In Hwan, Park, Jong-Min, Kang, Yun-Hwan, Lim, Gah-Hyun, Kim, Dong Hee, Yang, Jin-Young
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09-01-2023; MDPI
• Subjects: Aglycones; Animals; Antibodies; Bacteria; Bioconversion; Body weight; Body weight loss; Caco-2 Cells; Chemical compounds; Citrus; Citrus unshiu; Citrus unshiu peel; Cloning; Colitis; Colitis - chemically induced; Colitis - drug therapy; Colon - metabolism; Dextran; dextran sodium sulfate; Dextran sulfate; Dextran Sulfate - pharmacology; Dextrans; Diabetes; Digestive system; Disease; Disease Models, Animal; Enzymes; Ethanol; Flavanones - metabolism; Flavonoids; Helper cells; Hesperidin; Homeostasis; Humans; Inflammation; Inflammation - metabolism; Inflammatory bowel disease; Intestinal microflora; intestinal tight junction; Intestine; Kinases; Lamina propria; Lymphocytes T; Metabolites; Mice; Mice, Inbred C57BL; Microbiomes; Microbiota; Microorganisms; mRNA; Naringenin; natural extract; Natural products; Oral administration; Permeability; Pharmacology; Sodium sulfate; Sulfates; T helper 17 cell; Weight loss; United States > US; commensal microbiota; natural extract; Citrus unshiu peel; dextran sodium sulfate; T helper 17 cell; inflammatory bowel disease; intestinal tight junction
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu15020319

Flavanones in
peel (CUP) have been used as therapeutic agents to reduce intestinal inflammation; however, the anti-inflammatory effects of their biometabolites remain ambiguous. Here, we identified aglycone-type flavanones, such as hesperetin and naringenin, which were more abundant in the bioconversion of the CUP than in the ethanol extracts of the CUP. We found that the bioconversion of the CUP induced the canonical nuclear factor-κB pathway via degradation of IκB in Caco-2 cells. To check the immune suppressive capacity of the aglycones of the CUP in vivo, we orally administered the bioconversion of the CUP (500 mg/kg) to mice for two weeks prior to the 3% dextran sulfate sodium treatment. The CUP-pretreated group showed improved body weight loss, colon length shortage, and intestinal inflammation than the control mice. We also found a significant decrease in the population of lamina propria Th17 cells in the CUP-pretreated group following dextran sodium sulfate (DSS) treatment and an increase in mRNA levels of occludin in CUP-treated Caco-2 cells. Pyrosequencing analysis revealed a decreased abundance of
and an increased abundance of
in the feces of the CUP-pretreated mice compared to those of the control mice. Overall, these findings suggest that the pre-administration of CUP biometabolites may inhibit the development of murine colitis by modulating intestinal permeability and the gut microbiome.