Oryzanol Ameliorates DSS-Stimulated Gut Barrier Damage via Targeting the Gut Microbiota Accompanied by the TLR4/NF-κB/NLRP3 Cascade Response In Vivo

Abstract

Inflammatory bowel disease (IBD) is a global chronic disease with a long duration and repeated relapse. Currently, there is still a lack of effective approaches to prevent IBD. Food-derived oryzanol (ORY) possesses extensive biological activities, such as ameliorating bowel diseases, antioxidation, and antiobesity. However, the mechanism of ORY in preventing colitis remains unclear. The present research aims to explore the potential mechanism of ORY in dextran sulfate sodium (DSS)-stimulated colitis in a rat model. The results showed that the symptoms of colitis were significantly improved with the administration of ORY. Mechanismly, the expression levels of Zonula occludens-1 (ZO-1), Claudin-1, Occludin, MUC2, and TFF3 were elevated through ORY treatment, suggesting that oral ORY relieved the degree of gut barrier damage of colitis rats. Meanwhile, 16S sequencing results found that ORY supplementation increased the abundances of Alloprevotella, Roseburia, Treponema, Muribaculaceae, and Ruminococcus, which are associated with the synthesis of short-chain fatty acids (SCFAs). Moreover, GC-MS results confirmed that ORY supplementation reversed the DSS-induced reduction of acetic acid, butyric acid, and total acid. Further research indicated that ORY intervention downregulated the TLR4/NF-κB/NLRP3 pathway, which is closely linked to the expression of proinflammatory cytokines and colon injury. Taken together, ORY ameliorates DSS-stimulated gut barrier damage and inflammatory responses via the gut microbiota–TLR4/NF-κB/NLRP3 signaling axis.

Galactooligosaccharide or 2′-Fucosyllactose Modulates Gut Microbiota and Inhibits LPS/TLR4/NF-κB Signaling Pathway to Prevent DSS-Induced Colitis Aggravated by a High-Fructose Diet in Mice

“…Besides, butyrate activates genes that encode Tj components and protein reassembly with transcription factors, such as signal transducer and activator of transcription 3 and specificity protein 1, enhancing barrier integrity. , Improved intestinal barrier integrity reduces TLR4/NF-κB activation by LPS. SCFAs also suppressed inflammation by inhibiting histone deacetylases and directly regulating the TLR4/NF-κB signaling pathway. , This may be a potential mechanism by which GOS and FL improve gut barrier function in HFrD-fed mice through gut microbiota-mediated pathways. SCFAs have been characterized as effective inhibitors of oxidative stress and inflammatory responses .…”

“…SCFAs also suppressed inflammation by inhibiting histone deacetylases and directly regulating the TLR4/NF-κB signaling pathway. 82,83 This may be a potential mechanism by which GOS and FL improve gut barrier function in HFrD-fed mice through gut microbiota-mediated pathways. SCFAs have been characterized as effective inhibitors of oxidative stress and inflammatory responses.…”

Epigallocatechin Gallate Alleviates Staphylococcal Enterotoxin A-Induced Intestinal Barrier Damage by Regulating Gut Microbiota and Inhibiting the TLR4-NF-κB/MAPKs-NLRP3 Inflammatory Cascade

“…Remarkably, intestinal barrier dysfunction and bacterial translocation are often accompanied by inflammation. 19,23 Inflammatory reactions can also further aggravate intestinal barrier damage. 19,29 The activation of the pattern recognition receptor TLR4 (responsible for recognizing and binding to LPS) is closely related to intestinal barrier damage, inflammatory response, and even immune system dysfunction.…”

“…19,23 Inflammatory reactions can also further aggravate intestinal barrier damage. 19,29 The activation of the pattern recognition receptor TLR4 (responsible for recognizing and binding to LPS) is closely related to intestinal barrier damage, inflammatory response, and even immune system dysfunction. 30 The overactivation of the TLR4 pathway can further activate downstream inflammation-related signaling pathways, such as NF-κB, MAPKs, and NLRP3 inflammasome, which leads to the maturation and release of the proinflammatory cytokines (IL-18 and IL-1β) and plays a crucial role in the progression of inflammatory intestinal barrier injury.…”

“…8,17 Meanwhile, LPS can bind to Toll-like receptor 4 (TLR4), a pathogen pattern recognition receptor in the innate immune system, which further activates the downstream NF-κB, MAPK, and NLRP3 pathways and causes a strong inflammatory response. 8,18,19 Thus, it is speculated that blocking LPS-mediated activation of the TLR4-NF-κB/MAPKs-NLRP3 inflammatory cascade by targeting the gut microbiota may be a key mode for EGCG to alleviate intestinal barrier damage and the inflammatory response induced by SEA.…”