Periodontitis-associated metabolite isoleucine impairs intestinal barrier function and exacerbates intestinal
Xiaoxue Wang1, Yilin Luo1, Jie Ren1
1Department of Stomatology, The Eighth Affiliated Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Foshan, China.
Objective:
Periodontitis-associated metabolite isoleucine (Ile) plays an important role in periodontitis aggravating colitis. However, how Ile exacerbates colitis is largely unknown.
Methods:
C57BL/6J mice were used to establish experimental periodontitis and colitis models. Histological alterations of the periodontium and colon were observed by HE staining. The gut barrier function was evaluated by intestinal permeability using FITC-dextran. The expression of tight junctions (ZO-1 and occludin) was detected by immunohistochemical staining or immunofluorescence. The NF-κB signaling pathway was detected using qRT-PCR and Western blot.
Results:
Experimental periodontitis and periodontitis-associated metabolite Ile increased the intestinal permeability, downregulated the expression of tight junctions (ZO-1 and occludin), and enhanced the NF-κB signaling pathway of intestinal epithelial cells in dextran sulfate sodium (DSS)-induced colitis mice. Ile downregulated the expression of tight junctions (ZO-1 and occludin) and enhanced the NF-κB signaling pathway in intestinal organoids or IEC-6 cells under inflammatory conditions. IKK-16 (a selective inhibitor of IKKβ that prevents NF-κB activation) rescued excessive inflammatory responses induced by Ile in IEC-6 cells with LPS treatment. In addition, IKK-16 relieved the impairment of intestinal barrier function and inflammatory response induced by Ile in DSS-induced colitis mice.
Conclusion:
Our study unraveled that periodontitis contributed to intestinal barrier function damage and inflammation of intestinal epithelial cells by potentiating NF-κB signaling in the context of colitis and that this was associated with periodontitis-associated metabolite Ile.
Related Concept Videos
01:17Irritable Bowel Syndrome I: Introduction
IBS is a chronic condition that can persist over a long period or recur frequently.
The pathogenesis of IBS involves a complex interplay of the following factors:
Altered...
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
01:30Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
01:22Pathophysiology of Peptic Ulcer Disease: Injurious Factors
In the antrum region, G cells secrete the gastrin hormone that binds to gastrin-cholecystokinin-B (CCK2) receptors on parietal and enterochromaffin-like (ECL) cells in the fundic glands. Simultaneously, the vagus nerve releases acetylcholine, which binds...