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Melatonin attenuates chronic intermittent hypoxia-induced intestinal barrier dysfunction in mice.
- Source :
-
Microbiological Research . Nov2023, Vol. 276, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
-
Abstract
- Chronic intermittent hypoxia (CIH) triggers subclinical intestinal barrier disruption prior to systemic low-grade inflammation. Increasing evidence suggests therapeutic effects of melatonin on systemic inflammation and gut microbiota remodelling. However, whether and how melatonin alleviates CIH-induced intestinal barrier dysfunction remains unclear. C57BL/6 J mice and Caco-2 cell line were treated. We evaluated gut barrier function spectrophotometrically using fluorescein isothiocyanate (FITC)-labelled dextran. Immunohistochemical and immunofluorescent staining were used to detect morphological changes in the mechanical barrier. Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) revealed the expression of tight junctions, signal transducer and activator of transcription 3 (STAT3) levels. 16 S rRNA analysis of the colonic contents microflora. Flow cytometry was used to detect cytokines and Th17 cells with and without melatonin supplementation. We found that CIH could induce colonic mucosal injury, including reduction in the number of goblet cells and decrease the expression of intestinal tight junction proteins. CIH could decrease the abundance of the beneficial genera Clostridium , Akkermansia, and Bacteroides , while increasing the abundance of the pathogenic genera Desulfovibrio and Bifidobacterium. Finally, CIH facilitated Th17 differentiation via the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in vitro and elevated the circulating pro-inflammatory cytokine in vivo. Melatonin supplementation ameliorated CIH-induced intestinal mucosal injury, gut microbiota dysbiosis, enteric Th17 polarization, and systemic low-grade inflammation reactions mentioned-above. Melatonin attenuated CIH-induced intestinal barrier dysfunction by regulating gut flora dysbiosis, mucosal epithelium integrity, and Th17 polarization via STAT3 signalling. [Display omitted] • CIH disrupted the intestinal mechanical barrier, increased colonic permeability and decreased flora composition. • CIH promoted pathological Th17 cells-mediated intestinal immune barrier dysfunction via JAK2/STAT3 signaling. • Melatonin supplementation ameliorated the CIH-induced intestinal immune barrier by maintaining the Th17 balance. • Melatonin targeted CIH-activated STAT3 signaling, enhanced anti-inflammatory effects. [ABSTRACT FROM AUTHOR]
- Subjects :
- *INTESTINES
*MELATONIN
*T helper cells
*GUT microbiome
*FLUORESCEIN isothiocyanate
Subjects
Details
- Language :
- English
- ISSN :
- 09445013
- Volume :
- 276
- Database :
- Academic Search Index
- Journal :
- Microbiological Research
- Publication Type :
- Academic Journal
- Accession number :
- 171954888
- Full Text :
- https://doi.org/10.1016/j.micres.2023.127480