期刊
GUT MICROBES
卷 6, 期 1, 页码 10-23出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/19490976.2014.990790
关键词
cannabinoid receptors; colonic motility; gut commensal microbiota; innate immune system; intestinal dysbiosis; opioid receptors; visceral sensitivity
资金
- Ministerio de Ciencia e Innovacion (Spain) [BFU2009-08229, BES-2010-037699]
- Generalitat de Catalunya [2009SGR708]
Alterations in the composition of the commensal microbiota (dysbiosis) seem to be a pathogenic component of functional gastrointestinal disorders, mainly irritable bowel syndrome (IBS), and might participate in the secretomotor and sensory alterations observed in these patients.We determined if a state antibiotics-induced intestinal dysbiosis is able to modify colonic pain-related and motor responses and characterized the neuro-immune mechanisms implicated in mice. A 2-week antibiotics treatment induced a colonic dysbiosis (increments in Bacteroides spp, Clostridium coccoides and Lactobacillus spp and reduction in Bifidobacterium spp). Bacterial adherence was not affected. Dysbiosis was associated with increased levels of secretory-IgA, up-regulation of the antimicrobial lectin Regllly, and toll-like receptors (TLR) 4 and 7 and down-regulation of the antimicrobial-peptide Resistin-Like Molecule-beta and TLR5. Dysbiotic mice showed less goblet cells, without changes in the thickness of the mucus layer. Neither macroscopical nor microscopical signs of inflammation were observed. In dysbiotic mice, expression of the cannabinoid receptor 2 was up-regulated, while the cannabinoid 1 and the mu-opioid receptors were down-regulated. In antibiotic-treated mice, visceral pain-related responses elicited by intraperitoneal acetic acid or intracolonic capsaicin were significantly attenuated. Colonic contractility was enhanced during dysbiosis. Intestinal dysbiosis induce changes in the innate intestinal immune system and modulate the expression of pain-related sensory systems, an effect associated with a reduction in visceral pain-related responses. Commensal microbiota modulates gut neuro-immune sensory systems, leading to functional changes, at least as it relates to viscerosensitivity. Similar mechanisms might explain the beneficial effects of antibiotics or certain probiotics in the treatment of IBS.
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