1 Department of Microecology, College of Basic Medical Science, Dalian Medical University, Dalian, China P.R.
2 Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China P.R.
Benef Microbes. 2018 Apr 25;9(3):453-464. doi: 10.3920/BM2017.0062. Epub 2018 Apr 10.
Constipation has a significant influence on quality of life. Patients with constipation have slow waves in their gastrointestinal smooth muscles and less faecal water contents, which are closely associated with down-regulation of the interstitial cells of Cajal (ICC) in the gastrointestinal muscles and the aquaporin protein AQP3 expressed in colon epithelial cells. Recent studies supported that patients with constipation have altered intestinal microbial structures compared with healthy controls. Intestinal dysbiosis might be one possible pathophysiological mechanism causing constipation. Bacterial strains, such as Lactobacillus spp., have shown many beneficial effects on the amelioration of constipation. However, few studies reported the structural changes of intestinal microbiota post-intervention of probiotics. In this study, a bacterial mixture was administrated to rats with loperamide-induced constipation. Effects of the bacterial mixture on small intestine transit (SIT), faecal water content, and the intestinal microbiome in rats were evaluated. Meanwhile, we investigated several factors involved in signalling pathways that regulate function of ICC and expression of AQP3 to discuss the possible underlying molecular mechanisms. Intervention of the bacterial mixture improved SIT and faecal water content in constipated rats. The up-regulation of C-kit/SP signalling pathways in ICC and AQP3 significantly contributed to improvements. These changes were closely associated with the manipulation of intestinal dysbiosis in constipated rats. Furthermore, our results revealed the important role of intestinal microbiota in affecting gut motility through regulation of serotonin biosynthesis. This monoamine neurotransmitter, secreted from enterochromaffin cells, up-regulated both substance P/neurokinin 1 receptors pathway of ICC and the expression of AQP3 in intestinal epithelial cells. Our study suggested that the disrupted microbiome in patients could be a potential therapeutic target for the improvement of constipation.
便秘对生活质量有重大影响。便秘患者的胃肠道平滑肌存在慢波，粪便含水量较少，这与胃肠道平滑肌中的 Cajal 间质细胞（ICC）下调和结肠上皮细胞中表达的水通道蛋白 AQP3 密切相关。最近的研究支持便秘患者的肠道微生物结构与健康对照组相比发生了改变。肠道菌群失调可能是导致便秘的一种潜在病理生理机制。细菌菌株，如乳杆菌属，已显示出对改善便秘有许多有益的影响。然而，很少有研究报道益生菌干预后肠道微生物群的结构变化。在这项研究中，给洛哌丁胺诱导的便秘大鼠施用了一种混合细菌。评估了细菌混合物对小肠转运（SIT）、粪便含水量和大鼠肠道微生物组的影响。同时，我们研究了几个参与调节 ICC 功能和 AQP3 表达的信号通路的相关因素，以探讨可能的潜在分子机制。细菌混合物的干预改善了便秘大鼠的 SIT 和粪便含水量。ICC 中的 C-kit/SP 信号通路和 AQP3 的上调显著促进了这些改善。这些变化与便秘大鼠肠道菌群失调的调节密切相关。此外，我们的结果揭示了肠道微生物群通过调节 5-羟色胺生物合成来影响肠道运动的重要作用。这种单胺神经递质由肠嗜铬细胞分泌，可上调 ICC 中的 P 物质/神经激肽 1 受体途径和肠道上皮细胞中的 AQP3 表达。我们的研究表明，患者肠道中被破坏的微生物群可能是改善便秘的一个潜在治疗靶点。
