Abstract
Chronic constipation (CC) is one of the most common gastrointestinal disorders worldwide. Its pathogenesis, however, remains largely unclear. The purpose of the present work was to gain an insight into the role of contractility and microbiota in the etiology of CC. To this end, we studied spontaneous and evoked contractile activity of descending colon segments from patients that have undergone surgery for refractory forms of CC. The juxta-mucosal microbiota of these colon samples were characterized with culture-based and 16S rRNA sequencing techniques. In patients with CC the spontaneous colonic motility remained unchanged compared to the control group without dysfunction of intestinal motility. Moreover, contractions induced by potassium chloride and carbachol were increased in both circular and longitudinal colonic muscle strips, thus indicating preservation of contractile apparatus and increased sensitivity to cholinergic nerve stimulation in the constipated intestine. In the test group, the gut microbiota composition was assessed as being typically human, with four dominant bacterial phyla, namely Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria, as well as usual representation of the most prevalent gut bacterial genera. Yet, significant inter-individual differences were revealed. The phylogenetic diversity of gut microbiota was not affected by age, sex, or colonic anatomy (dolichocolon, megacolon). The abundance of butyrate-producing genera Roseburia, Coprococcus, and Faecalibacterium was low, whereas conventional probiotic genera Lactobacillus and Bifidobacteria were not decreased in the gut microbiomes of the constipated patients. As evidenced by our study, specific microbial biomarkers for constipation state are absent. The results point to a probable role played by the overall gut microbiota at the functional level. To our knowledge, this is the first comprehensive characterization of CC pathogenesis, finding lack of disruption of motor activity of colonic smooth muscle cells and insufficiency of particular members of gut microbiota usually implicated in CC.
Highlights
Chronic constipation (CC), frequently referred to as functional constipation, colonic inertia, slow transit constipation, is a prevalent, distressing gastrointestinal disorder
In this study we compared colon muscle contractility of eight patients with refractory forms of CC (gender distribution: 2/6 (m/f), average age: 40 years (σ = ±12), range: 20–55 years) with that of a control group consisted of five patients with smallcarcinoma of the sigmoid or rectosigmoid colon (T2-3N0M0) not associated with intestinal motility dysfunction (gender distribution: 2/3 (m/f), average age: 67 years (σ = ±5), range: 61–73 years) (S1 Table)
In this study we have demonstrated that the spontaneous motor activity of smooth muscle cells remains unchanged in patients with CC
Summary
Chronic constipation (CC), frequently referred to as functional constipation, colonic inertia, slow transit constipation, is a prevalent, distressing gastrointestinal disorder. CC may develop as the result of sedentary lifestyle, the intake of harmful food, bad ecology, anomaly of colonic structure and its location in the abdominal cavity. Constipation syndrome may be associated with dolichocolon, idiopathic megacolon, Payr’s syndrome, ptosis of the transverse colon, sigmocele, or may occur without anatomical abnormalities [4, 5]. Conservative treatment of CC remains prevalent, surgical colonic resection has become more frequent nowadays, in severe cases involving gut anatomical abnormality and dilatation, and has demonstrated long-term positive results [9,10,11,12]
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