1. Hypersensitivity to cholinergic nerve stimulation were found in colons of patients with chronic constipation, while their gut microbiota was found to resemble a typical gut microbiome.
Evidence Rating Level: 3 (Average)
Chronic constipation (CC) is a gastrointestinal condition that drastically impacts quality of life, with greater prevalence at increasing age. However, the physiological cause of this condition is relatively unknown. Past research has shown that CC patients may have smooth muscle contractions in the colon with lower frequency, amplitude, and duration. There have been mixed results regarding cholinergic innervation, with some literature showing decreased colonic cholinergic nerve activity of CC patients, and other research demonstrating hypersensitivity to cholinergic stimulation. As well, analyses on gut microbiota from constipated patients have yielded conflicting results, most likely due to different methodologies used (culture-based vs metagenomic approaches). It is also unknown if differences in gut microbiota cause CC, or if instead, these differences are a result of CC. This study aimed to analyze the contractile and microbiota characteristics of colonic tissue from CC patients. When comparing colon muscle strips from CC and non-CC patients, the circular smooth muscle from both groups showed spontaneous contractile activity, and the patterns of spontaneous contractile activity observed were comparable in both groups. In both circular and longitudinal smooth muscle, CC patient specimens exhibited higher amplitudes of evoked contractions, which suggests increased sensitivity to cholinergic nerve stimulation. For instance, in the presence of 70 mM KCl, the mean±SEM amplitude for longitudinal muscle was 0.129±0.026 in CC patients and 0.050±0.006 in the control group (p = 0.028). In circular muscle, it was 0.192±0.033 in CC patients and 0.073±0.014 in the control (p = 0.028). In the microbiota analyses, butyrate-producing genera (Coprococcus, Faecalibacterium, Roseburia) were found to be in low amounts, suggesting they were unlikely to hinder colonic motility. The genera Bifidobacterium and Lactobacillus, which are commonly found in non-CC patient guts, were not found to be less prevalent in CC patients. Furthermore, any variations in microbiota among CC patients were unaffected by age, sex, and colonic anatomy. While this study did not reveal a specific microbial culprit for chronic constipation, heightened cholinergic sensitivity in the colon may be a physiological indicator of CC.
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