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A Shigella species variant is causally linked to intractable functional constipation.

ABSTRACT: Intractable functional constipation (IFC) is the most severe form of constipation, but its etiology has long been unknown. We hypothesized that IFC is caused by refractory infection by a pathogenic bacterium. Here, we isolated from patients with IFC a Shigella species - peristaltic contraction-inhibiting bacterium (PIB) - that significantly inhibited peristaltic contraction of the colon by production of docosapentenoic acid (DPA). PIB colonized mice for at least 6 months. Oral administration of PIB was sufficient to induce constipation, which was reversed by PIB-specific phages. A mutated PIB with reduced DPA was incapable of inhibiting colonic function and inducing constipation, suggesting that DPA produced by PIB was the key mediator of the genesis of constipation. PIBs were detected in stools of 56% (38 of 68) of the IFC patients, but not in those of non-IFC or healthy individuals (0 of 180). DPA levels in stools were elevated in 44.12% (30 of 68) of the IFC patients but none of the healthy volunteers (0 of 97). Our results suggest that Shigella sp. PIB may be the critical causative pathogen for IFC, and detection of fecal PIB plus DPA may be a reliable method for IFC diagnosis and classification.

SUBMITTER: Chen X

PROVIDER: S-EPMC9282927 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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A Shigella species variant is causally linked to intractable functional constipation.

Chen Xin X Qiu Tian-Tian TT Wang Ye Y Xu Li-Yang LY Sun Jie J Jiang Zhi-Hui ZH Zhao Wei W Tao Tao T Zhou Yu-Wei YW Wei Li-Sha LS Li Ye-Qiong YQ Zheng Yan-Yan YY Zhou Guo-Hua GH Chen Hua-Qun HQ Zhang Jian J Feng Xiao-Bo XB Wang Fang-Yu FY Li Ning N Zhang Xue-Na XN Jiang Jun J Zhu Min-Sheng MS

The Journal of clinical investigation 20220701 14

Intractable functional constipation (IFC) is the most severe form of constipation, but its etiology has long been unknown. We hypothesized that IFC is caused by refractory infection by a pathogenic bacterium. Here, we isolated from patients with IFC a Shigella species - peristaltic contraction-inhibiting bacterium (PIB) - that significantly inhibited peristaltic contraction of the colon by production of docosapentenoic acid (DPA). PIB colonized mice for at least 6 months. Oral administration of ...[more]

PMID: 35617029

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Project description:BackgroundChildren with intractable functional constipation (IFC) who are refractory to traditional pharmacological intervention develop severe symptoms that can persist even in adulthood, resulting in a substantial deterioration in their quality of life. In order to better manage IFC patients, efficient subtyping of IFC into its three subtypes, normal transit constipation (NTC), outlet obstruction constipation (OOC), and slow transit constipation (STC), at early stages is crucial. With advancements in technology, machine learning can classify IFC early through the use of validated questionnaires and the different serum concentrations of gastrointestinal motility-related hormones.MethodA hundred and one children with IFC and 50 controls were enrolled in this study. Three supervised machine-learning methods, support vector machine, random forest, and light gradient boosting machine (LGBM), were used to classify children with IFC into the three subtypes based on their symptom severity, self-efficacy, and quality of life which were quantified using certified questionnaires and their serum concentrations of the gastrointestinal hormones evaluated with enzyme-linked immunosorbent assay. The accuracy of machine learning subtyping was evaluated with respect to radiopaque markers.ResultsOf 101 IFC patients, 37 had NTC, 49 had OOC, and 15 had STC. The variables significant for IFC subtype classification, according to SelectKBest, were stool frequency, the satisfaction domain of the Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL), the emotional self-efficacy for Functional Constipation questionnaire (SEFCQ), motilin serum concentration, and vasoactive intestinal peptide serum concentration. Among the three models, the LGBM model demonstrated an accuracy of 83.8%, a precision of 84.5%, a recall of 83.6%, a f1-score of 83.4%, and an area under the receiver operating characteristic curve (AUROC) of 0.89 in discriminating IFC subtypes.ConclusionUsing clinical characteristics measured by certified questionnaires and serum concentrations of the gastrointestinal hormones, machine learning can efficiently classify pediatric IFC into its three subtypes. Of the three models tested, the LGBM model is the most accurate model for the classification of IFC, with an accuracy of 83.8%, demonstrating that machine learning is an efficient tool for the management of IFC in children.

Project description:BackgroundFew studies have examined intestinal motility disorders, which are disabling conditions associated with chronic functional constipation, whose pathogenesis is actually not well-defined.AimTo investigate the relationship between serum 25-hydroxyvitamin D levels and functional chronic constipation associated to intestinal motility disorders.MethodsWe performed a prospective case-control study, from May-June to November 2017. Glucose/lactulose breath tests, radiopaque markers (multiple capsule techniques) and wireless motility capsule analysis were used to assess colonic and oro-cecal transit time, after excluding small-intestinal bacterial overgrowth condition. Then, we measured 25-hydroxyvitamin D levels in patients with intestinal motility disorders and we further evaluated the influence of intestinal motility disorders on psychological symptoms/quality of life using validated questionnaires, the Irritable Bowel Syndrome Quality of life (IBS-QOL), the Short Form Health Survey 12, and the Hospital Anxiety and Depression Scale 14 (HADS-14 A and HADS-14 D).ResultsWe enrolled 86 patients with chronic functional constipation associated to intestinal motility disorders and 86 matched healthy subjects. Patients with intestinal motility disorders had lower 25-hydroxyvitamin D levels (P < 0.001), and they showed a significant impairment of all health-related quality of life and psychological tests (IBS-QOL, Short Form Health Survey 12-Physical Component Summary, Short Form Health Survey 12-Mental Component Summary, HADS-14 A and HADS-14 D), as compared to the control group (P < 0.001), which significantly correlated with low vitamin D levels (r = - 0.57, P < 0.001; r = 0.21, P = 0.01; r = - 0.48, P < 0.001; r = - 0.57, P < 0.001; r = - 0.29, P < 0.001, respectively). At multivariate analysis vitamin D low levels remained a significant independent risk factor for the occurrence of intestinal motility disorder (odds ratio = 1.19; 95% confidence interval: 1.14-1.26, P < 0.001).ConclusionVitamin D deficiency, anxiety and depression symptoms are commonly associated with chronic functional constipation induced by intestinal motility disorders. Vitamin D serum levels should be routinely measured in these patients.

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A Shigella species variant is causally linked to intractable functional constipation.

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A Shigella species variant is causally linked to intractable functional constipation.

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