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Dysbiosis contributes to chronic constipation development via regulation of serotonin transporter in the intestine.

ABSTRACT: Chronic constipation is a prevalent functional gastrointestinal disorder accompanied with intestinal dysbiosis. However, causal relationship between dysbiosis and constipation remains poorly understood. Serotonin transporter (SERT) is a transmembrane transport protein which re-uptakes excessive 5-hydroxytryptamine (5-HT) from effective location to terminate its physiological effects and involves in regulating gastrointestinal motility. In this study, fecal microbiota from patients with constipation and healthy controls were transplanted into the antibiotic depletion mice model. The mice which received fecal microbiota from patients with constipation presented a reducing in intestinal peristalsis and abnormal defecation parameters including the frequency of pellet expulsion, fecal weight and fecal water content. After fecal microbiota transplantation, the SERT expression in the colonic tissue was significantly upregulated, and the content of 5-HT was decreased which negatively correlated with the gastrointestinal transit time. Moverover, fecal microbiota from the mice which received fecal microbiota from patients with constipation also upregulated SERT in Caco-2 cells. Besides, this process accompanied with the decreased abundance of Clostridium, Lactobacillus, Desulfovibrio, and Methylobacterium and an increased tend of Bacteroides and Akkermansia, which also involved in the impairment of intestinal barrier after FMT. Taken together, intestinal dysbiosis may upregulate the SERT expression and contribute to the development of chronic constipation.

SUBMITTER: Cao H

PROVIDER: S-EPMC5583244 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Dysbiosis contributes to chronic constipation development via regulation of serotonin transporter in the intestine.

Cao Hailong H Liu Xiang X An Yingying Y Zhou Guoqiong G Liu Yanrong Y Xu Mengque M Dong Wenxiao W Wang Sinan S Yan Fang F Jiang Kui K Wang Bangmao B

Scientific reports 20170904 1

Chronic constipation is a prevalent functional gastrointestinal disorder accompanied with intestinal dysbiosis. However, causal relationship between dysbiosis and constipation remains poorly understood. Serotonin transporter (SERT) is a transmembrane transport protein which re-uptakes excessive 5-hydroxytryptamine (5-HT) from effective location to terminate its physiological effects and involves in regulating gastrointestinal motility. In this study, fecal microbiota from patients with constipat ...[more]

PMID: 28871143

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Project description:ObjectiveFunctional constipation is the most common form of constipation, and its exact aetiology is still unclear. However, it is known that deficiencies in hormonal factors cause constipation by changing physiological mechanisms. Motilin, ghrelin, serotonin acetylcholine, nitric oxide, and vasoactive intestinal polypeptide are factors that play a role in colon motility. There are a limited number of studies in the literature where hormone levels and gene polymorphisms of serotonin and motilin are examined. Our study aimed to investigate the role of motilin, ghrelin, and serotonin gene/receptor/transporter polymorphisms in constipation pathogenesis in patients diagnosed with functional constipation according to the Rome 4 criteria.MethodsSociodemographic data, symptom duration, accompanying findings, the presence of constipation in the family, Rome 4 criteria, and clinical findings according to Bristol scale of 200 cases (100 constipated patients and 100 healthy control) who applied to Istanbul Haseki Training and Research Hospital, Pediatric Gastroenterology Outpatient Clinic, between March and September 2019 (6-month period) were recorded. Polymorphisms of motilin-MLN (rs2281820), serotonin receptor-HTR3A (rs1062613), serotonin transporter-5-HTT (rs1042173), ghrelin-GHRL (rs27647), and ghrelin receptor-GHSR (rs572169) were detected by real-time PCR.ResultsThere was no difference between the two groups in terms of sociodemographic characteristics. Notably, 40% of the constipated group had a family history of constipation. The number of patients who started to have constipation under 24 months was 78, and the number of patients who started to have constipation after 24 months was 22. There was no significant difference between constipation and control groups in terms of genotype and allele frequencies in MLN, HTR3A, 5-HTT, GHRL, and GHSR polymorphisms (p<0.05). Considering only the constipated group, the rates of gene polymorphism were similar among those with/without a positive family history of constipation, constipation onset age, those with/without fissures, those with/without skin tag, and those with type 1/type 2 stool types according to the Bristol stool scale.ConclusionOur study results showed that gene polymorphisms of these three hormones may not be related to constipation in children.

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Dysbiosis contributes to chronic constipation development via regulation of serotonin transporter in the intestine.

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Dysbiosis contributes to chronic constipation development via regulation of serotonin transporter in the intestine.

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