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Intestinal barrier function is maintained with aging - a comprehensive study in healthy subjects and irritable bowel syndrome patients.

ABSTRACT: Animal studies have shown that intestinal barrier function is compromised with aging. We aimed to assess the effects of aging on intestinal barrier function in humans in vivo and ex vivo. In this cross-sectional study, healthy subjects and subjects with irritable bowel syndrome (IBS) of older (65-75 years) and young adult age (18-40 years) were compared. In vivo gastrointestinal site-specific permeability was assessed by a multi-sugar test, taking into account potential confounders. Sigmoid biopsies were collected from subgroups of healthy young adults and elderly for ex vivo Ussing chamber experiments, gene transcription of barrier-related genes and staining of junctional proteins. No significant differences between healthy young adults and elderly were found for small intestinal, colonic and whole gut permeability (P???0.142). In IBS patients, gastroduodenal and colonic permeability did not differ significantly (P???0.400), but small intestinal and whole gut permeability were higher in elderly versus young adults (P???0.009), mainly driven by the IBS-diarrhea subtype. Ussing chamber experiments with or without stressor (P???0.052), and relative expression of intestinal barrier-related genes (P???0.264) showed no significant differences between healthy elderly and young adults, as confirmed by immunofluorescent stainings. Overall, the functional capacity of the intestinal barrier is maintained in elderly.

SUBMITTER: Wilms E

PROVIDER: S-EPMC6965102 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Intestinal barrier function is maintained with aging - a comprehensive study in healthy subjects and irritable bowel syndrome patients.

Wilms Ellen E Troost Freddy J FJ Elizalde Montserrat M Winkens Bjorn B de Vos Paul P Mujagic Zlatan Z Jonkers Daisy M A E DMAE Masclee Ad A M AAM

Scientific reports 20200116 1

Animal studies have shown that intestinal barrier function is compromised with aging. We aimed to assess the effects of aging on intestinal barrier function in humans in vivo and ex vivo. In this cross-sectional study, healthy subjects and subjects with irritable bowel syndrome (IBS) of older (65-75 years) and young adult age (18-40 years) were compared. In vivo gastrointestinal site-specific permeability was assessed by a multi-sugar test, taking into account potential confounders. Sigmoid biop ...[more]

PMID: 31949225

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Project description:AimThe herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model.MethodsA rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g · kg(-1) · d(-1), ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4(+) and CD8(+) cells were counted and IL-1? and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier.ResultsPI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4(+)/CD8(+) cell ratio in lamina propria and submucosa, and increased IL-1? and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4(+)/CD8(+) cell ratio and expression of IL-1? and IL-4.ConclusionChang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects.

Project description:We conducted a microarray study of sigmoid mucosal gene expression in pilot sample of Rome III+ IBS patients and age and sex-matched HCs. This sample was balanced by sex, free of active psychiatric disease and had limited use of medications. Rome III+ IBS patients and HCs ages 18-55 were recruited primarily by community advertisement. Bowel habit subtypes (IBS with diarrhea (IBS-D), constipation (IBS-C) and mixed pattern (IBS-M)) were based on the Rome III criteria. The diagnosis was confirmed by a clinician with expertise in IBS. Rome III+a IBS patients and HCs ages 18-55 were recruited primarily by community advertisement. Bowel habit subtypes (IBS with diarrhea (IBS-D), constipation (IBS-C) and mixed pattern (IBS-M)) were based on the Rome III criteria. The diagnosis was confirmed by a clinician with expertise in IBS. HCs had no personal or family history of IBS or other chronic pain conditions. Additional exclusion criteria for all subjects included: infectious or inflammatory disorders, active psychiatric illness over the past 6 months as assessed by structured clinical interview for the DSM-IV (MINI),b use of corticosteroids in the past six months, use of narcotics, antidepressants or other medications that could affect neuroendocrine function in the past two months, or current tobacco or alcohol abuse. Participants were compensated. Our goal was to evaluate women during the follicular phase or days 4-14 of their menstrual cycle if on oral contraceptive pills. Phase was determined by date of last menstrual period and progesterone levels. The study was approved by the UCLA Institutional Review Board, and all subjects signed a written informed consent prior to start of study. IBS symptom severity over the prior week was assessed with a numeric rating scale (0-20).c Current anxiety and depression symptoms were measured with the Hospital Anxiety and Depression (HAD) scale.d Sigmoid biopsies (30cm from the anal verge) were obtained by flexible sigmoidoscopy following tap water enemas. Specimens were immediately flash frozen in liquid nitrogen. RNA was extracted with TRIzol. Sigmoid biopsies (30cm from the anal verge) were obtained by flexible sigmoidoscopy following tap water enemas. Specimens were immediately flash frozen in liquid nitrogen. Differential expression analysis was done on mRNA only (\\ormalized_Unfiltered_mRNAonly.txt\\) using limma[1]. Weighted gene coexpression network analysis (WGCNA[2]) was done using all targets after removing those on X and Y chromosomes and filtered by mean raw signal >200. 1. Smyth GK. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 2004;3:Article3. 2. Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559.\

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Intestinal barrier function is maintained with aging - a comprehensive study in healthy subjects and irritable bowel syndrome patients.

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Intestinal barrier function is maintained with aging - a comprehensive study in healthy subjects and irritable bowel syndrome patients.

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