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Prospective study reveals a microbiome signature that predicts the occurrence of post-operative enterocolitis in Hirschsprung disease (HSCR) patients.

ABSTRACT: Hirschsprung disease (HSCR) is a birth defect with an approximate incidence of 1/5,000 live births, and up to one-third of HSCR patients develop Hirschsprung-associated enterocolitis (HAEC), the leading cause of HSCR-related death. Very little is known about the pathogenesis, prevention, and early diagnosis of HAEC. Here, we used a prospective study to investigate the enteric microbiome composition at the time of surgery as a predictor for developing postoperative HAEC. We identified a microbiome signature containing 21 operational taxonomic units (OTUs) that can potentially predict postoperative HAEC with ~85% accuracy. Furthermore, we identified exclusive breastfeeding as a novel protective factor for total HAEC (i.e., preoperative and postoperative HAEC combined). In addition, we discovered that breastfeeding was associated with a lowered risk for HAEC potentially mediated by modulating the gut microbiome composition characterized by a lower abundance of Gram-negative bacteria and lower LPS concentrations. In conclusion, modulating the gut microbiome by encouraging breastfeeding might prevent HAEC progression in HSCR patients.

SUBMITTER: Tang W

PROVIDER: S-EPMC7524399 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Prospective study reveals a microbiome signature that predicts the occurrence of post-operative enterocolitis in Hirschsprung disease (HSCR) patients.

Tang Weibing W Su Yang Y Yuan Chen C Zhang Yuqing Y Zhou Lingling L Peng Lei L Wang Pin P Chen Guanglin G Li Yang Y Li Hongxing H Zhi Zhengke Z Chang Hang H Hang Bo B Mao Jian-Hua JH Snijders Antoine M AM Xia Yankai Y

Gut microbes 20200116 4

Hirschsprung disease (HSCR) is a birth defect with an approximate incidence of 1/5,000 live births, and up to one-third of HSCR patients develop Hirschsprung-associated enterocolitis (HAEC), the leading cause of HSCR-related death. Very little is known about the pathogenesis, prevention, and early diagnosis of HAEC. Here, we used a prospective study to investigate the enteric microbiome composition at the time of surgery as a predictor for developing postoperative HAEC. We identified a microbiom ...[more]

PMID: 31944159

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Project description:PurposeHirschsprung-associated enterocolitis (HAEC) is the most frequent potentially life-threatening complication in children with Hirschsprung disease (HSCR) even after definitive corrective surgery. Mounting evidence suggests that intestinal microbiota likely contribute to the etiology of enterocolitis, so the aim of this study was to use a mouse model of post pull-through HAEC to compare the fecal bacterial communities of animals which developed HAEC to those free of enterocolitis.MethodsTen Ednrb -/- and 8wild type mice underwent the microsurgical pull-through surgery, and stool was collected at the time of surgery, and then either at 2 and 4 weeks after the operation, or when the mice developed enterocolitis. The mid-colon of all animals was collected, prepared and histologically graded for enterocolitis. Fecal DNA was isolated and bacterial 16S rRNA genes analyzed using Illumina sequencing.ResultsSix Ednrb-/- mice developed HAEC with a mean enterocolitis score of 5.7, while the remaining 4 mutant and 8 WT mice remained free of enterocolitis by 4 weeks. The HAEC group had lower alpha diversity by Chao1 analysis compared with WT group, while the Ednrb-/- mice demonstrated distinct bacterial communities from WT mice on beta diversity analysis. The most striking finding was increased proportion of Akkermansia and reduced Bacteroidetes compared with the NO HAEC and WT groups, suggesting Akkermansia may contribute to development of enterocolitis while Bacteroidetes may be protective. Less abundant genera that were reduced in HAEC were Dysgonomas and Clostridium XIVa which may play a protective role.ConclusionsThis is the first study to identify Akkermansia as potentially playing a role in HAEC, either as a pathobiont taxa contributing to pathogenesis of enterocolitis, or possibly a protective commensal taxa expanded in response to inflammation. These findings characterized the dynamic shifts in the gut microbial communities through the onset of post pull-through HAEC, and suggests that there may be identifiable bacterial community differences in HSCR patients that are high risk for developing HAEC.

Project description:ImportanceTrichiasis surgery programs globally have faced high rates of poor surgical outcomes. Identifying correctable risk factors for improving long-term outcomes is essential for countries targeting elimination of trachoma as a public health problem.ObjectiveTo determine whether the location of trichiatic eyelashes prior to surgery influences development of post-operative trichiasis (PTT) within two years after surgery.DesignSecondary data analysis of four randomized clinical trials evaluating methods to improve trichiasis surgery outcomes. These include the Surgery for Trichiasis, Antibiotics for Recurrence (STAR) trial, Partnership for Rapid Elimination of Trachoma (PRET-Surgery), absorbable versus silk sutures trial, and epilation versus surgery for minor trichiasis trial.SettingPrimary trials were conducted in rural areas of Ethiopia and Tanzania.Interventions or exposuresTrichiasis surgery performed with either the bilamellar tarsal rotation procedure or posterior lamellar rotation procedure.Main outcomesPrevalence of PTT within two years after surgery, location of trichiatic eyelashes pre-operatively and post-operatively.Results6,747 eyelids that underwent first-time trichiasis surgery were included. PTT rates varied by study, ranging from 10-40%. PTT was less severe (based on number of trichiatic eyelashes) than initial trichiasis for 72% of those developing PTT, and only 2% of eyelids were worse at follow up than pre-operatively. Eyelids with central only-trichiasis pre-operatively had lower rates of PTT than eyelids with peripheral only trichiasis in each of the three trials that included severe TT cases. 10% of eyelids with peripheral trichiasis pre-operatively that develop PTT have central TT post-operatively.Conclusions and relevancePre-operative central trichiasis is less likely than peripheral trichiasis to be associated with subsequent PTT. Regardless of type of surgery, surgeon skill levels, or pre-operative trichiasis severity, the presence of peripheral trichiasis pre-operatively is associated with higher rates of PTT. Making an incision that extends the length of the eyelid and adequately rotating the nasal and temporal aspects of the eyelid when suturing may help to minimize the chance of developing peripheral PTT.Trial registrationClinicalTrials.gov PRET: NCT00886015; Suture: NCT005228560; Epilation: NCT00522912.

Project description:BackgroundHirschsprung-associated enterocolitis (HAEC) is a leading cause of serious morbidity and potential mortality in children with Hirschsprung's disease (HD). People with HAEC suffer from intestinal inflammation, and present with diarrhoea, explosive stools, and abdominal distension. Probiotics are live microorganisms with beneficial health effects, which can optimise gastrointestinal function and gut flora. However, the efficacy and safety of probiotic supplementation in the prevention of HAEC remains unclear.ObjectivesTo assess the effects of probiotic supplements used either alone or in combination with pharmacological interventions on the prevention of Hirschsprung-associated enterocolitis.Search methodsWe searched CENTRAL, PubMed, Embase, the China BioMedical Literature database (CBM), the World Health Organization International Clinical Trials Registry, ClinicalTrials.gov, the Chinese Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, and Clinical Trials Registry-India, from database inception to 27 February 2022. We also searched the reference lists of relevant articles and reviews for any additional trails.Selection criteriaRandomised controlled trials (RCTs) comparing probiotics and placebo, or any other non-probiotic intervention, for the prevention of HAEC were eligible for inclusion.Data collection and analysisTwo review authors independently extracted data and assessed the risk of bias of the included studies; disagreements were resolved by discussion with a third review author. We assessed the certainty of evidence using the GRADE approach. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes.Main resultsWe included two RCTs, with a total of 122 participants. We judged the overall risk of bias as high. We downgraded the evidence due to risk of bias (random sequence generation, allocation concealment, and blinding) and small sample size. The evidence is very uncertain about the effect of probiotics on the occurrence of HAEC (OR 0.58, 95% CI 0.10 to 3.43; I² = 74%; 2 studies, 120 participants; very low-certainty evidence). We found one included study that did not measure serious adverse events and one included study that reported no serious adverse events related to probiotics. Probiotics may result in little to no difference between probiotics and placebo in relation to the severity of children with HAEC at Grade I (OR 0.66, 95% CI 0.14 to 3.16; I² = 25%; 2 studies, 120 participants; low-certainty evidence). The effects of probiotics on the severity of HAEC at Grade II are very uncertain (OR 1.14, 95% CI 0.01 to 136.58; I² = 86%; 2 studies, 120 participants; very low-certainty evidence). Similarly, the evidence suggests that probiotics results in little to no difference in relation to the severity of HAEC at Grade III (OR 0.43, 95% CI 0.05 to 3.45; I² = 0%; 2 studies, 120 participants; low-certainty evidence). No overall mortality or withdrawals due to adverse events were reported. Probiotics may result in little to no difference in the recurrence of episodes of HAEC compared to placebo (OR 0.85, 95% CI 0.24 to 3.00; 1 study, 60 participants; low-certainty evidence).Authors' conclusionsThere is currently not enough evidence to assess the efficacy or safety of probiotics for the prevention of Hirschsprung-associated enterocolitis when compared with placebo. The presence of low- to very-low certainty evidence suggests that further well-designed and sufficiently powered RCTs are needed to clarify the true efficacy of probiotics.

Dataset Information

Prospective study reveals a microbiome signature that predicts the occurrence of post-operative enterocolitis in Hirschsprung disease (HSCR) patients.

Publications

Prospective study reveals a microbiome signature that predicts the occurrence of post-operative enterocolitis in Hirschsprung disease (HSCR) patients.

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