Dataset Information

Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients.

ABSTRACT: Ulcerative colitis is a chronic inflammatory disease of the colon that carries a significant disease burden in children. Therefore, new therapeutic approaches are being explored to help children living with this disease. Fecal microbiota transplantation (FMT) has been successful in some children with ulcerative colitis. However, the mechanism of its therapeutic effect in this patient population is not well understood. To characterize changes in gut microbial and metabolomic profiles after FMT, we performed 16S rRNA gene sequencing, shotgun metagenomic sequencing, virome analysis and untargeted metabolomics by gas chromatography-time of flight-mass spectrometry on stool samples collected before and after FMT from four children with ulcerative colitis who responded to this treatment. Alpha diversity of the gut microbiota increased after intervention, with species richness rising from 251 (S.D. 125) to 358 (S.D. 27). In responders, the mean relative abundance of bacteria in the class Clostridia shifted toward donor levels, increasing from 33% (S.D. 11%) to 54% (S.D. 16%). Patient metabolomic and viromic profiles exhibited a similar but less pronounced shift toward donor profiles after FMT. The fecal concentrations of several metabolites were altered after FMT, correlating with clinical improvement. Larger studies using a similar multi-omics approach may suggest novel strategies for the treatment of pediatric ulcerative colitis.

SUBMITTER: Nusbaum DJ

PROVIDER: S-EPMC6454419 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients.

Nusbaum David J DJ Sun Fengzhu F Ren Jie J Zhu Zifan Z Ramsy Natalie N Pervolarakis Nicholas N Kunde Sachin S England Whitney W Gao Bei B Fiehn Oliver O Michail Sonia S Whiteson Katrine K

FEMS microbiology ecology 20180901 9

Ulcerative colitis is a chronic inflammatory disease of the colon that carries a significant disease burden in children. Therefore, new therapeutic approaches are being explored to help children living with this disease. Fecal microbiota transplantation (FMT) has been successful in some children with ulcerative colitis. However, the mechanism of its therapeutic effect in this patient population is not well understood. To characterize changes in gut microbial and metabolomic profiles after FMT, w ...[more]

PMID: 30010747

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Project description:Ulcerative colitis (UC) is a complex chronic pathological condition of the gut in which microbiota targeted treatment, such as fecal microbiota transplantation (FMT), has shown an encouraging effect. The aim of the present study was to investigate the efficacy and safety of FMT in patients with mild or moderate UC. A single-center, open-label study was designed, including 47 patients with mild or moderate active UC who received three treatments of fresh FMT via colonic transendoscopic enteral tubing within 1 week. The inflammatory bowel disease questionnaire, partial Mayo scores, colonoscopy, erythrocyte sedimentation rate, C-reactive protein level and procalcitoin values were used to assess the efficacy of FMT and alteration in gut microbiota was detected by 16S ribosomal RNA-sequencing. Before FMT, microbiota Faecalibacterium prausnitzii (F. prausnitzii) levels were significantly decreased in patients with UC compared with healthy donors (P<0.01). At 4 weeks post-FMT, F. prausnitzii levels were significantly increased (P<0.05), and the Mayo score was significantly decreased (1.91±1.07 at baseline vs. 4.02±1.47 at week 4; P<0.001) in patients with UC compared with healthy donors. Steroid-free clinical responses were reported in 37 patients (84.1%), and steroid-free clinical remission was achieved in 31 patients (70.5%) at week 4 post-FMT, however, steroid-free remission was not achieved in any patient. No adverse events were reported in 41 (93.2%) patients after FMT or during the 12-week follow-up. Shannon's diversity index and Chao1 estimator were also improved in patients with UC receiving FMT. In conclusion, the results of the present study suggested that FMT resulted in clinical remission in patients with mild to moderate UC, and that the remission may be associated with significant alterations to the intestinal microbiota of patients with UC. Furthermore, F. prausnitzii may serve as a diagnostic and therapeutic biomarker for the use of FMT in UC.

Project description:Fecal microbiota transplantation (FMT) can induce clinical remission in ulcerative colitis (UC) patients. Enemas, nasoduodenal tubes, and colonoscopies are the most common routes for FMT administration. However, there is a lack of definitive evidence regarding the effectiveness of capsulized FMT treatment in UC patients. In this study, we administered capsulized FMT to 22 patients with active UC to assess the efficiency of capsulized FMT and determine the specific bacteria and metabolite factors associated with the response to clinical remission. Our results showed that the use of capsulized FMT was successful in the treatment of UC patients. Capsulized FMT induced clinical remission and clinical response in 57.1% (12 of 21) and 76.2% (16 of 21) of UC patients, respectively. Gut bacterial richness was increased after FMT in patients who achieved remission. Patients in remission after FMT exhibited enrichment of Alistipes sp. and Odoribacter splanchnicus, along with increased levels of indolelactic acid. Patients who did not achieve remission exhibited enrichment of Escherichia coli and Klebsiella and increased levels of biosynthesis of 12,13-DiHOME (12,13-dihydroxy-9Z-octadecenoic acid) and lipopolysaccharides. Furthermore, we identified a relationship between specific bacteria and metabolites and the induction of remission in patients. These findings may provide new insights into FMT in UC treatment and provide reference information about therapeutic microbial manipulation of FMT to enhance its effects. (This study has been registered at ClinicalTrails.gov under registration no. NCT03426683). IMPORTANCE Fecal microbiota transplantation has been successfully used in patients. Recently, capsulized FMT was reported to induce a response in patients with UC. However, limited patients were enrolled in such studies, and the functional factors of capsulized FMT have not been reported in the remission of patients with UC. In this study, we prospectively recruited patients with UC to receive capsulized FMT. First, we found that capsulized FMT could induce clinical remission in 57.1% of patients and clinical response in 76.2% after 12 weeks, which was more acceptable. Second, we found a relationship between the decrease of opportunistic pathogen and lipopolysaccharide synthesis in patients in remission after capsulized FMT. We also identified an association between specific bacteria and metabolites and remission induction in patients after capsulized FMT. These findings put forward a possibility for patients to receive FMT at home and provide reference information about therapeutic microbial manipulation of FMT to enhance its effects.

Dataset Information

Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients.

Publications

Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients.

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