Dataset Information

Gut Microbiota Offers Universal Biomarkers across Ethnicity in Inflammatory Bowel Disease Diagnosis and Infliximab Response Prediction.

ABSTRACT: Gut microbiota dysbiosis contributes to the onset and perpetuation of inflammatory bowel disease (IBD). Given that gut microbiotas vary across geography and ethnicity, it remains obscure whether any universal microbial signatures for IBD diagnosis and prognosis evaluation exist irrespective of populations. Here we profiled the fecal microbiota of a series of Chinese IBD patients and combined them with two Western IBD cohorts, PRISM and RISK, for meta-analyses. We found that the gut microbial alteration patterns in IBD are similar among Chinese and Westerners. Our prediction model based on gut microbiome for IBD diagnosis is robust across the cohorts, which showed 87.5% and 79.1% prediction accuracy in Crohn's disease (CD) and ulcerative colitis (UC) patients, respectively. A relative increase in the levels of Actinobacteria and Proteobacteria (Enterobacteriaceae) and a relative decrease in the levels of Firmicutes (Clostridiales) were strongly correlated with IBD severity (P < 0.05). Additionally, restoration of gut microbiota diversity and a significant increase in Clostridiales relative abundance were found in patients responding to infliximab (IFX [Remicade]) treatment compared to those in relapse. Moreover, certain microbes, mainly Clostridiales, predicted the treatment effectiveness with 86.5% accuracy alone and 93.8% accuracy in combination with calprotectin levels and Crohn's disease activity index (CDAI). Taking the results together, we conclude that gut microbiota can offer a set of universal biomarkers for diagnosis, disease activity evaluation, and infliximab treatment response prediction in IBD. IMPORTANCE In the present report, we show that the human fecal microbiota contains promising and universal biomarkers for the noninvasive evaluation of inflammatory bowel disease severity and IFX treatment efficacy, emphasizing the potential ability to mine the gut microbiota as a modality to stratify IBD patients and apply personalized therapy for optimal outcomes.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC5790872 | biostudies-literature | 2018 Jan-Feb

REPOSITORIES: biostudies-literature

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Gut Microbiota Offers Universal Biomarkers across Ethnicity in Inflammatory Bowel Disease Diagnosis and Infliximab Response Prediction.

Zhou Youlian Y Xu Zhenjiang Zech ZZ He Yan Y Yang Yunsheng Y Liu Le L Lin Qianyun Q Nie Yuqiang Y Li Mingsong M Zhi Fachao F Liu Side S Amir Amnon A González Antonio A Tripathi Anupriya A Chen Minhu M Wu Gary D GD Knight Rob R Zhou Hongwei H Chen Ye Y

mSystems 20180130 1

Gut microbiota dysbiosis contributes to the onset and perpetuation of inflammatory bowel disease (IBD). Given that gut microbiotas vary across geography and ethnicity, it remains obscure whether any universal microbial signatures for IBD diagnosis and prognosis evaluation exist irrespective of populations. Here we profiled the fecal microbiota of a series of Chinese IBD patients and combined them with two Western IBD cohorts, PRISM and RISK, for meta-analyses. We found that the gut microbial alt ...[more]

PMID: 29404425

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Project description:The tremendous boost in next generation sequencing and in the "omics" technologies makes it possible to characterize the human gut microbiome-the collective genomes of the microbial community that reside in our gastrointestinal tract. Although some of these microorganisms are considered to be essential regulators of our immune system, the alteration of the complexity and eubiotic state of microbiota might promote autoimmune and inflammatory disorders such as diabetes, rheumatoid arthritis, Inflammatory bowel diseases (IBD), obesity, and carcinogenesis. IBD, comprising Crohn's disease and ulcerative colitis, is a gut-related, multifactorial disease with an unknown etiology. IBD presents defects in the detection and control of the gut microbiota, associated with unbalanced immune reactions, genetic mutations that confer susceptibility to the disease, and complex environmental conditions such as westernized lifestyle. Although some existing studies attempt to unveil the composition and functional capacity of the gut microbiome in relation to IBD diseases, a comprehensive picture of the gut microbiome in IBD patients is far from being complete. Due to the complexity of metagenomic studies, the applications of the state-of-the-art machine learning techniques became popular to address a wide range of questions in the field of metagenomic data analysis. In this regard, using IBD associated metagenomics dataset, this study utilizes both supervised and unsupervised machine learning algorithms, (i) to generate a classification model that aids IBD diagnosis, (ii) to discover IBD-associated biomarkers, (iii) to discover subgroups of IBD patients using k-means and hierarchical clustering approaches. To deal with the high dimensionality of features, we applied robust feature selection algorithms such as Conditional Mutual Information Maximization (CMIM), Fast Correlation Based Filter (FCBF), min redundancy max relevance (mRMR), Select K Best (SKB), Information Gain (IG) and Extreme Gradient Boosting (XGBoost). In our experiments with 100-fold Monte Carlo cross-validation (MCCV), XGBoost, IG, and SKB methods showed a considerable effect in terms of minimizing the microbiota used for the diagnosis of IBD and thus reducing the cost and time. We observed that compared to Decision Tree, Support Vector Machine, Logitboost, Adaboost, and stacking ensemble classifiers, our Random Forest classifier resulted in better performance measures for the classification of IBD. Our findings revealed potential microbiome-mediated mechanisms of IBD and these findings might be useful for the development of microbiome-based diagnostics.

Project description:BackgroundThe pathogenesis of irritable bowel syndrome (IBS) is closely related to intestinal dysbacteriosis and can be controlled by moxibustion treatment. However, the mechanism underlying the therapeutic value of moxibustion in IBS treatment remains unknown.MethodsAn IBS rat model was established by colorectal distention (CRD) stimulus and mustard oil clyster. Sixty-five male rats were randomly divided into six groups: normal, IBS model, moxibustion, electroacupuncture (EA), Bifid-triple Viable Capsule (BTVC) and Pinaverium Bromide (PB) groups. The moxibustion group was treated with mild moxibustion at the bilateral Tianshu (ST25) and Shangjuxu (ST37) for 10 min/day for 7 days, the EA group was given EA at ST25 and ST37 once daily for 7 days, while the BTVC group and PB groups received Bifid-triple Viable Capsule and Pinaverium Bromide solution (at the proportion of 1:0.018) respectively by gavage once daily for 7 days. After the treatment, abdominal withdrawal reflex (AWR) scores were determined based on CRD stimulus, gut microbiota profiling was conducted by 16S rRNA high-throughput sequencing.ResultsIrritable bowel syndrome model rats had significantly increased AWR scores at all intensities (20, 40, 60 and 80 mmHg) compared with the normal group. Moxibustion treatment significantly reduced AWR scores compared with the IBS model group at all intensities. Across all groups the most abundant phyla were Bacteroidetes and Firmicutes followed by Proteobacteria and Candidatus Saccharibacteria. At genus level IBS model rats had a higher abundance of Prevotella, Bacteroides and Clostridium XI and a lower abundance of Lactobacillus and Clostridium XIVa compared with normal rats. These changes in microbiota profiles could however be reversed by moxibustion treatment. Alpha diversity was decreased in IBS model rats compared with normal rats, yet significantly increased in moxibustion- and PB-treated rats compared with IBS rats.ConclusionOur findings suggest that moxibustion treats IBS by modulating the gut microbiota.Electronic supplementary materialThe online version of this article (10.1186/s13020-018-0220-y) contains supplementary material, which is available to authorized users.

Dataset Information

Gut Microbiota Offers Universal Biomarkers across Ethnicity in Inflammatory Bowel Disease Diagnosis and Infliximab Response Prediction.

Publications

Gut Microbiota Offers Universal Biomarkers across Ethnicity in Inflammatory Bowel Disease Diagnosis and Infliximab Response Prediction.

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