Gut Microbiota Offers Universal Biomarkers across Ethnicity in Inflammatory Bowel Disease Diagnosis and Infliximab Response Prediction
Youlian Zhou,
Zhenjiang Zech Xu,
Yan He,
Yunsheng Yang,
Le Liu,
Qianyun Lin,
Yuqiang Nie,
Mingsong Li,
Fachao Zhi,
Side Liu,
Amnon Amir,
Antonio González,
Anupriya Tripathi,
Minhu Chen,
Gary D. Wu,
Rob Knight,
Hongwei Zhou,
Ye Chen
Affiliations
Youlian Zhou
Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
Zhenjiang Zech Xu
Department of Pediatrics, University of California, San Diego, La Jolla, California, USA
Yan He
Department of Environmental Health, School of Public Health and Tropical Medicine, State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China
Yunsheng Yang
Institute of Digestive Diseases, Chinese PLA General Hospital, Beijing, China
Le Liu
Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
Qianyun Lin
Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
Yuqiang Nie
Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, China
Mingsong Li
Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
Fachao Zhi
Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
Side Liu
Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
Amnon Amir
Department of Pediatrics, University of California, San Diego, La Jolla, California, USA
Antonio González
Department of Pediatrics, University of California, San Diego, La Jolla, California, USA
Anupriya Tripathi
Department of Pediatrics, University of California, San Diego, La Jolla, California, USA
Minhu Chen
Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
Gary D. Wu
Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Rob Knight
Department of Pediatrics, University of California, San Diego, La Jolla, California, USA
Hongwei Zhou
State Key Laboratory of Organ Failure Research, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Ye Chen
Department of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China
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.
