Profiles and interactions of gut microbiome and intestinal microRNAs in pediatric Crohn’s disease
Yao Lv,
Changjun Zhen,
Ana Liu,
Yudie Hu,
Gan Yang,
Cuifang Xu,
Yue Lou,
Qi Cheng,
Youyou Luo,
Jindan Yu,
Youhong Fang,
Hong Zhao,
Kerong Peng,
Yu Yu,
Jingan Lou,
Jie Chen,
Yan Ni
Affiliations
Yao Lv
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Changjun Zhen
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Ana Liu
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Yudie Hu
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Gan Yang
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Cuifang Xu
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Yue Lou
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Qi Cheng
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Youyou Luo
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Jindan Yu
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Youhong Fang
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Hong Zhao
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Kerong Peng
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Yu Yu
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Jingan Lou
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Jie Chen
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
Yan Ni
Gastroenterology Department, Children’s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
ABSTRACT Gut dysbiosis is closely related to dysregulated microRNAs (miRNAs) in the intestinal epithelial cells, which plays an important role in the pathogenesis of Crohn’s disease (CD). We investigated the relationship between fecal gut microbiome (GM) and intestinal tissue miRNAs in different stages of pediatric CD. Metagenomic analysis and miRNA sequencing were conducted to examine the GM and intestinal miRNA profiles of CD patients before and after clinical induction therapy and the controls. Twenty-seven newly diagnosed, therapy-naïve pediatric patients with active CD and 11 non-inflammatory bowel disease (IBD) controls were recruited in this study. Among CD patients, 11 patients completed induction treatment and reached clinical remission. Both GM and miRNA profiles were significantly changed between CD patients and controls. Seven key bacteria were identified at species level including Defluviitalea raffinosedens, Thermotalea metallivorans, Roseburia intestinalis, Dorea sp. AGR2135, Escherichia coli, Shigella sonnei, and Salmonella enterica, the exact proportions of which were further validated by real-time quantitative PCR analysis. Eight key miRNAs were also identified including hsa-miR-215-5p, hsa-miR-194-5p, hsa-miR-12135, hsa-miR-509-3-5p, hsa-miR-212-5p, hsa-miR-4448, hsa-miR-501-3p, and hsa-miR-503-5p. The functional enrichment analysis of differential miRNAs indicated the significantly altered cyclin protein, cyclin-dependent protein, and cell cycle pathway. The close interactions between seven key bacteria and eight key miRNAs were further investigated by miRNA target prediction. The association between specific miRNA expressions and key gut bacteria at different stages of CD supported their important roles as potential molecular biomarkers. Understanding the relationship between them will help us to explore the molecular mechanisms of CD.IMPORTANCESince previous studies have focused on the change of the fecal gut microbiome and intestinal tissue miRNA in pediatric Crohn’s disease (CD), the relationship between them in different stages is still not clear. This is the first study to explore the gut microbiota and miRNA and their correlations with the Pediatric Crohn’s Disease Activity Index (PCDAI). Crohn’s Disease Endoscopic Index of Severity (CDEIS), and calprotectin, by applying two omics approach in three different groups (active CD, CD in remission with exclusive enteral nutrition or infliximab induction therapy, and the healthy controls). Both gut microbiome structure and the miRNA profiles were significantly changed in the different stage of CD. Seven key gut microbiome at species and eight key miRNAs were found, and their close interactions were further fully investigated by miRNA target prediction.
