Modulation of faecal metagenome in Crohn’s disease: Role of microRNAs as biomarkers

Abstract

BACKGROUNDThe gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. It has been shown that commensal bacterial species can regulate the expression of host genes. 16S rRNA gene sequencing has shown that the microbiota in inflammatory bowel disease (IBD) is abnormal and characterized by reduced diversity. MicroRNAs (miRNAs) have been explored as biomarkers and therapeutic targets, since they are able to regulate specific genes associated with Crohn’s disease (CD). In this work, we aim to investigate the composition of gut microbiota of active treatment-naïve adult CD patients, with miRNA profile from gut microbiota.AIMTo investigate the composition of gut microbiota of active treatment-naïve adult CD patients, with miRNA profile from gut microbiota.METHODSPatients attending the outpatient clinics at Valme University Hospital without relevant co-morbidities were matched according to age and gender. Faecal samples of new-onset CD patients, free of treatment, and healthy controls were collected. Faecal samples were homogenized, and DNA was amplified by PCR using primers directed to the 16S bacterial rRNA gene. Pyrosequencing was performed using GS-Junior platform. For sequence analysis, MG-RAST server with the database Ribosomal Project was used. MiRNA profile and their relative abundance were analyzed by quantitative PCR.RESULTSMicrobial community was characterized using 16S rRNA gene sequencing in 29 samples (n = 13 CD patients, and n = 16 healthy controls). The mean Shannon diversity was higher in the healthy control population compared to CD group (5.5 vs 3.7). A reduction in Firmicutes and an increase in Bacteroidetes were found. Clostridia class was also significantly reduced in CD. Principal components analysis showed a grouping pattern, identified in most of the subjects in both groups, showing a marked difference between control and CD groups. A functional metabolic study showed that a lower metabolism of carbohydrates (P = 0.000) was found in CD group, while the metabolism of lipids was increased. In CD patients, three miRNAs were induced in affected mucosa: mir-144 (6.2 ± 1.3 fold), mir-519 (21.8 ± 3.1) and mir-211 (2.3 ± 0.4).CONCLUSIONChanges in microbial function in active non-treated CD subjects and three miRNAs in affected vs non-affected mucosa have been found. miRNAs profile may serve as a biomarker.

Gut microbes from the phylogenetically diverse genusEubacteriumand their various contributions to gut health

“… 16S rRNA gene sequencing ↓ Ruminococus, Roseburia, Parabacteroides, Mesoplasma, Faecalibacterium, Eubacterium and Alistipes in CD samples compared to healthy controls. Rojas-Feria et al 93 447 children and adolescents (<17 years) with new-onset CD and a control population of 221 subjects were enrolled as part of the RISK cohort. Biopsies were collected from the terminal ileum and rectum.…”

MicroRNAs Regulate Intestinal Immunity and Gut Microbiota for Gastrointestinal Health: A Comprehensive Review

“…Studies on miR-194-5p, miR-148-3p, and miR-27b-3p reveal that these microRNAs could be intermediates between Enterobacteriaceae and gut inflammation, and they have a strong correlation with Proteobacteria, which were previously reported to be abundant in IL-10 knockout mice and IBD patients, indicating their roles as mediators in the pathogenesis of Proteobacteria and intestinal inflammation [ 11 , 100 ]. Relying on fecal microbiota transplantation, the germ-free mice received intestinal microbes from wild-type donor, which exhibited a significant difference in their fecal microRNA profiles, and several other microRNAs, such as miR-144, miR-519, and miR-211, have been considered as important modulators of gut microbiota and biomarkers for Crohn’s disease, verified in the adult CD patients [ 101 ]. Moreover, in a study based on the DSS-induced colitis mice model, miR-21 was mentioned as a factor for the pathogenicity of intestinal inflammatory diseases and colitis-associated colorectal cancer, primarily through stimulating IL-10 and prostaglandin E2, which further inhibit anti-tumor adaptive immunity [ 102 ].…”

Effects of Rearing Conditions and Sex on Cecal Microbiota in Ducks

“…The cecum plays important physiological functions, especially in poultry. It has a lower pH and higher content of easily fermentable compounds in chickens and ducks ( Rojas-Feria et al, 2018 ), and cecal microbiomes has a considerable effect on nutrient digestion, absorption, and metabolism ( Turnbaugh et al, 2006 ; Rinttilä and Apajalahti, 2013 ). In this study, we hypothesized that different feeding conditions might be related to the diversity and composition of the cecal microbiome, and that this microbiota might differ between male and female ducks under similar housing conditions.…”