Influence of Crohn’s disease related polymorphisms in innate immune function on ileal microbiome

We have previously identified NOD2 genotype and inflammatory bowel diseases (IBD) phenotype, as associated with shifts in the ileal microbiome (“dysbiosis”) in a patient cohort. Here we report an integrative analysis of an expanded number of Crohn's disease (CD) related genetic defects in innate immune function (NOD2, ATG16L1, IRGM, CARD9, XBP1, ORMDL3) and composition of the ileal microbiome by combining the initial patient cohort (Batch 1, 2005–2010, n = 165) with a second consecutive patient cohort (Batch 2, 2010–2012, n = 118). These combined patient cohorts were composed of three non-overlapping phenotypes: 1.) 106 ileal CD subjects undergoing initial ileocolic resection for diseased ileum, 2.) 88 IBD colitis subjects without ileal disease (predominantly ulcerative colitis but also Crohn’s colitis and indeterminate colitis, and 3.) 89 non-IBD subjects. Significant differences (FDR C. difficile infection, and NOD2 genotype on ileal dysbiosis in the expanded analysis. The relative abundance of the Proteobacteria phylum was positively associated with ileal CD and colitis phenotypes, but negatively associated with NOD2R genotype. Additional associations with ORMDL3 and XBP1 were detected at the phylum/subphylum level. IBD medications, such as immunomodulators and anti-TNFα agents, may have a beneficial effect on reversing dysbiosis associated with the IBD phenotype. Exploratory analysis comparing microbial composition of the disease unaffected region of the resected ileum between 27 ileal CD patients who subsequently developed endoscopic recurrence within 6–12 months versus 34 patients who did not, suggested that microbial biomarkers in the resected specimen helped stratify patients with respect to risk of post-surgical recurrence.</div

Gastroesophageal reflux and PPI exposure alter gut microbiota in very young infants

ImportanceInfants with symptomatic Gastroesophageal reflux are treated with pharmacological therapy that includes proton pump inhibitors (PPI) with clinical improvement. The alterations to gut microbiome profiles in comparison to infants without reflux is not known.ObjectiveTo determine the effect of PPI therapy on gut bacterial richness, diversity, and proportions of specific taxa in infants when compared to infants not exposed to acid suppressive therapy.Design, setting, and participantsThis cohort study was conducted at the Stony Brook Hospital in Stony Brook, NY between February 2016, and June 2019. Infants meeting inclusion criteria were enrolled in a consecutive fashion.ResultsA total of 76 Infants were recruited and 60 were enrolled in the study, Twenty nine infants met clinical criteria for reflux and were treated with PPI therapy: median [IQR] gestation: 38.0 weeks [34.7–39.6 weeks]; median [IQR] birthweight: 2.95 Kg [2.2–3.4]; 14 [46.7%] male) and 29 infant were healthy controls median [IQR] gestation: 39.1 weeks [38–40 weeks]; median [IQR] birthweight: 3.3 Kg [2.2–3.4]; 17 [58.6%] male); 58 stool samples from 58 infants were analyzed. There were differences in Shannon diversity between the reflux and control groups. The reflux group that was exposed to PPI therapy had increased relative abundance of a diverse set of genera belonging to the phylum Firmicutes. On the other hand, the control group microbiota was dominated by Bifidobacterium, and a comparatively lower level of enrichment and abundance of microbial taxa was observed in this group of infants.Conclusions and relevanceWe observed significant differences in both α- and β-diversity of the microbiome, when the two groups of infants were compared. The microbiome in the reflux group had more bacterial taxa and the duration of PPIs exposure was clearly associated with the diversity and abundance of gut microbes. These findings suggest that PPI exposure among infants results in early enrichment of the intestinal microbiome

Gut Microbiota Profiles of Children with Obesity or Metabolic Syndrome: Body Mass Index Is a Lead Actor

The worldwide prevalence of obesity and associated metabolic syndrome (MetS) has increased threefold over the last five decades. Among children, this trend is alarming due to the premature onset of MetS. The data regarding how the structure and composition of gastrointestinal (GIT) microbiota either promote or attenuate obesity and MetS are limited. Objectives: We carried out this study to investigate the relationship between microbial profiles and diagnosis of MetS among children with obesity. Fifty subjects with a diagnosis of obesity or Mets were enrolled. We collected clinical information, demographic data, dietary records, and stool specimens. Overall, there was no significant difference in the diversity of GIT microbiota between the two subgroups of children with obesity or MetS. We also found no differences in the diversity of GIT microbiota between the sexes and blood pressure categories. However, we observed a significant difference between the structure, composition, and diversity of the gut microbiome when the subjects were stratified using a BMI cut-off of 30. Subjects with a BMI ≥ 30 had a lower abundance of Bacteroidetes and a greater abundance of Actinobacteria and Firmicutes compared to those with a BMI value of less than 30. This gut microbiota signature is more like the GIT microbiome profile of adults with obesity and may represent accelerated changes among children. Additional studies are needed to investigate the role of obesity in the maturation of gut microbiota in children with morbid obesity