BackgroundGut microbiome dysbiosis has been demonstrated in subjects with newly diagnosed and chronic inflammatory bowel disease (IBD). In this study we sought to explore longitudinal changes in dysbiosis and ascertain associations between dysbiosis and markers of disease activity and treatment outcome.MethodsWe performed a prospective cohort study of 19 treatment-naïve pediatric IBD subjects and 10 healthy controls, measuring fecal calprotectin and assessing the gut microbiome via repeated stool samples. Associations between clinical characteristics and the microbiome were tested using generalized estimating equations. Random forest classification was used to predict ultimate treatment response (presence of mucosal healing at follow-up colonoscopy) or non-response using patients’ pretreatment samples.ResultsPatients with Crohn’s disease had increased markers of inflammation and dysbiosis compared to controls. Patients with ulcerative colitis had even higher inflammation and dysbiosis compared to those with Crohn’s disease. For all cases, the gut microbial dysbiosis index associated significantly with clinical and biological measures of disease severity, but did not associate with treatment response. We found differences in specific gut microbiome genera between cases/controls and responders/non-responders including Akkermansia, Coprococcus, Fusobacterium, Veillonella, Faecalibacterium, and Adlercreutzia. Using pretreatment microbiome data in a weighted random forest classifier, we were able to obtain 76.5 % accuracy for prediction of responder status.ConclusionsPatient dysbiosis improved over time but persisted even among those who responded to treatment and achieved mucosal healing. Although dysbiosis index was not significantly different between responders and non-responders, we found specific genus-level differences. We found that pretreatment microbiome signatures are a promising avenue for prediction of remission and response to treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0331-y) contains supplementary material, which is available to authorized users.
We demonstrate that low IFX levels are associated with development of immunogenicity to IFX as measured by ATI. We demonstrate that interval shortening rather than dose escalation results in higher IFX levels. We suggest that given the high number of IFX levels below 3 μg/mL in patients, early IFX level evaluation or primary initiation of Q6 week dosing be considered.
In our cohort, 60% of the IBD-U subjects remained as unclassified at 2 years; of those subsequently classified, a higher percentage followed a course more similar to UC. Most of the IBD-U subjects at diagnosis had serological and molecular signatures that are very similar to UC. Although the atypical presentations made the clinician to make an interim diagnosis of IBD-U, results of the molecular and serological factors performed at the time of diagnosis suggests that they were very similar to UC. However, long-term studies are needed to better understand the natural history and molecular characterization of pediatric onset IBD-U. 10.1093/ibd/izy136_video1Video 1.Video 1. Watch now at https://academic.oup.com/ibd/article-lookup/doi/10.1093/ibd/izy136izy136.video15791389938001.
Backgrounds
Recent studies have identified the role of serologic markers in
characterizing disease phenotype, location, complications, and severity
among Northern Europeans (NE) with Crohn’s disease (CD). However,
very little is known about the role of serology in CD among African
Americans (AA). Our study explored the relationship between serology and
disease phenotype in AA with CD, while controlling for genetic ancestry.
Methods
AAs with CD were enrolled as participants through multicenter
collaborative efforts. Serological levels of IgA anti-Saccharomyces
cervisiae antibody (ASCA), IgG ASCA, E. coli
outermembrane porin C, anti-CBir1, and ANCA were measured using
enzyme-linked immunosorbent assays. Genotyping was performed using Illumina
immunochip technology; an admixture rate was calculated for each subject.
Multiple imputation by chained equations was performed to account for data
missing at random. Logistic regression was used to calculate adjusted odds
ratio (OR) for associations between serological markers and both complicated
disease and disease requiring surgery.
Results
A total of 358 patients were included in the analysis. The majority
of our patients had inflammatory, noncomplicated disease (58.4%),
perianal disease (55.7%), and documented colonic inflammation
(86.8%). On multivariable analysis, both IgG ASCA and OmpC were
associated with complicated disease (OR, 2.67; 95% CI,
1.67–4.28; OR, 2.23; 95% CI, 1.41–3.53,
respectively) and disease requiring surgery (OR, 2.51; 95% CI,
1.49–4.22; OR, 3.57; 95% CI, 2.12–6.00). NE
admixture to the African genome did not have any associations or
interactions in relation to clinical outcome.
Conclusions
Our study comprises the largest cohort of AAs with CD. The utility of
serological markers for the prognosis of CD in NE applies equally to AA
populations.
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