Concept: Helminthic therapy
Shotgun metagenomic DNA sequencing is a widely applicable tool for characterizing the functions that are encoded by microbial communities. Several bioinformatic tools can be used to functionally annotate metagenomes, allowing researchers to draw inferences about the functional potential of the community and to identify putative functional biomarkers. However, little is known about how decisions made during annotation affect the reliability of the results. Here, we use statistical simulations to rigorously assess how to optimize annotation accuracy and speed, given parameters of the input data like read length and library size. We identify best practices in metagenome annotation and use them to guide the development of the Shotgun Metagenome Annotation Pipeline (ShotMAP). ShotMAP is an analytically flexible, end-to-end annotation pipeline that can be implemented either on a local computer or a cloud compute cluster. We use ShotMAP to assess how different annotation databases impact the interpretation of how marine metagenome and metatranscriptome functional capacity changes across seasons. We also apply ShotMAP to data obtained from a clinical microbiome investigation of inflammatory bowel disease. This analysis finds that gut microbiota collected from Crohn’s disease patients are functionally distinct from gut microbiota collected from either ulcerative colitis patients or healthy controls, with differential abundance of metabolic pathways related to host-microbiome interactions that may serve as putative biomarkers of disease.
To further resolve the genetic architecture of the inflammatory bowel diseases ulcerative colitis and Crohn’s disease, we sequenced the whole genomes of 4,280 patients at low coverage and compared them to 3,652 previously sequenced population controls across 73.5 million variants. We then imputed from these sequences into new and existing genome-wide association study cohorts and tested for association at ∼12 million variants in a total of 16,432 cases and 18,843 controls. We discovered a 0.6% frequency missense variant in ADCY7 that doubles the risk of ulcerative colitis. Despite good statistical power, we did not identify any other new low-frequency risk variants and found that such variants explained little heritability. We detected a burden of very rare, damaging missense variants in known Crohn’s disease risk genes, suggesting that more comprehensive sequencing studies will continue to improve understanding of the biology of complex diseases.
Inflammatory bowel diseases (IBD), which include ulcerative colitis and Crohn’s disease, cause chronic inflammation of the digestive tract in approximately 1.6 million Americans. A signature of IBD is dysbiosis of the gut microbiota marked by a significant reduction of obligate anaerobes and a sharp increase in facultative anaerobes. Numerous experimental studies have shown that IBD is strongly correlated with a decrease of Faecalibacterium prausnitzii and an increase of Escherichia coli. One hypothesis is that chronic inflammation induces increased oxygen levels in the gut, which in turn causes an imbalance between obligate and facultative anaerobes.
The concept of fecal microbiota transplantation (FMT) has been used in traditional Chinese medicine at least since the 4(th) century. Evidence from recent human studies strongly supports the link between intestinal bacteria and inflammatory bowel disease. We proposed that standardized FMT might be a promising rescue therapy for refractory inflammatory bowel disease. However, there were no reports of FMT used in patients with severe Crohn’s disease (CD). Here, we report the successful treatment of standardized FMT as a rescue therapy for a case of refractory CD complicated with fistula, residual Barium sulfate and formation of intraperitoneal large inflammatory mass. As far as we know, this is the first case of severe CD treated using FMT through mid-gut.
Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that compromise quality of life and may increase mortality. This study compared the mortality risk with prolonged corticosteroid use vs. antitumor necrosis factor-α (anti-TNF) drugs in IBD.
Geographical variation in the incidence of Crohn’s disease (CD) and ulcerative colitis (UC) according to the latitude of residence has been reported in Europe. However, there are no comparable data in the USA. The incidence of CD and UC in relation to latitude was assessed in a geographically diverse population of women enrolled in two large prospective studies in the USA.
Recent drug approvals have increased the availability of biologic therapies for inflammatory bowel disease (IBD), making it difficult for patients with ulcerative colitis (UC) and Crohn’s disease (CD) to navigate treatment options. Here we developed a conjoint analysis to examine patient decision-making surrounding biologic medicines for IBD. We used the results to create an online patient decision aid that generates a unique “preferences report” for each patient to assist with shared decision-making with their provider.
Breastfeeding is a modifiable factor that may influence development of inflammatory bowel diseases. However, literature on this has been inconsistent and not accounted for heterogeneity in populations and exposure.
Genome-wide association studies (GWAS) have identified 200 inflammatory bowel disease (IBD) loci, but the genetic architecture of Crohn’s disease (CD) and ulcerative colitis (UC) remains incompletely defined. Here we aimed to identify novel associations between IBD and functional genetic variants using the Illumina ExomeChip.
Ulcerative colitis and Crohn’s disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of the IBD risk loci, the direction and magnitude of effect are consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency (NOD2) or effect size (TNFSF15 and ATG16L1) or a combination of these factors (IL23R and IRGM). Our results provide biological insights into the pathogenesis of IBD and demonstrate the usefulness of trans-ancestry association studies for mapping loci associated with complex diseases and understanding genetic architecture across diverse populations.