Biology subjects

Sanderson, J. D.

Publications and source records attributed to Sanderson, J. D..

4 recordsLinked to original sources

bioRxiv2018

Streptococcus salivarius - a potential salivary biomarker for orofacial granulomatosis and Crohn’s disease?

ObjectiveOrofacial granulomatosis (OFG) is a rare disease characterised by chronic, non-caseating, granulomatous inflammation primarily affecting the oral cavity. Histologically, it is similar to Crohns disease (CD) and a proportion of patients have both OFG and CD. The cause of OFG remains elusive but it has been suggested that microbial interactions may be involved. The aim of this study was to compare the salivary microbial composition of subjects with OFG and/or CD and healthy controls.\n\nDesign261 subjects were recruited, of whom 78 had OFG only, 40 had both OFG and CD, 97 had CD only with no oral symptoms and 46 were healthy controls. Bacterial community profiles were obtained by sequencing the V1-V3 region of the 16S rRNA gene.\n\nResultsThere were no differences in richness or diversity of the salivary bacterial communities between patient groups and controls. The relative abundance of the Streptococcus salivarius-group were raised in patients with OFG or CD only compared to controls while that of the Streptococcus mitis -group was lower in CD compared to both OFG and controls. One S. salivarius oligotype made the major contribution to the increased proportions seen in patients with OFG and CD.\n\nConclusionThe salivary microbiome of individuals with OFG and CD was similar to that found in health although the proportions of S. salivarius, a common oral Streptococcus were raised. One specific strain-level oligotype was found to be primarily responsible for the increased levels seen.

microbiology↗

bioRxiv2017

Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota

BACKGROUNDThe dietary methylamines choline, carnitine and phosphatidylcholine are used by the gut microbiota to produce a range of metabolites, including trimethylamine (TMA). However, little is known about the use of trimethylamine N-oxide (TMAO) by this consortium of microbes.\n\nRESULTSA feeding study using deuterated TMAO in C57BL6/J mice demonstrated microbial conversion of TMAO to TMA, with uptake of TMA into the bloodstream and its conversion to TMAO. Microbial activity necessary to convert TMAO to TMA was suppressed in antibiotic-treated mice, with deuterated TMAO being taken up directly into the bloodstream. In batch-culture fermentation systems inoculated with human faeces, growth of Enterobacteriaceae was stimulated in the presence of TMAO. Human-derived faecal and caecal bacteria (n = 66 isolates) were screened on solid and liquid media for their ability to use TMAO, with metabolites in spent media analysed by 1H-NMR. As with the in vitro fermentation experiments, TMAO stimulated the growth of Enterobacteriaceae; these bacteria produced most TMA from TMAO. Caecal/small intestinal isolates of Escherichia coli produced more TMA from TMAO than their faecal counterparts. Lactic acid bacteria produced increased amounts of lactate when grown in the presence of TMAO, but did not produce large amounts of TMA. Clostridia (sensu stricto), bifidobacteria and coriobacteria were significantly correlated with TMA production in the mixed fermentation system but did not produce notable quantities of TMA from TMAO in pure culture.\n\nCONCLUSIONSReduction of TMAO by the gut microbiota (predominantly Enterobacteriaceae) to TMA followed by host uptake of TMA into the bloodstream from the intestine and its conversion back to TMAO by host hepatic enzymes is an example of metabolic retroconversion. TMAO influences microbial metabolism depending on isolation source and taxon of gut bacterium.\n\nCorrelation of metabolomic and abundance data from mixed microbiota fermentation systems did not give a true picture of which members of the gut microbiota were responsible for converting TMAO to TMA; only by supplementing the study with pure culture work and additional metabolomics was it possible to increase our understanding of TMAO bioconversions by the human gut microbiota.

microbiology↗

bioRxiv2017

Exome sequencing and genotyping identify a rare variant in NLRP7 gene associated with ulcerative colitis.

Background and aimsAlthough genome-wide association studies (GWAS) in inflammatory bowel disease (IBD) have identified a large number of common disease susceptibility alleles for both Crohns disease (CD) and ulcerative colitis (UC), a substantial fraction of IBD heritability remains unexplained, suggesting that rare coding genetic variants may also have a role in pathogenesis. We used high-throughput sequencing in families with multiple cases of IBD, followed by genotyping of cases and controls, to investigate whether rare protein altering genetic variants are associated with susceptibility to IBD.\n\nMethodsWhole exome sequencing was carried out in 10 families in which 3 or more individuals were affected with IBD. A stepwise filtering approach was applied to exome variants to identify potential causal variants. Follow-up genotyping was performed in 6,025 IBD cases (2,948 CD; 3,077 UC) and 7,238 controls.\n\nResultsOur exome variant analysis revealed coding variants in the NLRP7 gene that were present in affected individuals in two distinct families. Genotyping of the two variants, p.S361L and p.R801H, in IBD cases and controls showed that the p.S361L variant was significantly associated with an increased risk of ulcerative colitis (odds ratio 4.79, p=0.0039) and IBD (odds ratio 3.17, p=0.037). A combined analysis of both variants showed suggestive association with an increased risk of IBD (odds ratio 2.77, p=0.018).\n\nConclusionsThe results suggest that NLRP7 signalling and inflammasome formation may be a significant component in the pathogenesis of IBD.

genetics↗

bioRxiv2017

Predictors of intestinal inflammation in asymptomatic first-degree relatives of patients with Crohn’s disease

ObjectiveRelatives of individuals with Crohns disease (CD) carry an increased number of CD-associated genetic variants and are at increased risk of developing the disease. Multiple environmental and genetic factors contribute to this increased risk. We aimed to estimate the utility of genotype, smoking, family history, and a panel of biomarkers to predict risk in asymptomatic first-degree relatives (FDRs) of CD patients.\n\nDesignWe calculated a combined genotype (72 CD-associated genetic markers) and smoking relative risk score in 454 FDRs, and performed capsule endoscopy and collected 22 biomarkers in individuals from the highest and lowest risk quartiles. We then predicted small intestinal inflammation using genetic risk score, smoking status, number of relatives with CD, capsule transit time, and the panel of biomarkers in 124 individuals with complete data. Our principal analysis was to calculate the predictive utility from two machine learning classifiers: an elastic net and a random forest.\n\nResultsBoth classifiers successfully predicted FDRs with intestinal inflammation: elastic net (AUC=0.80, 95% CI: 0.62-0.98), random forest (AUC=0.87, 95% CI: 0.75-1.00). The elastic net selected a 3-predictor solution: CD family history (OR=1.31), genetic risk score (OR=1.14), and faecal calprotectin (OR=1.04). The same 3 variables were among the top 5 most important predictors as ranked by the random forest.\n\nConclusionA readily collectable panel of genetic risk variants, added to family history and faecal calprotectin, predicts those at greatest risk for developing CD with a good degree of accuracy.

epidemiology↗