Using Volatile Organic Compounds to Investigate the Effect of Oral Iron Supplementation on the Human Intestinal Metabolome

Patients with iron deficiency anaemia are treated with oral iron supplementation, which is known to cause gastrointestinal side effects by likely interacting with the gut microbiome. To better study this impact on the microbiome, we investigated oral iron-driven changes in volatile organic compounds (VOCs) in the faecal metabolome. Stool samples from patients with iron deficiency anaemia were collected pre- and post-treatment (n = 45 and 32, respectively). Faecal headspace gas analysis was performed by gas chromatography–mass spectrometry and the changes in VOCs determined. We found that the abundance of short-chain fatty acids and esters fell, while aldehydes increased, after treatment. These changes in pre- vs. post-iron VOCs resemble those reported when the gut is inflamed. Our study shows that iron changes the intestinal metabolome, we suggest by altering the structure of the gut microbial community

Faecal and urine metabolites, but not gut microbiota, may predict response to low FODMAP diet in irritable bowel syndrome

BackgroundThe low FODMAP diet (LFD) leads to clinical response in 50%-80% of patients with irritable bowel syndrome (IBS). It is unclear why only some patients respond.AimsTo determine if differences in baseline faecal microbiota or faecal and urine metabolite profiles may separate clinical responders to the diet from non-responders allowing predictive algorithms to be proposed.MethodsWe recruited adults fulfilling Rome III criteria for IBS to a blinded randomised controlled trial. Patients were randomised to sham diet with a placebo supplement (control) or LFD supplemented with either placebo (LFD) or 1.8 g/d B-galactooligosaccharide (LFD/B-GOS), for 4 weeks. Clinical response was defined as adequate symptom relief at 4 weeks after the intervention (global symptom question). Differences between responders and non-responders in faecal microbiota (FISH, 16S rRNA sequencing) and faecal (gas-liquid chromatography, gas-chromatography mass-spectrometry) and urine (1 H NMR) metabolites were analysed.ResultsAt 4 weeks, clinical response differed across the 3groups with adequate symptom relief of 30% (7/23) in controls, 50% (11/22) in the LFD group and 67% (16/24) in the LFD/B-GOS group (p = 0.048). In the control and the LFD/B-GOS groups, microbiota and metabolites did not separate responders from non-responders. In the LFD group, higher baseline faecal propionate (sensitivity 91%, specificity 89%) and cyclohexanecarboxylic acid esters (sensitivity 80%, specificity 78%), and urine metabolite profile (Q2 0.296 vs. randomised -0.175) predicted clinical response.ConclusionsBaseline faecal and urine metabolites may predict response to the LFD

Visualising Viruses

Viruses pose a challenge to our imaginations. They exert a highly visible influence on the world in which we live, but operate at scales we cannot directly perceive and without a clear separation between their own biology and that of their hosts. Communication about viruses is therefore typically grounded in mental images of the virus particles that transmit viral genomes from one host cell to the next. Virus particles are an important entry point in discussing viruses. The ability to form them is characteristic of all viruses. They can, as the infectious stage of the viral replication cycle, be used to explain many directly observable properties of transmission, infection and immunity. Finally, and importantly, virus particles are often strikingly beautiful and can stimulate further interest in viruses. The structures of some virus particles have been determined experimentally in great detail, but for many important viruses a detailed description of the virus particle is lacking. This can be because they are challenging to describe with a single experimental method, or simply because of a lack of data. In these cases, methods from medical illustration can be applied to produce detailed visualisations of virus particles which integrate information from multiple sources. Here, we demonstrate how this approach was used to visualise the highly variable virus particles of influenza A viruses and, in the early months of the COVID-19 pandemic, the virus particles of the then newly-characterised and poorly described SARS-CoV-2. We show how constructing integrative illustrations of virus particles can challenge our thinking about the biology of viruses as well as providing tools for science communication, and we provide a set of science communication resources to help in visualising two viruses whose effects are extremely apparent to all of us

Faecal volatile organic compounds differ according to inflammatory bowel disease sub-type, severity, and response to treatment in paediatric patients.

Background Faecal volatile organic compounds (VOCs) differ with disease sub-type and activity in adults with established inflammatory bowel disease (IBD) taking therapy. Objective To describe patterns of faecal VOCs in children newly presented with IBD according to disease sub-type, severity, and response to treatment. Methods Children presenting with suspected IBD were recruited from three UK hospitals. Children in whom IBD was diagnosed were matched with a non-IBD child for age, sex, and recruitment site. Faecal VOCs were characterised by gas chromatography–mass spectrometry at presentation and 3 months later in children with IBD. Results In 132 case/control pairs, median (inter-quartile range) age in IBD was 13.3 years (10.2–14.7) and 38.6% were female. Compared with controls, the mean abundance of 27/62 (43.6%) faecal VOCs was statistically significantly decreased in Crohn's disease (CD), ulcerative colitis (UC) or both especially amongst ketones/diketones, fatty acids, and alcohols (p < 0.05). Short-chain, medium chain, and branched chain fatty acids were markedly reduced in severe colitis (p < 0.05). Despite clinical improvement in many children with IBD, the number and abundance of almost all VOCs did not increase following treatment, suggesting persistent dysbiosis. Oct-1-en-3-ol was increased in CD (p = 0.001) and UC (p = 0.012) compared with controls and decreased following treatment in UC (p = 0.01). In CD, propan-1-ol was significantly greater than controls (p < 0.001) and extensive colitis (p = 0.001) and fell with treatment (p = 0.05). Phenol was significantly greater in CD (p < 0.001) and fell with treatment in both CD (p = 0.02) and UC (p = 0.01). Conclusion Characterisation of faecal VOCs in an inception cohort of children with IBD reveals patterns associated with diagnosis, disease activity, and extent. Further work should investigate the relationship between VOCs and the microbiome in IBD and their role in diagnosis and disease monitoring

Characterisation of retroviruses in the horse genome and their transcriptional activity via transcriptome sequencing

The recently released draft horse genome is incompletely characterised in terms of its repetitive element profile. This paper presents characterisation of the endogenous retrovirus (ERVs) of the horse genome based on a data-mining strategy using murine leukaemia virus proteins as queries. 978 ERV gene sequences were identified. Sequences were identified from the gamma, epsilon and betaretrovirus genera. At least one full length gammaretroviral locus was identified, though the gammaretroviral sequences are very degenerate. Using these data the RNA expression of these ERVs were derived from RNA transcriptome data from a variety of equine tissues. Unlike the well studied human and murine ERVs there do not appear to be particular phylogenetic groups of equine ERVs that are more transcriptionally active. Using this novel approach provided a more technically feasible method to characterise ERV expression than previous studies

Inter-kingdom relationships in Crohn’s disease explored using a multi-omics approach

The etiology of Crohn’s disease (CD) is multifactorial. Bacterial and fungal microbiota are involved in the onset and/or progression of the disease. A bacterial dysbiosis in CD patients is accepted; however, less is known about the mycobiome and the relationships between the two communities. We investigated the interkingdom relationships, their metabolic consequences, and the changes in the fungal community during relapse and remission in CD. Two cohorts were evaluated: a British cohort (n = 63) comprising CD and ulcerative colitis patients, and controls. The fungal and bacterial communities of biopsy and fecal samples were analyzed, with the fecal volatiles; datasets were also integrated; and a Dutch cohort (n = 41) comprising CD patients and healthy controls was analyzed for stability of the gut mycobiome. A dysbiosis of the bacterial community was observed in biopsies and stool. Results suggest Bacteroides is likely key in CD and may modulate Candida colonization. A dysbiosis of the fungal community was observed only in the Dutch cohort; Malassezia and Candida were increased in patients taking immunosuppressants. Longitudinal analysis showed an increase in Cyberlindnera in relapse. Saccharomyces was dominant in all fecal samples, but not in biopsies, some of which did not yield fungal reads; amino acid degradation was the main metabolic change associated with CD and both bacteria and fungi might be implicated. We have shown that Bacteroides and yeasts may play a role in CD; understanding their role and relationship in the disease would shed new light on the development and treatment of CD