Browsing by Author "Hunter, John O."

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    Analysis of volatile organic compounds of bacterial origin in chronic gastrointestinal diseases
    (Wiley, 2013-07-17) Walton, Christopher; Fowler, Dawn P.; Turner, Claire; Jia, W.; Whitehead, Rebekah N.; Griffiths, Lesley; Dawson, Claire; Waring, Rosemary H.; Ramsden, David B.; Cole, Jeffrey A.; Cauchi, Michael; Bessant, Conrad M.; Hunter, John O.
    BACKGROUND: The aim of this study was to determine whether volatile organic compounds (VOCs) present in the headspace of feces could be used to diagnose or distinguish between chronic diseases of the gastrointestinal tract and apparently healthy volunteers. METHODS: A total of 87 people were recruited, divided between 4 categories: healthy volunteers (n = 19), Crohn's disease (n = 22), ulcerative colitis (n = 20), and irritable bowel syndrome (n = 26). They each supplied fecal samples before, and except for the healthy volunteers, after treatment. Fecal samples were incubated in a sample bag with added purified air at 40°C and headspace samples were taken and concentrated on thermal sorption tubes. Gas chromatography-mass spectrometry then desorbed and analyzed these. The concentrations of a selection of high-abundance compounds were determined and assessed for differences in concentration between the groups. RESULTS: Crohn's disease samples showed significant elevations in the concentrations of ester and alcohol derivates of short-chain fatty acids and indole compared with the other groups; indole and phenol were elevated in ulcerative colitis and irritable bowel syndrome but not at a statistically significant level. After treatment, the levels of many of the VOCs were significantly reduced and were more similar to those concentrations in healthy controls. CONCLUSIONS: The abundance of a number of VOCs in feces differs markedly between Crohn's disease and other gastrointestinal conditions. Following treatment, the VOC profile is altered to more closely resemble that of healthy volunteers.
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    Diversity and distribution of sulphate-reducing bacteria in human faeces from healthy subjects and patients with inflammatory bowel disease
    (2012-06-01T00:00:00Z) Jia, Wenjing; Whitehead, Rebekah N.; Griffiths, Lesley; Dawson, Claire; Bai, Hao; Waring, Rosemary H.; Ramsden, David B.; Hunter, John O.; Cauchi, Michael; Bessant, Conrad M.; Fowler, Dawn P.; Walton, Christopher; Turner, Claire; Cole, Jeffrey A.
    The relative abundance of different groups of sulphate-reducing bacteria (SRB) in faecal DNA collected before and after therapy from patients suffering from Crohn's disease (CD), irritable bowel syndrome (IBS) or ulcerative colitis (UC) has been compared with that from healthy controls. Growth tests revealed that SRB were not more abundant in samples from patients with CD before treatment than in the healthy control group. For most of the 128 samples available, these preliminary results were confirmed using degenerate PCR primers that amplify the dsrAB gene. However, some samples from patients with CD before treatment contained a growth inhibitor that was absent from IBS or UC samples. In-depth sequencing of PCR-generated dsrB fragments revealed that the diversity detected was surprisingly low, with only eight strains of SRB and the sulphite-reducing bacterium, Bilophila wadsworthia, detected above the 0.1% threshold. The proportion of the two major species detected, B.wadsworthia and Desulfovibrio piger, was as high as 93.5% of the total SRB population in the healthy control group and lower in all patient groups. Four previously undescribed species were found: it is impossible to predict whether they are sulphate or sulphite-reducing bacteria.
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    Enteral feeding reduces metabolic activity of the intestinal microbiome in Crohn’s disease: an observational study
    (Nature Publishing Group, 2016-05-11) Walton, Christopher; Montoya, M. P. B.; Fowler, Dawn P.; Turner, Claire; Jia, W.; Whitehead, Rebekah N.; Griffiths, Lesley; Waring, Rosemary H.; Ramsden, David B.; Cole, Jeffrey A.; Cauchi, Michael; Bessant, Conrad M.; Naylor, J.; Hunter, John O.
    BACKGROUND/OBJECTIVES: Enteral feeding will induce remission in as many as 80–90% of compliant patients with active Crohn’s disease (CD), but its method of action remains uncertain. This study was designed to examine its effects on the colonic microbiome. METHODS/SUBJECTS: Healthy volunteers and patients with CD followed a regimen confined to enteral feeds alone for 1 or 2 weeks, respectively. Chemicals excreted on breath or in faeces were characterised at the start and at the end of the feeding period by gas chromatography/mass spectrometry. RESULTS: One week of feeding in healthy volunteers caused significant changes in stool colour and deterioration in breath odour, together with increased excretion of phenol and indoles on the breath. Feeding for 2 weeks in patients with CD produced significant improvements in symptoms and a decrease in the concentration of C-reactive protein. The faecal concentrations of microbial products, including short-chain fatty acids (SCFAs), and potentially toxic substances, including 1-propanol, 1-butanol and the methyl and ethyl esters of SCFAs, showed significant falls. CONCLUSIONS: A significant change occurs in the production of microbial metabolites after enteral feeding in both healthy volunteers and patients with CD. Many of those detected in CD are toxic and may feasibly lead to the immunological attack on the gut microbiota, which is characteristic of inflammatory bowel disease. The reduction in the production of such metabolites after enteral feeding may be the reason for its effectiveness in CD.
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    An investigation into the effects of bacterial fermentation in autism
    (2006-11) Bilbao Montoya, Maria Pilar; Ritchie, Laurie; Hunter, John O.
    Gastrointestinal symptoms have been observed to be present very often in autistic children. These symptoms are very similar to those observed in Irritable Bowel Syndrome (IBS). An investigation to investigate whether there is a similar cause for autism as well as IBS was done. Methods for the analysis of breath VOCs and urine organic acids were developed to be applied afterwards in the research of biomarkers of autism and IBS. Bacterial metabolites in urine and breath were identified by restricting the diets of healthy volunteers to each of two enteral feeds. The way enteral feeds work in the treatment of Crohn’s disease (CD) was investigated. Enteral feeds work by reducing bacterial activity in the gut, measurably reducing their metabolic products. The urine of IBS patients was analysed and bacterial compounds investigated. Some gastrointestinal symptoms are frequently misdiagnosed as IBS. According to the symptoms and treatment that is successful for these different groups of patients three subgroups can be made: “retention and overflow”, “musculoskeletal” and “abnormal fermentation” IBS. When the urine of these subgroups was observed, different biomarkers for the various subgroups could be identified. Patients with abnormal fermentation IBS have increased bacterial products in urine, suggesting an increase in bacterial activity in the colon. These biomarkers decreased after an exclusion or fibre-free diet and symptoms improved. In a further study, potential biomarkers for autism were identified. The origin of the majority of these compounds is unknown, although some of them are of known bacterial origin. A conclusion of this is that autistic children may exhibit abnormal fermentation since GI symptoms manifest at almost the same time as the autistic behavioural symptoms start and may be present from birth. Autistic children share many symptoms with IBS patients, although the biomarkers are different, showing that the GI symptoms observed in autistic children are not IBS in the children studied. More research needs to be done to determine the origin of the autism biomarkers discovered in urine.
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    Use of the analysis of the volatile faecal metabolome in screening for colorectal cancer
    (PLOS (Public Library of Science), 2015-06-18) Batty, Claire A.; Cauchi, Michael; Lourenço, Célia; Hunter, John O.; Turner, Claire
    Diagnosis of colorectal cancer is an invasive and expensive colonoscopy, which is usually carried out after a positive screening test. Unfortunately, existing screening tests lack specificity and sensitivity, hence many unnecessary colonoscopies are performed. Here we report on a potential new screening test for colorectal cancer based on the analysis of volatile organic compounds (VOCs) in the headspace of faecal samples. Faecal samples were obtained from subjects who had a positive faecal occult blood sample (FOBT). Subjects subsequently had colonoscopies performed to classify them into low risk (non-cancer) and high risk (colorectal cancer) groups. Volatile organic compounds were analysed by selected ion flow tube mass spectrometry (SIFT-MS) and then data were analysed using both univariate and multivariate statistical methods. Ions most likely from hydrogen sulphide, dimethyl sulphide and dimethyl disulphide are statistically significantly higher in samples from high risk rather than low risk subjects. Results using multivariate methods show that the test gives a correct classification of 75% with 78% specificity and 72% sensitivity on FOBT positive samples, offering a potentially effective alternative to FOBT.