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Journal articleGhani R, Mullish BH, Roberts LA, et al., 2022,
Journal articlePowles STR, Gallagher KI, Chong LWL, et al., 2022,
Effects of bowel preparation on intestinal bacterial associated urine and faecal metabolites and the associated faecal microbiome, BMC Gastroenterology, Vol: 22
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Urinary and faecal metabolic profiling have been extensively studied in gastrointestinal diseases as potential diagnostic markers, and to enhance our understanding of the intestinal microbiome in the pathogenesis these conditions. The impact of bowel cleansing on the microbiome has been investigated in several studies, but limited to just one study on the faecal metabolome.</jats:p> </jats:sec><jats:sec> <jats:title>Aim</jats:title> <jats:p>To compare the effects of bowel cleansing on the composition of the faecal microbiome, and the urine and faecal metabolome.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Urine and faecal samples were obtained from eleven patients undergoing colonoscopy at baseline, and then at day 3 and week 6 after colonoscopy. 16S rRNA gene sequencing was used to analyse changes in the microbiome, and metabonomic analysis was performed using proton nuclear magnetic resonance (<jats:sup>1</jats:sup>H NMR) spectroscopy.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Microbiomic analysis demonstrated a reduction in alpha diversity (Shannon index) between samples taken at baseline and three days following bowel cleansing (<jats:italic>p</jats:italic> = 0.002), and there was no significant difference between samples at baseline and six weeks post colonoscopy. Targeted and non-targeted analysis of urinary and faecal bacterial associated metabolites showed no significant impact following bowel cleansing.</jats:p> </jats:sec><jats:sec>
Journal articleIaniro G, Mullish BH, Iqbal TH, et al., 2022,
Journal articleLythgoe MP, Mullish BH, Frampton AE, et al., 2022,
Journal articleHewitt RJ, Bartlett EC, Ganatra R, et al., 2022,
Journal articleForlano R, Sivakumar M, Mullish BH, et al., 2022,
Gut microbiota—a future therapeutic target for people with non-alcoholic fatty liver disease: a systematic review, International Journal of Molecular Sciences, Vol: 23, Pages: 1-13, ISSN: 1422-0067
Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease, affecting one-third of the population worldwide. Despite many medications being in the pipeline to treat the condition, there is still no pharmaceutical agent licensed to treat the disease. As intestinal bacteria play a crucial role in the pathogenesis and progression of liver damage in patients with NAFLD, it has been suggested that manipulating the microbiome may represent a therapeutical option. In this review, we summarise the latest evidence supporting the manipulation of the intestinal microbiome as a potential therapy for treating liver disease in patients with NAFLD.
Journal articleMullish BH, McDonald JAK, Marchesi JR, 2022,
Journal articleMolyneaux PL, Fahy WA, Byrne AJ, et al., 2022,
OBJECTIVES: Idiopathic pulmonary fibrosis (IPF) is a progressive and inevitably fatal condition for which there are a lack of effective biomarkers to guide therapeutic decision making. RATIONALE: To determine the relationship between serum levels of the cytokeratin fragment CYFRA 21-1 and disease progression and mortality in individuals with IPF enrolled in the PROFILE study. METHODS: CYFRA 21-1 was identified by immunohistochemistry in samples of human lung. Concentrations of CYFRA 21-1 were measured using an Elisa-based assay in serum, collected at baseline, 1- and 3-months, from 491 individuals with an incident diagnosis of IPF enrolled in the PROFILE study and from 100 control subjects. Study subjects were followed for a minimum of 3 years. MEASUREMENTS AND MAIN RESULTS: CYFRA 21-1 localises to hyperplastic epithelium in IPF lung. CYFRA 21-1 levels were significantly higher in IPF subjects compared to healthy controls in both discovery (n=132) (control 0.96±0.81 ng/mL versus IPF; 2.34±2.15 ng/mL, p < 0.0001) and validation (n=359) (control; 2.21±1.54 ng/mL and IPF; 4.13±2.77 ng/mL, p<0.0001) cohorts. Baseline levels of CYFRA 21-1 distinguished individuals at risk of 12-month disease progression (C-statistic 0.70 (95% CI 0.61-0.79), p < 0.0001) and were predictive of overall-mortality (HR 1.12 (1.06-1.19) per 1 ng/mL increase in CYFRA 21-1, p=0.0001). Furthermore, 3-month change in levels of CYFRA 21-1 separately predicted 12-month and overall survival in both the discovery and validation cohorts. CONCLUSIONS: CYFRA 21-1, a marker of epithelial damage and turnover, has the potential to be an important prognostic and therapeutic biomarker in individuals with IPF.
Journal articleAllen RJ, Stockwell A, Oldham JM, et al., 2022,
Journal articleAlexander JL, Mullish BH, Danckert NP, et al., 2022,
The gut microbiota and metabolome is associated with diminished COVID-19 vaccine-induced antibody responses in immunosuppressed inflammatory bowel disease patients
<jats:title>Abstract</jats:title> <jats:p>Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination. Forty-three infliximab-treated patients with IBD were recruited (30 Crohn’s disease, 12 ulcerative colitis, 1 IBD-unclassified; 26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.021). <jats:italic>Bilophila</jats:italic> abundance was associated with better serological response, while <jats:italic>Streptococcus</jats:italic> was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R<jats:sup>2</jats:sup>X 0.25, R&l
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