Benjamin H. Mullish

Review article: depression and the use of antidepressants in patients with chronic liver disease or liver transplantation

The scale of depression in patients with chronic liver disease (CLD) and those who have received orthotopic liver transplantation (OLT) is poorly characterised. Clinicians are uncertain of how best to manage depression within these patients.

Optimized Sample Handling Strategy for Metabolic Profiling of Human Feces

Fecal metabolites are being increasingly studied to unravel the host-gut microbial metabolic interactions. However, there are currently no guidelines for fecal sample collection and storage based on a systematic evaluation of the effect of time, storage temperature, storage duration, and sampling strategy. Here we derive an optimized protocol for fecal sample handling with the aim of maximizing metabolic stability and minimizing sample degradation. Samples obtained from five healthy individuals were analyzed to assess topographical homogeneity of feces and to evaluate storage duration-, temperature-, and freeze-thaw cycle-induced metabolic changes in crude stool and fecal water using a (1)H NMR spectroscopy-based metabolic profiling approach. Interindividual variation was much greater than that attributable to storage conditions. Individual stool samples were found to be heterogeneous and spot sampling resulted in a high degree of metabolic variation. Crude fecal samples were remarkably unstable over time and exhibited distinct metabolic profiles at different storage temperatures. Microbial fermentation was the dominant driver in time-related changes observed in fecal samples stored at room temperature and this fermentative process was reduced when stored at 4 °C. Crude fecal samples frozen at -20 °C manifested elevated amino acids and nicotinate and depleted short chain fatty acids compared to crude fecal control samples. The relative concentrations of branched-chain and aromatic amino acids significantly increased in the freeze-thawed crude fecal samples, suggesting a release of microbial intracellular contents. The metabolic profiles of fecal water samples were more stable compared to crude samples. Our recommendation is that intact fecal samples should be collected, kept at 4 °C or on ice during transportation, and extracted ideally within 1 h of collection, or a maximum of 24 h. Fecal water samples should be extracted from a representative amount (∼15 g) of homogenized stool sample, aliquoted, and stored at <-20 °C, avoiding further freeze-thaw cycles.

Anticoagulation in chronic liver disease

In this Grand Round presentation, the case of a man with decompensated liver disease is described. He subsequently developed a fatal pulmonary embolism, which may not have occurred if he had been prescribed prophylactic anticoagulation to prevent venous thromboembolic disease. The burden of thrombotic disease in those with chronic liver disease is discussed, before a more detailed analysis of the current evidence, safety data, and clinical dilemmas regarding the use of anticoagulation in patients with chronic liver disease. Finally, the future directions within this field are explored.

National survey of practice of faecal microbiota transplantation for Clostridium difficile infection in the UK

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Microbiome manipulation with faecal microbiome transplantation as a therapeutic strategy in Clostridium difficile infection

Faecal microbiome transplantation (FMT) has generated huge recent interest as it presents a potential solution to a significant clinical problem--the increasing incidence of Clostridium difficile infection (CDI). In the short term, however, there remain many practical questions regarding its use, including the optimal selection of donors, material preparation and the mechanics of delivery. In the longer term, enhanced understanding of the mechanisms of action of FMT may potentiate novel therapies, such as targeted manipulation of the microbiome in CDI and beyond.

Obstacles to establishing an NHS faecal transplant programme.

Having recently established a faecal microbiota transplantation (FMT) programme, we raise two points about Spector and Knight’s editorial on FMT.1 Firstly, despite the UK’s relatively permissive regulatory framework on FMT, we encountered considerable obstacles to establishing an NHS programme. Donor screening is expensive (>£500 (€703;

Faecal microbiota transplant: a novel biological approach to extensively drug-resistant organism-related non-relapse mortality.

755)/screen/donor, repeated regularly). It is unclear …

Functional microbiomics: Evaluation of gut microbiota-bile acid metabolism interactions in health and disease

Faecal microbiota transplant: a novel biological approach to extensively drug-resistant organism-related non-relapse mortality

Meeting update: faecal microbiota transplantation––bench, bedside, courtroom?

There is an ever-increasing recognition that bile acids are not purely simple surfactant molecules that aid in lipid digestion, but are a family of molecules contributing to a diverse range of key systemic functions in the host. It is now also understood that the specific composition of the bile acid milieu within the host is related to the expression and activity of bacterially-derived enzymes within the gastrointestinal tract, as such creating a direct link between the physiology of the host and the gut microbiota. Coupled to the knowledge that perturbation of the structure and/or function of the gut microbiota may contribute to the pathogenesis of a range of diseases, there is a high level of interest in the potential for manipulation of the gut microbiota-host bile acid axis as a novel approach to therapeutics. Much of the growing understanding of the biology of this area reflects the recent development and refinement of a range of novel techniques; this study applies a number of those techniques to the analysis of human samples, aiming to illustrate their strengths, drawbacks and biological significance at all stages. Specifically, we used microbial profiling (using 16S rRNA gene sequencing), bile acid profiling (using liquid chromatography-mass spectrometry), bsh and baiCD qPCR, and a BSH enzyme activity assay to demonstrate differences in the gut microbiota and bile metabolism in stool samples from healthy and antibiotic-exposed individuals.

Letter: improvements in mental health after faecal microbiota transplantation-an underexplored treatment-related benefit?

A group of stakeholders met, under the aegis of the British Society of Gastroenterology, to discuss the current landscape of faecal microbiota transplantation (FMT) within the UK and beyond. The meeting covered a wide range of topics, ranging from the practical aspects of establishing an FMT service and regulatory issues relating to its delivery, to research implications and likely future directions. Case report and case series data supportive of the efficacy of FMT as treatment for recurrent/refractory Clostridium difficile infection (CDI) have slowly accumulated over many decades, but randomised trial data supporting its use for this indication were lacking until as recently as 2013.1 There are now a growing number of randomised studies/trials that have consistently demonstrated the much greater efficacy of FMT than that of vancomycin in inducing remission from recurrent/refractory CDI; success from a single FMT is quoted at ≥80%, and for two FMTs as ≥90%.1 FMT appears to be similarly as efficacious for this indication regardless of whether the transplant is delivered via the upper gastrointestinal (GI)1 or lower GI tract.2 ,3 Based on this clinical evidence (along with data supporting the cost effectiveness of FMT in comparison with other treatment strategies),4 FMT has now been accepted as an appropriate treatment option for recurrent/refractory CDI by the National Institute for Health and Care Excellence,5 Public Health England6 and European guidelines.7 There is increasing recognition that a distinctive pattern of alteration of the structure of the gut microbiota (or ‘dysbiosis’) appears to characterise a number of conditions, including inflammatory bowel disease and metabolic syndrome. Although it remains largely unclear as to whether these microbiota changes are a cause of these conditions, consequence or incidental, there is much interest as to whether manipulation of the gut microbiota might be a …