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

A group of stakeholders met, under the aegis of the British Society of Gastroenterology, to discuss the current landscape of faecal microbiota transplant- ation (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 regu- latory issues relating to its delivery, to research implications and likely future directions

The implementation of omics technologies in cancer microbiome research

Whilst the interplay between host genetics and the environment plays a pivotal role in the aetiopathogenesis of cancer, there are other key contributors of importance as well. One such factor of central and growing interest is the contribution of the microbiota to cancer. Even though the field is only a few years old, investigation of the ‘cancer microbiome’ has already led to major advances in knowledge of the basic biology of cancer risk and progression, opened novel avenues for biomarkers and diagnostics, and given a better understanding of mechanisms underlying response to therapy. Recent developments in microbial DNA sequencing techniques (and the bioinformatics required for analysis of these datasets) have allowed much more in-depth profiling of the structure of microbial communities than was previously possible. However, for more complete assessment of the functional implications of microbial changes, there is a growing recognition of the importance of the integration of microbial profiling with other omics modalities, with metabonomics (metabolite profiling) and proteomics (protein profiling) both gaining particular recent attention. In this review, we give an overview of some of the key scientific techniques being used to unravel the role of the cancer microbiome. We have aimed to highlight practical aspects related to sample collection and preparation, choice of the modality of analysis, and examples of where different omics technologies have been complementary to each other to highlight the significance of the cancer microbiome

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

The role of bile-metabolising enzymes in the pathogenesis of Clostridioides difficile infection, and the impact of faecal microbiota transplantation

The pathogenesis of Clostridioides difficile infection (CDI), and mechanisms of efficacy of faecal microbiota transplant (FMT) in treating recurrent CDI (rCDI), remain poorly-understood. Certain bile acids affect the ability of C. difficile to undergo germination or vegetative growth. Loss of gut microbiota-derived bile-metabolising enzymes may predispose to CDI via perturbation of bile metabolism, and restitution of gut bile-metabolising functionality could mediate FMT’s efficacy. Initially, human samples were analysed, i.e.: 1) biofluids collected from rCDI patients pre- and post-FMT (and their donors), and 2) stool samples from primary CDI patients, including both recurrers and non-recurrers. Analysis included: 16S rRNA gene sequencing; liquid chromatography-mass spectrometry for bile acid profiling; gas chromatography-mass spectrometry for short chain fatty acid (SCFA) quantification; bile salt hydrolase (BSH) enzyme activity; and qPCR of bsh/ baiCD genes involved in bile metabolism. Human results were validated in C. difficile batch cultures and a rCDI mouse model. A reduced proportion of the stool microbiota of rCDI patients pre-FMT contained BSH-producing bacteria compared to donors or post-FMT. Pre-FMT stool was enriched in taurocholic acid (TCA; a potent trigger to C. difficile germination); TCA levels negatively correlated with bacterial genera containing BSH-producing organisms. Post-FMT stool demonstrated recovered BSH activity and microbial bsh/ baiCD gene copy number compared with pre-treatment (p<0.05), and recovery of SCFA including valerate (p<0.001). Dynamics of stool bile acids/ BSH activity differed in primary CDI patients with and without disease recurrence. In batch cultures, culture supernatant from engineered bsh-expressing E. coli reduced TCA-mediated C. difficile germination relative to supernatant from BSH-negative E. coli. C. difficile total viable counts were ~70% reduced in a rCDI mouse model after administration of BSH-expressing E. coli relative to mice receiving BSH-negative E. coli (p<0.05). These data demonstrate that gut microbiota BSH functionality is a key mechanism influencing vulnerability to CDI and efficacy of FMT.Open Acces

Grand round: anticoagulation in chronic liver disease

In this Grand Round, we first present a case of a man with decompensated liver disease who subsequently developed a fatal pulmonary embolism, having not been prescribed prophylactic anticoagulation to prevent venous thromboembolic disease. We go on to discuss the burden of thrombotic disease in those with chronic liver disease, before a more detailed discussion regarding the current evidence, safety data, and clinical dilemmas regarding the use of anticoagulation in patients with chronic liver disease, as well as discussing potential future directions within this field

Letter: Intestinal microbiota transfer – Updating the nomenclature to increase acceptability

This article is linked to Lai et al paper. To view this article, visit https://doi.org/10.1111/apt.1511