Over the last 10–15 years, our understanding of the composition and functions of the human gut microbiota has increased exponentially. To a large extent, this has been due to new ‘omic’ technologies that have facilitated large-scale analysis of the genetic and metabolic profile of this microbial community, revealing it to be comparable in influence to a new organ in the body and offering the possibility of a new route for therapeutic intervention. Moreover, it might be more accurate to think of it like an immune system: a collection of cells that work in unison with the host and that can promote health but sometimes initiate disease. This review gives an update on the current knowledge in the area of gut disorders, in particular metabolic syndrome and obesity-related disease, liver disease, IBD and colorectal cancer. The potential of manipulating the gut microbiota in these disorders is assessed, with an examination of the latest and most relevant evidence relating to antibiotics, probiotics, prebiotics, polyphenols and faecal microbiota transplantation.
Faecal microbiota transplantation is an effective treatment for recurrent and refractory Clostridium difficile infection, independent of preparation and route of delivery.
Interest in the therapeutic potential of faecal microbiota transplant (FMT) has been increasing globally in recent years, particularly as a result of randomised studies in which it has been used as an intervention. The main focus of these studies has been the treatment of recurrent or refractory infection (CDI), but there is also an emerging evidence base regarding potential applications in non-CDI settings. The key clinical stakeholders for the provision and governance of FMT services in the UK have tended to be in two major specialty areas: gastroenterology and microbiology/infectious diseases. While the National Institute for Health and Care Excellence (NICE) guidance (2014) for use of FMT for recurrent or refractory CDI has become accepted in the UK, clear evidence-based UK guidelines for FMT have been lacking. This resulted in discussions between the British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS), and a joint BSG/HIS FMT working group was established. This guideline document is the culmination of that joint dialogue.
The Editors of the Journals have agreed that joint publication of the article is justified to ensure dissemination of the guidance to all relevant healthcare professionals.
The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.
Background
Although a majority of patients with PSC have colitis [PSC-IBD; primary sclerosing cholangitis-inflammatory bowel disease], this is phenotypically different from ulcerative colitis [UC]. We sought to define further the pathophysiological differences between PSC-IBD and UC, by applying a comparative and integrative approach to colonic gene expression, gut microbiota and immune infiltration data.
Methods
Colonic biopsies were collected from patients with PSC-IBD [n = 10], UC [n = 10], and healthy controls [HC; n = 10]. Shotgun RNA-sequencing for differentially expressed colonic mucosal genes [DEGs], 16S rRNA analysis for microbial profiling, and immunophenotyping were performed followed by multi-omic integration.
Results
The colonic transcriptome differed significantly between groups [p = 0.01]. Colonic transcriptomes from HC were different from both UC [1343 DEGs] and PSC-IBD [4312 DEGs]. Of these genes, only 939 had shared differential gene expression in both UC and PSC-IBD compared with HC. Imputed pathways were predominantly associated with upregulation of immune response and microbial defense in both disease cohorts compared with HC. There were 1692 DEGs between PSC-IBD and UC. Bile acid signalling pathways were upregulated in PSC-IBD compared with UC [p = 0.02]. Microbiota profiles were different between the three groups [p = 0.01]; with inferred function in PSC-IBD also being consistent with dysregulation of bile acid metabolism. Th17 cells and IL17-producing CD4 cells were increased in both PSC-IBD and UC when compared with HC [p < 0.05]. Multi-omic integration revealed networks involved in bile acid homeostasis and cancer regulation in PSC-IBD.
Conclusions
Colonic transcriptomic and microbiota analysis in PSC-IBD point toward dysregulation of colonic bile acid homeostasis compared with UC. This highlights important mechanisms and suggests the possibility of novel approaches in treating PSC-IBD.
The aetiopathogenesis of inflammatory bowel diseases (IBD) involves the complex interaction between a patient’s genetic predisposition, environment, gut microbiota and immune system. Currently, however, it is not known if the distinctive perturbations of the gut microbiota that appear to accompany both Crohn’s disease and ulcerative colitis are the cause of, or the result of, the intestinal inflammation that characterizes IBD.With the utilization of novel systems biology technologies, we can now begin to understand not only details about compositional changes in the gut microbiota in IBD, but increasingly also the alterations in microbiota function that accompany these. Technologies such as metagenomics, metataxomics, metatranscriptomics, metaproteomics and metabonomics are therefore allowing us a deeper understanding of the role of the microbiota in IBD. Furthermore, the integration of these systems biology technologies through advancing computational and statistical techniques are beginning to understand the microbiome interactions that both contribute to health and diseased states in IBD.This review aims to explore how such systems biology technologies are advancing our understanding of the gut microbiota, and their potential role in delineating the aetiology, development and clinical care of IBD.
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