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.
Aim
Pouchitis is a clinically significant complication of ileal pouch–anal anastomosis with its prevalence varying in the literature. Pouchitis is thought to occur more commonly in patients with ...ulcerative colitis (UC) than in patients with familial adenomatous polyposis (FAP). We conducted a systematic review with meta‐analysis of all published literature to report the prevalence of pouchitis in all pouch patients as well as specifically in UC and FAP. We also investigated the prevalence of acute and chronic pouchitis in UC and FAP.
Methods
A meta‐analysis was conducted by searching the Embase, Embase Classic and PubMed databases between 1978 and 2021 exploring the prevalence of pouchitis in UC and FAP. We then performed a random effects model in order to find the pooled prevalence of pouchitis and used odds ratios to report differences in the prevalence of pouchitis in UC and FAP.
Results
Fifty‐nine full papers and conference s were included in the meta‐analysis comprising 18 117 patients with UC and 860 with FAP. The prevalence of pouchitis in UC was 0.32 (95% CI 0.27–0.37) and in FAP was found to be 0.06 (95% CI 0.03–0.15). The odds ratio of pouchitis in UC patients compared with FAP patients was 4.95 (95% CI 3.17–7.72, P < 0.0001).
Conclusions
Our findings support the consensus that the prevalence of pouchitis is higher in UC than in FAP. More significantly our findings suggest that the true prevalence of pouchitis is higher than commonly reported in the literature. This literature may help counsel patients prior to undergoing restorative proctocolectomy.
Bile acid diarrhoea (BAD) is a common disorder that results from an increased loss of primary bile acids and can result in a change in microbiome. The aims of this study were to characterise the ...microbiome in different cohorts of patients with BAD and to determine if treatment with a bile acid sequestrant, colesevelam, can alter the microbiome and improve microbial diversity.
Patients with symptoms of diarrhoea underwent 75-selenium homocholic acid (
SeHCAT) testing and were categorised into four cohorts: idiopathic BAD, post-cholecystectomy BAD, post-operative Crohn's disease BAD and
SeHCAT negative control group. Patients with a positive
SeHCAT (<15%) were given a trial of treatment with colesevelam. Stool samples were collected pre-treatment, 4-weeks, 8-weeks and 6-12 months post-treatment. Faecal 16S ribosomal RNA gene analysis was undertaken.
A total of 257 samples were analysed from 134 patients. α-diversity was significantly reduced in patients with BAD and more specifically, in the idiopathic BAD cohort and in patients with severe disease (SeHCAT <5%);
< 0.05. Colesevelam did not alter bacterial α/β-diversity but patients who clinically responded to treatment had a significantly greater abundance of
and
, both of which aid in the conversion of primary to secondary bile acids.
This is the first study to examine treatment effects on the microbiome in BAD, which demonstrated a possible association with colesevelam on the microbiome through bile acid modulation in clinical responders. Larger studies are now needed to establish a causal relationship with colesevelam and the inter-crosstalk between bile acids and the microbiome.
Electronic virtual chromoendoscopy (EVC) can demonstrate ongoing disease activity in ulcerative colitis (UC), even when Mayo subscores suggest healing. However, applicability of EVC technology ...outside the expert setting has yet to be determined.
Fifteen participants across 5 centers reviewed a computerized training module outlining high-definition and EVC (iScan) colonoscopy modes. Interobserver agreement was then tested (Mayo score, Ulcerative Colitis Endoscopic Index of Severity UCEIS, and the Paddington International Virtual Chromoendoscopy Score PICaSSO for UC), using a colonoscopy video library (30 cases reviewed pretraining and 30 post-training). Knowledge sustainability was retested in a second round (42 cases; 9/15 participants), 6 months after training provision.
Pretraining intraclass correlation coefficients (ICC) were good for the Mayo endoscopic subscore (ICC, .775), UCEIS scoring erosions/ulcers (ICC, .770), and UCEIS overall (ICC, .786) and for mucosal (ICC, .754) and vascular components of PICaSSO (ICC, .622). For the vascular components of UCEIS, agreement was only moderate (ICC, .429) and did not enhance post-training (ICC, .417); conversely, use of PICaSSO improved post-training (mucosal ICC, .848; vascular, .746). Histologic correlation using the New York Mt. Sinai System was strong for both PICaSSO components (Spearman’s ρ for mucosal: .925; vascular, .873; P < .001 for both). Moreover, accuracy in specifically discriminating quiescent from mild histologic strata was strongest for PICaSSO (area under the receiver operating characteristic curve AUROC for mucosal, .781; vascular, .715) compared with Mayo (AUROC, .708) and UCEIS (AUROC for UCEIS overall, .705; vascular, .562; bleeding, .645; erosions/ulcers, .696). Inter-rater reliability for PICaSSO was sustained by round 2 participants (round 1 and 2 ICC for mucosal, .873 and .869, respectively; vascular, .715 and .783, respectively), together with histologic correlation (ρ mucosal, .934; vascular, .938; P < .001 for both).
PICaSSO demonstrates good interobserver agreement across all levels of experience, providing excellent correlation with histology. Given the ability to discriminate subtle endoscopic features, PICaSSO may be applied to refine stratified treatment paradigms for UC patients.
Faecal microbiota transplantation (FMT) has previously been explored as a treatment for ulcerative colitis (UC) however, biomarkers that predict and / or are associated with clinical response are ...poorly defined. The aim of this systematic review was to identify donor and recipient clinical, microbial and metabolomic predictive biomarkers of response to FMT in UC.
A systematic search of the relevant literature of studies exploring FMT in UC was conducted. Data on microbial diversity, taxonomic changes, metabolic changes, donor and recipient microbiota relationship and baseline predictors was examined.
2852 studies were screened, and 25 papers were included in this systematic review. Following FMT, alpha diversity was seen to increase in responders along with increases in the abundance of Clostridiales clusters (order) and Bacteroides genus. Metabolomic analysis revealed short chain fatty acid (SCFA) production as a marker of FMT success. Donors or FMT batches with higher microbial alpha diversity and a greater abundance of taxa belonging to certain Bacteroides and Clostridia clusters were associated with clinical response to FMT. Baseline clinical predictors of response in patients with UC included younger age, less severe disease and possibly shorter disease duration. Baseline recipient microbial predictors at response consisted of higher faecal species richness, greater abundance of Candida and donor microbial profile similarity.
Distinct changes in gut microbiota profiles post-FMT indicate that certain baseline characteristics along with specific microbial and metabolomic alterations may predispose patients towards a successful therapeutic outcome. Opportunities towards a biomarker led precision medicine approach with FMT should be explored in future clinical studies.
There no specific funding to declare.
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.
IntroductionImbalance of the gut microbiome is key to the pathogenesis of ulcerative colitis (UC). Faecal microbiota transplant (FMT) is the transfer of homogenised and filtered faeces from a healthy ...individual to the gastrointestinal tract of a patient with disease. Published datasets show a positive signal for the use of FMT to treat UC, but the optimal route and dose of FMT remain unanswered.Methods and analysisThis prospective, multi-centre open-label, randomised pilot study will assess two possible routes of FMT delivery, via the nasogastric (NG) route or by delivery to the COLON, in 30 patients with active UC recruited from three sites in the UK. Stool will be collected from healthy screened donors, processed, frozen and stored under a Medicines and Healthcare products Regulatory Agency (MHRA) “specials” manufacturing licence held at the University of Birmingham Microbiome Treatment Centre. Thawed FMT samples will be administered to patients either via eight nasogastric infusions given initially over 4 days starting on the day of randomisation, and then again for 4 days in week 4 for foregut delivery (total of 240 g of stool) or via one colonoscopic infusion followed by seven weekly enemas according to the hindgut protocol (total of 360 g of stool). Patients will be followed up weekly for 8 weeks, and then at 12 weeks. The aims of this pilot study are (1) to determine which FMT administration route (NG or COLON) should be investigated in a randomised double-blind, placebo-controlled trial and (2) to determine if a full randomised controlled trial is feasible. The primary outcome will be a composite assessment of both qualitative and quantitative data based on efficacy (clinical response), acceptability and safety. At the end of the pilot study, decisions will be made regarding the feasibility of a full randomised double-blind, placebo-controlled trial and, if deemed feasible, which route of administration should be used in such a study.Ethics and disseminationEthical approval for this study has been obtained from the East Midlands-Nottingham Research Ethics Committee (REC 17/EM/0274). At the end of the study, findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals.Trial registration numberISRCTN74072945
Screening for colorectal cancer (CRC) reduces its mortality but has limited sensitivity and specificity. Aims We aimed to explore potential biomarker panels for CRC and adenoma detection and to gain ...insight into the interaction between gut microbiota and human metabolism in the presence of these lesions.
This multicenter case-control cohort was performed between February 2016 and November 2019. Consecutive patients ≥18 years with a scheduled colonoscopy were asked to participate and divided into three age, gender, body-mass index and smoking status-matched subgroups: CRC (n = 12), adenomas (n = 21) and controls (n = 20). Participants collected fecal samples prior to bowel preparation on which proteome (LC-MS/MS), microbiota (16S rRNA profiling) and amino acid (HPLC) composition were assessed. Best predictive markers were combined to create diagnostic biomarker panels. Pearson correlation-based analysis on selected markers was performed to create networks of all platforms.
Combining omics platforms provided new panels which outperformed hemoglobin in this cohort, currently used for screening (AUC 0.98, 0.95 and 0.87 for CRC vs controls, adenoma vs controls and CRC vs adenoma, respectively). Integration of data sets revealed markers associated with increased blood excretion, stress- and inflammatory responses and pointed toward downregulation of epithelial integrity.
Integrating fecal microbiota, proteome and amino acids platforms provides for new biomarker panels that may improve noninvasive screening for adenomas and CRC, and may subsequently lead to lower incidence and mortality of colon cancer.
Faecal microbiota transplant (FMT) has now been established into clinical guidelines for the treatment of recurrent and refractory Clostridioides difficile infection (CDI). Its therapeutic ...application in inflammatory bowel disease (IBD) is currently at an early stage. To date, there have been four randomized controlled trials for FMT in IBD and a multitude of observational studies. However, significant gaps in our knowledge regarding optimum methods for FMT preparation, technical aspects and logistics of its administration, as well as mechanistic underpinnings, still remain. In this article, we aim to highlight these gaps by reviewing evidence and making key recommendations on the direction of future studies in this field. In addition, we provide an overview of the current evidence of potential mechanisms of FMT in treating IBD.
Gut microbiome and autoimmune disorders Shaheen, Walaa Abdelaty; Quraishi, Mohammed Nabil; Iqbal, Tariq H
Clinical and experimental immunology,
08/2022, Letnik:
209, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Autoimmune diseases have long been known to share a common pathogenesis involving a dysregulated immune system with a failure to recognize self from non-self-antigens. This immune dysregulation is ...now increasingly understood to be induced by environmental triggers in genetically predisposed individuals. Although several external environmental triggers have been defined in different autoimmune diseases, much attention is being paid to the role of the internal micro-environment occupied by the microbiome, which was once termed "the forgotten organ." In this regard, the gut microbiome, serving as an intermediary between some of those external environmental effectors and the immune system, helps programming of the immune system to be tolerant to innocent external and self-antigens. However, in the presence of perturbed gut microbiota (dysbiosis), the immune system could be erroneously directed in favor of pro-inflammatory pathways to instigate different autoimmune processes. An accumulating body of evidence, including both experimental and human studies (observational and interventional), points to the role of the gut microbiome in different autoimmune diseases. Such evidence could provide a rationale for gut microbiome manipulation with therapeutic and even preventative intent in patients with established or predisposed to autoimmune diseases, respectively. Perturbations of the gut microbiome have been delineated in some immune mediated diseases, IBD in particular. However, such patterns of disturbance (microbiome signatures) and related pathogenetic roles of the gut microbiome are context dependent and cannot be generalized in the same exact way to other autoimmune disorders, and the contribution of the gut microbiome to different disease phenotypes has to be precisely defined. In this review, we revise the evidence for a role of the gut microbiome in various autoimmune diseases and possible mechanisms mediating such a role.
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