Dietary Emulsifier Exposure in People With Inflammatory Bowel Disease Compared With Healthy Controls: Is There a Cause for Concern?

BACKGROUND: Emulsifiers are implicated in the pathogenesis of inflammatory bowel disease (IBD). Few studies have examined emulsifier intake in people with existing IBD. We aimed to describe the frequency of exposure to 6 selected emulsifiers in a contemporary cohort of people with IBD and compare intake with healthy controls (HCs). METHODS: Baseline food records from participants in an Australian prospective cohort study examining the microbiome of IBD patients and HCs were analyzed. Exposure to inflammatory emulsifiers polysorbate-80 (P80); carboxymethylcellulose (CMC); carrageenan; xanthan gum (XG); lecithin (soy and sunflower) and mono- and diglycerides of fatty acids (MDGs) were determined by examining ingredient lists. Frequency of emulsifier exposure between groups (IBD vs HC, Crohn's disease [CD] vs ulcerative colitis [UC], IBD children vs adults, active disease vs remission) was examined after controlling for confounders. RESULTS: Records from 367 participants were analyzed (n = 176 IBD, of which there were 101 CD, 75 UC, and 191 HC patients). In total, 5022 unique food items were examined, with 18% containing 1 or more emulsifier of interest. Inflammatory bowel disease participants had significantly higher total daily emulsifier exposure compared with HCs (2.7 ±â€…1.8 vs 2.3 ±â€…1.6, P = .02). In IBD participants, emulsifiers with the highest daily exposure were MDGs (1.2 ±â€…0.93), lecithin (0.85 ±â€…0.93), and XG (0.38 ±â€…0.42). There were no recorded exposures to P80. CONCLUSIONS: Inflammatory bowel disease participants were exposed to more emulsifiers than HCs. Intake of inflammatory emulsifiers were low or nonexistent, suggesting their presence in the food supply are not as common as frequently stated.

Mucin-microbiome signatures shape the tumor microenvironment in gastric cancer.

BACKGROUND AND AIMS: We aimed to identify mucin-microbiome signatures shaping the tumor microenvironment in gastric adenocarcinomas and clinical outcomes. METHODS: We performed high-throughput profiling of the mucin phenotypes present in 108 gastric adenocarcinomas and 20 functional dyspepsia cases using validated mucin-based RT-qPCRs with subsequent immunohistochemistry validation and correlated the data with clinical outcome parameters. The gastric microbiota was assessed by 16S rRNA gene sequencing, taxonomy, and community composition determined, microbial networks analyzed, and the metagenome inferred in association with mucin phenotypes and expression. RESULTS: Gastric adenocarcinomas with an intestinal mucin environment or high-level MUC13 expression are associated with poor survival. On the contrary, gastric MUC5AC or MUC6 abundance was associated with a more favorable outcome. The oral taxa Neisseria, Prevotella, and Veillonella had centralities in tumors with intestinal and mixed phenotypes and were associated with MUC13 overexpression, highlighting their role as potential drivers in MUC13 signaling in GC. Furthermore, dense bacterial networks were observed in intestinal and mixed mucin phenotype tumors whereas the lowest community complexity was shown in null mucin phenotype tumors due to higher Helicobacter abundance resulting in a more decreased diversity. Enrichment of oral or intestinal microbes was mucin phenotype dependent. More specifically, intestinal mucin phenotype tumors favored the establishment of pro-inflammatory oral taxa forming strong co-occurrence networks. CONCLUSIONS: Our results emphasize key roles for mucins in gastric cancer prognosis and shaping microbial networks in the tumor microenvironment. Specifically, the enriched oral taxa associated with aberrant MUC13 expression can be potential biomarkers in predicting disease outcomes. Video Abstract.

Assessing the Relationship between the Gut Microbiota and Inflammatory Bowel Disease Therapeutics: A Systematic Review.

Current inflammatory bowel disease (IBD) treatments including non-biological, biological, and nutritional therapies aim to achieve remission and mucosal healing. Treatment efficacy, however, is highly variable, and there is growing evidence that the gut microbiota influences therapeutic efficacy. The aim of this study was to conduct a systematic review and meta-analysis to define changes in the gut microbiota following IBD treatment and to identify microbial predictors of treatment response. A systematic search using MEDLINE/Embase and PubMed was performed in July 2022. The review was conducted based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Studies were included if they reported longitudinal microbiota analysis (>2 weeks) using next-generation sequencing or high-throughput sequencing of faecal/mucosal samples from IBD patients commencing treatment. Meta-analysis on alpha-diversity changes following infliximab treatment was conducted. Thirty-nine studies met the inclusion criteria, and four studies were included in the meta-analysis. An increase in alpha diversity was observed following treatment with 5-aminosalicylates, corticosteroids, and biological therapies in most studies. Characteristic signatures involving the enrichment of short-chain-fatty-acid-producing bacteria including Faecalibacterium prausnitzii and a reduction of pathogenic bacteria including various Proteobacteria were demonstrated following treatment with specific signatures identified based on treatment outcome. The meta-analysis demonstrated a statistically significant increase in bacterial richness following infliximab treatment (standardised mean difference -1.16 (-1.50, -0.83), p < 0.00001). Conclusion: Distinct microbial signatures are seen following treatment and are associated with treatment response. The interrogation of large longitudinal studies is needed to establish the link between the gut microbiota and IBD therapeutic outcomes.

A systematic review, pairwise meta-analysis and network meta-analysis of randomized controlled trials exploring the role of fecal microbiota transplantation in irritable bowel syndrome.

BACKGROUND: Treatment is a challenge in Irritable Bowel Syndrome (IBS) and fecal microbiota transplantation (FMT) has attracted significant interest. Network meta-analysis (NWM) has been established as an evidence-synthesis tool that incorporates direct and indirect evidence in a collection of randomized controlled trials (RCTs) comparing therapeutic intervention competing for similar therapeutic results. No NWM exists concerning the comparative effectiveness and safety of various FMT modalities for IBS. AIM: We updated pairwise meta-analyses published in the past and assessed the comparative effectiveness and safety of various FMT delivery modalities for IBS. METHODS: Pairwise meta-analyses and Bayesian NWM were performed. Heterogeneity, consistency of results and publication bias were explored. RESULTS: Of 510 titles raised by initial search, seven RCTs were entered into meta-analyses and NWM. They included 470 patients and controls, in whom four FMT delivery modalities were used, that is via colonoscopy, nasojejunal tube, duodenoscope and capsules per os. In the pairwise meta-analysis, the pooled results showed that overall FMT was not superior to placebo, whereas the subgroup analyses showed that FMT via duodenoscope and nasojejunal tube was superior. The NWM showed that 60-g FMT via duodenoscope had the highest efficacy (OR, 26.38; 95% CI, 9.22-75.51) and was by far the highest in the efficacy ranking (SUCRA, 98.8%). CONCLUSION: The pooled results showed no overall advantage of FMT over placebo in IBS. However, upper GI delivery (via duodenoscopy or nasojejunal tube) proved to be effective. Consequently, well-designed RCTs are needed to ensure the efficacy and safety profile before FMT can be applied in everyday clinical practice for IBS patients.

The Role of the Microbiome in the Metabolic Health of People with Schizophrenia and Related Psychoses: Cross-Sectional and Pre-Post Lifestyle Intervention Analyses.

The microbiome has been implicated in the development of metabolic conditions which occur at high rates in people with schizophrenia and related psychoses. This exploratory proof-of-concept study aimed to: (i) characterize the gut microbiota in antipsychotic naïve or quasi-naïve people with first-episode psychosis, and people with established schizophrenia receiving clozapine therapy; (ii) test for microbiome changes following a lifestyle intervention which included diet and exercise education and physical activity. Participants were recruited from the Eastern Suburbs Mental Health Service, Sydney, Australia. Anthropometric, lifestyle and gut microbiota data were collected at baseline and following a 12-week lifestyle intervention. Stool samples underwent 16S rRNA sequencing to analyse microbiota diversity and composition. Seventeen people with established schizophrenia and five people with first-episode psychosis were recruited and matched with 22 age-sex, BMI and ethnicity matched controls from a concurrent study for baseline comparisons. There was no difference in α-diversity between groups at baseline, but microbial composition differed by 21 taxa between the established schizophrenia group and controls. In people with established illness pre-post comparison of α-diversity showed significant increases after the 12-week lifestyle intervention. This pilot study adds to the current literature that detail compositional differences in the gut microbiota of people with schizophrenia compared to those without mental illness and suggests that lifestyle interventions may increase gut microbial diversity in patients with established illness. These results show that microbiome studies are feasible in patients with established schizophrenia and larger studies are warranted to validate microbial signatures and understand the relevance of lifestyle change in the development of metabolic conditions in this population.

Therapeutic Drug Monitoring of Subcutaneous Infliximab in Inflammatory Bowel Disease-Understanding Pharmacokinetics and Exposure Response Relationships in a New Era of Subcutaneous Biologics.

CT-P13 is the first subcutaneous infliximab molecule approved for the management of inflammatory bowel disease (IBD). Compared to intravenous therapy, SC infliximab offers a range of practical, micro- and macroeconomic advantages. Data from the rheumatological literature suggest that subcutaneous CT-P13 may lead to superior disease outcomes in comparison to intravenous infliximab. Existing studies in IBD have focussed on pharmacokinetic comparisons and are inadequately powered to evaluate efficacy and safety differences between the two modes of administration. However, emerging clinical trial and real-world data support comparable clinical, biochemical, endoscopic and safety outcomes between subcutaneous and intravenous infliximab in both luminal Crohn's disease and ulcerative colitis. Across the available data, subcutaneous CT-P13 provides relative pharmacokinetic stability and higher trough drug levels when compared to intravenous administration. The clinical impact of this observation on immunogenicity and treatment persistence is yet to be determined. Trough levels between the two methods of administration should not be compared in isolation as any subcutaneous advantage must be considered in the context of comparable total drug exposure and the theoretical disadvantage of lower peak concentrations compared to intravenous therapy. Furthermore, target drug levels for subcutaneous CT-P13 associated with remission are not known. In this review, we present the available literature surrounding the pharmacokinetics of subcutaneous CT-P13 in the context of therapeutic drug monitoring and highlight the potential significance of these observations on the clinical management of patients with IBD.

Comprehensive Study of Antiretroviral Drug Permeability at the Cervicovaginal Mucosa via an In Vitro Model.

Modulation of drug transporter activity at mucosal sites of HIV-1 transmission may be exploited to optimize retention of therapeutic antiretroviral drug concentrations at target submucosal CD4+ T cells. Previously, we showed that darunavir was a substrate for the P-glycoprotein efflux drug transporter in colorectal mucosa. Equivalent studies in the cervicovaginal epithelium have not been reported. Here, we describe the development of a physiologically relevant model to investigate the permeability of antiretroviral drugs across the vaginal epithelium. Barrier properties of the HEC-1A human endometrial epithelial cell line were determined, in a dual chamber model, by measurement of transepithelial electrical resistance, immunofluorescent staining of tight junctions and bi-directional paracellular permeability of mannitol. We then applied this model to investigate the permeability of tenofovir, darunavir and dapivirine. Efflux ratios indicated that the permeability of each drug was transporter-independent in this model. Reduction of pH to physiological levels in the apical compartment increased absorptive transfer of darunavir, an effect that was reversed by inhibition of MRP efflux transport via MK571. Thus, low pH may increase the transfer of darunavir across the epithelial barrier via increased MRP transporter activity. In a previous in vivo study in the macaque model, we demonstrated increased MRP2 expression following intravaginal stimulation with darunavir which may further increase drug uptake. Stimulation with inflammatory modulators had no effect on drug permeability across HEC-1A barrier epithelium but, in the VK2/E6E7 vaginal cell line, increased expression of both efflux and uptake drug transporters which may influence darunavir disposition.

Review article: the future of microbiome-based therapeutics.

BACKGROUND: From consumption of fermented foods and probiotics to emerging applications of faecal microbiota transplantation, the health benefit of manipulating the human microbiota has been exploited for millennia. Despite this history, recent technological advances are unlocking the capacity for targeted microbial manipulation as a novel therapeutic. AIM: This review summarises the current developments in microbiome-based medicines and provides insight into the next steps required for therapeutic development. METHODS: Here we review current and emerging approaches and assess the capabilities and weaknesses of these technologies to provide safe and effective clinical interventions. Key literature was identified through Pubmed searches with the following key words, 'microbiome', 'microbiome biomarkers', 'probiotics', 'prebiotics', 'synbiotics', 'faecal microbiota transplant', 'live biotherapeutics', 'microbiome mimetics' and 'postbiotics'. RESULTS: Improved understanding of the human microbiome and recent technological advances provide an opportunity to develop a new generation of therapies. These therapies will range from dietary interventions, prebiotic supplementations, single probiotic bacterial strains, human donor-derived faecal microbiota transplants, rationally selected combinations of bacterial strains as live biotherapeutics, and the beneficial products or effects produced by bacterial strains, termed microbiome mimetics. CONCLUSIONS: Although methods to identify and refine these therapeutics are continually advancing, the rapid emergence of these new approaches necessitates accepted technological and ethical frameworks for measurement, testing, laboratory practices and clinical translation.

The role of mucins in gastrointestinal barrier function during health and disease.

Mucins are the gatekeepers of the mucosal barrier of the gastrointestinal tract and are aberrantly expressed in various gastrointestinal pathologies, including pathogen infection, inflammation, and uncontrolled growth and spread of abnormal cells. Although several studies have emphasised the role of mucins in dysfunction of the gastrointestinal mucosal barrier, they are often still considered to be passive mediators of this barrier instead of regulators or modulators. In this Review, we discuss the interactions between mucins and gastrointestinal barrier function during health and disease. We will focus on the bidirectional relationship between mucins and the gut microbiota and will also address the molecular mechanisms involved in key cell signalling pathways, such as inflammation, cell interactions, and cell differentiation, proliferation, and survival. Additionally, we highlight the potential use of mucins in the diagnosis, follow-up, and treatment of gastrointestinal diseases, such as chronic inflammatory diseases and cancer.

The Role of Microbiota in Gastrointestinal Cancer and Cancer Treatment: Chance or Curse?

The gastrointestinal (GI) tract is home to a complex and dynamic community of microorganisms, comprising bacteria, archaea, viruses, yeast, and fungi. It is widely accepted that human health is shaped by these microbes and their collective microbial genome. This so-called second genome plays an important role in normal functioning of the host, contributing to processes involved in metabolism and immune modulation. Furthermore, the gut microbiota also is capable of generating energy and nutrients (eg, short-chain fatty acids and vitamins) that are otherwise inaccessible to the host and are essential for mucosal barrier homeostasis. In recent years, numerous studies have pointed toward microbial dysbiosis as a key driver in many GI conditions, including cancers. However, comprehensive mechanistic insights on how collectively gut microbes influence carcinogenesis remain limited. In addition to their role in carcinogenesis, the gut microbiota now has been shown to play a key role in influencing clinical outcomes to cancer immunotherapy, making them valuable targets in the treatment of cancer. It also is becoming apparent that, besides the gut microbiota's impact on therapeutic outcomes, cancer treatment may in turn influence GI microbiota composition. This review provides a comprehensive overview of microbial dysbiosis in GI cancers, specifically esophageal, gastric, and colorectal cancers, potential mechanisms of microbiota in carcinogenesis, and their implications in diagnostics and cancer treatment.

Critical Assessment of Whole Genome and Viral Enrichment Shotgun Metagenome on the Characterization of Stool Total Virome in Hepatocellular Carcinoma Patients.

Viruses are the most abundant form of life on earth and play important roles in a broad range of ecosystems. Currently, two methods, whole genome shotgun metagenome (WGSM) and viral-like particle enriched metagenome (VLPM) sequencing, are widely applied to compare viruses in various environments. However, there is no critical assessment of their performance in recovering viruses and biological interpretation in comparative viral metagenomic studies. To fill this gap, we applied the two methods to investigate the stool virome in hepatocellular carcinoma (HCC) patients and healthy controls. Both WGSM and VLPM methods can capture the major diversity patterns of alpha and beta diversities and identify the altered viral profiles in the HCC stool samples compared with healthy controls. Viral signatures identified by both methods showed reductions of Faecalibacterium virus Taranis in HCC patients' stool. Ultra-deep sequencing recovered more viruses in both methods, however, generally, 3 or 5 Gb were sufficient to capture the non-fragmented long viral contigs. More lytic viruses were detected than lysogenetic viruses in both methods, and the VLPM can detect the RNA viruses. Using both methods would identify shared and specific viral signatures and would capture different parts of the total virome.

Systematic review with meta-analysis: dietary intake in adults with inflammatory bowel disease.

BACKGROUND: Poor dietary intake is associated with the development of malnutrition, micronutrient deficiencies, anaemia and osteoporosis in individuals with inflammatory bowel disease. While trials are underway to manipulate the diet of people with IBD, there has been no comprehensive systematic review of the dietary intake of adults with IBD. AIMS: To conduct a systematic evaluation and meta-analysis of the dietary intake of adults with IBD, including macronutrients, micronutrients and food group data. METHODS: CINAHL, Embase, Medline and Scopus were searched from 1 January 2000 to 25 September 2020 for cohort, case-control or cross-sectional studies that reported usual dietary intake in adults. Data were pooled and reported as weighted mean intake for: all adults with IBD; Crohn's disease; ulcerative colitis; active disease; remission; males; females. A random-effects meta-analysis model compared intake with healthy individuals. RESULTS: Forty studies were identified and 19 were included in the meta-analysis. All subgroups of adults with IBD consumed inadequate energy (mean intake in adults with IBD 1980 ± 130 kcal), fibre (14 ± 4 g), folate (246 ± 33 mg) and calcium (529 ± 114 mg) per day. Intake of breads and cereals, legumes, fruit, vegetables and dairy were inadequate. Compared to healthy individuals, adults with IBD consume significantly less dietary fibre (SMD -0.59; 95% CI: -0.73, -0.46). CONCLUSIONS: This review provides improved clarity about the dietary intake of adults with IBD. Future attention is required to improve diet quality and increase understanding of factors influencing dietary intake in IBD.

Inflammatory bowel disease and the gut microbiota.

Inflammatory bowel disease (IBD) is a group of immune-mediated disorders characterised by a chronic, relapsing-remitting inflammation predominantly affecting the gastrointestinal tract. IBD is incurable, affecting people in their most productive years. IBD is historically seen as a disease of Westernised nations although in recent times other countries have seen an exponential rise in cases. Although the exact pathogenesis remains unclear, evidence suggests that microbiota changes play a critical role in IBD pathogenesis. Over the past two decades, IBD has become one of the most studied human conditions linked to the gut microbiota. However, deciphering the intricate link between the gut microbiota and therapeutic efficacy remains elusive. This review will summarise the current evidence relating to the gut microbiota and its involvement in IBD pathogenesis as well as the impact of IBD treatments including pharmaceutical-, nutraceutical- and microbial-focused regimens on the gut microbiota.

Long-Term Iron Deficiency and Dietary Iron Excess Exacerbate Acute Dextran Sodium Sulphate-Induced Colitis and Are Associated with Significant Dysbiosis.

BACKGROUND: Oral iron supplementation causes gastrointestinal side effects. Short-term alterations in dietary iron exacerbate inflammation and alter the gut microbiota, in murine models of colitis. Patients typically take supplements for months. We investigated the impact of long-term changes in dietary iron on colitis and the microbiome in mice. METHODS: We fed mice chow containing differing levels of iron, reflecting deficient (100 ppm), normal (200 ppm), and supplemented (400 ppm) intake for up to 9 weeks, both in absence and presence of dextran sodium sulphate (DSS)-induced chronic colitis. We also induced acute colitis in mice taking these diets for 8 weeks. Impact was assessed (i) clinically and histologically, and (ii) by sequencing the V4 region of 16S rRNA. RESULTS: In mice with long-term changes, the iron-deficient diet was associated with greater weight loss and histological inflammation in the acute colitis model. Chronic colitis was not influenced by altering dietary iron however there was a change in the microbiome in DSS-treated mice consuming 100 ppm and 400 ppm iron diets, and control mice consuming the 400 ppm iron diet. Proteobacteria levels increased significantly, and Bacteroidetes levels decreased, in the 400 ppm iron DSS group at day-63 compared to baseline. CONCLUSIONS: Long-term dietary iron alterations affect gut microbiota signatures but do not exacerbate chronic colitis, however acute colitis is exacerbated by such dietary changes. More work is needed to understand the impact of iron supplementation on IBD. The change in the microbiome, in patients with colitis, may arise from the increased luminal iron and not simply from colitis.

The Impact of NOD2 Genetic Variants on the Gut Mycobiota in Crohn's Disease Patients in Remission and in Individuals Without Gastrointestinal Inflammation.

BACKGROUND AND AIMS: Historical and emerging data implicate fungi in Crohn's disease [CD] pathogenesis. However, a causal link between mycobiota, dysregulated immunity, and any impact of NOD2 variants remains elusive. This study aims to evaluate associations between NOD2 variants and faecal mycobiota in CD patients and non-CD subjects. METHODS: Faecal samples were obtained from 34 CD patients [18 NOD2 mutant, 16 NOD2 wild-type] identified from the UK IBD Genetics Consortium. To avoid confounding influence of mucosal inflammation, CD patients were in clinical remission and had a faecal calprotectin <250 µg/g; 47 non-CD subjects were included as comparator groups, including 22 matched household [four NOD2 mutant] and 25 non-household subjects with known NOD2 genotype [14 NOD2 mutant] identified by the NIHR BioResource Cambridge. Faecal mycobiota composition was determined using internal transcribed spacer 1 [ITS1] sequencing and was compared with 16S rRNA gene sequences and volatile organic compounds. RESULTS: CD was associated with higher numbers of fungal observed taxonomic units [OTUs] [p = 0.033]. Principal coordinates analysis using Jaccard index [p = 0.018] and weighted Bray-Curtis dissimilarities [p = 0.01] showed Candida spp. clustered closer to CD patients whereas Cryptococcus spp. clustered closer to non-CD. In CD, we found higher relative abundance of Ascomycota [p = 0.001] and lower relative abundance Basidiomycota [p = 0.019] phyla. An inverse relationship was found between bacterial and fungal Shannon diversity in NOD2 wild-type which was independent of CD [r = -0.349; p = 0.029]. CONCLUSIONS: This study confirms compositional changes in the gut mycobiota in CD and provides evidence that fungi may play a role in CD pathogenesis. No NOD2 genotype-specific differences were observed in the faecal mycobiota.

Gut Mucosal Microbiome Signatures of Colorectal Cancer Differ According to BMI Status.

BACKGROUND: Carrying excess body weight is a strong risk factor for colorectal cancer (CRC) development with ~11% of CRC cases in Europe linked to being overweight. The mechanisms through which excess body weight influences CRC development are not well understood but studies suggest the involvement of the presence of chronic low-grade inflammation and changes in the gut microbiota are involved. AIM: To compare the mucosal associated microbiota of patients with CRC to understand whether carrying excess body weight was associated with a unique CRC microbial signature. METHODS: Microbiota signatures from colonic mucosal biopsies of CRC lesions and adjacent normal mucosal samples from 20 patients with overt CRC were compared with 11 healthy controls to see if having a BMI of >25 kg/m2 influenced colonic microbial composition. RESULTS: Colonic mucosa samples from patients with CRC confirmed previously reported over-abundance of Fusobacteria associated with CRC but also an increase in Fusobacteria and Prevotella were associated with a BMI of >25 kg/m2. Correlation analysis of bacterial taxa indicated co-exclusive relationships were more common in CRC patients with a BMI >25 kg/m2 with an increase in transphylum relationships also seen in this patient group. CONCLUSIONS: The findings suggest that gut microbiota composition in patients with CRC is influenced by BMI status. Further understanding/defining these differences will provide valuable information in terms of developing novel pre-onset screening and providing post-manifestation therapeutic intervention.

Biopsy Sampling in Upper Gastrointestinal Endoscopy: A Survey from 10 Tertiary Referral Centres Across Europe.

BACKGROUND: Guidelines give robust recommendations on which biopsies should be taken when there is endoscopic suggestion of gastric inflammation. Adherence to these guidelines often seems arbitrary. This study aimed to give an overview on current practice in tertiary referral centres across Europe. METHODS: Data were collected at 10 tertiary referral centres. Demographic data, the indication for each procedure, endoscopic findings, and the number and sampling site of biopsies were recorded. Findings were compared between centres, and factors influencing the decision to take biopsies were explored. RESULTS: Biopsies were taken in 56.6% of 9,425 procedures, with significant variation between centres (p < 0.001). Gastric biopsies were taken in 43.8% of all procedures. Sampling location varied with the procedure indication (p < 0.001) without consistent pattern across the centres. Fewer biopsies were taken in centres which routinely applied the updated Sydney classification for gastritis assessment (46.0%), compared to centres where this was done only upon request (75.3%, p < 0.001). This was the same for centres stratifying patients according to the OLGA system (51.8 vs. 73.0%, p < 0.001). More biopsies were taken in centres following the MAPS guidelines on stomach surveillance (68.1 vs. 37.1%, p < 0.001). Biopsy sampling was more likely in younger patients in 8 centres (p < 0.05), but this was not true for the whole cohort (p = 0.537). The percentage of procedures with biopsies correlated directly with additional costs charged in case of biopsies (r = 0.709, p = 0.022). CONCLUSION: Adherence to guideline recommendations for biopsy sampling at gastroscopy was inconsistent across the participating centres. Our data suggest that centre-specific policies are applied instead.

A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group.

BACKGROUND: Faecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of faeces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council. OBJECTIVE: Several European and international consensus statements concerning faecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document. METHODS: Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about faecal microbiota transplantation. RESULTS: A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening. CONCLUSION: The implementation of faecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor faeces preparations for patients.

Microbiome Understanding in Maternity Study (MUMS), an Australian prospective longitudinal cohort study of maternal and infant microbiota: study protocol.

INTRODUCTION: Pregnancy induces significant physiological and cardiometabolic changes, and is associated with alterations in the maternal microbiota. Increasing rates of prepregnancy obesity, metabolic abnormalities and reduced physical activity, all impact negatively on the microbiota causing an imbalance between the commensal microorganisms (termed dysbiosis), which may drive complications, such as gestational diabetes or hypertensive disorders. Considerable work is needed to define the inter-relationships between the microbiome, nutrition, physical activity and pregnancy outcomes. The role of the microbiota during pregnancy remains unclear. The aim of the study is to define microbiota signatures longitudinally throughout pregnancy and the first year post birth, and to identify key clinical and environmental variables that shape the female microbiota profile during and following pregnancy. METHODS AND ANALYSIS: The Microbiome Understanding in Maternity Study (MUMS) is an Australian prospective longitudinal cohort study involving 100 mother-infant pairs. Women are enrolled in their first trimester and followed longitudinally. Assessment occurs at <13+0, 20+0-24+6 and 32+0-36+6 weeks gestation, birth and 6 weeks, 6 months and 12 months postpartum. At each assessment, self-collected oral, vaginal and faecal samples are collected with an additional postpartum skin swab and breastmilk sample. Each infant will have oral, faecal and skin swab samples collected. Measurements include anthropometrics, body composition, blood pressure, serum hormonal and metabolic parameters and vaginal pH. Dietary intake, physical activity and psychological state will be assessed using validated self-report questionnaires, and pregnancy and infant outcomes recorded. Parametric and non-parametric hypothesis tests will be used to test the association between high-risk and low-risk pregnancies and their outcomes. ETHICS AND DISSEMINATION: The study received the following approval: South Eastern Sydney Local Health District Research Ethics Committee (17/293 (HREC/17/POWH/605). Results will be made available to the participants of MUMS, their families and the funding bodies; in the form of a summary document. Results for the greater maternity care community and other researchers will be disseminated through conferences, local, national and international presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ACTRN12618000471280 (prospectively registered).