Explore the vast range of titles available.

Clostridioides difficile infection (CDI) results in significant morbidity and mortality in hospitalised patients. The pathogenesis of CDI is intrinsically related to the ability of C. difficile to shuffle between active vegetative cells and dormant endospores through the processes of germination and sporulation. Here, we hypothesise that dysregulation of microbiome-mediated bile salt metabolism contributes to CDI and that its alleviation can limit the pathogenesis of CDI. We engineer a genetic circuit harbouring a genetically encoded sensor, amplifier and actuator in probiotics to restore intestinal bile salt metabolism in response to antibiotic-induced microbiome dysbiosis. We demonstrate that the engineered probiotics limited the germination of endospores and the growth of vegetative cells of C. difficile in vitro and further significantly reduced CDI in model mice, as evidenced by a 100% survival rate and improved clinical outcomes. Our work presents an antimicrobial strategy that harnesses the host-pathogen microenvironment as the intervention target to limit the pathogenesis of infection. Clostridioides difficile infection (CDI) results in significant morbidity and mortality in hospitalised patients. Here the authors engineer probiotics to restore intestinal bile salt metabolism in response to antibiotic-induced microbiome dysbiosis significantly inhibit Clostridioides difficile infection in model mice, presenting a microbiome-based antimicrobial strategy

BackgroundIt is widely recognized that there are significant differences in the epidemiology of Upper Gastrointestinal Bleeding (UGIB) between Eastern and Western populations. We aim to provide an update of the prevalence of UGIB aetiologies in an Asian population in Singapore and to compare with recent data from a Western population.MethodsA retrospective, observational review of all patients who underwent oesophagogastroduodenoscopy for the indications of UGIB from 2011 to 2020 in the National University Hospital, Singapore, was analysed. We included cases performed for the following indications: haematemesis, coffee ground vomitus, melaena and bleeding gastrointestinal tract, The primary endoscopic findings were extracted and this provided a snapshot of aetiologies in the time period examined. The results were compared to that of other recent published prevalence data in other populations.Results5,691 cases were analysed. The three most common aetiologies of UGIB were peptic ulcer disease (PUD) (43.6%), non-ulcer mucosal lesions (27.6%) (gastritis, erosive gastritis, duodenitis, and erosive duodenitis) and oesophageal varices (8.03%) (IDDF2021-ABS-0160 Figure 1. Aetiology of GI Bleeding 2011-2020).Comparing with a large representative US cohort (Wuerth 2017), although the overall prevalence of gastroduodenal ulcers/erosions was similar with PUD (47.1%), there was more oesophagitis (15.2% vs 5.6%) and less oesophageal varices (1.8% vs 9.59%) (p<0.001).Abstract IDDF2021-ABS-0160 Figure 1ConclusionsThese results provide an updated prevalence of GI bleeding aetiology in a large retrospective multi-ethnic Asian cohort. Of note, while the proportions of peptic ulcer disease and inflammatory conditions (erosive gastritis etc.) are similar between reported literature and the referenced US cohort, there is considerably more esophageal variceal bleeding and less esophagitis. These differences are likely due to underlying differences in disease patterns of the populations with Asia having more chronic viral hepatitis B and less reflux disease compared with western populations.

Computer-aided diagnosis (CADx) of polyp histology could support endoscopists in clinical decision-making. However, this has not been validated in a real-world setting. We performed a prospective, multicenter study comparing CADx and endoscopist predictions of polyp histology in real-time colonoscopy. Optical diagnosis based on visual inspection of polyps was made by experienced endoscopists. After this, the automated output from the CADx support tool was recorded. All imaged polyps were resected for histological assessment. Primary outcome was difference in diagnostic performance between CADx and endoscopist prediction of polyp histology. Subgroup analysis was performed for polyp size, bowel preparation, difficulty of location of the polyps, and endoscopist experience. A total of 661 eligible polyps were resected in 320 patients aged ≥40 years between March 2021 and July 2022. CADx had an overall accuracy of 71.6% (95% confidence interval [CI] 68.0-75.0), compared with 75.2% (95% CI 71.7-78.4) for endoscopists ( P = 0.023). The sensitivity of CADx for neoplastic polyps was 61.8% (95% CI 56.9-66.5), compared with 70.3% (95% CI 65.7-74.7) for endoscopists ( P < 0.001). The interobserver agreement between CADx and endoscopist predictions of polyp histology was moderate (83.1% agreement, κ 0.661). When there was concordance between CADx and endoscopist predictions, the accuracy increased to 78.1%. The overall diagnostic accuracy and sensitivity for neoplastic polyps was higher in experienced endoscopists compared with CADx predictions, with moderate interobserver agreement. Concordance in predictions increased this diagnostic accuracy. Further research is required to improve the performance of CADx and to establish its role in clinical practice.

Dysbiosis is associated with gastric cancer (GC) development. However, no longitudinal study was carried out to identify key bacteria that could predict for GC progression. Here, we aimed to investigate changes in bacterial metagenome prior to GC and develop a microbiome-based predictive model to accurately classify patients at risk of GC. Bacterial 16S rDNA was sequenced from 89 gastric antral biopsies obtained from 43 participants. This study was nested in a prospective, longitudinal study, whereby study participants underwent screening gastroscopy, with further 1-2 yearly surveillance gastroscopies for at least 5 years. Putative bacterial taxonomic and functional features associated with GC carcinogenesis were identified by comparing between controls, patients with gastric intestinal metaplasia (IM) and patients with early gastric neoplasia (EGN). Patients with EGN had enrichment of (in particular genus) and depletion of (in particular family) in their gastric mucosa. Sequencing identified more patients with compared to histopathological assessment, while was also significantly enriched in EGN Furthermore, a total of 261 functional features, attributing to 97 KEGG pathways were differentially abundant at baseline between patients who subsequent developed EGN (n = 13/39) and those who did not. At the same time, a constellation of six microbial taxonomic features present at baseline, provided the highest classifying power for subsequent EGN (AUC = 0.82). Our study highlights early microbial changes associated with GC carcinogenesis, suggesting a potential role for prospective microbiome surveillance for GC.

Background The human gut harbors trillions of microbes that play dynamic roles in health. While the microbiome contributes to many cardiometabolic traits by modulating host inflammation and metabolism, there is an incomplete understanding regarding the extent that and mechanisms by which individual microbes impact risk and development of cardiovascular disease (CVD). The Framingham Heart Study (FHS) is a multi-generational observational study following participants over decades to identify risk factors for CVD by correlating genetic and phenotypic factors with clinical outcomes. As a large-scale population-based cohort with extensive clinical phenotyping, FHS provides a rich landscape to explore the relationships between the gut microbiome and cardiometabolic traits. Methods We performed 16S rRNA gene sequencing on stool from 1423 participants of the FHS Generation 3, OMNI2, and New Offspring Spouse cohorts. Data processing and taxonomic assignment were performed with the 16S bioBakery workflow using the UPARSE pipeline. We conducted statistical analyses to investigate trends in overall microbiome composition and diversity in relation to disease states and systematically examined taxonomic associations with a variety of clinical traits, disease phenotypes, clinical blood markers, and medications. Results We demonstrate that overall microbial diversity decreases with increasing 10-year CVD risk and body mass index measures. We link lifestyle factors, especially diet and exercise, to microbial diversity. Our association analyses reveal both known and unreported microbial associations with CVD and diabetes, related prescription medications, as well as many anthropometric and blood test measurements. In particular, we observe a set of microbial species that demonstrate significant associations with CVD risk, metabolic syndrome, and type 2 diabetes as well as a number of shared associations between microbial species and cardiometabolic subphenotypes. Conclusions The identification of significant microbial taxa associated with prevalent CVD and diabetes, as well as risk for developing CVD, adds to increasing evidence that the microbiome may contribute to CVD pathogenesis. Our findings support new hypothesis generation around shared microbe-mediated mechanisms that influence metabolic syndrome, diabetes, and CVD risk. Further investigation of the gut microbiomes of CVD patients in a targeted manner may elucidate microbial mechanisms with diagnostic and therapeutic implications.

IntroductionColonic diverticula are outpouchings of the large bowel. As the association between diverticulosis with gut microbiome has been less studied, we aim to characterise the gut microbiome of patients with diverticulosis.Methods364 consecutive patients underwent colonoscopy between 2017–2020 at National University Hospital, Singapore. Stool samples were collected prior to colonoscopy. DNA was extracted using FastDNA™ Spin Kit (MP Biomedicals)). Metagenomic libraries were generated using the NEBNext® Ultra™ IIDNA Library Preparation kit and sequenced with the NovaSeq 6000 system (Illumina®). Metagenomic taxonomic and functional profiles were generated using the bioBakery meta’omics workflow. All analyses were performed in R v3.6.2. Microbial diversity indices were calculated using Vegan v2.5. Association analyses were performed using an additive general linear model of log-transformed abundances via MaAsLin2. Statistical significance was corrected for multiple testing with significant associations identified at FDR <0.05.ResultsOne third of the subjects (33.8%) had diverticulosis. Subjects with diverticulosis were significantly older (mean age 65.1±7.5 vs 61.3±7.6 years old). There were no significant differences in the microbial diversity amongst subjects with or without diverticulosis. Correcting for age, we identified 16 microbial species and 63 microbial enzymes associated with diverticulosis. There was increased abundance of Ruminococcus species in subjects with diverticulosis, such as R. bromii, R. torques and R. inulinivorans, Subjects with diverticulosis were found with increased microbial L-glutamate metabolism, microbial methanogenesis, fatty acid synthesis, and bile acid dihydroxylation. Those without diverticulosis had have increased 4-aminobutanoate metabolism.ConclusionsSubjects with diverticulosis have distinct stool microbial signatures. The increased abundance of Ruminococcus bromii amongst subjects with diverticulosis, which is usually associated with increased intake resistant starches, may call to question the traditional concept of a fibre-deficient diet attributing towards diverticulosis.Abstract P255 Figure 1Boxplots of the 16 significant microbial species differentially abundant amongst subjects with (yellow) and without (grey) diverticulosis

Kombucha is a fermented tea known for its health-enhancing properties owing to the bioactive compounds generated by acetic acid bacteria (AAB) and lactic acid bacteria (LAB). We compared the distribution of AAB and LAB across nine kombucha products in Singapore (Product A to I) using shotgun metagenomics. High prevalence of Komagataeibacter species including Komagataeibacter saccharivorans (82.93% in B), Komagataeibacter xylinus (93.38% in D), and Komagataeibacter rhaeticus (92.20% and 30.62% in G and I) was detected in AAB-dominant kombucha. LAB-dominant kombucha was represented mainly by Bacillus coagulans (~99% in E and F) and Lactobacillus nagelii (~60% in H). Despite differences in bacterial composition, all kombucha harbour pathways involved in the biosynthesis of short-chain fatty acids (SCFAs), amino acids and vitamin B12. Interestingly, \"fatty acid and beta-oxidation II (peroxisome)\" and \"fatty acid and beta-oxidation I\" were only present in LAB-dominant kombucha. Further study is required to elucidate the significance of the discrepancies.

BackgroundIsolated terminal ileal ulcers (ITU) of unknown cause is a relatively uncommon finding and data on its natural history is still scarce. In this study, we aim to evaluate the outcome of ITU which was found during index ileocolonoscopy at a tertiary academic referral centre.MethodsA 12-year electronic database review of all patients undergoing ileocolonoscopy from 1 Jan 2008 to 15 Sep 2020 at National University Hospital Singapore was performed. All patients with findings of ‘ulcer’ in ‘terminal ileum’ in the electronic database during index endoscopy were included in the analysis for the presence of interval ileocolonoscopy and the outcome of initial ITU. Patients with a clear diagnosis (cancer, inflammatory bowel disease (IBD), tuberculosis, Behcet’s disease) based on clinical, radiology, and histological findings, and those with concomitant colonic inflammation (ulcers or colitis), were excluded from the analysis.ResultsThere were a total of 258 patients with ITU at index endoscopy, of which 71 patients subsequently underwent interval colonoscopy. Out of these 71 patients, 53 patients (74.6% of those with interval endoscopy; 20.5% of those with ITU at index endoscopy) presented with symptoms of gastrointestinal bleeding (25/71; 35.2%), altered bowel habit (16/71; 22.5%), abdominal discomfort (5/71; 7.0%), weight loss (3/71; 4.2%), anemia (3/71; 4.2%), and vomiting (1/71; 1.4%). The rest are asymptomatic (18/71; 25.3%) and underwent endoscopy for screening. In these 71 patients with interval ileocolonoscopy, ITU has healed in the majority of patients (44/71; 62.0%) with the remaining persisted (27/71; 38.0%). No significant differences were found in the presenting symptoms, or the lack of it, between those with persistent ulcers and those with healed ulcers.ConclusionsA small proportion of patients with ‘idiopathic’ terminal ileal ulcer developed symptoms requiring repeat ileocolonoscopy (20.6% of patients in this study). The majority of ulcers (62.0%) healed during interval ileocolonoscopy.

BackgroundSingapore and Malaysia are neighbouring countries with similar ethnic make-up: Chinese, Indian, and Malays. However, Singapore is a high-income economy while Malaysia is a middle-income economy. Such a difference has resulted in some levels of dichotomy in diet and lifestyles. In this study, we sought to investigate the gut-ethnic variation across the two neighbouring countries with varying levels of economic development.MethodsA total of 439 relatively healthy Malaysian (n=190) and Singaporean (n=249) adults (>18) were included, comprising Chinese (n=240), Indian (n=74), Malay (n=40), and the indigenous Jakun community (n=85). The sequences were processed with DADA2 and annotated using the SILVA database.ResultsCountry of origin explained the most variation in the gut microbiota (PERMANOVA, Pseudo-F=80.798, R2=0.156, p=0.001; IDDF2021-ABS-0150 Figure 1. Ordination). Importantly, ethnicity was still significantly associated with the gut microbiota even after adjusting for the country, age and sex (PERMANOVA, Pseudo-F=4.206, R2=0.019, p=0.001). Several taxa were found to be differentially abundant across ethnicity (ANCOM-BC, q<0.05). Notably, Ligilactobacillus, a lactic acid bacteria, was elevated among Indians (IDDF2021-ABS-0150 Figure 2. Ancom.ci) and reduced among Malay (IDDF2021-ABS-0150 Figure 3. Ancom.cm) relative to Chinese, suggesting that differences in the dietary pattern were responsible for the observed gut variation. Jakun exhibited the most differentially abundant gut microbiota (IDDF2021-ABS-0150 Figure 4. Ancom), with an elevated abundance of 18, 6, 5, and 1 genera, families, order, and class, respectively. The higher diversity of the Jakun was likely a reflection of their more traditional way of life, which has been associated with better gut diversity and health, compared to the Chinese, Indian and Malay of both countries, in particular, the higher abundance of Methanobacteria in Jakun has been inversely associated with irritable bowel syndrome.Abstract IDDF2021-ABS-0150 Figure 1Abstract IDDF2021-ABS-0150 Figure 2Abstract IDDF2021-ABS-0150 Figure 3Abstract IDDF2021-ABS-0150 Figure 4ConclusionsGut-ethnic differences persist across geographical regions, which was likely due to similar lifestyle and cultural practices by individuals sharing similar ancestry. These signals provide potential biomarkers on the role of the gut microbiota in the aetiology of the unequal disease burdens affecting the different ethnic groups in this multicultural region.