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Background The gut microbiome plays an instrumental role in cardiovascular, metabolic and gastrointestinal health (Valdes et al. 2018). In Traditional Chinese Medicine (TCM), one’s health status can be described by nine body constitutions (BCs) which are broadly classified as ‘Neutral’, indicating optimal health, or ‘Unbalanced’, indicating suboptimal health. Similar to the gut microbiome, BCs are strongly influenced by lifestyle and diet. We evaluated the gut microbial composition of Neutral, Qi-Deficiency (QD), Phlegm-dampness (PD) and Damp Heat (DH) subjects. The latter three are unbalanced BCs, with QD associated with heart disease (Zhu et al. 2017), PD with obesity and metabolic syndrome (Wang et al. 2013), and DH with gastrointestinal disease (Liang et al. 2020). Methods Stool samples were collected from 211 healthy subjects and gut microbial composition was profiled using 16S rRNA amplicon sequencing of the V3-V4 regions. BCs were determined using the Constitution in Chinese Medicine Questionnaire (Wang, 2005). Alpha diversity of QD, PD and DH was inferred and compared against that of Neutral using the Kruskal-Wallis test. Differentially abundant bacterial phyla, family and species were identified by calculating Log2FoldChange of taxa in the unbalanced BCs compared to Neutral. Results There were 135 Neutral, 59 QD, 24 PD and 12 DH subjects. 16 participants exhibited two or more unbalanced BCs. PD exhibited significantly lower alpha diversity (Shannon, Simpson) than Neutral (p Conclusions Varying TCM BCs exhibit unique microbiota signatures. Participants with unbalanced BCs are associated with greater dysbiosis compared to participants with Neutral BC. The lower alpha diversity in PD is consistent with that in obese and metabolic syndrome patients (Stanislawski et al. 2019; Oh et al. 2021). Streptococcus gallolyticus, a species associated with gastrointestinal malignancy (Chand et al. 2016), was significantly higher in all three unbalanced BCs and thus may serve as a potential biomarker for identifying patients with unbalanced BCs.

ObjectiveTo investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC.MethodsA prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN).ResultsThere were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; pH. pylori. Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II–IV.ConclusionsWe suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III–IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.

Background Blastocystis is a common anaerobic colonic protist in humans with controversial pathogenicity. Clostridium difficile (C. difficile) is the commonest cause of infectious diarrhea in healthcare settings. The prevalence and subtype (ST) characteristics of Blastocystis in patients with C. difficile infection (CDI) are rarely documented. Therefore, the present study was conducted to investigate the prevalence and subtype characteristics of Blastocystis in patients with suspicion of CDI in Singapore. Methods Fecal samples were collected from 248 patients presenting with suspected CDI from a single tertiary hospital in Singapore. C. difficile was diagnosed through positive glutamate dehydrogenase (GDH) with or without toxin A/B using enzyme immunoassay methods. The prevalence and subtype genetic characteristics of Blastocystis were determined by polymerase chain reaction (PCR) amplification and analysis of the barcode region of the SSU rRNA gene. Results The proportion of C. difficile in patients with healthcare-associated diarrhea in this study was 44% (109/248). Among the 109 C. difficile-positive patients, 59 (54.1%, 59/109) tested positive for toxigenic C. difficile, which was considered CDI. Based on the sequence analyses of the barcode region of the SSU rRNA gene, 10.1% (25/248) of the patients were found to be Blastocystis-positive, and three subtypes were identified: ST7 (64%, 16/25), ST1 (20%, 5/25), and ST3 (16%, 4/25). Remarkably, we found five patients with Blastocystis and C. difficile coinfection, and further subtype analysis showed two with ST7, two with ST1, and one with ST3. Conclusions To the best of our knowledge, this is the first study to investigate the subtype distributions of Blastocystis in patients with CDI in Singapore. We found ST7 to be the predominant subtype in diarrheal patients. The pathogenicity of ST7 has been strongly suggested in previous in vitro and mouse model experiments, further confirming its potential pathogenicity to humans. Graphical Abstract

Summary The intestinal microbiome is a key determinant of responses to biologic therapy in inflammatory bowel disease (IBD). However, diverse therapeutics and variable responses among IBD patients have posed challenges in predicting clinical therapeutic success. In this prospective study, we profiled baseline stool and blood in patients with moderate-to-severe Crohn's disease or ulcerative colitis initiating anti-cytokine therapy (anti-TNF or -IL12/23) or anti-integrin therapy. Patients were assessed at 14 weeks for clinical remission and 52 weeks for clinical and endoscopic remission. Baseline microbial richness indicated preferential responses to anti-cytokine therapy and correlated with the abundance of microbial species capable of 7α/β-dehydroxylation of primary to secondary bile acids. Serum signatures of immune proteins reflecting microbial diversity identified patients more likely to achieve remission with anti-cytokine therapy. Remission-associated multi-omic profiles were unique to each therapeutic class. These profiles may facilitate a priori determination of optimal therapeutics for patients and serve as targets for newer therapies.

Background While many studies have found an association between irritable bowel syndrome (IBS) and obesity, many others did not. Hence, this systematic review with meta-analysis aims to evaluate the relationship between obesity and IBS, and determine whether obesity correlates differently with the various IBS endotypes. Methods A systematic review of published literature was conducted in concordance with the PRISMA guidelines and followed by a meta-analysis of relevant studies using the random-effects model. The 34 included studies assessed obesity among non-IBS controls and IBS subjects, either as continuous or dichotomous outcomes, using body mass index (BMI) and waist circumference (WC). The standardized mean difference (SMD) and 95% confidence interval (CI); and the odds ratio (OR) and 95% CI were obtained for continuous and dichotomous outcomes respectively. Meta-regression was performed to identify sources of heterogeneity. Results We found a weak association between IBS and obesity, but this was not statistically significant. For BMI, the overall SMD was +0.227 (95% CI: –0.093 to 0.547, p = 0.164) and OR was 1.312 (95% CI: 0.974 to 1.767, p = 0.074). For WC, the overall SMD was +1.020 cm (95% CI: –1.768 to 3.807, p = 0.473). However, subgroup analysis revealed significantly higher BMI among IBS-diarrhoea (IBS-D) subjects compared to controls (SMD = +1.940; 95% CI: 0.679 to 3.200, p = 0.003) and significantly lower BMI among IBS-constipation (IBS-C) subjects compared to IBS-D subjects (SMD = –1.720; 95% CI: –2.489 to –0.950, p Conclusions In conclusion, our systematic review with meta-analysis showed that obesity is positively associated with diarrhoea-predominant IBS, but not IBS in general. Our findings support the exploration of shared pathophysiology between IBS-D and obesity.

Second forward view (SFV) examination of the right colon (RC) in colonoscopy was suggested to improve the adenoma detection rate (ADR), but multicenter data to inform its routine use remain limited. We performed an international multicenter randomized trial comparing SFV vs a standard single forward view examination of the RC on adenoma detection.Asymptomatic individuals undergoing screening or surveillance colonoscopies from 6 Asia Pacific regions were invited for study. A forward view examination of the RC was first performed in all patients, followed by randomization at the hepatic flexure to either SFV examination of the RC and standard withdrawal examination from the hepatic flexure to rectum, or a standard withdrawal colonoscopy (SWC) examination from the hepatic flexure to rectum. The primary outcome was RC ADR.Between 2016 and 2019, there were 1011 patients randomized (SFV group, 502 patients; SWC group, 509 patients). Forty-five endoscopists performed the colonoscopies. The RC ADR was significantly higher in the SFV group than in the SWC group (27.1% vs 21.6%; P = .042). The whole-colon ADR was high in both groups (49.0% vs 45.0%; P =.201). The SFV examination identified 58 additional adenomas in 49 patients (9.8%), leading to a change in surveillance recommendations in 15 patients (3.0%). The median overall withdrawal time was 1.5 minutes longer in the SFV group (12.0 vs 10.5 min; P.001). Older age, male sex, ever smoking, and longer RC withdrawal time were independent predictors of right-sided adenoma detection.In this multicenter trial, SFV examination significantly increased the RC ADR in screening and surveillance colonoscopies. Routine RC SFV examination should be considered. ClinicalTrials.gov ID: NCT03121495.

A significant proportion of the non-alcoholic fatty liver disease (NAFLD) population is non-obese. Prior studies reporting the severity of NAFLD amongst non-obese patients were heterogenous. Our study, using data from the largest biopsy-proven NAFLD international registry within Asia, aims to characterize the demographic, metabolic and histological differences between non-obese and obese NAFLD patients.1812 biopsy-proven NAFLD patients across nine countries in Asia assessed between 2006 and 2019 were pooled into a curated clinical registry. Demographic, metabolic and histological differences between non-obese and obese NAFLD patients were evaluated. The performance of Fibrosis-4 index for liver fibrosis (FIB-4) and NAFLD fibrosis score (NFS) to identify advanced liver disease across the varying obesity subgroups was compared. A random forest analysis was performed to identify novel predictors of fibrosis and steatohepatitis in non-obese patients.One-fifth (21.6%) of NAFLD patients were non-obese. Non-obese NAFLD patients had lower proportions of NASH (50.5% vs 56.5%, p = 0.033) and advanced fibrosis (14.0% vs 18.7%, p = 0.033). Metabolic syndrome in non-obese individuals was associated with NASH (OR 1.59, 95% CI 1.01-2.54, p = 0.047) and advanced fibrosis (OR 1.88, 95% CI 0.99-3.54, p = 0.051). FIB-4 performed better than the NFS score (AUROC 81.5% vs 73.7%, p 0.001) when classifying patients with F2-4 fibrosis amongst non-obese NAFLD patients. Haemoglobin, GGT, waist circumference and cholesterol are additional variables found on random forest analysis useful for identifying non-obese NAFLD patients with advanced liver disease.A substantial proportion of non-obese NAFLD patients has NASH or advanced fibrosis. FIB-4, compared to NFS better identifies non-obese NAFLD patients with advanced liver disease. Serum GGT, cholesterol, haemoglobin and waist circumference, which are neither components of NFS nor FIB-4, are important biomarkers for advanced liver disease in non-obese patients.

Gastric cancer is a deadly disease for which current therapeutic options are extremely limited. Vascular endothelial growth factor receptors and platelet-derived growth factor receptors regulate gastric cancer cell proliferation, invasion, and tumor angiogenesis. In the present study, we report that sorafenib therapy effectively inhibited tumor growth and angiogenesis in tumor xenografts. These were associated with reduction in the phosphorylation of vascular endothelial growth factor receptor-2 Tyr951, c-Kit Tyr568/570, platelet-derived growth factor receptor-β Tyr1021, and Akt Ser473 and Thr308, down-regulation of positive cell cycle regulators, increased apoptosis, and up-regulation of p27. Sorafenib treatment also caused up-regulation of p-c-Raf Ser338 and p-extracellular signal-regulated kinase (ERK) Thr202/Tyr204 in gastric cancer xenografts. The combination of sorafenib and MAP/ERK kinase inhibitor AZD6244 enhances the effectiveness of each compound alone. Potential effect of sorafenib/AZD6244 included increase in proapoptotic Bim. Our data show that MAP/ERK kinase inhibition enhances the antitumor activity of sorafenib in vivo, supporting a rationale for multitargeted suppression of the angiogenesis and ERK signaling network in gastric cancer therapy. [Mol Cancer Ther 2009;8(9):2537–45]

Conventional white light endoscopy remains the current standard in routine clinical practice for early detection of gastric cancer. However, it may not accurately diagnose preneoplastic gastric lesions. The technological advancements in the field of endoscopic imaging for gastric lesions are fast growing. This article reviews currently available advanced endoscopic imaging modalities, in particular chromoendoscopy, narrow band imaging and confocal laser endomicroscopy, and their corresponding evidence shown to improve diagnosis of preneoplastic gastric lesions. Raman spectrometry and polarimetry are also introduced as promising emerging technologies.