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Abstract Background The burden of cancer can be altered by screening. The field of cancer screening is constantly evolving; from the initiation of program for new cancer types as well as exploring innovative screening strategies (e.g. new screening tests). The aim of this study was to perform a landscape analysis of existing cancer screening programs in South-East Asia and the Western Pacific. Methods We conducted an overview of cancer screening in the region with the goal of summarizing current designs of cancer screening programs. First, a selective narrative literature review was used as an exploration to identify countries with organized screening programs. Second, representatives of each country with an organized program were approached and asked to provide relevant information on the organizations of their national or regional cancer screening program. Results There was wide variation in the screening strategies offered in the considered region with only eight programs identified as having an organized design. The majority of these programs did not meet all the essential criteria for being organized screening. The greatest variation was observed in the starting and stopping ages. Conclusions Essential criteria of organized screening are missed. Improving organization is crucial to ensure that the beneficial effects of screening are achieved in the long-term. It is strongly recommended to consider a regional cancer screening network.

Abstract With new advances in next generation sequencing (NGS) technology at reduced costs, research on bacterial genomes in the environment has become affordable. Compared to traditional methods, NGS provides high-throughput sequencing reads and the ability to identify many species in the microbiome that were previously unknown. Numerous bioinformatics tools and algorithms have been developed to conduct such analyses. However, in order to obtain biologically meaningful results, the researcher must select the proper tools and combine them to construct an efficient pipeline. This complex procedure may include tens of tools, each of which require correct parameter settings. Furthermore, an NGS data analysis involves multiple series of command-line tools and requires extensive computational resources, which imposes a high barrier for biologists and clinicians to conduct NGS analysis and even interpret their own data. Therefore, we established a public gut microbiome database, which we call Twnbiome, created using healthy subjects from Taiwan, with the goal of enabling microbiota research for the Taiwanese population. Twnbiome provides users with a baseline gut microbiome panel from a healthy Taiwanese cohort, which can be utilized as a reference for conducting case-control studies for a variety of diseases. It is an interactive, informative, and user-friendly database. Twnbiome additionally offers an analysis pipeline, where users can upload their data and download analyzed results. Twnbiome offers an online database which non-bioinformatics users such as clinicians and doctors can not only utilize to access a control set of data, but also analyze raw data with a few easy clicks. All results are customizable with ready-made plots and easily downloadable tables. Database URL: http://twnbiome.cgm.ntu.edu.tw/ .

Abstract Evaluating the magnitude of overdiagnosis associated with stool-based service screening for colorectal cancer (CRC) beyond a randomized controlled trial is often intractable and understudied. We aim to estimate the proportion of overdiagnosis in population-based service screening programs for CRC with the fecal immunochemical test (FIT). The natural process of overdiagnosis-embedded disease was first built up to learn transition parameters that quantify the pathway of non-progressive and progressive screen-detected cases calibrated with sensitivity, while also taking competing mortality into account. The Markov algorithms were then developed for estimating these transition parameters based on Taiwan FIT service CRC screening data on 5,417,699 residents aged 50–69 years from 2004 to 2014. Following the digital twin design with the parallel universe structure for emulating the randomized controlled trial, the screened twin, mirroring the control group without screening, was virtually recreated by the application of the above-mentioned trained parameters to predict CRC cases containing overdiagnosis. The ratio of the predicted CRCs derived from the screened twin to the observed CRCs of the control group minus 1 was imputed to measure the extent of overdiagnosis. The extent of overdiagnosis for invasive CRCs resulting from FIT screening is 4.16% (95% CI: 2.61–5.78%). The corresponding figure is increased to 9.90% (95% CI: 8.41–11.42%) for including high grade dysplasia (HGD) and further inflated to 15.83% (95% CI: 15.23–16.46%) when the removal adenoma is considered. The modest proportion of overdiagnosis modelled by the digital twin method, dispensing with the randomized controlled trial design, suggests the harm done to population-based FIT service screening is negligible.

Background/Aims Anti-reflux mucosal ablation (ARMA) is a promising endoscopic intervention for proton pump inhibitor (PPI)-dependent gastroesophageal reflux disease (GERD). However, the effect of ARMA on esophageal motility remains unclear. Methods Twenty patients with PPI-dependent GERD receiving ARMA were prospectively enrolled. Comprehensive self-report symptom questionnaires, endoscopy, 24-hour impedance-pH monitoring, and high-resolution impedance manometry were performed and analyzed before and 3 months after ARMA. Results All ARMA procedures were performed successfully. Symptom scores, including GerdQ (11.16 ± 2.67 to 9.11 ± 2.64, P = 0.026) and reflux symptom index (11.63 ± 5.62 to 6.11 ± 3.86, P = 0.001), improved significantly, while 13 patients (65%) reported discontinuation of PPI. Total acid exposure time (5.84 ± 4.63% to 2.83 ± 3.41%, P = 0.024) and number of reflux episodes (73.05 ± 19.34 to 37.55 ± 22.71, P < 0.001) decreased significantly after ARMA. Improved esophagogastric junction (EGJ) barrier function, including increased lower esophageal sphincter resting pressure (13.89 ± 10.78 mmHg to 21.68 ± 11.5 mmHg, P = 0.034), 4-second integrated relaxation pressure (5.75 ± 6.42 mmHg to 9.99 ± 5.89 mmHg, P = 0.020), and EGJ-contractile integral (16.42 ± 16.93 mmHg·cm to 31.95 ± 21.25 mmHg·cm, P = 0.016), were observed. Esophageal body contractility also increased significantly (distal contractile integral, 966.85 ± 845.84 mmHg·s·cm to 1198.8 ± 811.74 mmHg·s·cm, P = 0.023). Patients with symptom improvement had better pre-AMRA esophageal body contractility. Conclusions ARMA effectively improves symptoms and reflux burden, EGJ barrier function, and esophageal body contractility in patients with PPIdependent GERD during short-term evaluation. Longer follow-up to clarify the sustainability of ARMA is needed. [ABSTRACT FROM AUTHOR]

Abstract Background Serum pepsinogen (PG) is recommended as a screening test for premalignant gastric lesions. However, real-world evidence demonstrating its applicability and equivalence between different test brands is limited. Methods Mass screening began in 2018 in a high-risk Taiwanese population after eradication of Helicobacter pylori, with the first stage of two PG tests (GastroPanel®, Helsinki, Finland and LZ-Test®, Tokyo, Japan) and the second stage of endoscopy. A positive test was defined as PG-I

Abstract Background Late cancellations of physical examination has severe impact on the operations of a physical examination center since it is often too late to fill vacancy. A booking control policy that considers overbooking is then one natural solution. Unlike appointment scheduling problems for clinics and hospitals, in which treating a patient mostly requires only one type of resource, a physical examination set typically requires multiple types of resources. Traditional methods that do not consider set-resource relationship thus may be inapplicable. Methods We formulate a stochastic mathematical programming model that maximizes the expected net reward, which is the examination revenue minus overage cost. A complete search algorithm and a greedy search algorithm are designed to search for optimal booking limits for all examination sets. To estimate the late cancellation probability for each individual consumer, we apply logistic regression to identify significant factors affecting the probability. After clustering is used to estimate individual probabilities, Monte Carlo simulation is conducted to generate probability distributions for the number of consumers without late cancellations. A discrete-event simulation is performance to evaluate the effectiveness of our proposed solution. Results We collaborate with a leading physical examination center to collect real data to evaluate our proposed overbooking policies. We show that the proposed overbooking policy may significantly increase the expected net reward. Our simulation results also help us understand the impact of overbooking on the expected number of customers and expected overage. A sensitivity analysis is conducted to demonstrate that the benefit of overbooking is insensitive to the accuracy of cost estimation. A Pareto efficiency analysis gives practitioners suggestions regarding policy determination considering multiple performance indications. Conclusions Our proposed overbooking policies may greatly enhance the overall performance of a physical examination center.

BackgroundMutations in leucine-rich repeat kinase 2 (LRRK2) comprise a common genetic risk factor for Parkinson’s disease (PD) and inflammatory bowel disease (IBD). We investigated the expression of LRRK2 in colonic biopsies obtained from a cohort of PD patients and healthy controls.MethodsA cohort of 51 PD patients and 40 age- and gender-matched controls who have colonic biopsied samples were recruited. Among these participants, 26 individuals (12 PD patients and 14 controls) had a series of colon biopsies. For the patients with PD, the first biopsies were taken before the PD diagnosis. The colonic expression of LRRK2 was assayed by immunohistochemical staining.ResultsThe fraction of LRRK2-positive cells among the total cell count in biopsied colonic tissues was significantly higher in PD patients than controls (0.81% ± 0.53% vs. 0.45% ± 0.39%; P = 0.02). Colonic LRRK2 immunoreactivity was higher in those with LRRK2 genetic variants compared to those with wild type LRRK2 (2.44% ± 1.15% vs. 0.21 ± 0.13%, P < 0.01). Age had no effect on LRRK2 expression (P = 0.96). LRRK2 expression correlated with disease severity in regards to motor symptoms measured by the UPDRS part III scores (r = 6335, P < 0.001) and cognitive dysfunction measured by the mini-mental status examination scores (r = -0.5774, P < 0.001). PD patients in the prodromal phase had a steeper increase in colonic LRRK2 expression compared to controls during the serial colon biopsy assessment (P < 0.01).ConclusionColonic LRRK2 expression was increased in PD patients compared to controls, and the expression level correlated with disease severity.

Background/ObjectivesPolycystic ovary syndrome (PCOS) and irritable bowel syndrome (IBS) share similar clinical and psychosocial features. We aimed to investigate the clinical characteristics of IBS in women with PCOS, and its relationship with obesity, metabolic and hormonal profiles, as well as sleep and psychiatric disorders.Subjects/MethodsThis is a cross-sectional case-control study of 431 untreated women with PCOS and 259 healthy volunteers. All participants were assessed with a comprehensive clinical evaluation and two questionnaires: the Athens Insomnia Scale (AIS) and the Brief Symptom Rating Scale (BSRS-5). IBS was diagnosed using the Rome III criteria. Obesity was defined as a BMI ≥30 kg/m2. Anthropometric measurements, metabolic, hormonal profiles, and psychosocial morbidities were compared.ResultsWomen with PCOS were more likely to have IBS (10.7% vs 5.8%, p=0.029) and obesity (29% vs 4%, p

BackgroundPatient participation in colorectal cancer (CRC) screening via a stool test and colonoscopy is suboptimal, but participation can be improved by the development of a blood test. However, the suboptimal detection abilities of blood tests for advanced neoplasia, including advanced adenoma (AA) and CRC, limit their application. We aimed to investigate the proteomic landscape of small extracellular vesicles (sEVs) from the serum of patients with colorectal neoplasia and identify specific sEV proteins that could serve as biomarkers for early diagnosis.Materials and MethodsWe enrolled 100 patients including 13 healthy subjects, 12 non-AAs, 13 AAs, and 16 stage-I, 15 stage-II, 16 stage-III, and 15 stage-IV CRCs. These patients were classified as normal control, early neoplasia, and advanced neoplasia. The sEV proteome was explored by liquid chromatography-tandem mass spectrometry. Generalized association plots were used to integrate the clustering methods, visualize the data matrix, and analyze the relationship. The specific sEV biomarkers were identified by a decision tree via Orange3 software. Functional enrichment analysis was conducted by using the Ingenuity Pathway Analysis platform.ResultsThe sEV protein matrix was identified from the serum of 100 patients and contained 3353 proteins, of which 1921 proteins from 98 patients were finally analyzed. Compared with the normal control, subjects with early and advanced neoplasia exhibited a distinct proteomic distribution in the data matrix plot. Six sEV proteins were identified, namely, GCLM, KEL, APOF, CFB, PDE5A, and ATIC, which properly distinguished normal control, early neoplasia, and advanced neoplasia patients from each other. Functional enrichment analysis revealed that APOF+ and CFB+ sEV associated with clathrin-mediated endocytosis signaling and the complement system, which have critical implications for CRC carcinogenesis.ConclusionPatients with colorectal neoplasia had a distinct sEV proteome expression pattern in serum compared with those patients who were healthy and did not have neoplasms. Moreover, the six identified specific sEV proteins had the potential to discriminate colorectal neoplasia between early-stage and advanced neoplasia. Collectively, our study provided a six-sEV protein biomarker panel for CRC diagnosis at early or advanced stages. Furthermore, the implication of the sEV proteome in CRC carcinogenesis via specific signaling pathways was explored.

Background/purpose: Although performing balloon enteroscopy soon after the onset of small bowel bleeding appeared to enhance diagnostic rate, the optimal timing was unclear. Methods: A retrospective cohort study in a single referral center. Patients with overt, suspected small bowel bleeding who underwent primary single-balloon enteroscopy (SBE) were evaluated to determine the association between procedure timing and diagnostic yield rates. Results: A total of 220 patients were enrolled (47.7% males; mean age, 65.6 ± 18.1 years). They were stratified into four groups based on the timing of SBE: emergency (7 days (n = 87). A significant trend of decreasing diagnostic yields was observed across the groups (90.6%, 67.9%, 68.3%, and 44.8%, respectively, P 7 days groups (P

Abstract Background Although fecal hemoglobin concentration (f-Hb) was highly associated with the risk of colorectal neoplasms, current studies on this subject are hampered by skewedness of the data and the ordinal property of f-Hb has not been well studied yet. Our aim was to develop a quantile-based method to estimate adjusted percentiles (median) of fecal hemoglobin concentration and their derived prediction for the risk of multistage outcomes of colorectal disease. Methods We used a 6-year follow-up cohort of Taiwanese nationwide colorectal screening program with fecal immunochemical testing (FIT) to obtain fecal hemoglobin concentration and applied accelerated failure time multi-variable analyses to make the comparison of adjusted median and other percentitles of fecal hemoglobin across four categories of colorectal carcinogenesis. We then predicted the risk of colorectal neoplasms on the basis of the corresponding percentile values by using accelerated failure time model with Bayesian inversion method. Results The adjusted median fecal hemoglobin concentration of nonadvanced adenoma, advanced adenoma, and colorectal cancer were 57, 82, and 163 μg/g feces as opposed to 0 μg/g feces for the normal group. At 90 μg/g of f-Hb, the highly suspected cut-off for colorectal disease, the risks were 17% for non-advanced adenoma, 6% for advanced adenoma, and 9% for CRC. Life-time risks of each colorectal neoplasm were derived by percentiles of fecal hemoglobin concentration. Conclusion Covariate-adjusted risk stratification for multistage outcomes of colorectal neoplasia were provided by using the quantiles of fecal hemoglobin concentration, yielding the estimated life-time risks of 25th to 75th quantitles, ranging from 0.5 to 44% for colorectal cancer, 0.2 to 46% for non-advanced adenoma, and 0.1 to 20% for advanced adenoma.

The roles of ambient fine particulate matter (PM 2.5 ) in the prevention of colorectal cancer (CRC) have been scarcely highlighted as there is short of empirical evidence regarding the influences of PM 2.5 on multistep carcinogenic processes of CRC. A retrospective cohort design with multistate outcomes was envisaged by linking monthly average PM 2.5 concentrations at 22 city/county level with large-scale cohorts of cancer-screened population to study the influences of PM 2.5 on short-term inflammatory process and multistep carcinogenic processes of CRC. Our study included a nationwide CRC screening cohort of 4,628,995 aged 50–69 years who attended first screen between 2004 and 2009 and continued periodical screens until 2016. We aimed to illustrate the carcinogenesis of PM 2.5 related to CRC by applying both hierarchical logistical and multistate Markov regression models to estimate the effects of air pollution on fecal immunochemical test (FIT) positive (a proxy of inflammatory marker) and pre-clinical and clinical states of CRC in the nationwide cohort. We found a significant association of high PM 2.5 exposure and FIT-positive by an increased risk of 11% [95% confidence interval (CI), 10–12]. PM 2.5 enhanced the risk of being preclinical state by 14% (95% CI, 10–18) and that of subsequent progression from pre-clinical to clinical state by 21% (95% CI, 14–28). Furthermore, the elevated risks for CRC carcinogenesis were significantly higher for people living in high PM 2.5 pollution areas in terms of yearly averages and the number days above 35 µg/m 3 than those living in low PM 2.5 pollution areas. We concluded that both short-term and long-term PM 2.5 exposure were associated with multistep progression of CRC, which were useful to design precision primary and secondary prevention strategies of CRC for people who are exposed to high PM 2.5 pollution.

Abstract Background Colorectal cancer remains a considerable challenge in healthcare nowadays. Most patients’ disease develops via the adenoma–carcinoma sequence; colonoscopy with polypectomy effectively reduces both mortality and incidence by removing precancerous adenomas. Previous studies showed that polypectomy without electrocautery (cold snaring polypectomy) is a safe and time-saving procedure to manage polyps

Colorectal cancer (CRC) is the most common cancer in Taiwan, and is the third leading cause of cancer-related death. Screening has been proven the most effective way to reduce CRC mortality, and stool-based screening is currently the most popular method of screening worldwide. In 2004, Taiwanese government launched a nationwide screening program and fecal immunochemical test (FIT) is offered biennially to individuals aged 50 to 75. The results from the program have demonstrated that FIT screening could effectively reduce the mortality from CRC.Nevertheless, there were some problems needed to deal with. First, the occurrence of interval cancers, which are associated with the performance of screening tests or quality of colonoscopy, has affected the program sensitivity. Second, increasing participation in the program has increased the demand for colonoscopy and the burden on public health workers. Third, some individuals are non-compliant with FIT screening, and with the recommendation for colonoscopy after a positive FIT, which may be the result of insufficient awareness toward CRC and screening of the public. Fourth, long-lasting financial support for this program is necessary for its success. All of these problems need to be solved via collaboration between the screening organizer, screening distributor, and professional societies. Keywords: Colonoscopy, Colorectal cancer, Fecal immunochemical test, Mortality, Screening

IntroductionMany health organizations have promoted the importance of the health-related benefits of physical fitness and physical activity. Studies have evaluated effective public health practice aiming to understand the cognition of physical activity among youths and adolescents. However, studies investigating the level of cognition and knowledge of physical fitness among Asian adults are lacking.PurposeThis study aimed to investigate the self-awareness level of physical fitness and exercise prescription and the demand for physical fitness assessment among Taiwanese adults.MethodsIn January-July 2019, a cross-sectional anonymous survey was conducted using Research Electronic Data Capture to gather data on demographic data, cognition investigation of physical fitness and exercise prescription, cognitive test of physical fitness and exercise prescription, and demand for physical fitness assessment.ResultsThe questionnaire was answered by 200 respondents. The rating for cognition investigation of physical fitness was 2.63-3.13 (unclear to mostly clear) and for exercise prescription was 2.05-2.76 (unclear) (rated on a 5-point Likert scale). Results show that lack of awareness was highest for health-related physical fitness, exercise prescription, and exercise progress planning. 98% of subjects did not know the latest recommended guidelines for physical activity, despite most agreeing that physical fitness and exercise are good for health. Most subjects (72%) indicated a willingness to accept self-pay service for physical fitness assessments.ConclusionsThis is the first study to report on the demand for cognition, assessment, and promotion of physical fitness among Taiwanese adults. The study shows that the subjects widely lack knowledge in the cognition of physical fitness and exercise prescription. Furthermore, a self-pay service for the physical fitness assessment and individualized exercise prescription were acceptable to most subjects, especially those undergoing regular health examinations. The findings are encouraging and will aid support for health organizations and professionals in the development and management of promotion strategies on health-related physical fitness in preventive medicine and health promotion.

Background and study aims Image enhanced endoscopy (IEE) allows endoscopists to improve recognition and characterization of gastrointestinal neoplasia. The Asian Novel Bio-Imaging and Intervention Group (ANBIG) conducted a standardized training program in endoscopic diagnosis and treatment of early gastrointestinal cancers in Asia. We embarked on a study to investigate the effect of this module on endoscopic diagnosis of early gastrointestinal neoplasia. Methods This prospectively collected database was from workshops conducted on training for endoscopic diagnosis of early gastrointestinal neoplasia. All workshops were conducted in a standardized format, which included a pretest, a learning phase consisting of didactic lectures, case discussion, and live demonstration followed by a post-test to assess knowledge gained. The pretest and post-training tests were standardized questions addressing four domains, including basic knowledge of imaging and diagnosis of esophageal, gastric, and colonic neoplasia. Results From November 2013 to November 2016, 41 ANBIG workshops were conducted in 13 countries. A total of 1863 delegates and 40 faculty participated in these workshops. Of the delegates, 627 completed both tests. There was a significant improvement after training in all domains of the tests. There was a trend in general lack of knowledge across all domains for delegates from “low” healthcare cost countries before training. All delegates demonstrated significant improvement in knowledge of all domains after the workshop irrespective of whether they were from “high” or “low” healthcare cost per capita countries. Conclusion A standardized teaching program on IEE improved the diagnostic ability and quality of endoscopists in recognizing early gastrointestinal neoplasia in Asia.

Background and study aims Cold snare polypectomy (CSP) is considered to be effective in reducing risk of delayed bleeding but randomized trials fail to support this owing to the small sample size. The current study aimed to compare risk of delayed bleeding before and after implementation of CSP in a screening colonoscopy setting. Patients and methods This study retrospectively analyzed a prospectively maintained screening colonoscopy database in a university hospital in Taiwan. We compared the rate of delayed bleeding before and after implementation within similar periods (18 months and 15 months) and the respective number of polypectomies (1,304 and 1,255) performed to remove small and diminutive polyps. The main outcome measurement was delayed bleeding within the two periods. Multivariate analysis was performed to adjust for major confounders. Results A total of 1,304 and 1,225 subjects received hot snare polypectomy (HSP) and CSP in two separate periods, respectively. Compared with the HSP, the CSP had a lower rate of delayed bleeding (0.1 % vs. 1.1 %, P

An alternative screening test is needed to efficiently eradicate Helicobacter pylori from a population with prevalent upper gastrointestinal lesions. We evaluated the performance of a new one-step fecal test for H. pylori for diagnosis of H. pylori infection in Taiwan. Methods: We developed a fecal test to detect H. pylori based on the immunochronomatographic assay and a mixture of monoclonal antibodies. We first recruited symptomatic patients from the primary care setting to evaluate fecal test performance using a reference standard consisting of 13C urea breath test, rapid urease test, and histology. We also compared the performance of the fecal test with that of others. Next, we recruited asymptomatic participants from the mass screening setting to evaluate population attendance for the fecal test and compared its performance with that of 13C urea breath test. Results: In the primary care setting, 117 patients were recruited; H. pylori infection was confirmed in 58 (49.6%). Fecal test sensitivity, specificity, positive and negative predictive values, and accuracy were 88.0% [95% confidence interval (CI): 79.6–96.4%], 100%, 100%, 89.4% (95% CI, 82.0–96.8%), and 94% (95% CI, 89.7–98.3%), respectively. Fecal test specificity and positive predictive value were significantly higher than those of the serological test, whereas the sensitivity and negative predictive value were lower than those of the 13C urea breath test (p

Screening colonoscopy is one of the most effective methods to detect and prevent colorectal cancer by removing neoplastic polyps. The recent discovery of serrated polyps with neoplastic potential has reclassified these polyps into hyperplastic polyps (HPs), sessile serrated adenoma (SSA), and traditional serrated adenoma (TSA) on the basis of macroscopic morphology and microscopic histology. In this study, we aimed to revisit HPs identified during screening endoscopy by histological reevaluation and genetic alterations. Methods: A total of 253 HPs found by screening endoscopy were rechecked by two pathologists, and mutual agreement on the diagnosis of polyps was subjected for further statistical analysis. Direct sequencing for gene mutation at BRAF V600E and KRAS G12D was performed. Results: Among the 253 HPs analyzed, 175 were classified as serrated polyps, while 78 were reclassified into other diagnosis. The concordance among pathologists in diagnosing these serrated polyps was substantial (κ = 0.6672). About 11.5% of the reviewed HPs turned out to be with neoplastic potential, including 7 SSAs, 5 TSAs, as well as 17 conventional adenomas. Results of subgroup analyses revealed that polyps >10 mm were more likely to be found in proximal colon (p = 0.0006) and tended to harbor neoplastic components. We found that two SSAs and one TSA had BRAF mutation, while one TSA had KRAS mutation. The mean size of these mutated adenomas (9.0 mm) was larger than those with wild-type genes (4.9 mm). Conclusion: Serrated polyps with neoplastic potential were prone to be overlooked as hyperplastic and innocent ones during screening colonoscopy. Therefore, both endoscopists and pathologists should pay attention to understand the importance of recognizing serrated adenomas, especially for those polyps >10 mm, or those that are located in the proximal colon.

The prevalence of metabolic syndrome (MS) has increased rapidly in Taiwan and worldwide. We aim to determine the association between sleep-disordered breathing (SDB) and MS in a Chinese general population.This case-control study recruited subjects who have undergone a prospective electrocardiogram-based cardiopulmonary coupling (CPC) sleep spectrogram as part of the periodic health check-ups at the National Taiwan University Hospital. Comprehensive anthropometrics, blood biochemistry, prevalence of MS and its individual components were compared with Bonferroni correction between 40 subjects with SDB, defined as the CPC-derived apnea-hypopnea index (CPC-AHI) >5 event/hour and 80 age- and sex-matched controls, defined as CPC-AHI

Gut microbial metabolism of L-carnitine, which leads to the production of detrimental trimethylamine N-oxide (TMAO), offers a plausible link between red meat consumption and cardiovascular risks. Several microbial genes, including cntA/B, the cai operon, and the recently identified gbu gene cluster, have been implicated in the conversion of dietary L-carnitine into TMA(O). However, the key microbial genes and associated gut microbes involved in this pathway have not been fully explored. Utilizing the oral carnitine challenge test (OCCT), which specifically measures TMAO production from L-carnitine intake and identifies TMAO producer phenotypes, we compared the abundance of microbial genes between low- and high-TMAO producers across three independent cohorts. Our findings consistently revealed that the gbu gene cluster, rather than cntA/B or the cai operon, was significantly enriched in high-TMAO producers. We further analyzed 292 paired multi-omic datasets from OCCT and shotgun metagenomic sequencing, which demonstrated a significant positive correlation between the abundance of fecal gbu genes and L-carnitine-induced TMAO production, with gbuB showing the strongest correlation. Interestingly, these fecal gbu genes were found to increase with L-carnitine supplementation and decrease with a plant-based diet. Notably, we verified a previously uncultured gbu-containing bacterium, JAGTTR01 sp018223385, as the major contributor to TMA formation in the human gut. We isolated these gbu-containing gut microbes and confirmed their role in TMA/TMAO production using anaerobic incubation and a gnotobiotic mouse model. Using an in-house collection of gbu-containing isolates, we developed a qPCR-based method to quantify fecal gbuB and validated its correlation with L-carnitine-mediated TMAO production as measured by OCCT. Overall, these findings suggest that gbu-containing gut microbes are crucial for TMAO increases following L-carnitine intake and may serve as biomarkers or targets for personalized nutrition.