Distinct changes in serum metabolites and lipid species in the onset and progression of NAFLD in Obese Chinese.

Introduction: Metabolic disturbances are major contributors to the onset and progression of non-alcoholic fatty liver disease (NAFLD), which includes a histological spectrum ranging from single steatosis (SS) to non-alcoholic steatohepatitis (NASH). This study aimed to identify serum metabolites and lipids enriched in different histological stages of NAFLD and to explore metabolites/lipids as non-invasive biomarkers in risk prediction of NAFLD and NASH in obese Chinese. Methods: Serum samples and liver biopsies were obtained from 250 NAFLD subjects. Untargeted metabolomic and lipidomic profiling were performed using Liquid Chromatography-Mass Spectrometry. Significantly altered metabolites and lipids were identified by MaAsLin2. Pathway enrichment was conducted with MetaboAnalyst and LIPEA. WGCNA was implemented to construct the co-expression network. Logistic regression models were developed to classify different histological stages of NAFLD. Results: A total of 263 metabolites and 550 lipid species were detected in serum samples. Differential analysis and pathway enrichment analysis revealed the progressive patterns in metabolic mechanisms during the transition from normal liver to SS and to NASH, including N-palmitoyltaurine, tridecylic acid, and branched-chain amino acid signaling pathways. The co-expression network showed a distinct correlation between different triglyceride and phosphatidylcholine species with disease severity. Multiple models classifying NAFLD versus normal liver and NASH versus SS identified important metabolic features associated with significant improvement in disease prediction compared to conventional clinical parameters. Conclusion: Different histological stages of NAFLD are enriched with distinct sets of metabolites, lipids, and metabolic pathways. Integrated algorithms highlight the important metabolic and lipidomic features for diagnosis and staging of NAFLD in obese individuals.

Ten metabolites-based algorithm predicts the future development of type 2 diabetes in Chinese.

INTRODUCTION: Type 2 diabetes (T2D) is a heterogeneous metabolic disease with large variations in the relative contributions of insulin resistance and ß-cell dysfunction across different glucose tolerance subgroups and ethnicities. A more precise yet feasible approach to categorize risk preceding T2D onset is urgently needed. This study aimed to identify potential metabolic biomarkers that could contribute to the development of T2D and investigate whether their impact on T2D is mediated through insulin resistance and ß-cell dysfunction. METHODS: A non-targeted metabolomic analysis was performed in plasma samples of 196 incident T2D cases and 196 age- and sex-matched non-T2D controls recruited from a long-term prospective Chinese community-based cohort with a follow-up period of âˆ¼ 16 years. RESULTS: Metabolic profiles revealed profound perturbation of metabolomes before T2D onset. Overall metabolic shifts were strongly associated with insulin resistance rather than ß-cell dysfunction. In addition, 188 out of the 578 annotated metabolites were associated with insulin resistance. Bi-directional mediation analysis revealed putative causal relationships among the metabolites, insulin resistance and T2D risk. We built a machine-learning based prediction model, integrating the conventional clinical risk factors (age, BMI, TyG index and 2hG) and 10 metabolites (acetyl-tryptophan, kynurenine, γ-glutamyl-phenylalanine, DG(18:2/22:6), DG(38:7), LPI(18:2), LPC(P-16:0), LPC(P-18:1), LPC(P-20:0) and LPE(P-20:0)) (AUROC = 0.894, 5.6% improvement comparing to the conventional clinical risk model), that successfully predicts the development of T2D. CONCLUSIONS: Our findings support the notion that the metabolic changes resulting from insulin resistance, rather than ß-cell dysfunction, are the primary drivers of T2D in Chinese adults. Metabolomes as a valuable phenotype hold potential clinical utility in the prediction of T2D.

Specific triacylglycerol, diacylglycerol, and lyso-phosphatidylcholine species for the prediction of type 2 diabetes: a ~ 16-year prospective study in Chinese.

BACKGROUND: Bioactive lipids play an important role in insulin secretion and sensitivity, contributing to the pathophysiology of type 2 diabetes (T2D). This study aimed to identify novel lipid species associated with incident T2D in a nested case-control study within a long-term prospective Chinese community-based cohort with a median follow-up of ~ 16 years. METHODS: Plasma samples from 196 incident T2D cases and 196 age- and sex-matched non-T2D controls recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS) were first analyzed using untargeted lipidomics. Potential predictive lipid species selected by the Boruta analysis were then verified by targeted lipidomics. The associations between these lipid species and incident T2D were assessed. Effects of novel lipid species on insulin secretion in mouse islets were investigated. RESULTS: Boruta analysis identified 16 potential lipid species. After adjustment for body mass index (BMI), triacylglycerol/high-density lipoprotein (TG/HDL) ratio and the presence of prediabetes, triacylglycerol (TG) 12:0_18:2_22:6, TG 16:0_11:1_18:2, TG 49:0, TG 51:1 and diacylglycerol (DG) 18:2_22:6 were independently associated with increased T2D risk, whereas lyso-phosphatidylcholine (LPC) O-16:0, LPC P-16:0, LPC O-18:0 and LPC 18:1 were independently associated with decreased T2D risk. Addition of the identified lipid species to the clinical prediction model, comprised of BMI, TG/HDL ratio and the presence of prediabetes, achieved a 3.8% improvement in the area under the receiver operating characteristics curve (AUROC) (p = 0.0026). Further functional study revealed that, LPC O-16:0 and LPC O-18:0 significantly potentiated glucose induced insulin secretion (GSIS) in a dose-dependent manner, whereas neither DG 18:2_22:6 nor TG 12:0_18:2_22:6 had any effect on GSIS. CONCLUSIONS: Addition of the lipid species substantially improved the prediction of T2D beyond the model based on clinical risk factors. Decreased levels of LPC O-16:0 and LPC O-18:0 may contribute to the development of T2D via reduced insulin secretion.

Factors associated with high compliance behaviour against COVID-19 in the early phase of pandemic: a cross-sectional study in 12 Asian countries.

INTRODUCTION: Regardless of having effective vaccines against COVID-19, containment measures such as enhanced physical distancing and good practice of personal hygiene remain the mainstay of controlling the COVID-19 pandemic. Countries across Asia have imposed these containment measures to varying extents. However, residents in different countries would have a differing degree of compliance to these containment measures potentially due to differences in the level of awareness and motivation in the early phase of pandemic. OBJECTIVES: In our study, we aimed to describe and correlate the level of knowledge and attitude with the level of compliance with personal hygiene and physical distancing practices among Asian countries in the early phase of pandemic. METHODS: A multinational cross-sectional study was carried out using electronic surveys between May and June 2020 across 14 geographical areas. Subjects aged 21 years and above were invited to participate through social media, word of mouth and electronic mail. RESULTS: Among the 2574 responses obtained, 762 (29.6%) participants were from East Asia and 1812 (70.4%) were from Southeast Asia (SEA). A greater proportion of participants from SEA will practise physical distancing as long as it takes (72.8% vs 60.6%). Having safe distancing practices such as standing more than 1 or 2 m apart (AdjOR 5.09 95% CI (1.08 to 24.01)) or more than 3 or 4 m apart (AdjOR 7.05 95% CI (1.32 to 37.67)), wearing a mask when they had influenza-like symptoms before the COVID-19 pandemic, preferring online news channels such as online news websites/applications (AdjOR 1.73 95% CI (1.21 to 2.49)) and social media (AdjOR 1.68 95% CI (1.13 to 2.50) as sources of obtaining information about COVID-19 and high psychological well-being (AdjOR 1.39 95% CI (1.04 to 1.87)) were independent factors associated with high compliance. CONCLUSIONS: We found factors associated with high compliance behaviour against COVID-19 in the early phase of pandemic and it will be useful to consider them in risk assessment, communication and pandemic preparedness.

Association between well-being and compliance with COVID-19 preventive measures by healthcare professionals: A cross-sectional study.

IMPORTANCE: Knowledge and attitude influence compliance and individuals' practices. The risk and protective factors associated with high compliance to these preventive measures are critical to enhancing pandemic preparedness. OBJECTIVE: This survey aims to assess differences in mental health, knowledge, attitudes, and practices (KAP) of preventive measures for COVID-19 amongst healthcare professionals (HCP) and non-healthcare professionals. DESIGN: Multi-national cross-sectional study was carried out using electronic surveys between May-June 2020. SETTING: Multi-national survey was distributed across 36 countries through social media, word-of-mouth, and electronic mail. PARTICIPANTS: Participants ≥21 years working in healthcare and non-healthcare related professions. MAIN OUTCOME: Risk factors determining the difference in KAP towards personal hygiene and social distancing measures during COVID-19 amongst HCP and non-HCP. RESULTS: HCP were significantly more knowledgeable on personal hygiene (AdjOR 1.45, 95% CI -1.14 to 1.83) and social distancing (AdjOR 1.31, 95% CI -1.06 to 1.61) compared to non-HCP. They were more likely to have a positive attitude towards personal hygiene and 1.5 times more willing to participate in the contact tracing app. There was high compliance towards personal hygiene and social distancing measures amongst HCP. HCP with high compliance were 1.8 times more likely to flourish and more likely to have a high sense of emotional (AdjOR 1.94, 95% CI (1.44 to 2.61), social (AdjOR 2.07, 95% CI -1.55 to 2.78), and psychological (AdjOR 2.13, 95% CI (1.59-2.85) well-being. CONCLUSION AND RELEVANCE: While healthcare professionals were more knowledgeable, had more positive attitudes, their higher sense of total well-being was seen to be more critical to enhance compliance. Therefore, focusing on the well-being of the general population would help to enhance their compliance towards the preventive measures for COVID-19.

Impact of the coronavirus disease 2019 pandemic on irritable bowel syndrome.

BACKGROUND AND AIM: Gastrointestinal manifestations of the coronavirus disease 2019 (COVID-19) pandemic may mimic irritable bowel syndrome (IBS), and social distancing measures may affect IBS patients negatively. We aimed to study the impact of COVID-19 on respondents with self-reported IBS. METHODS: We conducted an anonymized survey from May to June 2020 in 33 countries. Knowledge, attitudes, and practices on personal hygiene and social distancing as well as psychological impact of COVID-19 were assessed. Statistical analysis was performed to determine differences in well-being and compliance to social distancing measures between respondents with and without self-reported IBS. Factors associated with improvement or worsening of IBS symptoms were evaluated. RESULTS: Out of 2704 respondents, 2024 (74.9%) did not have IBS, 305 (11.3%) had self-reported IBS, and 374 (13.8%) did not know what IBS was. Self-reported IBS respondents reported significantly worse emotional, social, and psychological well-being compared with non-IBS respondents and were less compliant to social distancing measures (28.2% vs 35.3%, P = 0.029); 61.6% reported no change, 26.6% reported improvement, and 11.8% reported worsening IBS symptoms. Higher proportion of respondents with no change in IBS symptoms were willing to practice social distancing indefinitely versus those who deteriorated (74.9% vs 51.4%, P = 0.016). In multivariate analysis, willingness to continue social distancing for another 2-3 weeks (vs longer period) was significantly associated with higher odds of worsening IBS. CONCLUSION: Our study showed that self-reported IBS respondents had worse well-being and compliance to social distancing measures than non-IBS respondents. Future research will focus on occupational stress and dietary changes during COVID-19 that may influence IBS.

Atopic Patients Who Fulfilled Rome III Criteria for Irritable Bowel Syndrome Had Higher Animal Danders Sensitization.

BACKGROUND/AIMS: The relationship between animal exposure and irritable bowel syndrome (IBS) is debated. Epidemiological studies have shown that atopy is more prevalent in IBS patients and vice versa. We set out to examine the association between animal danders sensitization and IBS-like symptoms in atopic patients. METHODS: We recruited 69 consecutive atopic patients from the allergy clinic of a tertiary hospital. Subjects completed validated bowel questionnaires, underwent skin prick test, blood was collected for serum total immunoglobulin E, and ImmunoCAP immune solidphase allergen chip (ISAC) IgE multiplex assay. RESULTS: Twenty-eight (41.0%) atopic patients fulfilled the Rome III IBS criteria (atopy-IBS). There were no differences in gender, age, pet ownership, total serum IgE, or food allergen sensitization between atopy-IBS group and atopy-non-IBS group. We found that atopy- IBS group had significantly higher number of positive skin prick test for cat dander (64.3% vs 24.4%, P < 0.001), dog dander (64.3% vs 41.5%, P = 0.015) and weed pollens (32.1% vs 14.6%, P = 0.050) compared to atopy-non-IBS group. Out of 112 components from 51 allergen sources (both aeroallergen and food allergens), only Fel d1 (a major cat dander antigen) IgE is significantly higher in atopy-IBS group than atopy-non-IBS group (21.4% vs 2.4%, P = 0.029). Majority of atopy-IBS patients had mixed-type IBS. CONCLUSIONS: We demonstrated an association between animal danders sensitization, in particular cat dander sensitization, and IBS-like symptoms in atopic patients. Future studies are needed to explore the relationship between aeroallergen and functional gastrointestinal disorders. Sensitization may be related to the pathophysiology of IBS or it could be that we are missing aeroallergen-induced gut allergy.

Gut Microbiome Fermentation Determines the Efficacy of Exercise for Diabetes Prevention.

Exercise is an effective strategy for diabetes management but is limited by the phenomenon of exercise resistance (i.e., the lack of or the adverse response to exercise on metabolic health). Here, in 39 medication-naive men with prediabetes, we found that exercise-induced alterations in the gut microbiota correlated closely with improvements in glucose homeostasis and insulin sensitivity (clinicaltrials.gov entry NCT03240978). The microbiome of responders exhibited an enhanced capacity for biosynthesis of short-chain fatty acids and catabolism of branched-chain amino acids, whereas those of non-responders were characterized by increased production of metabolically detrimental compounds. Fecal microbial transplantation from responders, but not non-responders, mimicked the effects of exercise on alleviation of insulin resistance in obese mice. Furthermore, a machine-learning algorithm integrating baseline microbial signatures accurately predicted personalized glycemic response to exercise in an additional 30 subjects. These findings raise the possibility of maximizing the benefits of exercise by targeting the gut microbiota.

A symptom severity questionnaire for patients suffering from functional gastrointestinal disorder: FGI-Checklist.

BACKGROUND AND AIM: A well-validated, comprehensive checklist of functional gastrointestinal (FGI) disorder (FGID) symptom severity for tracking symptom profile changes over time is lacking. We aim to develop and validate a comprehensive symptom severity checklist for FGID. METHODS: A 20-item scale, including both upper and lower gastrointestinal symptoms, was generated to measure the symptom severity commonly found in FGID. Patients who experienced at least monthly symptoms of FGID with negative endoscopy findings were invited to complete the FGI-Checklist, Patient Health Questionaire-9 for assessing depressive symptoms, and Patient Health Questionnaire-15 for assessing somatic symptoms at baseline. A subset of patients who met Rome III diagnostic criteria of gastroesophageal reflux disease, functional dyspepsia, and irritable bowel syndrome received medication treatment for 8-12 weeks and completed the FGI-Checklist again at a follow-up visit. Exploratory factor analysis was performed for subscales formation and psychometric properties were measured. RESULTS: Six hundred and forty-one patients were recruited for current study and 108 (16.8%) of them completed the FGI-Checklist again at follow-up. Exploratory factor analysis identified a five-factor solution accounting for 66.8% of the total variance. The five factors are named esophageal syndrome, reflux syndrome, functional dyspepsia syndrome, nausea and vomiting syndrome, and abdominal and bowel syndrome. The FGI-Checklist total score correlated with Patient Health Questionaire-9 and Patient Health Questionnaire-15 (all P < 0.001), which demonstrated good construct validity. Good item-internal consistency was found (Cronbach's alphas: 0.69-0.87). Responsiveness for reflux syndrome subscale, functional dyspepsia syndrome subscale, and abdominal and bowel syndrome subscale after medication treatment was significant (paired-t-test: all P < 0.01). CONCLUSION: The instrument, Checklist, is valid and reliable.

Functional dyspepsia susceptibility is associated with TGFB1 gene polymorphisms (RS4803455, RS1800469) in H pylori-negative Chinese population.

BACKGROUND: We previously published that altered expression of gastric TRPV1, BDNF, and peripheral cytokines was present in patients with functional dyspepsia. We herein examine whether genetic predisposition in altered biomarkers influences dyspeptic, sleep, and mood symptoms in patients with FD without previous infection. METHODS: Consecutive adult FD patients (Rome III) with no recent history of gastroenteritis and asymptomatic age- and sex-matched healthy controls were recruited for upper endoscopy. Subjects with GERD and IBS as predominant symptoms, diabetes mellitus, current or previous H pylori infection, psychiatric illness, and recent use of NSAID or PPI were excluded. The genetic associations with dyspeptic symptoms, sleep quality, and mood symptoms were evaluated. Genetic polymorphisms in TRPV1, TGFB1, TNF, COMT, BDNF, IL6, IL8, IL10, and IL12 were analyzed. KEY RESULTS: Twenty-nine male FD patients and 104 female FD patients were age matched (±3 years) with 81 healthy subjects. All had postprandial distress syndrome (PDS) as predominant subtype (PDS: 130, EPS: 3). SNPs in TGFB1 showed significant associations in dyspeptic patients after age and sex adjustment [for RS4803455: in the codominant model (C/A, OR = 0.34 (0.18-0.65), P = .004); in the dominant model (genotype C/C vs C/A-A/A, OR = 0.42 (0.23-0.77), P = .004); and in the overdominant model (genotype C/C-A/A vs C/A, OR = 0.38 (0.21-0.70), P < .001)] [for RS1800469: in dominant model (genotype A/A vs A/G-G/G, OR = 0.52 (0.27-0.99), P = .043)]. A allele in RS4803455 was associated with higher HADS depression score (P = .05) and epigastric burning sensation(P = .01). CONCLUSIONS AND INFERENCES: Our data showed that dyspeptic patients predispose genetic difference in TGFB1 which may influence the severity of dyspepsia.

Vitamin D3 activates the autolysosomal degradation function against Helicobacter pylori through the PDIA3 receptor in gastric epithelial cells.

Helicobacter pylori (H. pylori) is a common human pathogenic bacterium. Once infected, it is difficult for the host to clear this organism using the innate immune system. Increased antibiotic resistance further makes it challenging for effective eradication. However, the mechanisms of immune evasion still remain obscure, and novel strategies should be developed to efficiently eliminate H. pylori infection in stomachs. Here we uncovered desirable anti-H. pylori effect of vitamin D3 both in vitro and in vivo, even against antibiotic-resistant strains. We showed that H. pylori can invade into the gastric epithelium where they became sequestered and survived in autophagosomes with impaired lysosomal acidification. Vitamin D3 treatment caused a restored lysosomal degradation function by activating the PDIA3 receptor, thereby promoting the nuclear translocation of PDIA3-STAT3 protein complex and the subsequent upregulation of MCOLN3 channels, resulting in an enhanced Ca2+ release from lysosomes and normalized lysosomal acidification. The recovered lysosomal degradation function drives H. pylori to be eliminated through the autolysosomal pathway. These findings provide a novel pathogenic mechanism on how H. pylori can survive in the gastric epithelium, and a unique pathway for vitamin D3 to reactivate the autolysosomal degradation function, which is critical for the antibacterial action of vitamin D3 both in cells and in animals, and perhaps further in humans. Abbreviations: 1,25D3: 1α, 25-dihydroxyvitamin D3; ATG5: autophagy related 5; Baf A1: bafilomycin A1; BECN1: beclin 1; CagA: cytotoxin-associated gene A; CFU: colony-forming unit; ChIP-PCR: chromatin immunoprecipitation-polymerase chain reaction; Con A: concanamycin A; CQ: chloroquine; CRISPR: clustered regularly interspaced short palindromic repeats; CTSD: cathepsin D; GPN: Gly-Phe-ß-naphthylamide; H. pylori: Helicobacter pylori; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MCOLN1: mucolipin 1; MCOLN3: mucolipin 3; MCU: mitochondrial calcium uniporter; MOI: multiplicity of infection; NAGLU: N-acetyl-alpha-glucosaminidase; PDIA3: protein disulfide isomerase family A member 3; PMA: phorbol 12-myristate 13-acetate; PRKC: protein kinase C; SQSTM1: sequestosome 1; STAT3: signal transducer and activator of transcription 3; SS1: Sydney Strain 1; TRP: transient receptor potential; VacA: vacuolating cytotoxin; VD3: vitamin D3; VDR: vitamin D receptor.

Low-dose imipramine for refractory functional dyspepsia: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Guidelines recommend the use of neuromodulators in patients with functional dyspepsia not responding to proton pump inhibitors (PPIs) and prokinetics; however, there is a lack of data from randomised controlled trials supporting their use. We aimed to assess the safety and efficacy of imipramine, a tricyclic antidepressant (TCA), in treatment-refractory functional dyspepsia. METHODS: In this single-centre, double-blind, randomised controlled trial, we enrolled consecutive patients with Rome II functional dyspepsia aged 18-80 years. Eligible patients were Helicobacter pylori-negative, had a normal upper gastrointestinal endoscopy and abdominal ultrasound, and remained symptomatic after open-label treatment with 8 weeks of esomeprazole and 4 weeks of domperidone. Patients completed questionnaires assessing dyspepsia symptoms, mood, and insomnia, and were then randomly assigned (1:1) via a computer-generated list of random numbers to receive imipramine (at a dose of 25 mg once nightly for the first 2 weeks, and then 50 mg thereafter) or placebo for 12 weeks. The primary endpoint was overall satisfactory relief of global dyspepsia symptoms at 12 weeks, via patient-reported assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00164775, and is completed. FINDINGS: Between Sept 11, 2005, and Aug 20, 2010, 107 patients with treatment-refractory functional dyspepsia were randomly assigned to receive imipramine (n=55) or placebo (n=52). Relief of global dyspepsia symptoms at 12 weeks occurred in 35 (63·6%, 95% CI 50·4-75·1) of 55 patients on imipramine compared with 19 (36·5%, 95% CI 24·8-50·1) of 52 on placebo (p=0·0051). Ten (18%) patients on imipramine discontinued the study due to adverse events (three dry mouth, two constipation, two drowsiness, and one each insomnia, palpitations, and blurred vision), compared with four (8%) on placebo (one dry mouth and constipation, and one each palpitations, worsening of gastro-oesophageal reflux, and limb paraesthesia). There were no serious adverse events. INTERPRETATION: Low-dose imipramine should be considered as a possible therapy for patients with functional dyspepsia refractory to both PPIs and prokinetics, although patients should be cautioned about the adverse event profile. FUNDING: None.

Fecal microbiota transplantation confers beneficial metabolic effects of diet and exercise on diet-induced obese mice.

Diet and exercise are conventional methods for controlling body weight and are linked to alterations in gut microbiota. However, the associations of diet, exercise, and gut microbiota in the control of obesity remain largely unknown. In the present study, using 16S rRNA amplicon sequencing and fecal microbiota transplantation (FMT), normal fat diet (NFD), exercise and their combination resulted in improved metabolic profiles in comparison to sedentary lifestyle with high fat diet (HFD). Moreover, diet exerted more influence than exercise in shaping the gut microbiota. HFD-fed mice receiving FMT from NFD-exercised donors not only showed remarkably reduced food efficacy, but also mitigated metabolic profiles (p < 0.05). The transmissible beneficial effects of FMT were associated with bacterial genera Helicobacter, Odoribacter and AF12 and overrepresentation of oxidative phosphorylation and glycolysis genes. Our findings demonstrate that the beneficial effects of diet and exercise are transmissible via FMT, suggesting a potential therapeutic treatment for obesity.

Genetic polymorphism in pathogenesis of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a complex symptom-based disorder without established biomarkers or putative pathophysiology. IBS is a common functional gastrointestinal disorder which is defined as recurrent abdominal pain or discomfort that has at least two of the following symptoms for 3 d per month in the past 3 mo according to ROME III: relief by defecation, onset associated with a change in stool frequency or onset with change in appearance or form of stool. Recent discoveries revealed genetic polymorphisms in specific cytokines and neuropeptides may possibly influence the frequencies and severity of symptoms, as well as the therapeutic responses in treating IBS patients. This review gives new insights on how genetic determinations influence in clinical manifestations, treatment responses and potential biomarkers of IBS.

Decreased Basal and postprandial plasma serotonin levels in patients with functional dyspepsia.

BACKGROUND & AIMS: Patients with diarrhea-predominant irritable bowel syndrome (IBS) have been found to have increased postprandial levels of serotonin (5-HT). Functional dyspepsia (FD) and IBS have been proposed to have common methods of pathogenesis, but little is known about the role of 5-HT in FD. METHODS: We measured postprandial levels of 5-HT in 54 patients with FD (based on Rome III criteria) and 28 asymptomatic healthy individuals (controls). Patients with gastroesophageal reflux disease and IBS as their predominant symptom were excluded. After an overnight fast, the subjects drank a liquid meal (Ensure; 1.06 kcal/mL at 30 mL/min) and underwent a (13)C-octanoic acid breath test to measure gastric emptying times. Blood samples were collected at 0, 30, 60, 90, and 120 minutes after the liquid meal for the 5-HT assay. RESULTS: Thirty-five patients with FD (65%) had postprandial distress syndrome, and 6 (11%) had a combination of postprandial distress syndrome and epigastric pain syndrome. There were no differences in rates of gastric emptying between patients with FD (103.6 ± 19.4 minutes) and controls (83.1 ± 4.0 minutes; P = .30). However, patients with FD had lower caloric intake (823.40 ± 44.1 kcal) than controls (1021 ± 68.2 kcal; P = .026). Patients with FD also had lower basal (P = .03) and postprandial plasma levels of serotonin at 30 minutes (P = .04), 60 minutes (P = .01), 90 minutes (P = .02), and 120 minutes (P = .002) than controls, as well as area under the curve values over the 120-minute time period (P = .005). Repeated-measures analysis of variance correlated 5-HT level with FD (P < .001). CONCLUSIONS: In contrast to patients with diarrhea-predominant IBS, those with FD have decreased basal and postprandial plasma levels of 5-HT. These findings indicate that the pathogenic mechanism of FD differs from that of diarrhea-predominant IBS, and that strategies to alter 5-HT levels or activity might be developed to treat patients with FD.