Functional Dyspepsia Subtypes Research Articles

Low-FODMAP diet on postprandial distress syndrome type of functional dyspepsia with mixed type of irritable bowel syndrome patient: A case report

Functional dyspepsia is a complex collection of symptoms from the gastroduodenal, while irritable bowel syndrome (IBS) is a disease that chronically weakens gastrointestinal. The occurrences of both of these diseases are common; however, the new approach therapy introducing the low-FODMAP diet (low fructose, oligosaccharides, disaccharides, monosaccharides, and polyols) is rarely discussed. The aim of this case report was to present a case of functional dyspepsia with IBS mixed type treated with a low-FODMAP diet. A female 37 years old reported complaints of heartburn worsening over the last seven months. Based on IBS-symptom severity scale (IBS-SSS) assessment, the patient had 75% scale on belly pain and 50% abdominal distention, which interfered the daily activity significantly. The patient was diagnosed with functional dyspepsia subtype postprandial distress syndrome with IBS mixed type. In addition, the low-FODMAP diet was started immediately, together with pharmacological therapy (oral omeprazole and domperidone), and followed up each week. On the first week of evaluation, the patient was feeling much better as IBS-SSS assessment scores decreased, and the pharmacological therapy was stopped. On the second week of evaluation, the patient had no more complaints with IB-SSS assessment markedly decreased. This case highlights that low-FODMAP diet could be a new approach therapy for IBS that could improve the IBS symptoms.

Treatment of functional dyspepsia in Chinese adult patients with domperidone: A multicenter, randomized, double-blind, placebo-controlled pilot study.

This pilot study aimed to evaluate the efficacy and safety of domperidone for the treatment of Chinese patients with functional dyspepsia (FD) who were diagnosed according to the Rome IV criteria and to identify the FD subtypes that potentially responded better to domperidone. This multicenter prospective study was conducted in China from August 2018 to July 2020, consisting of a 1-week screening phase and a 2-week double-blind treatment phase. Participants were randomized to receive domperidone 10 mg or matching placebo tablets thrice daily for 14 days. The primary end-point was the overall treatment effect (OTE) response rate after 2-week therapy. Altogether 160 patients were included, with 80 patients in each group. The OTE response rate after 2-week therapy was significantly higher for domperidone compared with placebo (60.7% vs 46.0%; relative risk [RR] 1.318, 95% confidence interval [CI] 0.972-1.787). Moreover, the OTE response rate after 2-week domperidone or placebo treatment was 60.3% versus 54.9% for postprandial distress syndrome (PDS) (RR 1.098, 95% CI 0.750-1.607) and 60.6% versus 35.2% for overlapping PDS-epigastric pain syndrome (EPS) (RR 1.722, 95% CI 0.995-2.980). Adverse events were reported by seven patients in the domperidone group and 12 patients in the placebo group. None of the adverse events in the domperidone group were serious. Domperidone showed a positive pattern regarding OTE response rates after 2-week therapy compared to placebo in patients with FD, as well as in subtypes of PDS and overlapping PDS-EPS. No new safety issue was observed.

Association between genetic polymorphisms of NOD1, Interleukin-1B, and cagA strain with low-grade duodenal eosinophilia in Helicobacter pylori-related dyspepsia.

Functional dyspepsia (FD) is a multifactorial disorder. Helicobacter pylori (H. pylori)-related dyspepsia (HpD) may be considered a separate entity. Duodenal eosinophilia is a potential pathogenic mechanism in FD. However, the impact of duodenal eosinophilia and host genetic polymorphism of innate and pro-inflammatory cascade, nucleotide-binding oligomerization domain 1 (NOD-1), and interleukin-1 beta (IL-1β) in HpD was not explored. To evaluate the association of NOD1-796G>A and IL-1B-511C>T gene variants and low-grade duodenal eosinophilia in HpD. A multicenter cross-sectional study was conducted. A total of 253 patients who met Rome-IV criteria were selected before upper endoscopy and 98 patients were included after unremarkable upper endoscopy and positive H. pylori in gastric biopsies were assessed. Clinical parameters, H. pylori cagA and duodenal histology, were evaluated. Sixty-four (65%) patients had epigastric pain syndrome (EPS), 24 (25%) postprandial distress syndrome (PDS), and 10 (10%) EPS/PDS overlap. FD subtypes were not associated with NOD1-796G>A and IL-1B-511C>T gene variants. Low-grade duodenal eosinophilia was significantly increased in NOD1-796 GG versus single A-allele, but not in IL-1B-511 single T-allele or CC-allele. This association is dependent of cagA infection, since harboring cagA strain was significantly associated with low-grade duodenal eosinophilia with isolated variants NOD1-796 GG and IL-1B-511 single T-allele, but not without cagA. When we performed combined polymorphism analysis with NOD1-796 GG/IL-1B-511 single T-allele, a synergistic effect on low-grade duodenal eosinophilia was found between these two loci irrespective of cagA strain status in HpD. Our findings suggest that low-grade duodenal eosinophilia is significantly associated with NOD1-796 GG allele specially in cagA strain and with allelic combination NOD1-796 GG/IL-1B-511 single T-allele independent of cagA strain infection in HpD patients.

Clinical Implications of Low-grade Duodenal Eosinophilia in Functional Dyspepsia: A Prospective Real-life Study.

Functional dyspepsia (FD) is a multifactorial disorder with no targeted therapy. Duodenal eosinophilia and low-grade inflammation are potential pathogenic mechanisms. However, the impact of duodenal eosinophils (D-EO) histologic evaluation in real-life clinical practice was not explored. To evaluate the clinical utility of D-EO and low-grade inflammation in FD in real-life practice. A multicenter prospective study was conducted. A total of 636 patients who meet Rome-III criteria were selected before upper endoscopy and 516 patients were included after normal endoscopy were assessed. Clinical parameters, Helicobacter pylori (H. pylori), and duodenal histology were evaluated. FD subtypes were 231 (45%) patients who had epigastric pain syndrome (EPS), 168 (33%) postprandial distress syndrome (PDS), and 117 (22%) EPS/PDS overlap. Two hundred fifty-nine (50.3%) patients were H. pylori+. Histologic duodenal grading of chronic inflammation and intraepithelial lymphocytes showed no difference between FD subtypes. Increased in D-EO densities (>10 per high power field) was significant in PDS compared with EPS and EPS/PDS overlap subtypes. The odds ratio of PDS in subjects with duodenal eosinophilia densities was 2.28 (95% CI, 1.66-3.14; P<0.0001), adjusting for age, gender, H. pylori and nonsteroidal anti-inflammatory drug the odds ratio was 3.6 (95% CI, 2.45-5.28; P<0.0001). receiver operating characteristic curve analysis further demonstrated that low-grade duodenal eosinophilia, in particular H. pylori-, was highly accurate for PDS with the area under the curve 0.731 compared with H. pylori+ area under the curve 0.598. Furthermore, low-grade duodenal eosinophilia was significantly correlated with treatment response under 4 to 6 weeks of proton pump inhibitor therapy. Our findings suggest that low-grade duodenal eosinophilia is associated with PDS subtype non-H. pylori FD patients and could be a useful marker of treatment response.

Placebo response in pharmacological trials in patients with functional dyspepsia-A systematic review and meta-analysis.

Pharmacological trials in functional dyspepsia (FD) are associated with high placebo response rates. We aimed to identify the magnitude and contributing factors to the placebo response. We conducted a systematic review and meta-analysis including randomized controlled trials (RCTs) with a dichotomous outcome in adult patients with FD that compared an active pharmacotherapeutic treatment with placebo. Our main outcome was identification of the magnitude of the pooled placebo response rate for the following endpoints: symptom responder, symptom-free responder, adequate relief responder, and combined endpoint responder (i.e., the primary endpoint of each specific trial regarding treatment response). Several putative moderators (i.e., patient, disease, and trial characteristics) were examined. We included 26 RCTs in our analysis. The pooled placebo response rate was 39.6% (95% CI 30.1-50.0) using the symptom responder definition, 20.5% (12.8-31.0) using the symptom-free responder definition, 38.5% (33.8-43.6) using the adequate relief responder definition, and 35.5% (31.6-39.7) using the combined endpoint responder definition. A lower overall baseline symptom score was significantly associated with a higher placebo response rate. No other moderators were found to significantly impact the placebo response rate. Due to the lack of data, no analyses could be performed according to individual FD subtypes or symptoms. The pooled placebo response rate in pharmacological trials in FD is about 39%, depending on which responder definitions is used. Future trials should consider applying an entry criterion based on minimal level of symptom severity to decrease the placebo response. We also suggest separate reporting of core FD symptoms pending more concrete harmonization efforts in FD trials.

Eosinophil and Mast Cell Counts in the Stomach and Duodenum of Patients with Functional Dyspepsia without a Helicobacter pylori infection.

Symptom-based subtyping of functional dyspepsia (FD) is used to segregate patients into groups with homogenous pathophysiological mechanisms. This study examined whether subtyping could reflect the duodenal and gastric microinflammation in FD patients. Twenty-one FD patients without Helicobacter pylori infection were recruited. An endoscopic biopsy was performed in the duodenum 2nd portion, stomach antrum, and body. The eosinophil and mast cell counts per high-power field (×40) were investigated by H&E and c-kit staining, respectively. The degree of inflammatory cell infiltration, atrophy, and intestinal metaplasia was also determined by H&E staining in the stomach. The baseline characteristics and eosinophil and mast cell infiltrations were compared among the three groups (epigastric pain syndrome, postprandial distress syndrome, and overlap). According to the symptom assessment, seven subjects were classified into the epigastric pain syndrome group, 10 into the postprandial syndrome group, and four into the overlap group. The baseline variables were similar in the three groups. Eosinophil infiltration was more prominent in the duodenum than in the stomach. In contrast, mast cell infiltration was similar in the duodenum and stomach. The eosinophil counts in the duodenum were similar in the three groups. The eosinophil counts in the stomach and mast cell counts in the duodenum and stomach were also similar in the three groups. Duodenal eosinophil infiltration was prominent in FD patients, but the eosinophil counts were similar regardless of the symptom-based subtypes of FD. Hence, the current symptom-based subtyping of FD does not reflect duodenal eosinophil and mast cell infiltration.

Comparison of clinical characteristics, eating behaviors, and clinical symptoms following fat intake in functional dyspepsia with functional dyspepsia with pancreatic enzyme abnormalities between Singapore and Japan.

To clarify whether there were any significant differences in clinical symptoms and eating patterns between functional dyspepsia (FD) patients and FD with pancreatic enzyme abnormalities (FD-P) patients as refractory FD, we compared these factors in multicenter studies in Singapore and Japan. One hundred ninety-eight consecutive patients presenting with FD (n=88), FD-P patients (n=81) based on Rome III classification and controlled group (n=39) recruited from six institutions in Singapore and Japan. Clinical characteristics, clinical symptoms for dietary fat intake, and eating behaviors were estimated using questionnaires. Anxiety and health-related quality of life were determined by STAI-state/-trait and SF-8, respectively. There were no significant differences in age, sex, BMI, smoking, alcohol intake, past medical history, and history of allergy in FD and FD-P patients between Singapore and Japan. There were no significant differences in FD subtypes, gastrointestinal symptom rating scale score, severity of FD symptoms, and eating pattern in Singapore and Japan. Moreover, there were significant differences in certain eating behaviors between FD and FD-P patients in Singapore and Japan. Interestingly, epigastric pain and early satiety following fat meals in FD-P patients were significantly (P=0.003 and P=0.008, respectively) higher compared with those in FD patients in Japan. Physical component score in FD-P patients was significantly (P=0.019) disturbed compared with those in FD patients in Japan. Epigastric pain and early satiety following fat meals in FD-P patients may be useful tools to differentiate FD-P patients from FD patients in Japan.

Functional dyspepsia symptom diary is correlated with other questionnaires and associated with severity in patients with functional dyspepsia: a multicenter, prospective observational study.

Functional dyspepsia symptom diary (FDSD) is a newly designed questionnaire of functional dyspepsia (FD). The relationships between FDSD and other FD-related questionnaires and patient-reported severity remain unclear. This study aims to investigate the correlations between FDSD and other questionnaires and to determine the relationships between FDSD and FD severity. Consecutive outpatients with FD were prospectively enrolled in four tertiary hospitals. All patients were evaluated by six FD-related questionnaires, including FDSD, Dyspepsia Symptom Severity Index (DSSI), Gastrointestinal Symptom Rating Scale, Short-Form Nepean Dyspepsia Index, and Hamilton Depression and Anxiety Scale (HAMD and HAMA). The severity of FD was also graded as mild, moderate, and severe by patients themselves. Correlations between different scores were assessed by Spearman correlation coefficient (ρ), and risk factors for patient-reported severity were identified. For 512 enrolled FD patients, the overall median FDSD score was 19 (2-42). FDSD was well correlated with DSSI (ρ=0.64) and fairly correlated with the other four scores (ρ=0.32-0.55) (all P<0.001). Mild, moderate, and severe FD were reported by 18.5%, 55.9%, and 25.6% of patients, respectively. There were seven factors associated with the severe FD, including education level, duration, and subtypes of FD, prior treatment, FDSD, HAMD, and HAMA scores (all P<0.10). FDSD≥20 (odds ratio [OR] 3.3, 95% confidence interval [CI]: 2.0-5.2, P<0.001) and HAMD≥13 (OR 2.9, 95% CI: 1.8-4.6, P<0.001) were independently associated with patient-reported severe FD. This study firstly revealed that the newly developed FDSD correlated with other FD-related questionnaires. FDSD≥20 and HAMD≥13 were independently associated with severe FD reported by patients (clinicaltrials.gov number: NCT04953975).

Epidemiology and Clinical Characteristics Based on the Rome III and IV Criteria of Japanese Patients with Functional Dyspepsia.

The subtypes of functional dyspepsia (FD) differ depending on whether the Rome III criteria or the Rome IV criteria are used. We investigated the ability to diagnose FD patients using the Rome III and IV criteria. The subtypes of FD were evaluated using the Rome questionnaire. The Gastrointestinal Symptom Rating Score, health-related quality of life (HR-QOL; SF-8), and psychological scores (HADS, STAI) were evaluated. The questionnaire was collected from a total of 205 patients, and 54.1% were FD patients. The ratio of FD patients under the Rome III criteria was 19% for epigastric pain syndrome (EPS), 38% for postprandial distress syndrome (PDS), and 43% for an overlap of EPS and PDS, but under the Rome IV criteria overlap decreased to 17% and PDS increased to 64%. Patients whose subtype changed from overlap under the Rome III criteria to PDS under the Rome IV criteria were compared with PDS patients whose subtype did not change between the Rome III and IV criteria. The comparison showed that the former had significantly lower early satiation rates and significantly higher acid reflux and abdominal pain scores, demonstrating that EPS symptoms due to acid reflux after meals were clearly present. As a result of changing from the Rome III criteria to the Rome IV criteria, the number of overlap patients decreased, and the number of PDS patients increased.

Overlap of heartburn, functional dyspepsia, and irritable bowel syndrome in a population sample: Prevalence, temporal stability, and associated comorbidities.

Co-occurring (overlapping) irritable bowel syndrome (IBS), functional dyspepsia (FD), and heartburn has been observed. However, whether it is a distinct entity has not been established, nor what clinical, demographic, lifestyle, and psychological traits are associated with it. This study sought to estimate the prevalence and temporal stability of this overlap and to identify features specific to it in order to gain some insights into the potential etiopathogenesis. Two waves of a survey to a population-representative sample were conducted 3years apart, recruiting 1312 individuals for this study. The chance-expected probability of complete overlap (CO) was calculated and compared with the observed CO. A range of demographic, lifestyle factors, medical diagnoses, sleep quality, and psychological distress were tested to identify predictors of overlap using logistic regression. CO was observed in 2.1% (95% confidence interval 1.9, 3.7) of the sample and was closely replicated in wave 2 at 2.0%. The observed CO was greater than expected by chance (0.2%) to a statistically significant extent (p<0.001). Overlap between IBS subtypes, FD subtypes, and heartburn was also elevated above chance expectation. Individuals with CO were separately differentiated from others with respect to elevated rates of self-reported medically diagnosed asthma, elevated psychological distress score, and elevated impact on sleep quality. The discrimination provided by these factors was further independent of age and sex. Overlap between IBS, FD, and heartburn (GERD) appears to be a distinct entity that has a profile including psychological morbidity, sleep disturbance, and elevated rates of atopy.

Eradication of intestinal bacterial overgrowth as a treatment method for functional dyspepsia

Functional dyspepsia (FD) is one of the most common gastrointestinal functional diseases, occurring in an average of 10 % of the adult population. Recently, much attention is being paid to the infectious factor in FD pathophysiology. In addition to H. pylori infection and acute gastrointestinal infections, consideration is given to the syndrome of intestinal bacterial overgrowth (SIBO), in which the number of bacteria in the small intestine increases significantly.&#x0D; Objective — to establish the SIBO prevalence in patients with different FD subtypes and to establish the clinical and microbiological efficacy of rifaximin‑a (Alpha Normix®) at this pathology.&#x0D; Materials and methods. To refine the SIBO prevalence, 118 patients with FD were examined in three gastroenterological centers, including 45 men, 73 women aged 22 to 45 years (mean age — 35 ± 10 years). The control group consisted of 30 clinically healthy people with the mean age 33 ± 12 years. The diagnosis of FD and establishment of its subtype was performed according to Rome IV criteria. All patients underwent upper endoscopy with biopsy and H. pylori testing, which did not show any structural abnormalities. To diagnose SIBO, all patients underwent H2‑breath test with lactulose (H2‑LBT). All patients, depending on the FD subtype, received basic therapy with either a proton pump inhibitor (Omeprazole 20 mg once a day) at FD with epigastric pain syndrome (EPS) (group 1, n = 37), or prokinetic (Itopride in a dose of 50 mg three times a day) at FD with postprandial distress syndrome (PDS) (group 2, n = 36) for two weeks. Patients with positive H2‑LBT result, which predicted SIBO presence, were administered monotherapy with rifaximin‑a (Alpha Normix®) in a dose of 1200 mg/day for 10 days. The effectiveness of the treatment was assessed after 2 and 4 weeks based on the dynamics of the scores of SAGIS (Structured Assessment of Gastrointestinal Symptom) scale.&#x0D; Results. According to the positive H2‑LBT results, SIBO presence was recorded in 45 of 118 patients with FD (38.1 %) and 2 (6.6 %) subjects from the control group. Positive H2‑LBT result was significantly more often recorded in patients with FD‑PDS (45.4 %) compared with patients with FD‑EPS (28.8 %, p &lt; 0.01) and all patients with FD (38.1 %). Moreover, SIBO was significantly more common in patients with postinfectious FD (50 % of patients, p &lt; 0.01). The use of rifaximin in a dose of 1200 mg/day for 10 days was accompanied by the clinical improvement in 28 of 45 patients (62.2 %) after 4 weeks of treatment. The clinical efficacy of rifaximin in FD patients on the SAGIS scale did not differ significantly from the efficacy of PPIs and prokinetics used in FD‑EPS and FD‑PDS, respectively. After 4 weeks, in 36 of 45 patients, repeated H2‑LBT was negative, which indirectly indicated the SIBO eradication and high antibacterial efficacy of rifaximin. Rifaximin treatment was safe, and minor side effects were observed in only 3 patients (6.6 %).&#x0D; Conclusions. SIBO is quite often associated with FD and is observed in more than every third patient. In patients with FD‑PDS, SIBO was found significantly more often than in patients with FD‑EPS, which emphasizes the important role of slowing gastric emptying in the development of SIBO. Also, SIBO is significantly more common in patients with postinfectious FD, which emphasizes the important role of the intestinal microbiome in maintaining the stability of the structural and functional state of the gastrointestinal tract. The obtained data allow to consider SIBO as a possible pathogenetic factor of FD, at least in some patients. This requires timely diagnosis and correction of SIBO in patients with FD, in particular with the use of rifaximin‑a.

Low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet versus traditional dietary advice for functional dyspepsia: a randomized controlled trial.

Prospective trials evaluating efficacy of specific diet restriction in functional dyspepsia (FD) are scarce. We aimed to assess efficacy of low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet in FD, compared with traditional dietary advice (TDA). In this prospective, single-blind trial, patients with FD (Rome IV) were randomized into low FODMAP diet (LFD) and TDA groups, for 4weeks (phase I). In phase II (4-12weeks), LFD group was advised systematic re-introduction of FODMAPs. Symptom severity and quality of life were assessed using "Short-Form Nepean Dyspepsia Index (SF-NDI)." Primary outcome was symptomatic response (symptom score reduction of ≥50%), at 4weeks. Study was registered with CTRI (2019/06/019852). Of 184 patients screened, 105 were randomized to LFD (n=54) and TDA (n=51) groups. At 4weeks, both groups showed significant reduction in SF-NDI symptom scores compared with baseline, with no significant difference in inter-group response rates [LFD: 66.7% (36/54); TDA: 56.9% (29/51); P=0.32]. On sub-group analysis, patients with postprandial distress syndrome or bloating had significantly better symptomatic response with LFD (P=0.04). SF-NDI quality of life scores improved significantly in both groups. On multivariate analysis, factors predicting response to LFD were bloating and male gender. Incidences of adverse events (minor) were similar in both groups. In patients with FD, LFD and TDA lead to significant symptomatic and quality of life improvement. Patients with postprandial distress syndrome or bloating respond significantly better to LFD. Therefore, dietary advice for FD should be individualized according to FD subtype.

The Usefulness of Symptom-based Subtypes of Functional Dyspepsia for Predicting Underlying Pathophysiologic Mechanisms and Choosing Appropriate Therapeutic Agents.

Functional dyspepsia (FD) is considered to be a heterogeneous disorder with different pathophysiological mechanisms or pathogenetic factors. In addition to traditional mechanisms, novel concepts regarding pathophysiologic mechanisms of FD have been proposed. Candidates of therapeutic agents based on novel concepts have also been suggested. FD is a symptom complex and currently diagnosed by symptom-based Rome criteria. In the Rome criteria, symptom-based subtypes of FD including postprandial distress syndrome and epigastric pain syndrome are recommended to be used, based on the assumption that each subtype is more homogenous in terms of underlying pathophysiologic mechanisms than FD as a whole. In this review, the usefulness of symptom-based subtypes of FD for predicting underlying pathophysiologic mechanisms and choosing appropriate therapeutic agents was evaluated. Although several classic pathophysiologic mechanisms are suggested to be associated with individual dyspeptic symptoms, symptom-based subtypes of FD are not specific for a certain pathogenetic factor or pathophysiologic mechanism, and may be frequently associated with multiple pathophysiologic abnormalities. Novel concepts on the pathophysiology of FD show complex interactions between pathophysiologic mechanisms and pathogenetic factors, and prediction of underlying mechanisms of individual patients simply by the symptom pattern or symptom-based subtypes may not be accurate in a considerable proportion of cases. Therefore, subtyping by the Rome criteria appears to have limited value to guide therapeutic strategy, suggesting that the addition of objective parameters or subclassification reflecting physiologic or pathologic tests may be necessary for the targeted therapeutic approaches, particularly when therapeutic agents targeting novel mechanisms are available.

Small Intestinal Bacterial Overgrowth in Functional Dyspepsia: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to determine the role of small intestinal bacterial overgrowth (SIBO) in patients with functional dyspepsia (FD). Electronic databases were searched until July 2020 for studies reporting prevalence of SIBO in FD. The prevalence rates, odds ratio, and 95% confidence intervals (CIs) of SIBO in FD and controls were calculated. Seven studies with 263 patients with FD and 84 controls were identified. The odds for SIBO in patients with FD were significantly higher as compared to that in controls (odds ratio = 4.3, 95% CI, 1.1-17.5, 4 studies, 234 participants); however, there was moderate heterogeneity in this analysis. Including high-quality, case-control studies (all using glucose breath tests [GBTs]), the risk of SIBO in patients with FD as compared to controls was 2.8 higher (95% CI 0.8-10.0, 3 studies, 200 participants) with minimal heterogeneity in this analysis. Using the lactulose breath test, SIBO prevalence in FD was significantly higher (53.4%, 95% CI 33.9-71.9, 3 studies, 110 participants) as compared to that with GBT (17.2%, 95% CI 8.6-31.6, 4 studies, 153 participants). Substantial heterogeneity was found in studies using the lactulose breath test but not in studies using GBT. There was no significant difference in SIBO prevalence in patients with FD according to FD subtype. This meta-analysis suggests a link between FD and SIBO. The quality of evidence is low and can be largely attributed to the type of breath test for SIBO diagnosis and clinical heterogeneity. More appropriately designed studies are required to confirm the link between SIBO and FD.

Effects of the Rome IV Criteria to Functional Dyspepsia Symptoms in Saudi Arabia: Epidemiology and Clinical Practice

Limited data is available in Saudi Arabia (SA) regarding the prevalence of functional dyspepsia (FD) symptoms and its subtypes, as defined by the ROME IV criteria. This study evaluated the burden of self-reported FD symptoms in the adult general population of SA and the current clinical practices. A web-based national cross-sectional health survey of the general population of SA was conducted using the Rome IV Diagnostic Questionnaire for Functional Gastrointestinal Disorders in Adults with additional questions on the presence of symptoms compatible with functional heartburn (FH) and irritable bowel syndrome (IBS). The quality of life and somatization questionnaires were also included. Overall, 3,114 adults completed the questionnaire, but 303 (9.7%) were excluded due to inconsistent responses. Of the 2,811 consistent responders, 532 (18.3%) fulfilled the Rome IV criteria for FD symptoms. These were distributed into the FD subtypes as follows: 208 (7.4%) had postprandial distress syndrome, 228 (8.1%) had epigastric pain syndrome, and 96 (3.4%) had the overlapping variant. IBS-like symptoms were reported in 232 (44%) and FH in 102 (19%) 19% (102) of the subjects with functional dyspepsia. H. pylori-associated dyspepsia was reported by 25% (87/348). High somatization, lower quality of life scores, younger age, and female sex were associated more with the FD symptoms participants than those without. Approximately 1/5 respondents used over-the-counter medications to relieve the FD symptoms. In this population-based survey, FD affected almost 1/5 of the responding adult population in SA, which was less than previously reported.

High Prevalence of Small Intestinal Bacterial Overgrowth among Functional Dyspepsia Patients

Background: Small intestinal bacterial overgrowth (SIBO), characterized by either increased numbers or presence of colonic type bacteria in the small bowel has been previously described in functional dyspepsia (FD), based on breath testing. In this study, we aim to examine the prevalence of SIBO among FD patients using small bowel aspirate culture. Methods: We prospectively enrolled outpatients fulfilling Rome IV criteria for FD. Severity of symptoms was graded using the patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) questionnaire. Patients underwent upper gastrointestinal endoscopy and duodenal fluid was aspirated in sterile traps. SIBO was defined as ≥10³ colony forming units/mL of duodenal aspirate and/or presence of colonic type bacteria. Patients undergoing gastroscopy due to gastroesophageal reflux symptoms – control group (CG) – and patients with irritable bowel syndrome (IBS) fulfilling Rome IV criteria were also recruited. Results: We enrolled 227 FD subjects, 30 CG, and 90 IBS patients. Among FD patients, 144 (63.4%), 64 (28.2%), and 19 (8.4%) had postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), and overlapping PDS-EPS syndrome, respectively. SIBO prevalence was 20.8%, 12.5%, and 31.6% among PDS, EPS, and overlapping PDS-EPS FD subtypes, respectively. Overall, SIBO prevalence was significantly higher in FD (44/227 [19.4%]) compared to CG (1/30 [3.3%]) (p = 0.037) and similar to IBS (44/227 [19.4%] vs. 15/90 [16.7%], p = 0.63) subjects. SIBO presence was associated neither with total nor with any subscale score of the PAGI-SYM questionnaire. Conclusion: In a cohort of Greek FD patients, SIBO prevalence was similar to that of IBS subjects and higher compared to that of controls.

Functional Dyspepsia: Diagnostic and Therapeutic Approaches.

Functional dyspepsia is a common functional gastrointestinal (GI) disorder of gastroduodenal origin, diagnosed clinically in the presence of prototypical symptoms of epigastric pain and meal-related symptoms, and without structural explanation. The most recent diagnostic criteria provide for two functional dyspepsia subtypes, epigastric pain syndrome (EPS) and post-prandial distress syndrome (PDS) based on the predominant symptom pattern. The evaluation of dyspepsia should keep laboratory, imaging, and invasive testing to a minimum, as extensive or repetitive investigations are of rather low diagnostic yield in the absence of localizing symptoms or alarm features. Factors with etiopathologic relationships to functional dyspepsia include micro-inflammation, GI infections, abnormalities of gastroduodenal motility, visceral hypersensitivity, disturbances along the brain-gut axis, and psychological factors; all of these causative mechanisms have potential to partially explain symptoms in some functional dyspepsia patients, thus providing a rationale for the efficacy of a diversity of therapeutic approaches to functional dyspepsia. Management of dyspepsia symptoms relies upon both pharmacologic treatments and non-pharmacologic approaches, including psychological and complementary interventions. The evidence in support of established functional dyspepsia therapies is reviewed, and forms the basis for an effective functional dyspepsia treatment strategy emphasizing the patient's current symptom severity, pattern, and impact on the function and quality of life of the individual.

Expression of Tight Junction Proteins According to Functional Dyspepsia Subtype and Sex.

Background/AimsTo determine whether the expression of tight junction proteins (TJPs) differs depending on the subtype of functional dyspepsia (FD) and sex.MethodsControl (n = 95) and FD (n = 165) groups based on Rome III criteria were prospectively enrolled. Gastric mucosal mRNA expression levels of various TJPs (claudins [CLDN] 1, 2, and 4; zonula occludens-1; occludin [OCLN]) were assessed by reverse transcription polymerase chain reaction. Western blot was performed to determine the levels of various TJPs. Helicobacter pylori infection status was evaluated by histology, rapid urease test, and culture. Questionnaires were analyzed.ResultsIn all groups irrespective of H. pylori, FD group showed significantly higher CLDN2 mRNA levels than control group (P = 0.048). The level of CLDN4 mRNA expression was significantly lower in female FD group than in male FD group (P = 0.018). In H. pylori uninfected subjects, the level of CLDN1 mRNA expression in female FD group was significantly lower than that of male FD group (P = 0.014). The level of CLDN2 mRNA expression was significantly higher in the male postprandial distress syndrome (P = 0.001) and male epigastric pain syndrome (P = 0.023) groups than in the male control group. In Western blot analysis, the expression of OCLN was significantly elevated 48 hour after the culture with H. pylori strain 43504.ConclusionsH. pylori can affect a variety of TJPs, particularly claudin-4 and occludin. Claudin-2 is thought to be involved in FD irrespective of H. pylori status, especially in the pathophysiology of male FD.

Clinical Practice Guidelines for Functional Dyspepsia in Korea.

Functional dyspepsia (FD) is a chronic upper gastrointestinal (GI) symptom complex that routine diagnostic work-up, such as endoscopy, blood laboratory analysis, or radiological examination, fails to identify a cause. It is highly prevalent in the World population, and its response to the various available therapeutic strategies is only modest because of the heterogenous nature of its pathogenesis. Therefore, FD represents a heavy medical burden for healthcare systems. We constituted a guideline development committee to review the existing guidelines on the management of functional dyspepsia. This committee drafted statements and conducted a systematic review and meta-analysis of various studies, guidelines, and randomized control trials. External review was also conducted by selected experts. These clinical practice guidelines for FD were developed based on evidence recently accumulated with the revised version of FD guidelines released in 2011 by the Korean Society of Neurogastroenterology and Motility. These guidelines apply to adults with chronic symptoms of FD and include the diagnostic role of endoscopy, Helicobacter pylori screening, and systematic review and meta-analyses of the various treatment options for FD (proton pump inhibitors, H.pylori eradication, and tricyclic antidepressants), especially according to the FD subtype. The purpose of these new guidelines is to aid the understanding, diagnosis, and treatment of FD, and the targets of the guidelines are clinicians, healthcare workers at the forefront of patient care, patients, and medical students. The guidelines will continue to be revised and updated periodically.

Similarity and diversity of spontaneous brain activity in functional dyspepsia subtypes.

Functional dyspepsia (FD) subtypes may differ in terms of pathophysiology, but the underlying mechanisms remain poorly understood. To explore spontaneous brain activity in two main FD subtypes, namely epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), using the amplitude of low-frequency fluctuation (ALFF). Thirty-one FD patients (18 EPS and 13 PDS) and 22 matched healthy controls (HC) underwent resting-state functional MRI scanning. Spontaneous brain activity was evaluated by measuring the ALFF and then compared among the EPS, PDS, and HC groups with ANOVA test. Pearson correlation analysis was performed between the ALFF values and clinical indices. Compared to healthy controls, both EPS and PDS patients had increased ALFF in the bilateral precentral/postcentral gyri, insula, and thalami. Furthermore, only the EPS patients displayed increased ALFF in the right middle and inferior frontal gyri, and only the PDS patients showed increased ALFF in the left posterior cingulate cortex (PCC). The ALFF values in the left thalamus were positively correlated with the sleep disturbance in EPS patients, and the ALFF values in the right precentral/postcentral gyri showed a positive correlation with the symptom score in PDS patients. EPS and PDS had similarities of higher spontaneous brain activity in the primary motor/sensory areas and homeostatic-afferent network regions, and differences in the prefrontal region and PCC, providing evidence to suggest the similarity and diversity of pathophysiology in FD subtypes.