Functional Dyspepsia and Its Subgroups: Prevalence and Impact in the Rome IV Global Epidemiology Study

J Tack; O S Palsson; S I Bangdiwala; J Schol; F Carbone; K Van Den Houte; B Broeders; D Drossman; D L Dumitrascu; X Fang; S Fukudo; U C Ghoshal; J Kellow; R Khatun; E Okeke; E M Quigley; M Schmulson; M Simrén; W E Whitehead; P Whorwell; A D Sperber

doi:10.1111/apt.70189

. 2025 May 28;62(3):330–339. doi: 10.1111/apt.70189

Functional Dyspepsia and Its Subgroups: Prevalence and Impact in the Rome IV Global Epidemiology Study

J Tack ^1,^2,^3,^4,^✉, O S Palsson ¹, S I Bangdiwala ^1,^5,⁶, J Schol ², F Carbone ³, K Van Den Houte ², B Broeders ², D Drossman ¹, D L Dumitrascu ⁷, X Fang ⁸, S Fukudo ⁹, U C Ghoshal ¹⁰, J Kellow ¹¹, R Khatun ^1,^5,⁶, E Okeke ¹², E M Quigley ¹³, M Schmulson ¹⁴, M Simrén ^1,⁴, W E Whitehead ¹⁵, P Whorwell ¹⁶, A D Sperber ^1,¹⁷

^¹Rome Foundation Research Institute, Raleigh, North Carolina, USA

^²Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Belgium

^³Gastroenterology‐Hepatology Division, Leuven University Hospitals, Leuven, Belgium

^⁴Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

^⁵Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada

^⁶Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada

^⁷Iuliu Hatieganu University of Medicine and Pharmacy, Cluj‐Napoca, Romania

^⁸Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

^⁹Tohoku University Graduate School of Medicine, Department of Behavioral Medicine, Sendai, Japan

^¹⁰Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI), Lucknow, India

^¹¹Discipline of Medicine, Northern Clinical School, University of Sydney, Sydney, Australia

^¹²Department of Medicine, University of Jos, Jos University Teaching Hospital, Jos, Nigeria

^¹³Center for Digestive Disorder, Gastroenterology and Hepatology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas, USA

^¹⁴Laboratory of Liver, Pancreas and Motility (HIPAM), unit of Research in Experimental Medicine, Faculty of Medicine, Universidad Nacional Autónoma de Mexico (UNAM). Hospital General de México, Mexico City, Mexico

^¹⁵Center for Functional GI & Motility Disorders, University of North Carolina‐Chapel Hill, Chapel Hill, North Carolina, USA

^¹⁶Neurogastroenterology Unit, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, UK

^¹⁷Faculty of Health Sciences, Ben‐Gurion University of the Negev, Beer‐Sheva, Israel

Correspondence: J. Tack (jan.tack@kuleuven.be)

^✉

Corresponding author.

PMCID: PMC12239946 PMID: 40434285

ABSTRACT

Background

Functional dyspepsia (FD) is one of the most common disorders of gut–brain interaction (DGBI). Varying reported population prevalences probably reflect different definitions and methodological approaches.

Aim

To study the prevalence and impact of FD and its subgroups in an internet survey.

Methods

A total of 54,127 respondents from 26 countries completed the survey including the Rome IV diagnostic questionnaire, Patient Health Questionnaire‐4 (PHQ‐4), PHQ‐12, PROMIS Global‐10, demographics, and medical history. Respondents reporting a history of relevant organic disease, or fulfilling criteria for self‐induced or cyclic vomiting, or cannabinoid hyperemesis were excluded.

Results

Rome IV FD prevalence was 7.2% (range 2.2%–12.3%), significantly higher in women and decreased with age. The most prominent subtype was postprandial distress syndrome (PDS) (66.6%). Rome IV IBS was found in 26.1% of those fulfilling FD criteria. Functional heartburn and chronic nausea and vomiting criteria were fulfilled in, respectively, 9.0% and 7.0%. Fulfilling FD symptom criteria was significantly associated with increased prevalence of anxiety and depression and with lower quality of life and higher healthcare seeking behaviour.

Conclusions

Rome IV FD is one of the most prevalent DGBI globally. Across countries, it is associated with female sex, younger age, psychological distress, reduced quality of life, and higher health care utilisation. PDS is the dominant subgroup. Overlapping other DGBI are present in a minority.

Prevalence of functional dyspepsia in the general population in each country of the internet survey of the Rome IV global epidemiology study.

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1. Introduction

Functional dyspepsia (FD) is one of the most common disorders of gut–brain interaction (DGBI), formerly referred to as functional gastrointestinal disorders [1]. While the Rome I and II consensus defined dyspepsia as pain or discomfort centred in the upper abdomen [2], the Rome III and IV consensus characterised dyspepsia by the presence of symptoms that are considered to originate from the gastroduodenal region [3, 4]. FD is defined by the presence of symptoms of gastroduodenal origin (early satiation, postprandial fullness, epigastric pain and epigastric burning), in the absence of organic, systemic, or metabolic disease that would explain the symptoms [3, 4].

Several studies have evaluated the epidemiology of FD over the last decades [5, 6, 7]. These reported highly variable prevalence results due to the different definitions used over time with the different Rome consensuses and due to different methodological approaches in individual studies. While the clinical algorithm for FD requires an upper endoscopy for diagnostic certainty [3, 4], most epidemiological studies did not use endoscopy. However, it is well established that endoscopy is normal in the vast majority of patients with dyspeptic symptoms [8], especially when taking into account the long duration of symptoms in the Rome consensus. No epidemiological reports have used the Rome IV consensus, published in 2016, for determining the prevalence of FD on a global scale [4].

The recently finalised Rome Foundation global epidemiology study enables assessment of the prevalence of chronic gastrointestinal symptoms and the Rome IV criteria in large population samples from globally distributed countries, collected in a uniform and systematic approach [9]. We used this database to estimate the global prevalence of dyspepsia and its subgroups according to the Rome IV definition, as well as the association with other gastrointestinal disorders and psychosocial factors, its impact on quality of life, and on healthcare utilisation.

2. Methods

2.1. Data Sources

We analysed data derived from the Rome Foundation global epidemiology study [6]. In this multinational epidemiological study, 73,076 respondents from 33 countries filled out an extensive survey comprising the complete Rome IV diagnostic questionnaire and an 80‐item supplemental questionnaire on sociodemographic characteristics, medical and health history, comorbid symptoms and conditions, gastrointestinal infections, health care utilisation, medications, quality of life, psychosocial variables, childhood and current living conditions, culture and religion. The item content of the entire global study questionnaire is shown in the supplementary material of the original article [6]. The questionnaire was administered as an online internet survey or household door‐to‐door survey and completed by at least 2000 individuals with an equal sex ratio and similar age distribution (40% for 18 to 39 years, 40% for 40 to 64 years, and 20% for above 65 years) in each country. Because of substantial differences in data collection methodology between the internet and household methods in this study, for the current study we only analysed the internet survey data, which included 54,127 respondents in 26 countries (Argentina, Australia, Belgium, Brazil, Canada, China, Colombia, Egypt, France, Germany, Holland, Israel, Italy, Japan, Mexico, Poland, Romania, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Turkey, United Kingdom and United States). All survey participants signed an electronic informed consent form. Ethical review was completed in each country and the study was approved or exempted from ethics board oversight due to anonymisation during the survey.

3. Factors Used in the Analyses

3.1. Identification of Subjects With Functional Dyspepsia and Its Subgroups

Using the Rome IV Diagnostic Questionnaire, we included individuals fulfilling the Rome IV criteria for FD (presence of postprandial fullness and/or early satiety, at least 2–3 days per week, or epigastric pain and/or burning at least 1 day per week, for more than 6 months). We excluded patients who self‐reported a relevant organic gastrointestinal disease, such as celiac disease, inflammatory bowel disease, cancer, peptic ulcer, or who fulfilled criteria for self‐induced vomiting, cyclic vomiting syndrome, or cannabinoid hyperemesis syndrome. We also determined the subgroups of postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) using the Rome IV questionnaire [4]. The Rome IV questionnaires were also used to determine the overlap with irritable bowel syndrome (IBS), chronic nausea and vomiting, and functional heartburn. The latter would require absence of pathological oesophageal reflux exposure, which cannot be assessed in an epidemiological study. However, in the Rome global epidemiology study, reported lack of response of heartburn to acid‐suppressive therapy was used as an indicator of functional heartburn [6].

3.2. Demographics and Comorbidities

Study variables included participant demographics (age, sex, body mass index (BMI)), and living conditions. We extracted DGBI comorbidities, including functional heartburn, chronic nausea and vomiting, rumination syndrome, and IBS.

3.3. Quality of Life and Mood and Anxiety States

The survey comprised different questionnaires. The Patient‐Reported Outcomes Measurement Information System (PROMIS Global‐10), which includes physical and mental health component scores, was used to evaluate quality of life (QoL) [7]. The Patient Health Questionnaire‐4 (PHQ‐4), which includes the Patient Health Questionnaire‐2 (PHQ‐2) for depression and the Generalised Anxiety Disorder‐2 (GAD‐2) for anxiety, was used for anxiety and depression status [8]. Scale scores ≥ 3 of the PHQ‐2 and the GAD‐2 were used to define probable cases of depression or anxiety, respectively. The Patient Health Questionnaire‐12 (PHQ‐12) score was used as a measure for nongastrointestinal symptom severity (or somatization) [9].

3.4. Health Care Utilisation

Health care utilisation was quantified by assessing general health care utilisation, including general practitioner or specialist visits, number of surgeries, current medication usage, and access to healthcare.

3.5. Statistical Analysis

The prevalence of FD and its subgroups was calculated as a percentage of all participants for each country. Global pooled prevalence rates were calculated using Yang's meta‐prevalence method [10] which combines separate population survey prevalence estimates into an overall meta‐prevalence estimate. Overall, and age‐ and sex‐specific prevalence was reported as a percentage with 95% confidence intervals (CI). Subgroups of patients with FD or its subgroups were characterised by appropriate descriptive statistics (means, standard deviations, and percentages). A logistic regression was performed with FD as a dependent variable, evaluating the effects of demographic and comorbidity factors. In addition, logistic regression was performed with QoL as dependent variable evaluating the role of demographics, presence of FD (or PDS or EPS), IBS, nausea and vomiting, and functional heartburn. All data are reported as mean or percentage followed by 95% CI. Throughout, the statistical significance level used was 0.05. To compare two groups, t‐tests were used for continuous data and Pearson's chi‐square tests were used for nominal/categorical values.

4. Results

4.1. Global Prevalence of Functional Dyspepsia

The pooled mean Rome IV FD prevalence in the entire sample was 7.2% (95% CI 7.1–7.4). FD prevalence was significantly higher in women than in men; (odds ratio (OR) 1.56; 95% CI 1.46–1.67). The prevalence of FD decreased with age, from 9.5% (95% CI 9.1–9.9) in those 18–35 years old to 3.9% (95% CI 3.5–4.3) in those above 65 (Table 1). BMI did not differ significantly in subjects with or without FD symptoms (25.81(25.6, 26.0) vs. 25.57 (25.5, 25.6) kg/m²). A postinfection onset of their symptoms was acknowledged by 35.8 (34.3, 37.3) % of those identified with FD symptoms.

TABLE 1.

Prevalence of meeting criteria for Rome IV functional dyspepsia and its two subtypes without regard to overlap (% and 95% CI) by sex and age groups in the combined population‐based sample of 54,127 adults in 26 countries.

	Sex	Age group
		18–34	35–49	50–64	65+	All ages
FD	Females	10.8 (10.1, 11.4)	8.8 (8.2, 9.5)	7.4 (6.7, 8.1)	5.2 (4.5, 5.9)	8.7 (8.4, 9.1)
	Males	8.0 (7.4, 8.6)	6.2 (5.7, 6.8)	4.5 (4.0, 5.1)	2.9 (2.5, 3.4)	5.7 (5.5, 6.1)
	Overall	9.5 (9.1. 9.9)	7.5 (7.1, 7.9)	5.9 (5.5, 6.4)	3.9 (3.5, 4.3)	7.2 (7.0, 7.4)
PDS	Females	9.3 (8.7, 9.9)	7.5 (6.9, 8.1)	6.3 (5.7, 7.0)	4.5 (3.8, 5.1)	7.5 (7.2, 7.8)
	Males	6.9 (6.4, 7.5)	5.1 (4.6, 5.5)	3.7 (3.2, 4.2)	2.5 (2.0, 2.9)	4.8 (4.6, 5.1)
	Overall	8.2 (7.8, 8.6)	6.3 (5.9, 6.6)	4.9 (4.5, 5.3)	3.3 (2.9, 3.7)	6.1 (5.9, 6.3)
EPS	Females	3.2 (2.8, 3.5)	3.3 (2.9, 3.6)	2.4 (2.0, 2.9)	1.7 (1.2, 2.1)	2.8 (2.6, 3.0)
	Males	2.4 (2.1, 2.8)	2.6 (2.2, 2.9)	1.7 (1.4, 2.0)	0.8 (0.6, 1.0)	2.0 (1.8, 2.2)
	Overall	2.8 (2.6, 3.1)	2.9 (2.7, 3.2)	2.0 (1.8, 2.3)	1.2 (0.9, 1.4)	2.4 (2.3, 2.5)

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The most prominent subtype was PDS. The distribution was 66.6% PDS, 15.3% EPS, and 18.1% overlapping PDS and EPS (Figure 1). As for the total FD population, both PDS and EPS were more prevalent in women (OR 1.60; 95% CI 1.49–1.72 for PDS, and 1.42; 95% CI 1.27–1.59 for EPS) and decreased with age (Table 1). BMI did not differ between FD subgroups.

Prevalence of PDS and EPS and their overlap in the internet survey countries of the Rome IV global epidemiology.

4.2. Differences Between Countries

Table 2 displays the number of participants per country and the prevalence of FD and its subgroups. Dyspeptic symptom rates ranged between 2.2% (Japan) and 12.3% (Egypt) (Table 2). Other countries with a high prevalence (above 10%) include Brazil, Russia, South Africa, and the U.S.A. (Table 2) (Figure 2). The prevalence rates for PDS, the largest subgroup, were mostly in agreement with those for dyspeptic symptoms (Figure 3). A low proportion of EPS (less than 10% of total) was registered in Singapore, whereas higher proportions were found in Mexico, Colombia, and Spain (Figure 4).

TABLE 2.

Prevalence of adults meeting Rome IV criteria for functional dyspepsia and its subtypes (% and 95% CI) by country in the internet survey countries from the Rome Foundation global epidemiology study.

Internet survey	N	FD	PDS	EPS	PDS + EPS
Argentina	2057	6.90 (5.8, 8.0)	4.04 (3.2, 4.9)	1.07 (0.6, 1.5)	1.80 (1.2, 2.4)
Australia	2036	7.17 (6.0, 8.3)	5.70 (4.7, 6.7)	0.69 (0.3, 1.0)	0.79 (0.4, 1.2)
Belgium	2021	5.00 (4.0, 5.9)	3.71 (2.9, 4.5)	0.69 (0.3, 1.1)	0.59 (0.3, 0.9)
Brazil	2004	10.58 (9.2, 11.9)	6.19 (5.1, 7.2)	1.70 (1.1, 2.3)	2.69 (2.0, 3.4)
Canada	2029	7.84 (6.7, 9.0)	5.08 (4.1, 6.0)	1.43 (0.9, 1.9)	1.33 (0.8, 1.8)
China	2914	5.87 (5.0, 6.7)	4.46 (3.7, 5.2)	0.62 (0.3, 0.9)	0.79 (0.5, 1.1)
Colombia	2007	7.17 (6.0, 8.3)	3.84 (3.0, 4.7)	1.64 (1.1, 2.2)	1.69 (1.1, 2.3)
Egypt	2020	12.28 (10.8, 13.7)	9.50 (8.2, 10.8)	1.39 (0.9, 1.9)	1.39 (0.9, 1.9)
France	2019	8.52 (7.3, 9.7)	5.50 (4.5, 6.5)	1.68 (1.1, 2.2)	1.34 (0.8, 1.8)
Germany	2020	6.88 (5.8, 8.0)	4.21 (3.3, 5.1)	1.44 (0.9, 2.0)	1.24 (0.8, 1.7)
Holland	2008	4.08 (3.2, 5.0)	2.89 (2.2, 3.6)	0.80 (0.4, 1.2)	0.40 (0.1, 0.7)
Israel	2012	3.63 (2.8, 4.4)	2.93 (2.2, 3.7)	0.35 (0.1, 0.6)	0.35 (0.1, 0.6)
Italy	2063	9.06 (7.8, 10.3)	5.82 (4.8, 6.8)	0.97 (0.5, 1.4)	2.28 (1.6, 2.9)
Japan	2504	2.44 (1.8, 3.0)	2.12 (1.6, 2.7)	0.28 (0.1, 0.5)	0.04 (0.0, 0.1)
South Korea	2022	4.95 (4.0, 5.9)	3.61 (2.8, 4.4)	0.84 (0.4, 1.2)	0.49 (0.2, 0.8)
Mexico	2001	6.60 (5.5, 7.7)	3.30 (2.5, 4.1)	1.50 (1.0, 2.0)	1.80 (1.2, 2.4)
Poland	2057	8.26 (7.1, 9.5)	5.83 (4.8, 6.8)	0.83 (0.4, 1.2)	1.60 (1.1, 2.1)
Romania	2049	7.42 (6.3, 8.6)	4.83 (3.9, 5.8)	1.27 (0.8, 1.8)	1.32 (0.8, 1.8)
Russia	2000	10.30 (9.0, 11.6)	6.65 (5.6, 7.7)	1.45 (0.9, 2.0)	2.20 (1.6, 2.8)
Singapore	2047	5.91 (4.9, 6.9)	4.93 (4.0, 5.9)	0.39 (0.1, 0.7)	0.59 (0.3, 0.9)
South Africa	2021	11.03 (9.7, 12.4)	7.97 (6.8, 9.1)	1.29 (0.8, 1.8)	1.78 (1.2, 2.4)
Spain	2072	7.38 (6.3, 8.5)	3.33 (2.6, 4.1)	1.50 (1.0, 2.0)	2.56 (1.9, 3.2)
Sweden	2084	8.21 (7.0, 9.4)	5.95 (4.9, 7.0)	1.63 (1.1, 2.2)	0.62 (0.3, 1.0)
Turkey	2010	5.32 (4.3, 6.3)	3.18 (2.4, 4.0)	1.14 (0.7, 1.6)	1.00 (0.6, 1.4)
USA	2023	10.13 (8.8, 11.4)	6.03 (5.0, 7.1)	1.38 (0.9, 1.9)	2.72 (2.0, 3.4)
UK	2027	6.56 (5.5, 7.6)	4.24 (3.4, 5.1)	1.13 (0.7, 1.6)	1.18 (0.7, 1.7)
Pooled overall prevalence	54,127	7.22 (7.0, 7.4)	4.81 (4.6, 5.0)	1.10 (1.0, 1.2)	1.31 (1.2, 1.4)

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Prevalence of functional dyspepsia in the general population in each country of the internet survey of the Rome IV global epidemiology study.

Prevalence of PDS in the general population in each country of the internet survey of the Rome IV global epidemiology study.

Prevalence of EPS in the general population in each country of the internet survey of the Rome IV global epidemiology study.

4.3. Overlapping Conditions

In terms of comorbidities, overlapping Rome IV IBS was found in 26.1% of those fulfilling dyspeptic symptom criteria. Overlapping functional heartburn and chronic nausea and vomiting criteria were fulfilled in, respectively, 9.0% and 7.0% of subjects with dyspeptic symptoms (Table 3). These overlapping conditions were more prevalent in the EPS than the PDS subgroup, but the highest overlap was seen in patients with both EPS and PDS (respectively 60.7%, 26.7% and 17.6% for IBS, functional heartburn and nausea/vomiting overlap). Tables S1A–C summarise the findings for comorbidities in adults meeting Rome IV criteria for FD and its subgroups in individual internet survey countries.

TABLE 3.

Prevalence of overlapping DGBI diagnosis in adults meeting Rome IV functional dyspepsia criteria (% and 95% CI) in the internet survey countries from Rome Foundation global epidemiology study.

Internet survey	FD	PDS	EPS	PDS + EPS
Prevalence of comorbid IBS
Pooled overall prevalence	26.11 (24.7, 27.5)	13.13 (11.8, 14.4)	42.21 (38.3, 46.2)	60.23 (56.6, 63.8)
Prevalence of comorbid functional heartburn (95% CI)
Pooled overall prevalence	8.95 (8.1, 9.8)	3.84 (3.1, 4.6)	10.22 (7.8, 12.6)	26.66 (23.5, 29.8)
Prevalence of comorbid CNVS (95% CI)
Pooled overall prevalence	7.03 (6.2, 7.8)	4.30 (3.5, 5.1)	6.37 (4.4, 8.3)	17.63 (14.9, 20.4)

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A logistic regression analysis confirmed female sex, younger age, and comorbid IBS, chronic nausea and vomiting syndrome (CNVS), and functional heartburn as independent risk factors for FD symptoms, with the highest ORs for IBS and functional heartburn comorbidity (Table 4).

TABLE 4.

Logistic regression model evaluating the role of demographics and comorbidities with functional dyspepsia as the dependent variable.

Effects	Odds Ratio (95% CI)	p
Sex: Female vs. Male	1.36 (1.27, 1.47)	< 0.0001
Age category: 18–39 vs. Age > =65	1.98 (1.75, 2.24)	< 0.0001
Age category 40–64 vs. Age > =65	1.49 (1.32, 1.69)	0.1590
Functional Heartburn Yes vs. No	10.4 (8.60, 12.6)	< 0.0001
IBS Yes vs. No	10.6 (9.65, 11.7)	< 0.0001
CNVS Yes vs. No	8.74 (7.09, 10.8)	< 0.0001

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In the presence of FD, the ORs adjusted for age and sex were significantly higher for fulfilling criteria for IBS (13.5 (12.3; 14.8), p < 0.0001) and functional heartburn (18.7 (15.9; 22.0), p < 0.0001), but not for CNVS (1.52 (1.05; 2.22) p = 0.973).

4.4. Quality of Life and Psychosocial Comorbidities

QoL physical and mental scores on the PROMIS Global‐10 were significantly lower in those fulfilling FD criteria than the rest of the population (physical 12.38 (95% CI 12.30–12.47) vs. 14.63 (95% CI 14.61–14.65) and mental 11.84 (95% CI 11.73–11.95) vs. 13.69 (95% CI 13.66–13.72)) quality of life component.

Fulfilling FD symptom criteria was significantly associated with higher scores for anxiety (30.4% (95% CI 28.9%–31.9%) compared to 10.2% (95% CI 10.0%–10.5%)) and depression (30.2% (95% CI 28.8–31.6) vs. 9.9% (95% CI 9.6–10.2)) on the PHQ‐4. Tables S2 and S3 summarise the QoL scores and the anxiety and depression scores in adults meeting Rome IV criteria for FD and its subgroups in individual internet survey countries.

A logistic regression analysis confirmed that fulfilling FD criteria was independently associated with lower physical but not mental scores on the PROMIS Global‐10 (respectively 0.80 (0.79, 0.81), p < 0.0001 and 1.02 (1.00, 1.04), p = 0.062), when correcting for age, sex, and comorbid IBS, CNVS, and functional heartburn. Fulfilling FD (OR and 95% CI 0.55 (0.51, 0.60)), or EPS (0.62 (0.55, 0.71)) or PDS (0.57 (0.52, 0.61)) criteria was independently associated with decreased physical QoL scores, besides female sex (OR and 95% CI 0.91 (0.88, 0.95)), age range between 40 and 65 (0.76 (0.71, 0.81)), and comorbid IBS (0.51 (0.46, 0.56)) or comorbid chronic nausea and vomiting (0.69 (0.57, 0.83)).

4.5. Health Economic Impact

In total, 53.1% (95% CI (51.6–54.7)) of subjects fulfilling FD criteria had visited a physician for these symptoms. Visits were mainly with primary care physicians (39.9 (38.4–41.4)%) and gastroenterologists (27.1(25.8–28.5)%). The proportion visiting a physician was significantly higher in the PDS/EPS overlap group compared to those with PDS or EPS alone (respectively, 70.1 (66.7–73.5)% vs. 34.4 (34.0–34.8)% and 34.5(34.1–34.9)%).

As a group, subjects fulfilling FD criteria had a higher prevalence of being diagnosed with fibromyalgia (4.4 (3.7–5.0) vs. 1.9 (1.8–2.0)%), and had higher rates of cholecystectomy (7.4 (6.6–8.2) vs. 4.8 (4.6–5.0)%), hysterectomy (4.8 (4.2–5.5) vs. 3.1 (3.0–3.3)%), and appendicectomy (14.3 (13.3–15.4) vs. 11.5 (11.2–11.8)%). These persisted when subjects with overlapping IBS were eliminated from the analysis (all p < 0.01). The increased rates of surgeries were almost entirely attributable to the PDS/EPS overlap subgroup (respectively 6.2 (4.4–8.0) vs. 2.0 (1.9–2.1)%; 11.3 (9.1–13.5) vs. 4.9(4.7–5.1)%; 6.3 (4.6–8.1) vs. 3.2 (3.1–3.4)%; 21.2 (18.2–24.1) vs. 11.6 (11.3–11.8)%) (all p < 0.05).

Subjects fulfilling FD criteria also reported higher intakes of acid‐suppressive agents (43.0 (41.5–44.6)% vs. 18.7 (18.3–19.0)% in those not fulfilling FD criteria), prescription medications for pain (32.9 (31.5–34.4) vs. 16.1 (15.8–6.5)%) and for nausea (14.0 (12.9–15.0) vs. 3.8 (3.7–4.0)%) (all p < 0.05). Again, these differences were almost entirely attributable to the PDS/EPS overlap subgroup (66.7 (63.3,70.1) vs. 19.8 (19.5–20.1)%; 48.7 (45.0–52.3) vs. 16.9 (16.6,17.2)%; 28.9 (25.7,32.1) vs. 4.2 (4.1–4.4)% respectively) (all p < 0.05). Subjects fulfilling FD criteria were also more likely to report treatment with anxiolytic agents (19.7 (18.5–20.9) vs. 8.1 (7.8–8.3)%), antidepressants (17.2 (16.1–18.4) vs. 8.0 (7.7–8.2)%) or sleeping pills (19.5 (18.3–20.7) vs. 8.7 (8.5–9.0)%). These were also attributable to the PDS/EPS overlap group (respectively 25.8 (22.7–29.0) vs. 8.7 (8.5–8.9)%; 23.4 (20.4–26.4) vs. 8.4 (8.2–8.7)% and 28.8 (25.5–32.0) vs. 9.2 (9.0–9.5)%) (all p < 0.05).

5. Discussion

In this study, we report the most uniform and comprehensive analysis of the prevalence and impact on dyspeptic symptoms, assessed using the Rome IV criteria, in the general population from globally distributed countries. The results confirm that dyspeptic symptoms are highly prevalent in the adult population on a global scale, have an important impact on quality of life, and are associated with comorbidities and health care utilisation.

In agreement with previous epidemiological research, dyspeptic symptoms are more prevalent in women than in men [11, 12]. In the current global epidemiological study, dyspeptic symptoms decreased with age. This is a striking finding, which differs or is even the opposite of the findings in some previous analyses [11, 12]. However, several of these surveys used different questionnaires and some of them allowed overlapping reflux symptoms, which are known to increase with age [13]. FD, which is the likely diagnosis in most subjects with dyspeptic symptoms in the general population, also has its highest prevalence in younger adults [2, 3, 4, 5]. A postinfection onset of symptoms was reported by more than one‐third of those fulfilling FD criteria. This percentage is high in comparison to reports in IBS, where the postinfection onset has been studied in more detail and is conservatively estimated at approximately 10% of the patients [14, 15]. Relatively high proportions of postinfection onset, in up to 25%, have also been reported in tertiary care FD cohorts [15, 16, 17]. Unfortunately, the questionnaire used in the present study did not include information on the timing or type of infection in those with reported postinfection onset.

The overall high prevalence of dyspeptic symptoms in the adult general population showed some variation among countries. Surprisingly, the lowest prevalence was found in Japan, a country with a very active medical interest in, and awareness of, this condition [18]. High prevalence rates were found in Egypt, Brazil, Russia, and the USA, although for the latter country underrecognition and underdiagnosis by physicians has been reported [19]. Hence, it seems that differences in prevalence are not explained by medical awareness. The validated translations of questionnaires in the Rome IV global epidemiology allow achieving accurate understanding of the symptom questionnaires, but influences of cultural and linguistic variance on symptom recognition, understanding, and interpretation, and hence on diagnostic criteria fulfilment, cannot be entirely excluded [11, 12, 20].

The Rome III and Rome IV consensus distinguished two subgroups in FD: PDS and EPS. Previous patient and epidemiological surveys indicated that PDS is the more predominant of these, accounting for approximately 60% of the FD population, the rest fulfilling criteria for EPS or an overlapping EPS–PDS group [6, 21]. The predominance of PDS is confirmed in the current study, across continents and countries. PDS shares the features of female predominance and decreasing age‐dependent prevalence, with the entire FD group. However, EPS is also characterised by female predominance and a decrease with age. The distinction between EPS and PDS was based on the assumption of a different underlying pathophysiology and a differential response to specific types of therapy [3, 4]. In terms of pathophysiology, elevated duodenal eosinophil counts have been associated with PDS [22]. Some treatments also seem more effective in particular subgroups [23, 24, 25, 26].

Several studies, in patient cohorts as well as in the general population, have highlighted increased levels of anxiety and depression in patients with FD [27, 28, 29, 30, 31, 32, 33, 34]. A number of studies also reported higher depression rates in patients with FD [34, 35, 36, 37], which was also confirmed in the current global study, where subjects with dyspeptic symptoms had higher anxiety and depression scores. The cross‐sectional nature of this study does not enable an analysis of temporal (causative) relationships. However, population follow‐up studies have shown a bidirectional interaction between FD and anxiety or depression [30, 31, 32].

Subjects with dyspeptic symptoms also had a significantly lower quality of life than those without dyspeptic symptoms, for the physical and the mental component. The quality‐of‐life impact was similar in PDS, EPS, and those with overlapping PDS and EPS. When correcting for comorbid conditions, FD or its subgroups PDS and EPS were independently associated with decreased quality of life.

FD symptoms are associated with considerable healthcare seeking, one third of subjects having visited a physician, and with intake of acid‐suppressive, analgesic, and antinausea drugs. This was most prominent in overlapping PDS/EPS. The overlap group also had the highest use of antidepressant, anxiolytic, and sleep medications. In addition, subjects fulfilling FD criteria reported high rates of abdominal surgeries such as cholecystectomy, appendicectomy, and hysterectomy, also most clearly in the overlapping PDS/EPS subgroup. The excess of surgeries was not explained by IBS comorbidity. These findings are reminiscent of the high surgery rates reported for IBS [38, 39, 40, 41] and may reflect inappropriate surgical attempts to control symptoms.

The global epidemiological study also documented significant overlap between dyspeptic symptoms and other gastroduodenal, oesophageal, or bowel DGBIs. The biggest overlap was with IBS, found in up to 26% of subjects, followed by functional heartburn and chronic nausea and vomiting in, respectively, approximately 9% and 7%. However, the presence of FD symptoms was independently associated with lower physical quality of life scores. In terms of subgroups of subjects with dyspeptic symptoms, all overlapping conditions were more prevalent in EPS than in PDS, but the highest prevalence was seen in the subgroup with overlapping EPS and PDS symptoms. Overlap between dyspeptic symptoms and heartburn has been attributed to common underlying pathophysiological events such as impaired accommodation or low‐grade duodenal inflammation [42, 43]. However, a highly likely candidate mechanism to explain the overlap group is the presence of visceral hypersensitivity, which has previously been shown to determine symptom severity and overlapping DGBIs [44, 45].

Our study has several strengths, including the large sample size across several countries obtained with a uniform and robust methodology ensuring that the questionnaires are identical and validated in all languages, and that cases with missing data and false data were excluded from the data collection process. The scale and uniformity of methodology used in this study make it the definitive statement on dyspepsia epidemiology. It also provides unprecedented information on overlapping conditions, health care and quality of life impact. Doing so, the paper adds major new information over the summary paper from the Rome IV global epidemiology study [6]. The use of a large questionnaire also allowed analysis of several demographic, psychosocial and comorbid factors, and their potential associations with dyspeptic symptoms. Furthermore, the data confirm that dyspeptic symptoms are highly prevalent on a global level, with limited differences between countries.

Our study also has some limitations. The Rome IV criteria require a negative endoscopy to make a firm diagnosis of FD⁴, and this is outside the scope of an epidemiological survey. However, in clinical practice, investigations such as endoscopy are normal in most patients [2, 3, 4, 5], allowing us to extrapolate our findings on uninvestigated dyspepsia to FD. Although this is a strength, the analysis of subjects from different cultures and language settings includes the risk of variation in understanding the meaning of the questions and the symptoms they address. However, the Rome IV diagnostic questionnaire and the supplemental questionnaire were translated by professional translators and underwent cultural adaptation and linguistic validation in all study countries, minimising the impact of linguistic factors on the results. Finally, while country‐specific results are available, there is insufficient information on race/ethnicity for countries with heterogeneous populations, and the role of socio‐economic status, access to healthcare, alcohol use, and smoking.

In conclusion, the findings of this 26‐nation survey demonstrate a high global prevalence of dyspeptic symptoms which are associated with female sex, younger age, psychological distress, reduced quality of life, and higher healthcare utilisation. The highest prevalence is the subgroup with PDS symptoms. The subgroup of overlapping EPS and PDS symptoms has the highest rate of overlap with other DGBI. Awareness of the high prevalence of dyspeptic/PDS symptoms should focus clinical research towards pathophysiological and therapeutic investigations.

Author Contributions

J. Tack: conceptualization, investigation, writing – original draft, supervision, writing – review and editing, visualization. O. S. Palsson: project administration, conceptualization, investigation, methodology, validation, supervision, writing – review and editing, software, formal analysis. S. I. Bangdiwala: writing – review and editing, conceptualization, investigation, formal analysis, supervision, methodology, validation. J. Schol: writing – review and editing. F. Carbone: writing – review and editing. B. Broeders: writing – review and editing. D. Drossman: writing – review and editing, conceptualization, investigation, funding acquisition, methodology, validation, resources, supervision. D. L. Dumitrascu: writing – review and editing. X. Fang: writing – review and editing. S. Fukudo: writing – review and editing. U. C. Ghoshal: writing – review and editing. J. Kellow: writing – review and editing. R. Khatun: investigation, writing – review and editing, formal analysis, validation, data curation, supervision. E. Okeke: writing – review and editing. E. M. Quigley: writing – review and editing. M. Schmulson: writing – review and editing. M. Simrén: writing – review and editing. W. E. Whitehead: writing – review and editing. P. Whorwell: writing – review and editing. A. D. Sperber: conceptualization, investigation, methodology, validation, writing – review and editing, formal analysis, data curation, supervision, resources.

Supporting information

Tables S1‐S3:

APT-62-330-s001.docx^{(35.7KB, docx)}

Handling Editor: Alexander Ford

Funding: The authors received no specific funding for this work.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Tables S1‐S3:

APT-62-330-s001.docx^{(35.7KB, docx)}

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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[apt70189-bib-0008] 8. Kroenke K., Spitzer R. L., Williams J. B., and Löwe B., “An Ultra‐Brief Screening Scale for Anxiety and Depression: The PHQ‐4,” Psychosomatics 50, no. 6 (2009): 613–621. [DOI] [PubMed] [Google Scholar]

[apt70189-bib-0009] 9. Kroenke K., Spitzer R. L., and Williams J. B., “The PHQ‐15: Validity of a New Measure for Evaluating the Severity of Somatic Symptoms,” Psychosomatic Medicine 64, no. 2 (2002): 258–266. [DOI] [PubMed] [Google Scholar]

[apt70189-bib-0010] 10. Yang B., “Meta Prevalence Estimates. Generating Combined Prevalence Estimates From Separate Population Surveys: NSW Department of Health, Center for Epidemiology and Research,” (2007).

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[apt70189-bib-0017] 17. Schol J., Carbone F., Holvoet L., et al., “Postinfectious Onset in Functional Dyspepsia Is a Risk Factor for Weight Loss,” Journal of Gastroenterology 57, no. 3 (2022): 156–163. [DOI] [PubMed] [Google Scholar]

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PERMALINK

Functional Dyspepsia and Its Subgroups: Prevalence and Impact in the Rome IV Global Epidemiology Study

J Tack

O S Palsson

S I Bangdiwala

J Schol

F Carbone

K Van Den Houte

B Broeders

D Drossman

D L Dumitrascu

X Fang

S Fukudo

U C Ghoshal

J Kellow

R Khatun

E Okeke

E M Quigley

M Schmulson

M Simrén

W E Whitehead

P Whorwell

A D Sperber

ABSTRACT

Background

Aim

Methods

Results

Conclusions

1. Introduction

2. Methods

2.1. Data Sources

3. Factors Used in the Analyses

3.1. Identification of Subjects With Functional Dyspepsia and Its Subgroups

3.2. Demographics and Comorbidities

3.3. Quality of Life and Mood and Anxiety States

3.4. Health Care Utilisation

3.5. Statistical Analysis

4. Results

4.1. Global Prevalence of Functional Dyspepsia

TABLE 1.

FIGURE 1.

4.2. Differences Between Countries

TABLE 2.

FIGURE 2.

FIGURE 3.

FIGURE 4.

4.3. Overlapping Conditions

TABLE 3.

TABLE 4.

4.4. Quality of Life and Psychosocial Comorbidities

4.5. Health Economic Impact

5. Discussion

Author Contributions

Supporting information

Data Availability Statement

References

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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