METHODS: For this systematic review and meta-analysis we searched MEDLINE (PubMed) and Embase electronic databases from inception until March 1, 2022, for original articles and conference abstracts of observational cross-sectional, case-controlled, or cohort design studies that reported the prevalence of DGBI overlap in adult participants (aged ≥18 years). We included only those studies where the diagnosis of DGBI was based on clinical assessment, questionnaire data, or specific symptom-based criteria. Studies were excluded if reporting on mixed populations of DGBI and organic diseases. Aggregate patient data were extracted from eligible published studies. The prevalence of DGBI overlap in all studies was pooled using the DerSimonian and Laird random effects model, and further analysis stratified by subgroups (care setting, diagnostic criteria, geographic region, and gross domestic product per capita). We also assessed the relationship between DGBI overlap with anxiety, depression, and quality of life symptom scores. This study was registered with PROSPERO (CRD42022311101).

FINDINGS: 46 of 1268 screened studies, reporting on 75 682 adult DGBI participants, were eligible for inclusion in this systematic review and meta-analysis. Overall, 24 424 (pooled prevalence 36·5% [95% CI 30·7 to 42·6]) participants had a DGBI overlap, with considerable between-study heterogeneity (I2=99·51, p=0·0001). In the tertiary health-care setting, overlap among participants with DGBI was more prevalent (8373 of 22 617, pooled prevalence 47·3% [95% CI 33·2 to 61·7]) compared with population-based cohorts (11 332 of 39 749, pooled prevalence 26·5% [95% CI 20·5 to 33·4]; odds ratio 2·50 [95% CI 1·28 to 4·87]; p=0·0084). Quality of life physical component scores were significantly lower in participants with DGBI overlap compared with participants without overlap (standardised mean difference -0·47 [95% CI -0·80 to -0·14]; p=0·025). Participants with DGBI overlap had both increased symptom scores for anxiety (0·39 [95% CI 0·24 to 0·54]; p=0·0001) and depression (0·41 [0·30 to 0·51]; p=0·0001).

INTERPRETATION: Overlap of DGBI subtypes is frequent, and is more prevalent in tertiary care settings and associated with more severe symptom manifestations or psychological comorbidities. Despite the large sample size, the comparative analyses revealed substantial heterogeneity, and the results should be interpreted with caution.

METHODS: We performed an ecological study utilizing peer-reviewed published datasets reporting for 26 countries prevalence rates of DGBI (Rome Foundation Global Epidemiology Study, RFGES), with six independent variables: Helicobacter pylori prevalence and household size as proxy measures for orofecal infections, gross domestic product per capita (GDP), and median age as a proxy measures for socioeconomic development, density of fast food outlets (FFO) per 100,000 population as proxy measure for processed food exposure, and suicide mortality rate per 100,000 people, and world happiness scores were used as a proxy for psychological stress. The data were retrieved from publicly accessible datasets (United Nations, CIA World Factbook, World Bank, World Happiness Report, commercial/financial reports of a global FFO chain). We used linear regression to assess variables in univariate and multivariate analysis and report standardized β coefficients with 95% confidence intervals (CI).

KEY RESULTS: The regression model revealed that the overall prevalence of DGBI was inversely associated with both GDP per capita (β = -0.57, 95% CI: -0.92, -0.22, p = 0.002) and happiness scores (β = -0.433 95% CI: 0.821, -0.065, p = 0.023), while being positively associated with H. pylori prevalence (β = 0.40, 95% CI: 0.008, 0.81, p = 0.046). The prevalence of functional constipation (FC) was also inversely associated with GDP per capita (β = -0.50, 95% CI: -0.86, -0.13, p = 0.01) and happiness scores (β = -0.497, 95% CI: -0.863, -0.132, p = 0.01), while being positively associated with H. pylori prevalence (β = 0.53, 95% CI: 0.16, 0.91, p = 0.007). The Multivariate model analysis revealed that combining the factors of H. pylori prevalence, suicide rate, household size and happiness scores showed statistically significant association with FC (p = 0.039). Household size (β = -0.43, 95% CI: -0.82, 0.038, p = 0.033) and suicide rates (β = 0.55, 95% CI: 0.19, 0.90, p = 0.004) were statistically significantly associated with functional diarrhea. Irritable bowel syndrome (IBS) was associated with GDP per capita (β = -0.40, 95% CI: -0.79, -0.014, p = 0.043) and happiness scores (β = -0.390, 95% CI: -0.778, -0.003, p = 0.049).

METHODS: Electronic databases were searched until February 2024, for articles reporting on changes in symptom severity in DGBI patients during the COVID-19 pandemic. The proportion of DGBI patients who reported a change in their symptom severity were pooled using a random-effects model, and subgroup analyses were conducted to assess the effect of socio-cultural modifiers on symptom severity in DGBI.

KEY RESULTS: Twelve studies including 3610 DGBI patients found that 31.4% (95% CI, 15.9-52.5) of DGBI patients experienced symptom deterioration, while 24.3% (95% CI, 10.2-47.5) experienced improvement. Countries with high gross domestic product (GDP) had a 43.5% (95% CI, 16.3-75.2) likelihood of symptom deterioration, compared to 9.2% (95% CI, 1.4-42.2) in lower GDP countries. Similarly, countries with low COVID fatality rates had a 60.1% (95% CI, 19.7-90.3) likelihood of symptom deterioration, compared to 18.3% (95% CI, 7.8-36.9) in higher fatality rate countries. Countries with lenient COVID policies had a 58.4% (95% CI, 14.1-92.3) likelihood of symptom deterioration, compared to 19% (95% CI, 8.2-38.1) in countries with stricter policies. Patients in high vaccine hesitancy countries had a 51.4% (95% CI, 19.5-82.2) likelihood of symptom deterioration, compared to 10.6% (95% CI, 2.7-33.4) in low vaccine hesitancy countries.