Holtmann, Gerald J

AbstractBackgroundThis SRMA reviewed and assessed the changes in the severity of disorders of gut‐brain interaction (DGBI) symptoms during the COVID‐19 pandemic, and evaluated factors associated with symptom severity changes.MethodsElectronic 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 ResultsTwelve 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.Conclusions & InferencesThis meta‐analysis reveals that a significantly higher proportion of DGBI patients experienced deterioration of symptoms during the COVID‐19 pandemic. Various sociocultural, economic and environmental factors potentially modify the effects of the COVID‐19 pandemic on DGBI.

AbstractBackgroundDisorders of gut–brain interaction (DGBI) are characterized by debilitating symptoms not explained by structural or biochemical abnormalities. While functional conditions present with complex, likely heterogeneous pathophysiology, we aimed to investigate if proxy measures of sociocultural and environmental factors are associated with the prevalence of various DGBI in populations across the world.MethodsWe 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 ResultsThe 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).Conclusions & InferencesUtilizing publicly available data, the prevalence of DGBI across diverse countries is linked to various socio‐cultural and environmental factors. Collectively, the data suggests that the prevalence of DGBI is increased in less prosperous regions of the world.

AbstractBackground and AimPatients with intestinal failure (IF) have abnormal intestinal anatomy, secretion, and dysmotility, which impairs intestinal homeostatic mechanisms and may lead to small intestinal bacterial overgrowth (SIBO). We conducted a systematic review and meta‐analysis to determine the prevalence of SIBO in patients with IF and to identify risk factors for SIBO.MethodsMEDLINE (PubMed) and Embase electronic databases were searched from inception to December 2023 for studies that reported the prevalence of SIBO in IF. The prevalence rates, odds ratio (OR), and 95% confidence intervals of SIBO in IF and the risk factors for SIBO in IF were calculated using random effects model.ResultsFinal dataset included nine studies reporting on 407 patients with IF. The prevalence of SIBO in IF was 57.5% (95% CI 44.6–69.4), with substantial heterogeneity in this analysis (I2 = 80.9, P = 0.0001). SIBO prevalence was sixfold higher in patients with IF who received parenteral nutrition (PN) compared with IF patients not on PN (OR = 6.0, 95% CI 3.0–11.9, P = 0.0001). Overall, the prevalence of SIBO in patients with IF using PPI/acid‐suppressing agents (72.0%, 95% CI 57.5–83.8) was numerically higher compared with IF patients not using these agents (47.6%, 95% CI 25.7–70.2).ConclusionsThis systematic review and meta‐analysis suggests that there is an increased risk of SIBO in patients with IF and that PN, and potentially, the use of PPI/acid‐suppressing agents is risk factors for SIBO development in patients with IF. However, the quality of evidence is low and can be attributed to lack of case–control studies and clinical heterogeneity seen in the studies.

Background: Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving treatment. Several studies have evaluated the effect of different biologic therapies on PSC with inconclusive findings. We conducted a systematic review and meta-analysis to assess the effects of biologics in PSC and associated inflammatory bowel disease (IBD). Methods: MEDLINE, Scopus, and Embase were searched up to July 31, 2023, for studies reporting the effects of biologics in patients with PSC-IBD. Effects of biologic therapy on alkaline phosphatase, total bilirubin, ulcerative colitis response score, and adverse events were calculated and expressed as standardized difference of means (SMD), proportions, and 95% CI using a random-effects model. Results: Six studies, including 411 PSC-IBD patients who received biologics, were included. Biologic treatment was associated with no change in alkaline phosphatase (SMD: 0.1, 95% CI: −0.07 −0.17, p=0.43), but a small and statistically significant increase in total bilirubin (SMD: 0.2, 95% CI: 0.05–0.35, p<0.01). 31.2% (95% CI: 23.8–39.7) of patients with IBD achieved endoscopic response, and there was a significant improvement in ulcerative colitis response score (SMD: −0.6,95% CI: −0.88 to 0.36, p<0.01). Furthermore, 17.6% (95% CI: 13.0–23.5) of patients experienced adverse events severe enough to discontinue therapy, and 29.9% (95% CI: 25.2–34.8) had a loss of response to biologics. Conclusions: Treatment of patients with PSC-IBD with biologics (vedolizumab, infliximab, and adalimumab) was not associated with improvement of biochemical markers of cholestasis. Biologics are effective in treating the colitis associated with PSC. Vedolizumab was associated with worsening liver enzymes in contrast to other biologics, a finding that warrants further study.

AbstractThe available COVID‐19 literature has focused on specific disease manifestations, infection control, and delivery or prioritization of services for specific patient groups in the setting of the acute COVID‐19 pandemic. Local health systems aim to contain the COVID‐19 pandemic and hospitals and health‐care providers rush to provide the capacity for a surge of COVID‐19 patients. However, the short, medium‐term, and long‐term outcomes of patients with gastrointestinal (GI) diseases without COVID‐19 will be affected by the ability to develop locally adapted strategies to meet their service needs in the COVID‐19 setting. To mitigate risks for patients with GI diseases, it is useful to differentiate three phases: (i) the acute phase, (ii) the adaptation phase, and (iii) the consolidation phase. During the acute phase, service delivery for patients with GI disease will be curtailed to meet competing health‐care needs of COVID‐19 patients. During the adaptation phase, GI services are calibrated towards a “new normal,” and the consolidation phase is characterized by rapid introduction and ongoing refinement of services. Proactive planning with engagement of relevant stakeholders including consumer representatives is required to be prepared for a variety of scenarios that are dictated by thus far undefined long‐term economic and societal impacts of the pandemic. Because substantial changes to the delivery of services are likely to occur, it is important that these changes are embedded into quality and research frameworks to ensure that data are generated that support evidence‐based decision‐making during the adaptation and consolidation phases.

The activity of pancreatic enzymes declines during aboral intestinal transit. We tested the hypothesis that survival of pancreatic enzyme activities during intestinal transit is affected by amounts or concentrations of calories, nutrients, bile acids, or pancreatic enzymes entering the segments of the small intestine. An oroileal tube was placed in 26 healthy humans. The tube had duodenal, jejunal, and ileal infusion ports for nonabsorbable markers and aspiration ports in the distal duodenum, distal jejunum, and distal ileum. Four infusates of different proportions of protein, fat, and carbohydrate were infused continuously into the duodenum at 40, 90, and 160 kcal/h. Of the nutrients infused into the proximal duodenum, 21 +/- 3, 51 +/- 7, and 39 +/- 5% of fat, protein, and carbohydrate, respectively, were delivered to the distal duodenum. During duodenoileal transit, lipase, chymotrypsin, amylase, and trypsin lost 71 +/- 5, 63 +/- 5, 43 +/- 7, and 38 +/- 9% of activity, respectively (P < 0.01 vs. distal duodenum). During duodenojejunal transit, the activity of each enzyme decreased more than 35% (P < 0.01 vs. distal duodenum), and infusion of more calories into the duodenum improved survival of all enzymes except trypsin (P < 0.05). During jejunoileal transit, greater amounts and concentrations of calories and carbohydrate improved survival of only lipolytic activity (P < 0.01, P < 0.05, respectively), and loss of lipolytic activity correlated directly with delivery of bile acids (r = 0.56, P = 0.05) and chymotrypsin (r = 0.80, P = 0.001) to the distal jejunum. We conclude that intraluminal nutrients increase survival of enzyme activities in the proximal intestine. After absorption of nutrients, the action of chymotrypsin and bile acids decrease lipolytic activity more than activity of other enzymes.