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There is evidence of perturbed microbial and host processes in the gastrointestinal tract of individuals with functional gastrointestinal disorders (FGID) compared to healthy controls. The faecal metabolome provides insight into the metabolic processes localised to the intestinal tract, while the plasma metabolome highlights the overall perturbances of host and/or microbial responses. This study profiled the faecal (n = 221) and plasma (n = 206) metabolomes of individuals with functional constipation (FC), constipation-predominant irritable bowel syndrome (IBS-C), functional diarrhoea (FD), diarrhoea-predominant IBS (IBS-D) and healthy controls (identified using the Rome Criteria IV) using multimodal LC-MS technologies. Discriminant analysis separated patients with the 'all constipation' group (FC and IBS-C) from the healthy control group and 'all diarrhoea' group (FD and IBS-D) from the healthy control group in both sample types. In plasma, almost all multimodal metabolite analyses separated the 'all constipation' or 'all diarrhoea' group from the healthy controls, and the IBS-C or IBS-D group from the healthy control group. Plasma phospholipids and metabolites linked to several amino acid and nucleoside pathways differed (p < 0.05) between healthy controls and IBS-C. In contrast, metabolites involved in bile acid and amino acid metabolism were the key differentiating classes in the plasma of subjects with IBS-D from healthy controls. Faecal lipids, particularly ceramides, diglycerides, and triglycerides, varied (p < 0.05) between healthy controls and the 'all constipation' group and between healthy controls and 'all diarrhoea' group. The faecal and plasma metabolomes showed perturbations between constipation, diarrhoea and healthy control groups that may reflect processes and mechanisms linked to FGIDs. [ABSTRACT FROM AUTHOR]

Background Frailty, malnutrition and low socioeconomic status may mutually perpetuate each other in a self-reinforcing and interdependent manner. The intertwined nature of these factors may be overlooked when investigating impacts on perioperative outcomes. This study aimed to investigate the impact of frailty, malnutrition and socioeconomic status on perioperative outcomes. Methods A multicentre cohort study involving six Australian tertiary hospitals was undertaken. All consecutive surgical patients who underwent an operation were included. Frailty was defined by the Hospital Frailty Risk Score, malnutrition by the Malnutrition Universal Screening Tool (MUST) and low socioeconomic status by the Index of Relative Socioeconomic Disadvantage. Linear mixed-effects and binary logistic generalised estimated equation models were performed for the outcomes: inpatient mortality, length of stay, 30-day readmission and re-operation. Results A total of 21 976 patients were included. After controlling for confounders, malnutrition and socioeconomic status, patients at high risk of frailty have a mean hospital length of stay 3.46 times longer (mean ratio = 3.46; 95% confidence interval (CI): 3.20, 3.73; P value < .001), odds of 30-day readmission 2.4 times higher (odds ratio = 2.40; 95% CI: 2.19, 2.63; P value < .001) and odds of in-hospital mortality 12.89 times greater than patients with low risk of frailty (odds ratio = 12.89; 95% CI: 4.51, 36.69; P value < .001). Elevated MUST scores were also significantly associated with worse outcomes, but to a lesser extent. Socioeconomic status had no association with outcomes. Conclusion Perioperative risk evaluation should consider both frailty and malnutrition as separate, significant risk factors. Despite strong causal links with frailty and malnutrition, socioeconomic disadvantage is not associated with worse postoperative outcomes. Additional studies regarding the prospective identification of these patients with implementation of strategies to mitigate frailty and malnutrition and assessment of perioperative risk are required. [ABSTRACT FROM AUTHOR]

Background and Aim: In immunochemical fecal occult blood test (iFOBT) positive subjects, colonoscopy screening can detect colorectal cancers and advanced adenomas, yet most iFOBT‐positive subjects find no relevant lower gastrointestinal lesions. Limited data are available on upper gastrointestinal (UGI) cancer risk in iFOBT‐positive patients. This study investigated the incidence of UGI malignancies diagnosed within 3 years post‐colonoscopy after a positive iFOBT. Methods: Retrospective analysis of iFOBT‐positive patients aged 50–75 years who underwent a colonoscopy at a single institution. All patients with a diagnosis of UGI cancer within 3 years post‐colonoscopy were identified by linking with the Queensland Cancer Register. This was used to compare to the geographical population aged 50–74 years based on the Australian Bureau of Statistics and Queensland Cancer Council data. Results: From 1748 eligible participants, 0.23% (95% confidence interval [CI] 0.06–0.58) were diagnosed with UGI cancer within 3 years post‐colonoscopy. This indicates an esophageal cancers rate of 114.42 per 100 000 (95% CI 100.56–298.28) and gastric cancer rate of 57.21 per 100 000 (95% CI 55.76–261.12). Of the patients with a UGI cancer, 75% would have had an unexplained iFOBT. Annual incidence for the same geographic region, ages, and period for the combined esophageal and gastric cancer was 36.08 per 100 000 (95% CI 32.87–39.52). Conclusions: Among individuals with a positive iFOBT in a bowel cancer screening program, the rates of gastric and esophageal cancers were 2.7 and 7.5 times higher than the general population. Adding gastroscopy to a colonoscopy for iFOBT‐positive patients in cancer surveillance programs may be justifiable. [ABSTRACT FROM AUTHOR]

Background and Aims: The group of disorders known as Disorders of Gut Brain Interaction (DGBI) were originally labeled functional GI disorders and were thought to be disorders of the gastrointestinal tract that had several psychological conditions as comorbidities. Despite mounting evidence that psychological morbidity plays an innate role in the etiology and maintenance of DGBI, none of the Rome IV criteria include any measure of psychological symptoms. This study tested the hypothesis that individuals would cluster differently if GI symptoms alone were considered versus GI symptoms combined with measures of psychological symptoms. Methods: Data were obtained from the Rome Foundation Global Epidemiology Study measuring Rome IV GI symptoms, psychological measures and demographic characteristics. Latent profile models were used to cluster individuals based on (i) GI symptoms only (GI only) and then (ii) GI and psychological measures (GI + Psych). Key Results: Individuals clustering into the same group of individuals whether formed via GI only or GI + Psych, ranged from 96% for a 2‐class solution (the most simplistic) to 76% with 6 classes (the parsimonious system) and 59% with twenty‐two classes (mimicking Rome IV). The generalisability of this finding between six geographic regions was confirmed with agreement varying between 95%–97% for 2 clusters and 71–79% for 6 classes and 51%–63% for 22 classes. These findings were also consistent between DGBI (range 94% with 2 classes to 50% with 22 classes) and non‐DGBI (range 97% with 2 clusters to 65% with 22 classes) groups. Conclusions & Inferences: Our data suggest that considering psychological as well as gastrointestinal symptoms would lead to a different clustering of individuals in more complex, and accurate, classification systems. For this reason, future work on DGBI classification should consider inclusion of psychological traits. [ABSTRACT FROM AUTHOR]

Background: Unsupervised machine learning describes a collection of powerful techniques that seek to identify hidden patterns in unlabeled data. These techniques can be broadly categorized into dimension reduction, which transforms and combines the original set of measurements to simplify data, and cluster analysis, which seeks to group subjects based on some measure of similarity. Unsupervised machine learning can be used to explore alternative subtyping of disorders of gut‐brain interaction (DGBI) compared to the existing gastrointestinal symptom‐based definitions of Rome IV. Purpose: This present review aims to familiarize the reader with fundamental concepts of unsupervised machine learning using accessible definitions and provide a critical summary of their application to the evaluation of DGBI subtyping. By considering the overlap between Rome IV clinical definitions and identified clusters, along with clinical and physiological insights, this paper speculates on the possible implications for DGBI. Also considered are algorithmic developments in the unsupervised machine learning community that may help leverage increasingly available omics data to explore biologically informed definitions. Unsupervised machine learning challenges the modern subtyping of DGBI and, with the necessary clinical validation, has the potential to enhance future iterations of the Rome criteria to identify more homogeneous, diagnosable, and treatable patient populations. [ABSTRACT FROM AUTHOR]

Summary: Background: There are inconsistencies in the results of the studies investigating the association between inflammatory bowel disease (IBD) and lymphoma. Aims: The aim of this study is to systematically appraise the risk of lymphoma development in patients with IBD. Methods: We searched Embase, PubMed and Scopus from inception to 30 April 2024 to identify population‐based cohort studies that evaluated the risk of lymphoma in patients with IBD in comparison with those without IBD. We carried out random‐effects meta‐analyses and estimated pooled relative risks (RRs) with 95% confidence intervals (CIs). Results: We identified 23 eligible studies reporting 2078 lymphoma events in 656,731 patients with IBD. Patients with IBD had 30% higher odds of lymphoma (RR = 1.30 [95% CI: 1.21–1.40]). The risk of developing both Hodgkin's lymphoma (nine studies, RR = 1.29 [95% CI: 1.06–1.53]) and non‐Hodgkin's lymphoma (16 studies, RR = 1.31 [95% CI: 1.20–1.42]) was increased in patients with IBD (p for interaction = 0.881). The increased risk of lymphoma was observed in both Crohn's disease (17 studies, RR = 1.54 [95% CI: 1.27–1.80]) and ulcerative colitis (20 studies, RR = 1.22 [95% CI: 1.09–1.35]) (p for interaction = 0.026). Meta‐regression demonstrated that mean age of patients, study year, mean study follow‐up duration, and percentages of immunomodulators and biologics use did not influence study outcome. Conclusions: The risk of lymphoma is only modestly increased in patients with IBD, with Crohn's disease having a slightly higher risk than ulcerative colitis. In IBD, there appears to be no difference between the risks of Hodgkin's and non‐Hodgkin's lymphoma. [ABSTRACT FROM AUTHOR]

Background and Aim: Barrett's oesophagus predisposes individuals to oesophageal adenocarcinoma (OAC), with the risk of progression to malignancy increasing with the degree of dysplasia, categorized as either low‐grade dysplasia (LGD) or high‐grade dysplasia (HGD). The reported incidence of progression to OAC in LGD ranges from 0.02% to 11.43% per annum. In patients with LGD, Australian guidelines recommend 6‐monthly endoscopic surveillance. We aimed to describe the surveillance practices within a tertiary centre, and to determine the predictive value of surveillance as well as other risk factors for progression. Methods: Endoscopy and pathology databases were searched over a 10‐year period to collate all cases of Barrett's oesophagus with LGD. Medical records were reviewed to document patient factors and endoscopic and histologic details. Because follow‐up times varied greatly, survival analysis techniques were employed. Results: Fifty‐nine patients were found to have LGD. Thirteen patients (22.0%) progressed to either HGD or OAC (10 (16.9%) and three (5.1%) respectively); the annual incidence rates of progression to HGD/OAC and OAC were 5.5% and 1.1% respectively. All patients who developed OAC had non‐guideline‐adherent surveillance. A Cox model found only two predictors of progression: (i) guideline‐adherent surveillance, performed in 16 (27.1%), detected progression to HGD/OAC four times earlier than non‐guideline‐adherent surveillance (95% confidence interval (CI) = 1.3–12.3; P = 0.016). (ii) The detection of visible lesions at exit endoscopy independently predicted progression (hazard ratio = 6.5; 95% CI = 1.9–22.8; P = 0.003). Conclusion: Barrett's oesophagus with LGD poses a significant risk of progression to HGD/OAC. Guideline‐recommended surveillance is effective, but is difficult to adhere to. Clinical predictors for those who are more likely to progress are yet to be defined. [ABSTRACT FROM AUTHOR]

Background: A subset of patients with irritable bowel syndrome (IBS) develop their symptoms after gastroenteritis, referred to as postinfectious IBS (PI‐IBS). PI‐IBS is associated with low‐grade intestinal inflammation. Previous studies have evaluated mesalamine, an anti‐inflammatory drug, in patients with IBS. We evaluated the efficacy of long‐acting mesalamine in patients with PI‐IBS. Methods: Sixty‐one patients who developed diarrhea‐predominant IBS (IBS‐D) after gastroenteritis were randomized to receive either 2.4 g of long‐acting mesalamine or placebo daily for 8‐weeks. The symptoms assessed were abdominal pain, bloating, stool frequency, stool consistency, severity of diarrhea and constipation, satisfaction with bowel habits, and IBS affecting or interfering with life. Quality‐of‐life (QOL) was assessed using the IBS‐QOL questionnaire. The prespecified primary outcome variable was the overall bowel symptom score (BSS) after 8‐weeks of treatment. Effect sizes were expressed as standardized mean differences (Cohen's d). Results: Fifty‐four patients completed the 8‐week treatment (n = 28 mesalamine, n = 26 placebo), 49 (91%) were male, and age range 23–71 years (mean ± SD 43 ± 13). Mesalamine demonstrated superior efficacy compared to placebo on the primary outcome variable, overall BSS (Cohen's d = 0.57, p = 0.042). Mesalamine was also superior for the secondary outcome of how much IBS affects your life in general (d = 0.72, p = 0.01). For the secondary outcomes of IBS symptoms, 7 of the 7 symptoms had trends of mesalamine superiority. For the secondary outcomes of IBS‐QOL subscales, 8 of 9 had trends of mesalamine superiority. Conclusion: In patients with PI‐IBS, long‐acting mesalamine demonstrated to be effective in reducing IBS symptoms and improving QOL. [ABSTRACT FROM AUTHOR]

Background: This 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. 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. Conclusions & Inferences: This 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. [ABSTRACT FROM AUTHOR]

Background: Disorders 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. Method s : 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). Conclusions & Inferences: Utilizing 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. [ABSTRACT FROM AUTHOR]

Background and Aims Diet plays an integral role in the modulation of the intestinal environment, with the potential to be modified for management of individuals with inflammatory bowel disease [IBD]. It has been hypothesised that poor 'Western-style' dietary patterns select for a microbiota that drives IBD inflammation and, that through dietary intervention, a healthy microbiota may be restored. This study aimed to systematically review the literature and assess current available evidence regarding the influence of diet on the intestinal microbiota composition in IBD patients, and how this may affect disease activity. Methods MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library were searched from January 2013 to June 2023, to identify studies investigating diet and microbiota in IBD. Results Thirteen primary studies met the inclusion criteria and were selected for narrative synthesis. Reported associations between diet and microbiota in IBD were conflicting due to the considerable degree of heterogeneity between studies. Nine intervention studies trialled specific diets and did not demonstrate significant shifts in the diversity and abundance of intestinal microbial communities or improvement in disease outcomes. The remaining four cross-sectional studies did not find a specific microbial signature associated with habitual dietary patterns in IBD patients. Conclusions Diet modulates the gut microbiota, and this may have implications for IBD; however, the body of evidence does not currently support clear dietary patterns or food constituents that are associated with a specific microbiota profile or disease marker in IBD patients. Further research is required with a focus on robust and consistent methodology to achieve improved identification of associations. [ABSTRACT FROM AUTHOR]

Background and Aim: Herbal products are widely used to treat patients with disorders of gut brain interaction but clinical efficacy and safety data for treatments lasting >4 weeks are widely lacking. We evaluated the efficacy and safety of 8 weeks of treatment with the herbal combination product STW 5‐II for patients with functional dyspepsia (FD) meeting Rome II criteria. We also conducted a post hoc analysis including patients meeting Rome IV criteria for FD and evaluated the effect of the G‐protein beta 3 (GNB3) subunit polymorphism (C825T) on therapeutic response. Methods: This multicenter, placebo‐controlled, double‐blind study included 272 FD patients meeting Rome II criteria in the intention‐to‐treat cohort and 266 meeting Rome IV criteria. We used the validated Gastrointestinal Symptom Score (GIS) to assess GI symptoms, defining response rate as the proportion of patients with ≥50% GIS improvement in at least three of four assessments. Results: After 8 weeks, the response rate was significantly higher in the STW 5‐II group versus placebo (61.2% vs 45.1%, P = 0.008). Mean GIS non‐significantly improved with STW 5‐II treatment (7.9 ± 4.41 vs 6.7 ± 4.91 with placebo; P = 0.07). In the Rome IV subgroup analysis, STW 5‐II yielded a better response rate (P = 0.01) versus placebo and greater postprandial distress symptom improvement (P = 0.04) versus placebo. Safety parameters did not differ between groups, and GNB3 status was not linked with therapeutic response. Conclusion: STW 5‐II is efficacious, with no observed safety signals at up to 8 weeks of treatment in patients with FD meeting Rome II or IV criteria. [ABSTRACT FROM AUTHOR]