Jørgen Valeur

“Gastric acid” and “gastric juice” are commonly used as interchangeable terms, thus obscuring a distinction that took physiologists generations to establish. Hydrochloric acid denatures dietary protein, activates pepsinogen, and maintains the pH at which pepsin is active, but it does not itself hydrolyze peptide bonds (i.e., digest). Disentangling the interplay between acid and pepsin required independent, near-simultaneous work in Germany and the United States in the early 1830s, followed by Theodor Schwann’s isolation, in 1836, of a separate heat-sensitive agent he named pepsin. The elimination logic Schwann used to reach that conclusion, testing and ruling out each plausible alternative in turn, offers a reasoning model still worth teaching today.

Irritable bowel syndrome (IBS) is a gastrointestinal disorder that is highly prevalent, often accompanied by considerable comorbidities and that places a substantial burden both on individuals and healthcare systems. Treatments are usually aimed at addressing symptoms but often fall short of long-term relief. Current dietary strategies primarily focus on what patients should avoid eating, while the potential physiological importance of when food is consumed has received little attention in IBS research. We hypothesize that gastrointestinal symptoms may, at least partially, be affected by a cumulative burden of epithelial injury as well as insufficient time for mucosal maintenance and repair. This paper explores the hypothesis that intermittent fasting regimens could represent underexplored therapeutic strategies for reducing IBS symptoms by promoting gut renewal and restoring homeostasis. We review the multifactorial pathophysiology of IBS and explore how fasting may impact relevant biological mechanisms. Several lines of evidence, from both preclinical and clinical studies, indicate that intermittent fasting may reduce inflammation, regulate gut motility and reshape the microbiota, thereby strengthening the gut barrier and dampening immune responses. Fasting also induces autophagy, a key cellular recycling process essential for intestinal barrier maintenance and microbial defense, which may be impaired in IBS. Hence, intermittent fasting may reduce cumulative epithelial injury and allow time for repair to alleviate symptoms in IBS. Although no randomized controlled trials on fasting regimens and IBS are available, evidence from related populations and mechanistic research supports further exploration of this accessible, low-cost approach.

Purpose: Iron deficiency impairs sports performance, and female athletes are particularly vulnerable. High-dose iron supplements, commonly used to prevent iron depletion and performance impairments, may cause gastrointestinal side effects and disrupt the gut microbiota. Whether lower doses can improve iron status without adverse effects remains unclear. The aim of this study was to characterize iron intake and iron status in female soccer players during the competitive season and investigate effects of low-dose iron supplementation on iron status, safety-related outcomes and gut microbiota. Methods: In a two-arm parallel randomized controlled trial, female soccer players (median age 21) were randomized to an intervention group (n=12) receiving 3-month low-dose iron supplementation (27 mg elemental iron/day) or a control group (n=11) without supplementation. Blood/fecal samples were collected at baseline and 3-month follow-up. Dietary intake was estimated using 7-day food diaries. Between-group differences were analyzed per protocol (n=18) using ANCOVA with baseline adjustment. Results: The players had inadequate baseline iron intake (median 11.2 mg/day) and 43% had serum ferritin indicating iron depletion (P P _group =0.05). No between-group differences were observed for gastrointestinal symptoms or liver damage biomarkers. On the contrary, the intervention led to lower IL-6 ( P _group =0.04) and higher gut microbial α-diversity ( P _group =0.01) compared to controls. Conclusions: The low-dose iron supplementation was well tolerated, attenuated decreases in iron stores, increased gut microbial diversity and attenuated systemic inflammation in female soccer players with suboptimal dietary iron intake. However, potential adverse effects of long-term exposure cannot be excluded. Clinical Trial Registration: This trial was registered at clinicaltrials.gov as NCT04526678 , first submitted on 2020-08-13 ( https://clinicaltrials.gov/study/NCT04526678 ).

Purpose: Ageing is associated with a decline in gastrointestinal (GI) functions, but data on GI symptoms in older adults remain limited. This study assessed the prevalence of GI symptoms, irritable bowel syndrome (IBS), and faecal short-chain fatty acids (SCFAs) in older adults, and associations between GI symptoms and faecal SCFAs, dietary intake, and BMI. Methods: 907 older adults (66–69 years, 50.7% females) from the community-based Hordaland Health Study 3 − Microbiota study were included. GI symptoms and IBS status were assessed by validated questionnaires (Gastrointestinal Symptom Rating Scale, Rome IV-criteria, IBS-Severity Scoring System), dietary intake by a 279-item food frequency questionnaire, and the concentration of SCFAs were measured from faecal samples. Results: 33.9% experienced at least one GI symptom, 16.4% reported IBS-like symptoms, and 5.0% had IBS according to Rome IV-criteria. Indigestion was the most common GI symptom (24.2%). Females had a higher total mean score of GI symptoms ( p = 0.021), with higher frequencies of constipation ( p = 0.006) and abdominal pain ( p = 0.031), compared to males. Males had higher concentration of total faecal SCFAs ( p = 0.004) and all major SCFAs compared to females. Total faecal SCFAs were negatively associated with constipation, independently of dietary fibre intake, total energy intake, sex and BMI (B = − 0.006, 95% CI [− 0.009, − 0.004], p < 0.001). We observed a positive correlation between total faecal SCFA concentrations and diarrhoea ( r = 0.072, p = 0.039) and looser stool consistency ( r = 0.185, p < 0.001); however, these associations did not persist in the regression analyses. All GI symptoms positively correlated with increasing BMI. Conclusion: GI symptoms are common in older adults, and IBS is at least as prevalent as observed in the general adult population. Improving dietary habits and preventing overweight and obesity may reduce the risk of GI symptoms and improve gut health in older adults.

Background and Aim: Despite the well-established involvement of the gut microbiome in inflammatory bowel disease (IBD), less is known about how the gut microbiome changes over time and how it varies with clinical disease activity and fecal calprotectin (f-calprotectin). To address this gap, we utilized samples from the population-based inception cohort of the Inflammatory Bowel Disease in South-Eastern Norway III (IBSEN III) study. Methods: Data and stool samples from study participants with IBD and symptomatic controls were collected at diagnosis and after 3, 6, and 12 months. Microbiome profiling of stool samples was performed targeting the V3-V4 region of the 16S rRNA gene, and a consensus-based approach of mixed models was employed for the longitudinal microbiome analysis. Results: We included 1251 samples from 744 patients with ulcerative colitis, 618 samples from 356 patients with Crohn’ s disease and 266 samples from 164 symptomatic non-IBD controls. In the IBD population, we observed that levels of f-calprotectin decreased over time, as did the patient-reported disease activity (P < .001). Distinct changes in the gut microbiome of IBD patients were observed throughout the first year, such as increased alpha diversity (P < .001) and significant taxonomic changes. Notably, there was no covariation between the changes in alpha diversity and f-calprotectin or symptom score. Conclusion: The gut microbiome during the first year after IBD diagnosis showed changes that paralleled inflammation and clinical disease activity, albeit without covariation, suggesting that there may be a disease-driving impact of gut microbiome independent of inflammation and inflammation-driven symptoms.

Background: Inflammatory bowel diseases (IBDs) are complex conditions marked by chronic inflammation in the gastrointestinal tract. Traditional classification separates IBD into Crohn’s disease and ulcerative colitis, but this division may not fully capture disease heterogeneity. Here, we examine whether microbiome-driven subtyping can describe novel clinical IBD phenotypes. To achieve this, we applied unsupervised clustering to fecal microbiota profiles from the population-based Inflammatory Bowel Disease in South-Eastern Norway III (IBSEN III) cohort. Methods: A Gaussian Mixture Model (GMM) was used to cluster participants with IBD based on microbiome composition and examine associations between clusters and clinical outcomes, including inflammatory markers and disease severity during the first year after inclusion. Results: Three microbiome-based clusters were identified: CLO (dominated by Clostridia UCG-014), ALF (Agathobacter, Lachnoclostridium, and Faecalibacterium), and RUM (Ruminococcus gnavus). Participants in the RUM cluster had a higher risk of future severe disease than those in the CLO cluster, even among participants with remission-to-mild disease at inclusion (21% vs. 6%, P < 0.00001). This association could not be explained by antibiotic use or baseline disease severity. Cluster membership alone performed comparably to fecal calprotectin in distinguishing severe disease, and a combined model significantly improved accuracy (P < 0.0001). Conclusion: Our findings demonstrate a connection between microbiome composition and the risk of severe disease development, which is partly independent of inflammation levels at the time of sampling. Microbiome-informed subgrouping could lead to more personalized treatment strategies. Further validation is needed to determine the clinical utility of these clusters.

Aims: Alcohol-related harm occurs at lower levels than previously recognized, warranting a need to identify mediators to reduce alcohol-associated risk in increased-risk drinkers. Stages of change (SOC) have been used to assess motivation for health behaviour alteration. The primary aim was to explore distribution on SOC among medical inpatients when comparing low-risk, increased-risk, and high-risk consumers as defined by Alcohol Use Disorder Identification Test-Consumption (AUDIT-C). Our secondary aim was to assess the distribution of SOC when consumption was stratified with a biomarker of alcohol use—phospatidylethanol 16:0/18:1. Methods: Cross-sectional study with three participating hospitals. Recruiting consecutive medical inpatients ≥18 years with regular alcohol consumption as screened by score ≥2 on the first question in AUDIT-C (N = 888). AUDIT-C score and SOC were assessed by questionnaires, and phospatidylethanol concentration in a blood sample. Odds ratios and the 95% confidence intervals were calculated through a univariate logistic regression analysis for each variable, and multivariable logistic regression models were then fit to calculate the adjusted odds ratio and 95% confidence interval. Results: Distributions of SOC differed between the three risk-groups. Distribution of SOC was comparable whether assessed by phospatidylethanol or AUDIT-C. Conclusions: Increased-risk consumers constitute the majority of those in action—the only stage associated with consecutive reduction in drinking. Potentially, these results can aid in reducing perceived barriers among health care professionals in screening and offering health advice to those with increased-risk consumption and inform further research on mediators in this subgroup.

Irritable bowel syndrome (IBS) is a prevalent disorder of gut–brain interaction (DGBI) with an adverse impact on quality of life. The global consumption of ultra-processed foods (UPF) is rapidly increasing, and UPF intake has recently been linked to a wide range of metabolic and chronic diseases. The potential role of UPF consumption in the onset and symptom generation of IBS is emerging but remains unclear. This narrative review synthesizes epidemiological evidence on the association between UPF consumption and IBS, integrates mechanistic insights from experimental and clinical studies and suggests clinical implications based on the current state of knowledge. Observational studies suggest that higher UPF intake may be associated with increased risk of IBS, although the evidence base is limited and subject to methodological challenges. Mechanistic studies indicate that additives including emulsifiers and non-nutritive sweeteners can alter pathways relevant to IBS symptom generation, such as gut microbiota composition, impair intestinal barrier function and trigger low-grade inflammation. Current evidence supports a possible link between UPF consumption and IBS. Increasing overall dietary quality and reducing UPF intake are promising complementary strategies to established dietary interventions. Future intervention trials may provide insights into relevant biological mechanisms, particularly if such changes co-occur with symptom improvement.

Background: We previously found that the fecal levels of short‐chain fatty acids (SCFAs) changed in irritable bowel syndrome (IBS) patients at 1 month and 1 year after fecal microbiota transplantation (FMT). This study analyzed SCFAs at 2 and 3 years after FMT in the same IBS patients included in those previous studies. Methods: This study randomized 113 IBS patients into placebo, 30‐g, and 60‐g groups, who received FMT with 30 g of their own feces and with 30 g and 60 g of the donor's feces, respectively. The patients completed four questionnaires to assess IBS symptoms, fatigue, and quality of life, and supplied fecal samples at the baseline and at 2 and 3 years after FMT. The fecal SCFA levels were measured using gas chromatography. Results: The butyric acid level was significantly increased at 2 and 3 years after FMT in the 30‐g and 60‐g groups, and was significantly higher than that in the placebo group. The total SCFA and acetic acid levels decreased significantly in the 30‐g and 60‐g groups at 2 and 3 years after FMT, while the propionic acid level decreased in the 60‐g group at both time points. The butyric acid level was inversely correlated with IBS symptoms and fatigue. Conclusion and Inferences: The increased butyric acid levels in IBS patients at 2 and 3 years after FMT and their inverse correlation with both IBS symptoms and fatigue suggest that butyric acid contributes to the long‐term improvement seen after FMT ( www.clinicaltrials.gov : NCT03822299).

Gastroparesis is a late complication of diabetes mellitus characterized by delayed gastric emptying and upper gastrointestinal symptoms. The disorder substantially impacts the quality of life, glycemic stability, nutrition and absorption of orally administered drugs. Since symptom severity is a poor predictor of gastric emptying status, the clinician has little to aid them in whom to refer for gastric emptying testing. In this study, we aim to identify clinical characteristics associated with delayed gastric emptying in diabetes patients with gastroparesis-like symptoms. Diabetes patients consecutively referred to Haukeland University Hospital for assessment of gastroparesis-like symptoms underwent gastric emptying scintigraphy, blood samples and questionnaires for assessing gastrointestinal symptoms (Gastrointestinal Symptom Rating Scale), neuroticism (Eysenck Personality Questionnaire-Short Form), and symptoms of anxiety and depression (Hospital Anxiety & Depression Scale). Results: Seventy-one patients were included in the study, of which 28 displayed delayed gastric emptying. Delayed gastric emptying was characterized by having type 1 diabetes, younger age, lower BMI, presence of other late complications including distal symmetric polyneuropathy and retinopathy, higher Hb1Ac levels and lower albumin and hemoglobin levels. Symptoms were not related to gastric emptying status. We identified several clinical variables associated with delayed gastric emptying in diabetes patients with gastroparesis-like symptoms. These variables are commonly assessed during a medical consultation and may be used to aid the clinician in choosing who to refer for gastric emptying testing.