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Background and aims:

Wholegrain rye foods have shown promising effects on metabolic regulation and weight-loss, which may be mediated via gut microbiota and derived metabolites. This study aimed to investigate effects of hypocaloric diets with wholegrain rye versus commonly consumed refined wheat on body weight, fat mass, metabolic risk markers and gut microbiota. The study also explored determinants of diet-induced weight loss..

Methods:

Participants with overweight or obesity were randomized (1:1) to 12-week hypocaloric diets, substituting habitual cereals with wholegrain rye or refined wheat foods. Body weight and composition were measured and fecal- and blood samples were collected at baseline, after 6 weeks and 12 weeks.

Results:

Of 255 participants, 229 completed the study. Weight loss was 3.2 kg in the rye-group and 2.9 kg in the wheat-group, with no significant difference between groups (p = 0.32). Plasma acetate and butyrate were higher after 12 weeks in the rye-group versus wheat-group (p = 0.003) and microbial taxa, previously associated with negative health outcomes were reduced in the rye-group. Reductions in CRP by 17 % (p = 0.03) were observed in the rye-group, while both CRP (r = 0.17, p = 0.001) and HOMAIR (r = 0.13, p = 0.02) at baseline were associated with fat mass change in the wheat-group. Additionally, acetate at baseline was inversely associated with body weight change across groups (r = -0.25, p < 0.001). Baseline gut microbiota was not associated with weight loss after 12 weeks.

Conclusions:

Wholegrain rye versus refined wheat foods as part of a hypocaloric diet did not result in larger weight loss. However, wholegrain rye reduced CRP and induced changes in gut microbiota and short-chain fatty acids which may have positive implications for cardiometabolic health. Notably, baseline HOMA-IR and CRP correlated with weight and fat mass reductions, suggesting that individuals with elevated inflammation and insulin resistance may benefit more from wholegrain rye foods. Gut microbiota at baseline was not associated with intervention-induced weight loss.

Trial Registration: ClinicalTrials.gov ID: NCT04203758. https://classic.clinicaltrials.gov/ct2/show/ NCT04203758?term=Rye&cond=Overweight+and+Obesity&cntry=SE& city=Gothenburg&draw=2&rank=3. 

Background

Small intestinal bacterial overgrowth (SIBO) is suggested in irritable bowel syndrome (IBS). Optimal hydrogen levels and time frame for diagnosing SIBO are still under discussion. Our primary aim was to consolidate a discriminating threshold for a positive lactulose hydrogen breath test (LHBT) in IBS. As a secondary aim, we optimized the diagnostic time frame for the small bowel.

Methods

LHBT was performed on 503 subjects who met the inclusion criteria. After excluding non-hydrogen producers, the remaining 462 subjects were 92 healthy individuals and 370 IBS patients. Peak hydrogen levels were summarized as median values with interquartile range.

Results

At the 80-min orocecal cut-off, healthy subjects showed a peak hydrogen of 8(4-11) ppm compared with 10(4-29) ppm in the overall IBS group (p <0.0001). Using >= 20 ppm cut-off, sensitivity was 38% and specificity 77%. Peak hydrogen was highest in IBS-D (24(9-40) ppm; p <0.0001), intermediate in IBS-M (7(4-14) ppm), and lowest in IBS-C (7(4-10) ppm), showing sensitivities of 61%, 23%, and 10%, respectively, with specificity 77%. After antibiotics, IBS patients with low hydrogen were unchanged, whereas most with high hydrogen reduced their hydrogen levels (p <0.01).

Conclusion

Using a cut-off level of >= 20 ppm during the first 80 minutes, LHBT can diagnose SIBO in people with IBS showing high breath hydrogen, as compared with those having low breath hydrogen. Hence, SIBO-positive patients can be separated from SIBO-negative IBS patients. To this end, a majority of SIBO-positive subjects respond to antibiotic treatment.

Background

While the acute phase of the COVID-19 pandemic has passed, understanding its pathophysiology remains critical for managing long-term sequelae and future viral threats. Oxidative stress is a proposed key driver of COVID-19 severity, but its relationship with the dynamic inflammatory cascade and its value as a standalone biomarker requires further validation.

Methods

Case-control study was conducted to quantify systemic oxidative stress burden in 109 hospitalized COVID-19 patients (56 severe, 53 mild-moderate) and 112 healthy controls. Serum total oxidant status (TOS) and total antioxidant status (TAS) were measured, and the oxidative stress index (OSI) was calculated and correlated to the inflammatory mediators (IL-6, IL-8, IL-10, IP-10, CRP, SAA).

Results

COVID-19 patients exhibited a profound redox imbalance, characterized by elevated TOS and OSI, and depleted TAS compared to controls (p < 0.05). This imbalance was exacerbated in severe disease, where TOS and OSI were significantly increased. The OSI demonstrated superior diagnostic performance for disease severity (AUC = 0.90; 95% CI: 0.86–0.95) compared to TOS (AUC = 0.89) and TAS (AUC = 0.78). Crucially, both TOS and OSI showed strong positive correlations with inflammatory cytokines and acute-phase proteins (IL-6, IL-10, IP-10, CRP, SAA; all p < 0.001). After adjusting for age, time from symptom onset, and comorbidity burden (Charlson Comorbidity Index), multivariate analysis confirmed that high OSI was independently associated with disease severity (adjusted OR: 4.8; 95% CI: 1.9–12.1).

Conclusions

The OSI is a robust, integrative biomarker that strongly reflects COVID-19 severity and is closely linked to the hyperinflammatory state. The OSI is strongly correlated with increased inflammatory cytokines and acute-phase proteins in acute COVID-19.

Objectives: Diarrhea is common and can exert a profound negative impact on social life due to unpredictable bowel movements and fecal incontinence. Liraglutide has been documented to be effective in patients with bile acid diarrhea (BAD), but documentation for the effect of semaglutide in patients with unspecific diarrhea is lacking. We report experiences with compassionate use of weekly semaglutide in patients with diarrhea of different etiologies.

Methods: Our cases comprised 15 patients with BAD, nine with idiopathic diarrhea, four with short bowel syndrome, two with collagenous colitis and one with radiation enteritis. All patients had undergone routine work-up for chronic diarrhea. Despite the use of anti-diarrheal agents, all patients were severely handicapped in social functioning and work-life due to extreme urgency, nocturnal diarrhea and fecal incontinence. After informed consent, the patients started treatment with semaglutide 0.25 mg every seven days titrated to an individually tailored dosage.

Results: After semaglutide was initiated, the median number of daily bowel movements decreased from 8 (interquartile range (IQR) 5-12) to 2 (IQR 1-3), p < .0001. All patients reported an almost immediate relief of urgency, fecal incontinence and nocturnal diarrhea. Fourteen patients shortened their dosing interval of semaglutide to every fifth or sixth day due to a time-dependent decrease in effect. One patient stopped treatment due to nausea, and in another, the dosage was reduced due to constipation.

Conclusion: Semaglutide may represent a rational symptomatic treatment option for selected patients with severe diarrhea, including those with BAD, short bowel syndrome and idiopathic diarrhea.

High stroma content, as measured by tumor-stroma ratio (TSR), is generally a negative prognostic parameter for epithelial cancers, including sporadic colorectal cancer (sCRC). Inflammatory bowel disease patients have higher risk for colorectal cancer than the background population. Evidence suggests that this colitis-associated colorectal cancer (CAC) is more aggressive and occurs at younger age than sCRC. CAC also differs from sCRC in oncogenesis and prognosis. This study tests the hypothesis that TSR in CAC tumors correlates with survival. Age at CAC diagnosis relative to TSR was also explored. TSR was quantified in 36 CAC cases. In routine hematoxylin–eosin staining, the amount of stroma was estimated in categorical steps of 10% increments per image field. The area with highest amount of stroma and tumor tissue at all quadrants of the visual field boundary was scored for TSR. For statistical analysis, tumors were divided into stroma-high (> 50%) or stroma-low (≤ 50%). Of all cases, 22 were stroma-high and 14 were stroma-low. Five-year survival in the stroma-high group was 32% (n = 22), compared to 71% (n = 14) in the stroma-low group (p = 0.049). High stroma content was more frequent if cancer diagnosis was before 60 years of age (17/23) compared to after 60 years of age (5/13). Despite differences in oncogenesis and tumor biology in CAC compared to sCRC, high stroma content also predicts worse outcome in CAC and is particularly common in younger patients.

Background/Objectives: Irritable bowel syndrome (IBS) is primarily treated via dietary modifications. Several diets have been shown to improve symptoms with similar efficacy. Other aspects of IBS, such as insufficient nutrient intake and being overweight, should also be considered when planning treatment options. The present scoping review aimed to identify various diets investigated in IBS-related clinical trials and to map the measured outcomes.

Methods: We performed a systematic search of three databases: PubMed, Embase, and CINAHL Ultimate. Our search was limited to papers published between January 2000 and February 2026, and included human studies published as peer-reviewed original articles in English that described dietary interventions in adult patients (≥18 years) with IBS.

Results: The titles and abstracts of 1261 studies were screened; 1147 studies were excluded; and 114 full-text articles were assessed for eligibility. Excluding articles outside the scope of our research resulted in a total of 71 included articles from 57 unique clinical trials. The most common interventions were low fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) (n = 43), traditional dietary advice (n = 13), and gluten-free diets (n = 11). The most common primary outcomes were the effect on IBS symptoms (n = 48), efficacy in terms of improving quality of life (n = 10), psychological well-being (n = 7), nutrient intake (n = 7), and adherence/applicability/feasibility to the diet (n = 7).

Conclusions: In conclusion, the most studied dietary intervention in IBS was low FODMAP, and an effect on GI symptoms was the most common outcome. Considering other conditions associated with IBS, the effects on anthropometric, endocrine, metabolic, and nutritional parameters should also be evaluated.

Studying the pathogenesis of human-adapted microorganisms is challenging, since small animal models often fail to recapitulate human physiology. Hence, the comprehensive genetic and regulatory circuits driving the infection process of principal human pathogens such as Shigella flexneri remain to be defined. We combined large-scale Shigella infections of enteroids and colonoids with transposon-directed insertion sequencing and Bayesian statistical modeling to address infection bottlenecks, thereby establishing the comprehensive genome-wide map of Shigella genes required to infect human intestinal epithelium. This revealed the Shigella virulence effectors essential for epithelial cell colonization across geometries and intestinal segments, identified over 100 chromosomal genes involved in the process and uncovered a post-transcriptional mechanism whereby tRNA-modification enzymes and differential codon usage exert global control of a bacterial virulence program. Our findings provide a broadly applicable framework for combining advanced organotypic tissue culture with functional genomics and computational tools to map human–microorganism interactions at scale.

Despite their relatedness, Salmonella and Shigella enteropathogens differ in infectious dose, pathogenesis, and disease kinetics. The prototype strains Salmonella enterica serovar Typhimurium (Salmonella) and Shigella flexneri (Shigella) use Type-3-secretion-systems (T3SSs) to colonize intestinal epithelial cells (IECs). However, they have evolved unique sets of T3SS effectors and accessory virulence factors. A synthesis of how these differences impact the temporal progression of infection in non-transformed human epithelia is missing. Here, we followed Salmonella and Shigella infections of human enteroids and colonoids by time-lapse imaging to pinpoint virulence factor modules that shape the divergent epithelial colonization strategies. By an apical targeting module that integrates flagella and the SPI-4-encoded adhesin system with T3SS-1, Salmonella accomplishes appreciable numbers of apical IEC invasion events. These are promptly counteracted by IEC death, thus fostering a polyclonal iterative epithelial colonization strategy. The lack of a corresponding apical targeting module in Shigella makes this pathogen reliant on external factors, for example, preexisting damage, for rare apical access to the intraepithelial environment. However, Shigella compensates for this ineptness by an intraepithelial expansion module reliant on the tight coupling of OspC3-dependent temporal delay of cell death and IcsA-mediated mobility. This module enables intraepithelial Shigella to evade the IEC death response just long enough to expand laterally, thus fostering an essentially monoclonal colonization strategy. Taken together, the study reveals how a small set of virulence factors shapes divergent epithelial colonization strategies by related enterobacteria.

Introduction

Understanding meal-induced changes of gut hormones, gastric motility, and appetite is crucial for developing therapies for obesity. We investigated glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), ghrelin, and motilin influences on gastric motility and appetite, to compare healthy individuals and people with obesity.

Methods

Subjects (healthy n = 41; obesity n = 32) consumed a 270-kcal meal and a wireless motility capsule. GIP, active GLP-1, acyl-ghrelin, and motilin were measured by electrochemiluminescence. MotiliGI and GIMS software were used for motility analysis, while visual analog scoring measured appetite.

Results

Gastric emptying was more rapid in people with obesity than in healthy individuals (p < 0.01). Gastric emptying time was negatively associated with motility index and hunger contractions (p < 0.01, p < 0.05) in healthy individuals, but not in individuals with obesity. In controls, gastric motility index correlated positively with acyl-ghrelin (p < 0.01) and motilin (p < 0.0001), and negatively with GIP (p < 0.05), but not aGLP-1. In people with obesity, no gut hormones correlated with the motility index. In both groups, GIP and aGLP-1 correlated with decreased hunger (p < 0.0001, p = 0.001) and (p < 0.0001, p < 0.05), along with increased satiety in controls (p < 0.0001, p = 0.001) and people with obesity (p = 0.049, p = 0.01). Acyl-ghrelin correlated positively with hunger (p < 0.0001) and negatively with satiety (p = 0.049) in controls, but not in obesity. Motilin was neither associated with hunger nor satiety.

Conclusion

In the gastric phase, people with obesity show rapid gastric emptying with altered hormone and motility meal responses. In healthy individuals, GIP promotes satiety, and ghrelin and motilin promote hunger through actions on motility. Like GIP, GLP-1 promotes satiety along with trending suppression of gastric motility.