The colonic epithelium is exposed to a mixture of compounds through diet, among which some are procarcinogens, whereas others have a protective effect. Therefore, the net impact of these compounds on human health depends on the overall balance between all factors involved. Strong scientific evidence has demonstrated the relationship between nitrosamines (NA), heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs), which are the major genotoxins derived from cooking and food processing, and cancer. The mechanisms of the relationship between dietary toxic xenobiotics and cancer risk are not yet well understood, but it has been suggested that differences in dietary habits affect the colonic environment by increasing or decreasing the exposure to mutagens directly and indirectly through changes in the composition and activity of the gut microbiota. Several changes in the proportions of specific microbial groups have been proposed as risk factors for the development of neoplastic lesions and the enrichment of enterotoxigenic microbial strains in stool. In addition, changes in the gut microbiota composition and activity promoted by diet may modify the faecal genotoxicity/cytotoxicity, which can be associated with a higher or lower risk of developing cancer. Therefore, the interaction between dietary components and intestinal bacteria may be a modifiable factor for the development of colorectal cancer in humans and deserves more attention in the near future.
The gut microbiota remains relatively stable during adulthood; however, certain intrinsic and environmental factors can lead to microbiota dysbiosis. Its restoration towards a healthy condition using best-suited prebiotics requires previous development of in vitro models for evaluating their functionality. Herein, we carried out fecal cultures with microbiota from healthy normal-weight and morbid obese adults. Cultures were supplemented with different inulin-type fructans (1-kestose, Actilight, P95, Synergy1 and Inulin) and a galactooligosaccharide. Their impact on the gut microbiota was assessed by monitoring gas production and evaluating changes in the microbiota composition (qPCR and 16S rRNA gene profiling) and metabolic activity (gas chromatography). Additionally, the effect on the bifidobacterial species was assessed (ITS-sequencing). Moreover, the functionality of the microbiota before and after prebiotic-modulation was determined in an in vitro model of interaction with an intestinal cell line. In general, 1-kestose was the compound showing the largest effects. The modulation with prebiotics led to significant increases in the Bacteroides group and Faecalibacterium in obese subjects, whereas in normal-weight individuals, substantial rises in Bifidobacterium and Faecalibacterium were appreciated. Notably, the results obtained showed differences in the responses among the tested compounds but also among the studied human populations, indicating the need for developing population-specific products.
16 May 2022 in United European Gastroenterology Journal
Background: Poor adherence to clinical practice guidelines for eosinophilic esophagitis (EoE) has been described and the diagnostic delay of the disease continues to be unacceptable in many settings.Objective: To analyze the impact of improved knowledge provided by the successive international clinical practice guidelines on reducing diagnostic delay and improving the diagnostic process for European patients with EoE.Methods: Cross‐sectional analysis of the EoE CONNECT registry based on clinical practice. Time periods defined by the publication dates of four major sets of guidelines over 10 years were considered. Patients were grouped per time period according to date of symptom onset.Results: Data from 1,132 patients was analyzed and median (IQR) diagnostic delay in the whole series was 2.1 (0.7‐6.2) years. This gradually decreased over time with subsequent release of new guidelines (p < 0.001), from 12.7 years up to 2007 to 0.7 years after 2017. The proportion of patients with stricturing of mixed phenotypes at the point of EoE diagnosis also decreased over time (41.3% vs. 16%; p < 0.001), as did EREFS scores. The fibrotic sub‐score decreased from a median (IQR) of 2 (1‐2) to 0 (0‐1) when patients whose symptoms started up to 2007 and after 2017 were compared (p < 0.001). In parallel, symptoms measured with the Dysphagia Symptoms Score reduced significantly when patients with symptoms starting before 2007 and after 2012 were compared. A reduction in the number of endoscopies patients underwent before the one that achieved an EoE diagnosis, and the use of allergy testing as part of the diagnostic workout of EoE, also reduced significantly over time (p = 0.010 and p < 0.001, respectively).Conclusion: The diagnostic work‐up of EoE patients improved substantially over time at the European sites contributing to EoE CONNECT, with a dramatic reduction in diagnostic delay.
Celiac disease (CD) is a genetically conditioned autoimmune process that appears in susceptible people. It can affect people of any age, and slightly predominates in females. It has a fairly homogenous global distribution, with an average prevalence of 1–2%, the frequency having increased in recent decades. The only effective treatment is a strict and permanent gluten-free diet (GFD), although the level of compliance is poor, at about 50% of cases. To monitor the effectiveness of the GFD, several procedures involving various approaches are employed: (a) Periodic visits by expert Nutritionists; (b) Clinical follow-up; (c) Serological time controls of specific antibodies; (d) Serial endoscopies with collection of duodenal biopsies; (e) Use of structured questionnaires; and (f) Determination of gluten peptides derived from gluten in faeces and/or urine. All of these procedures are useful when applied, alone or in combination, depending on the cases. Some patients will only need to consult to their doctors, while others will require a multidisciplinary approach to assess their compliance with the GFD. In children, normalization of duodenal mucosa was achieved in 95% of cases within two years, while it is more delayed in adults, whose mucosa take longer time (3–5 years) to heal completely.
Progressive intestinal mucosal damage occurs over years prior to colorectal cancer (CRC) development. The endoscopic screening of polyps and histopathological examination are used clinically to determine the risk and progression of mucosal lesions. We analyzed fecal microbiota compositions using 16S rRNA gene-based metataxonomic analyses and the levels of short-chain fatty acids (SCFAs) using gas chromatography in volunteers undergoing colonoscopy and histopathological analyses to determine the microbiota shifts occurring at the early stages of intestinal mucosa alterations. The results were compared between diagnosis groups (nonpathological controls and polyps), between samples from individuals with hyperplastic polyps or conventional adenomas, and between grades of dysplasia in conventional adenomas. Some microbial taxa from the Bacillota and Euryarchaeota phyla were the most affected when comparing the diagnosis and histopathological groups. Deeper microbiota alterations were found in the conventional adenomas than in the hyperplastic polyps. The Ruminococcus torques group was enriched in both the hyperplastic polyps and conventional adenomas, whereas the family Eggerthellaceae was enriched only in the hyperplastic polyps. The abundance of Prevotellaceae, Oscillospiraceae, Methanobacteriaceae, Streptococcaceae, Christensenellaceae, Erysipelotrichaceae, and Clostridiaceae shifted in conventional adenomas depending on the grade of dysplasia, without affecting the major SCFAs. Our results suggest a reorganization of microbial consortia involved in gut fermentative processes.
29 January 2024 in United European Gastroenterology Journal
Background: Swallowed topical corticosteroids (tC) are common therapy for patients with eosinophilic esophagitis (EoE). Widely heterogeneous results have occurred due to their active ingredients, formulations and doses.Objective: To assess the effectiveness of topical corticosteroid therapy for EoE in real‐world practice.Methods: Cross‐sectional study analysis of the multicentre EoE CONNECT registry. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom scores; histological remission was defined as a peak eosinophil count below 15 per high‐power field. The effectiveness in achieving clinico‐histological remission (CHR) was compared for the main tC formulations.Results: Overall, data on 1456 prescriptions of tC in monotherapy used in 866 individual patients were assessed. Of those, 904 prescriptions with data on formulation were employed for the induction of remission; 234 reduced a previously effective dose for maintenance. Fluticasone propionate formulations dominated the first‐line treatment, while budesonide was more common in later therapies. A swallowed nasal drop suspension was the most common formulation of fluticasone propionate. Doses ≥0.8 mg/day provided a 65% CHR rate and were superior to lower doses. Oral viscous solution prepared by a pharmacist was the most common prescription of budesonide; 4 mg/day provided no benefit over 2 mg/day (CHR rated being 72% and 80%, respectively). A multivariate analysis revealed budesonide orodispersible tablets as the most effective therapy (OR 18.9, p < 0.001); use of higher doses (OR 4.3, p = 0.03) and lower symptom scores (OR 0.9, p = 0.01) were also determinants of effectiveness.Conclusion: Reduced symptom severity, use of high doses, and use of budesonide orodispersible tablets particularly were all independent predictors of tC effectiveness.