Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 147
Filtrar
1.
Am J Gastroenterol ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39319824

RESUMO

BACKGROUND AIMS: Cyclic vomiting syndrome (CVS) is a disorder of gut-brain interaction (DGBI) of unknown origin. This study aimed to evaluate the global prevalence of this disorder and its associated factors. METHODS: Data were collected from nationwide Internet surveys in 26 countries, with subjects evenly distributed by age, sex and country. The survey included the Rome IV questionnaire as well as an extensive supplemental questionnaire to evaluate additional factors. RESULTS: 54,127 participants completed the questionnaire (51% male, mean age 44.3 years). The pooled prevalence of CVS was 0.3% (95% CI 0.3-0.4%; n=187), highest in Brazil (1%, 95% CI 0.6-1.5), and lowest in Japan and Germany (with no subject who fulfilled the criteria for CVS). The mean age of participants with CVS was 36.7 years (standard deviation 13.5) and it was more common in females (56.7% vs 43.5%). Factors independently associated with this syndrome were female sex (OR 1.52, 95% CI 1.13-2.03), young age (OR 2.57, 95% CI 1.34-4.94, for people between the ages of 18 and 39 years, compared to those older than 65 years), depression (OR 3.14, 95% CI 2.05-4.82, p<0.001) and anxiety (OR 1.79, 95% CI 1.15-2.78, p<0.001). Individuals with CVS had impaired quality of life (QoL) (PROMIS-10 score: physical QoL mean, 12.9 vs 15.5, p<0.001; mental QoL mean 12.3 vs 14.4, p<0.001) compared to others. CONCLUSIONS: CVS is a relatively common disorder that has a negative impact on quality of life. It is important to raise awareness on this syndrome to avoid underdiagnosis and improve clinical practice.

2.
Nutrients ; 16(17)2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39275354

RESUMO

A diet with low content of fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) is established treatment for irritable bowel syndrome (IBS), with well-documented efficiency. A starch- and sucrose-reduced diet (SSRD) has shown similar promising effects. The primary aim of this randomized, non-inferiority study was to test SSRD against low FODMAP and compare the responder rates (RR = ∆Total IBS-SSS ≥ -50) to a 4-week dietary intervention of either diet. Secondary aims were to estimate responders of ≥100 score and 50% reduction; effects on extraintestinal symptoms; saturation; sugar craving; anthropometric parameters; and blood pressure. 155 IBS patients were randomized to SSRD (n = 77) or low FODMAP (n = 78) for 4 weeks, with a follow-up 5 months later without food restrictions. The questionnaires Rome IV, IBS-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS) were completed at baseline and after 2 and 4 weeks and 6 months. Weight, height, waist circumference, and blood pressures were measured. Comparisons were made within the groups and between changes in the two groups. There were no differences between groups at baseline. The responder rate of SSRD was non-inferior compared with low FODMAPs at week 2 (79.2% vs. 73.1%; p = 0.661;95% confidence interval (CI) = -20-7.2) and week 4 (79.2% vs. 78.2%; p = 1.000;95%CI = -14-12). Responder rate was still high when defined stricter. All gastrointestinal and extraintestinal symptoms were equally improved (p < 0.001 in most variables). SSRD rendered greater reductions in weight (p = 0.006), body mass index (BMI) (p = 0.005), and sugar craving (p = 0.05), whereas waist circumference and blood pressure were equally decreased. Weight and BMI were regained at follow-up. In the SSRD group, responders at 6 months still had lowered weight (-0.7 (-2.5-0.1) vs. 0.2 (-0.7-2.2) kg; p = 0.005) and BMI (-0.25 (-0.85-0.03) vs. 0.07 (-0.35-0.77) kg/m2; p = 0.009) compared with baseline in contrast to non-responders. Those who had tested both diets preferred SSRD (p = 0.032). In conclusion, a 4-week SSRD intervention was non-inferior to low FODMAP regarding responder rates of gastrointestinal IBS symptoms. Furthermore, strong reductions of extraintestinal symptoms were found in both groups, whereas reductions in weight, BMI, and sugar craving were most pronounced following SSRD.


Assuntos
Síndrome do Intestino Irritável , Amido , Humanos , Síndrome do Intestino Irritável/dietoterapia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Amido/administração & dosagem , Resultado do Tratamento , Fermentação , Polímeros , Monossacarídeos , Dieta com Restrição de Carboidratos/métodos , Sacarose Alimentar/administração & dosagem , Oligossacarídeos , Dissacarídeos/administração & dosagem , Pressão Sanguínea
3.
Am J Physiol Heart Circ Physiol ; 327(4): H956-H964, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39150392

RESUMO

Traditional cardiovascular risk factors, including hypertension, only explain part of major adverse cardiac events (MACEs). Understanding what other risk factors contribute to MACE is essential for prevention. Constipation shares common risk factors with hypertension and is associated with an increased risk of several cardiovascular diseases. We hypothesized that constipation is an underappreciated risk factor for MACE. We used the population healthcare and genomic data in the UK Biobank (n = 408,354) to study the contribution of constipation (ICD10 K59.0) to the risk of MACE, defined by any episode of acute coronary syndrome (ACS), ischemic stroke, and heart failure (HF). Analyses were controlled for traditional cardiovascular risk factors. We also assessed genetic correlations (rg) between constipation and MACE. Constipation cases (n = 23,814) exhibited a significantly higher risk of MACE compared with those with normal bowel habits [odds ratio (OR) = 2.15, P < 1.00 × 10-300]. Constipation was also significantly associated with individual MACE subgroups, in order: HF (OR = 2.72, P < 1.00 × 10-300), ischemic stroke (OR = 2.36, P = 2.02 × 10-230), and ACS (OR = 1.62, P = 5.82 × 10-113). In comparison with patients with constipation-free hypertension, patients with hypertension with constipation showed significantly higher odds of MACE (OR = 1.68, P = 1.05 × 10-136) and a 34% increased risk of MACE occurrence (P = 2.3 × 10-50) after adjustment for medications that affect gut motility and other traditional cardiovascular risk factors. Finally, we detected positive genetic correlations between constipation and MACE subgroups ACS (rg = 0.27, P = 2.12 × 10-6), ischemic stroke (rg = 0.23, P = 0.011), and HF (rg = 0.21, P = 0.0062). We identified constipation as a potential risk factor independently associated with higher MACE prevalence. These findings warrant further studies on their causal relationship and identification of pathophysiological mechanisms.NEW & NOTEWORTHY Analyzing 408,354 participants of the UK Biobank, we show that constipation cases exhibited a significantly higher risk of major adverse cardiac events (MACEs) than those with regular bowel habits. In comparison with patients with constipation-free hypertension, patients with hypertension with constipation showed significantly higher odds of MACE and a 34% increased risk of subsequent MACE occurrence. Finally, we detected positive genetic correlations between constipation and MACE. This association holds potential for therapeutic exploitation and prevention based on individuals' risk assessment.


Assuntos
Constipação Intestinal , Insuficiência Cardíaca , Humanos , Constipação Intestinal/epidemiologia , Constipação Intestinal/genética , Feminino , Masculino , Reino Unido/epidemiologia , Pessoa de Meia-Idade , Idoso , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/fisiopatologia , AVC Isquêmico/epidemiologia , AVC Isquêmico/genética , Medição de Risco , Fatores de Risco , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/genética , Adulto , Fatores de Risco de Doenças Cardíacas , Predisposição Genética para Doença
5.
Aliment Pharmacol Ther ; 60(6): 765-777, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38997818

RESUMO

BACKGROUND: Faecal biomarkers can be used to assess inflammatory bowel disease (IBD). AIM: To explore the performance of some promising biomarkers in diagnosing and predicting disease course in IBD. METHODS: We included 65 patients with treatment-naïve, new-onset Crohn's disease (CD), 90 with ulcerative colitis (UC), 67 symptomatic controls (SC) and 41 healthy controls (HC) in this prospective observational study. We analysed faecal samples for calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein ECP and eosinophil-derived neurotoxin (EDN) and compared markers among groups. We assessed the diagnostic capability of biomarkers with receiver operating characteristic curves. Clinical disease course was determined for each patient with IBD and analysed the association with biomarkers by logistic regression. RESULTS: All markers were elevated at inclusion in patients with IBD compared with HC (p < 0.001) and SC (p < 0.001). FC (AUC 0.85, 95% CI: 0.79-0.89) and MPO (AUC 0.85, 95% CI: 0.80-0.89) showed the highest diagnostic accuracy in distinguishing IBD from SC. The diagnostic ability of biomarkers differed between IBD subtypes with the highest performance for FC and MPO in CD. The diagnostic accuracy was further improved by combining FC and MPO (p = 0.02). Levels of FC, MPO and HNL at inclusion were predictive of an aggressive disease course with MPO showing the strongest association (p = 0.006). CONCLUSIONS: This study provides new insight into the diagnostic and prognostic capability of neutrophil and eosinophil biomarkers in IBD and suggests that MPO, alone or in combination with FC, may add to the diagnostic power of faecal biomarkers.


Assuntos
Biomarcadores , Colite Ulcerativa , Neurotoxina Derivada de Eosinófilo , Fezes , Complexo Antígeno L1 Leucocitário , Peroxidase , Humanos , Biomarcadores/análise , Biomarcadores/metabolismo , Feminino , Masculino , Fezes/química , Adulto , Estudos Prospectivos , Complexo Antígeno L1 Leucocitário/análise , Pessoa de Meia-Idade , Peroxidase/metabolismo , Colite Ulcerativa/diagnóstico , Neurotoxina Derivada de Eosinófilo/análise , Neurotoxina Derivada de Eosinófilo/metabolismo , Doença de Crohn/diagnóstico , Proteína Catiônica de Eosinófilo/análise , Proteína Catiônica de Eosinófilo/metabolismo , Adulto Jovem , Doenças Inflamatórias Intestinais/diagnóstico , Estudos de Casos e Controles , Curva ROC , Progressão da Doença , Valor Preditivo dos Testes
6.
Nat Commun ; 15(1): 4567, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830848

RESUMO

Improved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a discovery cohort of incident treatment-naïve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making.


Assuntos
Biomarcadores , Doenças Inflamatórias Intestinais , Lipidômica , Humanos , Criança , Lipidômica/métodos , Masculino , Feminino , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/metabolismo , Biomarcadores/sangue , Adolescente , Fezes/química , Fosfatidilcolinas/sangue , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Pré-Escolar , Complexo Antígeno L1 Leucocitário/sangue , Complexo Antígeno L1 Leucocitário/análise , Estudos de Coortes
7.
Cell Mol Gastroenterol Hepatol ; 18(2): 101345, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38643935

RESUMO

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) shows genetic predisposition, and large-scale genome-wide association studies (GWAS) are emerging, based on heterogeneous disease definitions. We investigated the genetic architecture of IBS defined according to gold standard Rome Criteria. METHODS: We conducted GWAS meta-analyses of Rome III IBS and its subtypes in 24,735 IBS cases and 77,149 asymptomatic control subjects from 2 independent European cohorts (UK Biobank and Lifelines). Single-nucleotide polymorphism (SNP)-based heritability (h2SNP) and genetic correlations (rg) with other traits were calculated. IBS risk loci were functionally annotated to identify candidate genes. Sensitivity and conditional analyses were conducted to assess impact of confounders. Polygenic risk scores were computed and tested in independent datasets. RESULTS: Rome III IBS showed significant SNP-heritability (up to 13%) and similar genetic architecture across subtypes, including those with manifestations at the opposite ends of the symptom spectrum (rg = 0.48 between IBS-D and IBS-C). Genetic correlations with other traits highlighted commonalities with family history of heart disease and hypertension, coronary artery disease, and angina pectoris (rg = 0.20-0.45), among others. Four independent GWAS signals (P < 5×10-8) were detected, including 2 novel loci for IBS (rs2035380) and IBS-mixed (rs2048419) that had been previously associated with hypertension and coronary artery disease. Functional annotation of GWAS risk loci revealed genes implicated in circadian rhythm (BMAL1), intestinal barrier (CLDN23), immunomodulation (MFHAS1), and the cyclic adenosine monophosphate pathway (ADCY2). Polygenic risk scores allowed the identification of individuals at increased risk of IBS (odds ratio, 1.34; P = 1.1×10-3). CONCLUSIONS: Rome III Criteria capture higher SNP-heritability than previously estimated for IBS. The identified link between IBS and cardiovascular traits may contribute to the delineation of alternative therapeutic strategies, warranting further investigation.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Síndrome do Intestino Irritável , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Humanos , Síndrome do Intestino Irritável/genética , Feminino , Herança Multifatorial/genética , Masculino , Pessoa de Meia-Idade , Doenças Cardiovasculares/genética , Adulto , Estudos de Casos e Controles
8.
J Crohns Colitis ; 18(3): 349-359, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37768647

RESUMO

BACKGROUND AND AIMS: Microscopic colitis [MC] is currently regarded as an inflammatory bowel disease that manifests as two subtypes: collagenous colitis [CC] and lymphocytic colitis [LC]. Whether these represent a clinical continuum or distinct entities is, however, an open question. Genetic investigations may contribute important insight into their respective pathophysiologies. METHODS: We conducted a genome-wide association study [GWAS] meta-analysis in 1498 CC, 373 LC patients, and 13 487 controls from Europe and the USA, combined with publicly available MC GWAS data from UK Biobank and FinnGen [2599 MC cases and 552 343 controls in total]. Human leukocyte antigen [HLA] alleles and polymorphic residues were imputed and tested for association, including conditional analyses for the identification of key causative variants and residues. Genetic correlations with other traits and diagnoses were also studied. RESULTS: We detected strong HLA association with CC, and conditional analyses highlighted the DRB1*03:01 allele and its residues Y26, N77, and R74 as key to this association (best p = 1.4 × 10-23, odds ratio [OR] = 1.96). Nominally significant genetic correlations were detected between CC and pneumonia [rg = 0.77; p = 0.048] and oesophageal diseases [rg = 0.45, p = 0.023]. An additional locus was identified in MC GWAS analyses near the CLEC16A and RMI2 genes on chromosome 16 [rs35099084, p = 2.0 × 10-8, OR = 1.31]. No significant association was detected for LC. CONCLUSION: Our results suggest CC and LC have distinct pathophysiological underpinnings, characterised by an HLA predisposing role only in CC. This challenges existing classifications, eventually calling for a re-evaluation of the utility of MC umbrella definitions.


Assuntos
Colite Colagenosa , Colite Linfocítica , Colite Microscópica , Humanos , Estudo de Associação Genômica Ampla , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe II , Colite Microscópica/genética , Colite Linfocítica/genética
10.
Int J Cancer ; 154(1): 94-103, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37578112

RESUMO

Observational studies have suggested a protective role for eosinophils in colorectal cancer (CRC) development and implicated neutrophils, but the causal relationships remain unclear. Here, we aimed to estimate the causal effect of circulating white blood cell (WBC) counts (N = ~550 000) for basophils, eosinophils, monocytes, lymphocytes and neutrophils on CRC risk (N = 52 775 cases and 45 940 controls) using Mendelian randomisation (MR). For comparison, we also examined this relationship using individual-level data from UK Biobank (4043 incident CRC cases and 332 773 controls) in a longitudinal cohort analysis. The inverse-variance weighted (IVW) MR analysis suggested a protective effect of increased basophil count and eosinophil count on CRC risk [OR per 1-SD increase: 0.88, 95% CI: 0.78-0.99, P = .04; OR: 0.93, 95% CI: 0.88-0.98, P = .01]. The protective effect of eosinophils remained [OR per 1-SD increase: 0.88, 95% CI: 0.80-0.97, P = .01] following adjustments for all other WBC subtypes, to account for genetic correlation between the traits, using multivariable MR. A protective effect of increased lymphocyte count on CRC risk was also found [OR: 0.84, 95% CI: 0.76-0.93, P = 6.70e-4] following adjustment. Consistent with MR results, a protective effect for eosinophils in the cohort analysis in the fully adjusted model [RR per 1-SD increase: 0.96, 95% CI: 0.93-0.99, P = .02] and following adjustment for the other WBC subtypes [RR: 0.96, 95% CI: 0.93-0.99, P = .001] was observed. Our study implicates peripheral blood immune cells, in particular eosinophils and lymphocytes, in CRC development, highlighting a need for mechanistic studies to interrogate these relationships.


Assuntos
Neoplasias Colorretais , Eosinófilos , Humanos , Contagem de Leucócitos , Neutrófilos , Fenótipo , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Análise da Randomização Mendeliana/métodos , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único
11.
Front Nutr ; 10: 1268538, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37955017

RESUMO

Background: Irritable bowel syndrome is a heterogeneous syndrome and it is difficult to find an effective treatment. Previously, a starch- and sucrose-reduced diet (SSRD) demonstrated promising short-term outcomes. It was proposed that genetic variants in the sucrose-isomaltase gene might influence this success. Our aim in this work was to extend the follow-up study to 1 year and to analyse the effect of the genetic variants of genes involved in starch and sucrose metabolism. Methods: IBS-SSS questionnaire, IBS-QoL questionnaire and questionnaires about adherence, difficulty and food assessment were sent to 34 patients after 6 months and 1 year after the end of the dietary intervention. In addition, 11 genes involved in sucrose and starch metabolism were sequenced. Results: Twenty-three participants responded to the 6 months follow-up and 16 to the 1 year follow-up. IBS-SSS total value increased 59.71% in the 6 months follow-up compared with the end of the intervention (p = 0.0018), and 55.39% in the 1 year follow-up (p = 0.0166); while IBS-QoL score decreased 24.09% (p = 0.0002) and 18.07% (p = 0.0022), respectively. The adherence decreased by 29.11% (p = 4.8 × 10-5) and 27.21% (p = 0.0054), respectively. In addition, carriers of pathogenic variants on the SI gene showed a slightly better performance than non-carriers. Finally, the participants showed less satisfaction over time with 18 allowed foods in the diet. Conclusion: Over time the SSRD is difficult to follow and the genotype might affect the performance of the diet. Since this diet could be a promising therapeutic option, a larger cohort needs to be analysed to validate the results and to compare it with other diets.

12.
Cancers (Basel) ; 15(19)2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37835382

RESUMO

BACKGROUND: Some genetic polymorphisms (SNPs) have been proposed as predictors for different colorectal cancer (CRC) outcomes. This work aims to assess their performance in our cohort and find new SNPs associated with them. METHODS: A total of 833 CRC cases were analyzed for seven outcomes, including the use of chemotherapy, and stratified by tumor location and stage. The performance of 63 SNPs was assessed using a generalized linear model and area under the receiver operating characteristic curve, and local SNPs were detected using logistic regressions. RESULTS: In total 26 of the SNPs showed an AUC > 0.6 and a significant association (p < 0.05) with one or more outcomes. However, clinical variables outperformed some of them, and the combination of genetic and clinical data showed better performance. In addition, 49 suggestive (p < 5 × 10-6) SNPs associated with one or more CRC outcomes were detected, and those SNPs were located at or near genes involved in biological mechanisms associated with CRC. CONCLUSIONS: Some SNPs with clinical data can be used in our population as predictors of some CRC outcomes, and the local SNPs detected in our study could be feasible markers that need further validation as predictors.

14.
United European Gastroenterol J ; 11(8): 784-796, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37688361

RESUMO

BACKGROUND: Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction. OBJECTIVE: Genetic predisposition may play a role; however, investigation at the genome-wide level has not been performed. METHODS: We carried out a genome-wide association study (GWAS) meta-analysis on (i) 478 GP patients from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) compared to 9931 population-based controls from the University of Michigan Health and Retirement Study; and (ii) 402 GP cases compared to 48,340 non-gastroparesis controls from the Michigan Genomics Initiative. Associations for 5,811,784 high-quality SNPs were tested on a total of 880 GP patients and 58,271 controls, using logistic mixed models adjusted for age, sex, and principal components. Gene mapping was obtained based on genomic position and expression quantitative trait loci, and a gene-set network enrichment analysis was performed. Genetic associations with clinical data were tested in GpCRC patients. Protein expression of selected candidate genes was determined in full thickness gastric biopsies from GpCRC patients and controls. RESULTS: While no SNP associations were detected at strict significance (p ≤ 5 × 10-8 ), nine independent genomic loci were associated at suggestive significance (p ≤ 1 × 10-5 ), with the strongest signal (rs9273363, odds ratio = 1.4, p = 1 × 10-7 ) mapped to the human leukocyte antigen region. Computational annotation of suggestive risk loci identified 14 protein-coding candidate genes. Gene-set network enrichment analysis revealed pathways potentially involved in immune and motor dysregulation (pFDR ≤ 0.05). The GP risk allele rs6984536A (Peroxidasin-Like; PXDNL) was associated with increased abdominal pain severity scores (Beta = 0.13, p = 0.03). Gastric muscularis expression of PXDNL also positively correlated with abdominal pain in GP patients (r = 0.8, p = 0.02). Dickkopf WNT Signaling Pathway Inhibitor 1 showed decreased expression in diabetic GP patients (p = 0.005 vs. controls). CONCLUSION: We report preliminary GWAS findings for GP, which highlight candidate genes and pathways related to immune and sensory-motor dysregulation. Larger studies are needed to validate and expand these findings in independent datasets.


Assuntos
Gastroparesia , Estudo de Associação Genômica Ampla , Humanos , Gastroparesia/genética , Predisposição Genética para Doença , Dor Abdominal
15.
Therap Adv Gastroenterol ; 16: 17562848231156682, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37153501

RESUMO

Background: Irritable bowel syndrome (IBS) is a common gastrointestinal condition which entails a high burden in the quality of life (QoL) of patients. Nutritional interventions have been proposed to alleviate symptoms, since still no effective treatments exist for IBS. Objectives: Our aim is to analyse the feasibility of the use of starch- and sucrose-reduced diet (SSRD). Design: In this study, we used a SSRD accompanied by nutritional and culinary recommendations to measure the effects in IBS patients with diarrhoea. Methods: In all, 34 participants completed a 4-week nutritional intervention based on SSRD. Symptoms, QoL and dietary habits were assessed by several questionnaires that were completed at the beginning, daily, after 2 weeks, at the end, and after 2 months. Results: 85.29% of the participants reached the primary endpoint [reduction of 50 points or more in IBS-symptom severity scale (SSS)], and 58.82% the secondary endpoint (reduction of 50% or more in IBS-SSS). The relief of symptoms and improvement of the QoL were significant after 2 weeks of intervention, at the end and after 2 months. Dietary habits were consistent with the diet and high adherence was achieved. Conclusions: SSRD and individualized nutritional and culinary guidance improved symptoms and QoL of IBS patients with diarrhoea, with a high adherence.

16.
Clin Transl Gastroenterol ; 14(8): e00605, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37256716

RESUMO

INTRODUCTION: Fecal calprotectin (FC) is a noninvasive tool for examining response to biologics in inflammatory bowel disease (IBD), but its performance in relation to other novel fecal markers of various cellular origins is unknown. METHODS: We performed a prospective multicenter cohort study and included patients with active IBD who provided a fecal sample at initiation of biological therapy. Levels of FC, myeloperoxidase (MPO), human neutrophil lipocalin (HNL), and eosinophil-derived neurotoxin (EDN) were analyzed and related to clinical remission status at 3 months. Changes in levels of markers at 3 months were calculated, and the impact of concomitant use of corticosteroids at baseline was estimated. RESULTS: In patients achieving clinical remission (n = 27), a decrease in levels of FC ( P = 0.005), MPO ( P < 0.001), HNL ( P < 0.001), and EDN ( P < 0.001) was observed, whereas no significant decrease was seen in patients not achieving remission (n = 39). There was a significant difference in the change in the level of MPO ( P = 0.01) and HNL ( P = 0.02) between patients achieving clinical remission and those who did not, but changes in FC and EDN could not differentiate between these groups. Patients with concomitant systemic corticosteroids at inclusion had lower levels of HNL ( P = 0.01) and EDN ( P < 0.001) at baseline, compared with patients without corticosteroids. DISCUSSION: Fecal MPO, HNL, and EDN are all promising biomarkers for assessing the treatment outcome of biologics in patients with IBD. Fecal levels of EDN and HNL are significantly affected by corticosteroids indicating a greater sensitivity to the effects of corticosteroids compared with levels of FC and MPO.


Assuntos
Doenças Inflamatórias Intestinais , Neutrófilos , Humanos , Eosinófilos , Estudos Prospectivos , Estudos de Coortes , Doenças Inflamatórias Intestinais/tratamento farmacológico , Lipocalinas , Biomarcadores , Neurotoxina Derivada de Eosinófilo , Corticosteroides/uso terapêutico , Terapia Biológica
17.
J Crohns Colitis ; 17(2): 170-184, 2023 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-36029471

RESUMO

BACKGROUND: Epigenetic alterations may provide valuable insights into gene-environment interactions in the pathogenesis of inflammatory bowel disease [IBD]. METHODS: Genome-wide methylation was measured from peripheral blood using the Illumina 450k platform in a case-control study in an inception cohort (295 controls, 154 Crohn's disease [CD], 161 ulcerative colitis [UC], 28 IBD unclassified [IBD-U)] with covariates of age, sex and cell counts, deconvoluted by the Houseman method. Genotyping was performed using Illumina HumanOmniExpressExome-8 BeadChips and gene expression using the Ion AmpliSeq Human Gene Expression Core Panel. Treatment escalation was characterized by the need for biological agents or surgery after initial disease remission. RESULTS: A total of 137 differentially methylated positions [DMPs] were identified in IBD, including VMP1/MIR21 [p = 9.11 × 10-15] and RPS6KA2 [6.43 × 10-13], with consistency seen across Scandinavia and the UK. Dysregulated loci demonstrate strong genetic influence, notably VMP1 [p = 1.53 × 10-15]. Age acceleration is seen in IBD [coefficient 0.94, p < 2.2 × 10-16]. Several immuno-active genes demonstrated highly significant correlations between methylation and gene expression in IBD, in particular OSM: IBD r = -0.32, p = 3.64 × 10-7 vs non-IBD r = -0.14, p = 0.77]. Multi-omic integration of the methylome, genome and transcriptome also implicated specific pathways that associate with immune activation, response and regulation at disease inception. At follow-up, a signature of three DMPs [TAP1, TESPA1, RPTOR] were associated with treatment escalation to biological agents or surgery (hazard ratio of 5.19 [CI: 2.14-12.56], logrank p = 9.70 × 10-4). CONCLUSION: These data demonstrate consistent epigenetic alterations at diagnosis in European patients with IBD, providing insights into the pathogenetic importance and translational potential of epigenetic mapping in complex disease.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Epigenoma , Estudos de Casos e Controles , Doenças Inflamatórias Intestinais/genética , Colite Ulcerativa/genética , Colite Ulcerativa/diagnóstico , Epigênese Genética , Fatores Biológicos , Proteínas de Membrana/genética
19.
Cancers (Basel) ; 14(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36077729

RESUMO

Although the genetic contribution to colorectal cancer (CRC) has been studied in various populations, studies on the applicability of available genetic information in the Basque population are scarce. In total, 835 CRC cases and 940 controls from the Basque population were genotyped and genome-wide association studies were carried out. Mendelian Randomization analyses were used to discover the effect of modifiable risk factors and microbiota on CRC. In total, 25 polygenic risk score models were evaluated to assess their performance in CRC risk calculation. Moreover, 492 inflammatory bowel disease cases were used to assess whether that genetic information would not confuse both conditions. Five suggestive (p < 5 × 10−6) loci were associated with CRC risk, where genes previously associated with CRC were located (e.g., ABCA12, ATIC or ERBB4). Moreover, the analyses of CRC locations detected additional genes consistent with the biology of CRC. The possible contribution of cholesterol, BMI, Firmicutes and Cyanobacteria to CRC risk was detected by Mendelian Randomization. Finally, although polygenic risk score models showed variable performance, the best model performed correctly regardless of the location and did not misclassify inflammatory bowel disease cases. Our results are consistent with CRC biology and genetic risk models and could be applied to assess CRC risk in the Basque population.

20.
J Mol Med (Berl) ; 100(11): 1617-1627, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36121467

RESUMO

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT3Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D.


Assuntos
Síndrome do Intestino Irritável , Humanos , Feminino , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/metabolismo , Serotonina , Receptores de Serotonina/genética , Genótipo , Fatores de Risco , Estudos Multicêntricos como Assunto
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...