Investigating the causal relationship of gut microbiota with GERD and BE: a bidirectional mendelian randomization.

BACKGROUND: Gut microbiota(GM) have been proven associated with lots of gastrointestinal diseases, but its causal relationship with Gastroesophageal reflux disease(GERD) and Barrett's esophagus(BE) hasn't been explored. We aimed to uncover the causal relation between GM and GERD/BE and potential mediators by utilizing Mendelian Randomization(MR) analysis. METHODS: Summary statistics of GM(comprising 301 bacteria taxa and 205 metabolism pathways) were extracted from MiBioGen Consortium(N = 18,340) and Dutch Microbiome Project(N = 7,738), GERD and BE from a multitrait meta-analysis(NGERD=602,604, NBE=56,429). Bidirectional two-sample MR analysis and linkage disequilibrium score regression(LDSC) were used to explore the genetic correlation between GM and GERD/BE. Mediation MR analysis was performed for the risk factors of GERD/BE, including Body mass index(BMI), weight, type 2 diabetes, major depressive disorder(MDD), smoking initiation, alcohol consumption, and dietary intake(including carbohydrate, sugar, fat, protein intake), to detect the potential mediators between GM and GERD/BE. RESULTS: 11 bacterial taxa and 13 metabolism pathways were found associated with GERD, and 18 taxa and 5 pathways exhibited causal relationship with BE. Mediation MR analysis suggested weight and BMI played a crucial role in these relationships. LDSC identified 1 taxon and 4 metabolism pathways related to GERD, and 1 taxon related to BE. Specie Faecalibacterium prausnitzii had a suggestive impact on both GERD(OR = 1.087, 95%CI = 1.01-1.17) and BE(OR = 1.388, 95%CI = 1.03-1.86) and LDSC had determined their correlation. Reverse MR indicated that BE impacted 10 taxa and 4 pathways. CONCLUSIONS: This study established a causal link between gut microbiota and GERD/BE, and identified the probable mediators. It offers new insights into the role of gut microbiota in the development and progression of GERD and BE in the host.

Relationship between Helicobacter pylori Eradication and Barrett's Esophagus Elongation.

INTRODUCTION: Helicobacter pylori eradication therapy may worsen gastroesophageal reflux disease that is a significant risk factor for Barrett's esophagus. However, the relationship between eradication therapy and Barrett's esophagus remains controversial. This study evaluated the impact of Helicobacter pylori eradication on the lengthening of Barrett's esophagus. MATERIALS AND METHODS: We conducted a retrospective analysis of consecutive patients who successfully underwent Helicobacter pylori eradication between 2004 and 2017. Endoscopic images obtained before and after eradication therapy were compared for Barrett's esophagus length according to the Prague C&M criteria and the presence of reflux esophagitis based on the Los Angeles classification. RESULTS: A total of 340 patients were analyzed (mean age: 66.9 ± 12.9 years) for a median follow-up of 55 months (interquartile range: 29.8-89.3). At the initial endoscopic assessment, 187 patients (55%) had a hiatal hernia, and all patients had gastric atrophy (C-0 to I: 2%, C-II to III: 47%, O-I to III: 51%). Reflux esophagitis was detected in 7 patients (2%) before eradication and in 21 patients (6%) afterward, which was a significant increase (p = 0.007). Barrett's esophagus was identified in 69 patients (20%) before eradication, with a median length of C0M1. Elongation after treatment was observed in only 2 patients (0.6%). We observed no significant increase in either the prevalence (p = 0.85) or the median length (p = 0.5) of Barrett's esophagus. CONCLUSIONS: Only 0.6% of patients exhibited Barrett's esophagus lengthening after Helicobacter pylori eradication therapy, suggesting no significant impact of the treatment on the development or elongation of Barrett's esophagus.

Effect of Lactobacillus reuteri NCIMB 30351 drops on symptoms of infantile functional gastrointestinal disorders and gut microbiota in early infants: Results from a randomized, placebo-controlled clinical trial.

Infantile functional gastrointestinal disorders, such as colic, constipation, diarrhea, and gastroesophageal reflux (regurgitation), often occur in early infancy and, representing one of the causes of significant parental anxiety, lead to a significant strain on the healthcare resources. In this study, we aimed to evaluate the effects of Lactobacillus reuteri drops (L. reuteri NCIMB 30351) on the symptoms of infantile colic, constipation, diarrhea, and gastroesophageal reflux, as well as on the levels of intestinal microbiota in full-term newborns during the first months of life. A randomized, placebo-controlled, single-masked (blinded), post-marketing clinical study was conducted in two clinical units-Children's City Clinical Hospital of Moscow and Medical Center "St. Andrew's Hospitals-NEBOLIT" from March 2020 to May 2022 in 90 infants aged from 1 to 4 months (mean age (± SD) 12.3 ± 5.09 weeks; 53.3% females, 46.7% males). Patients with colic, regurgitation (single symptom or combination of several symptoms), and constipation or diarrhea were randomly allocated in two parallel arms to receive either 5 drops (2 × 108 colony forming unit) of L. reuteri NCIMB 30351 (n = 60) or masked placebo (n = 30) for 25 consecutive days. Two treatment arms had equal numbers of patients with constipation and diarrhea (n = 30 each). Daily crying times and their duration, evacuations, and regurgitations were recorded in a structured diary. The levels of gut microbiota were analyzed by deep sequencing of bacterial 16S rRNA gene. Infants with colic receiving supplementary L. reuteri NCIMB 30351 for 25 days had significant reduction in the numbers of colic (change from baseline - 6.3 (7.34) vs - 3.0 (7.29) in placebo, P < 0.05) and numbers of crying cases and mean duration of crying (decrease from baseline - 144 (70.7) minutes, lower in the diarrhea subgroup than in constipation infants, compared with - 80 (58.9) in placebo, P < 0.0001), as well as regurgitation numbers (decreased by - 4.8 (2.49) with L. reuteri vs - 3 (7.74) with placebo). We also observed increased numbers of evacuations in infants with constipation (L. reuteri 2.2 (2.4) vs 0.9 (1.06) in placebo, P < 0.05). There was a remarkable reduction of evacuations in infants with diarrhea, while not statistically significant. The analysis of bacterial 16S rRNA gene in the collected samples showed that L. reuteri positively influences the proportions of prevalent species, while it negatively affects both conditionally pathogenic and commensal microbes. Additional in vitro test for formation of Clostridium colonies in the presence of the probiotic demonstrated that L. reuteri effectively inhibits the growth of pathogenic Clostridium species. No adverse events were reported in this study.   Conclusion: The uptake of L. reuteri NCIMB 30351 leads to a significant reduction in the number of regurgitations, feeding-induced constipations, and diarrhea as well as mean daily numbers of crying and crying duration in infants during the first months of life. Our results suggest that L. reuteri NCIMB 30351 represents a safe and effective treatment for colic in newborns.  Trial registration: ClinicalTrials.gov : NCT04262648. What is Known: • Infantile functional gastrointestinal disorders, such as colic, constipation, diarrhea, and gastroesophageal reflux (regurgitation), often occur in early infancy and, represent one of the causes of significant parental anxiety. • A number of studies have shown that both the composition and diversity of the intestinal microbiota play important roles in the development and function of the gastrointestinal tract. What is New: • The uptake of L. reuteri NCIMB 30351 leads to a significant reduction in the number of regurgitations, feeding-induced constipations, and diarrhea as well as mean daily numbers of crying and crying duration in infants during the first months of life. • L. reuteri positively influences the proportions of prevalent species, while it negatively affects both conditionally pathogenic and commensal microbes in gut microbiota.

Causal effect between gut microbiota and gastroesophageal reflux disease: a bidirectional two-sample Mendelian randomization study.

Previous observational studies have found that the gut microbiota is closely related to the pathogenesis of gastroesophageal reflux disease (GERD), while their causal relationship is unclear. A two-sample multivariate Mendelian randomization analysis was implemented to estimate the causal effect of gut microbiota on GERD. The gut microbiota aggregated statistics were derived from a meta-analysis of the largest available genome-wide association studies (GWAS) conducted by the MiBioGen alliance ( n  = 13 266). GERD aggregated statistics were derived from published GWAS (129 080 cases and 473 524 controls). A bidirectional two-sample Mendelian randomization study was conducted to explore the causal relationship between gut microbiota and GERD using the inverse variance weighted (IVW), Mendelian randomization Egger, single model, weighted median, and weighted model. To verify the stability of the main results of Mendelian randomization analysis, we performed sensitivity analysis. Based on the results of IVW, we found that Anaerostipes was causally associated with an increased risk of GERD [odds ratio (OR): 1.09, P  = 0.018]. Eight gut microbiota taxa ( Actinobacteria, Bifidobacteriales, Bifidobacteriaceae, Clostridiales vadin BB60 group, Rikenellaceae, Lachnospiraceae UCG004, Methanobrevibacter , and unknown genus id.1000000073 ) are predicted to act causally in suppressing the risk of GERD ( P  < 0.05). In addition, reverse Mendelian randomization analyses revealed that the abundance of 15 gut microbiota taxon was found to be affected by GERD. No significant estimation of heterogeneity or pleiotropy is detected. Our study presents a complicated causal relationship between gut microbiota and GERD that offers guidance on the selection of appropriate probiotics as clinical interventions for GERD.

Beneficial Effect of Heat-Killed Lactic Acid Bacterium Lactobacillus johnsonii No. 1088 on Temporal Gastroesophageal Reflux-Related Symptoms in Healthy Volunteers: A Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Study.

A randomized, placebo-controlled, double-blind, parallel-group clinical study was conducted to examine the effects of ingesting a heat-killed lactic acid bacterium, Lactobacillus johnsonii No. 1088 (LJ88) on temporal gastroesophageal reflux-related symptoms in healthy volunteers. A total of 120 healthy Japanese volunteers of both sexes, aged between 21 and 63 years, whose Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) total score was 8 or greater, but who were not diagnosed with functional dyspepsia according to the Rome IV classification, were enrolled. They were randomly assigned to either the LJ88 or placebo group and instructed to ingest the test food (1 billion heat-killed LJ88 or placebo) once a day for six weeks. Gastroesophageal reflux-related symptoms were evaluated using FSSG scores as a primary endpoint. The Gastrointestinal Symptoms Rating Scale (GSRS), stomach state questionnaire, and serum gastrin concentration were used as secondary endpoints. In the FSSG evaluation, the heartburn score was significantly improved at 6 weeks in the LJ88 group compared to the placebo group. No severe adverse events related to the test food were observed. In conclusion, daily ingestion of heat-killed LJ88 improved temporal heartburn symptoms in non-diseased individuals.

Diagnostic value associated with the combination of saliva pepsin and microorganisms in functional heartburn and gastroesophageal reflux disease.

Heartburn is a common symptom shared by both gastroesophageal reflux disease (GERD) and functional heartburn (FHB), which can make it challenging to differentiate between the two conditions. However, examining oral manifestations of GERD can be a cost-effective and readily available method to aid in this differentiation process. It may serve as a valuable tool in distinguishing GERD from FHB.

II Consenso Brasileiro sobre Helicobacter pylori / Second Brazilian Consensus Conference on Helicobacter pylori infection

Avanços significativos ocorridos desde o Primeiro Consenso Brasileiro sobre H. pylori realizado em 1995, em Belo Horizonte, MG, justificam este segundo consenso. O evento foi organizado pela Federação Brasileira de Gastroenterologia e pelo Núcleo Brasileiro para Estudo do Helicobacter, sendo realizado em São Paulo nos dias 19 e 20 de junho de 2004. Contou com a participação das principais autoridades nacionais na área, a partir de lista elaborada pelas duas sociedades organizadoras do evento. Assim, participaram 36 delegados provenientes de 15 estados brasileiros, incluindo gastroenterologistas, patologistas, pediatras e microbiologistas. Os participantes foram alocados em um dos cinco sub-temas a serem contemplados no encontro, a saber: Helicobacter pylori e dispepsia funcional; Helicobacter pylori e AINEs; Helicobacter pylori e doença do refluxo gastroesofágico; tratamento Helicobacter pylori e retratamento Helicobacter pylori. Foi adotado como consensual as decisões que atingissem 70 por cento ou mais de concordância entre os participantes. Os resultados foram apresentados em outubro de 2004 durante sessão especial da VI Semana Brasileira do Aparelho Digestivo, realizada em Recife, PE, e esta publicação apresenta o sumário das principais recomendações e conclusões do evento.

Reflujo gastroesofágico en pacientes con gastritis y Helicobacter pylori

Se presentan 60 pacientes con síntomas consistentes con reflujo gastroesofágico (RGE) y gastritis crónica. Los síntomas más importantes encontrados fueron: pirosis 98.3 por ciento, regurgitación 93.8 por ciento, faringitis a repetición 83.3 por ciento, laringitis frecuente 80 por ciento, disfagia 80 por ciento, disfonía 78.3 por ciento, dolor epigástrico 98.3 por ciento, dispepsia 90 por ciento. todos los pacientes (100 por ciento) presentaron una gastritis crónica antral con 51.6 por ciento de tipo crónica superficial y 48.4 por ciento crónica atrófica. solamente seis pacientes (9.6 por ciento) tenían algún tipo de metaplasia. De los pacientes con gastritis crónica antral, 18 (30 por ciento) tenían Helicobacter pylori en las biopsias de antro. Veintidós pacientes (36.6 por ciento) presentaron una esofagitis péptica demostrada histológicamente pero ninguno mostró Helicobacter. Se discute la estrecha relación encontrada entre reflujo gastroesofágico y gastritis antral y su posible fisiopatología, así como la falta de correlacción entre el reflujo y la presencia delHelicobacter en el esófago.

Test respiratorio para detección de Helicobacter pylori / Breath test to detect the presence of Helicobacter pylori

El test respiratorio utilizando urea marcada con C es un método no invasivo empleado desde 1988 para detectar la presencia de Helicobacter pylori en pacientes portadores de enfermedad ácido péptica. Este método ha demostrado una sensibilidad del 90,2 por ciento y especificidad de 83,8 por ciento . En el Centro de Medicina Nuclear de Guanabara fueron realizados 1.200 test respiratorios, de los cuales el 67 por ciento se reportaron positivos, realizándose nuevos controles después del tratamiento médico, con resultados negativos

¿Es el helicobacter pylori un factor de proteccion para el desarrollo de reflujo gastroesofagico? / Helicobacter pylori and gastroesophageal reflux

Objetivos: determinar la asociación entre Helicobacter pylori y los síntomas de reflujo gastroesofágico. Diseño: estudio de casos y controles anidado en un estudio de prevalencia analítica. Lugar: hospital Pablo VI Bosa. Pacientes: durante dos años se evaluaron en el servicio de gastroenterología 1.400 pacientes consecutivos, remitidos por síntomas dispépticos, procedentes de consulta externa para realizar endoscopio de vías digestivas altas. Antes del procedimiento endoscópico, la información de cada paciente fue consignada en un formulario específico previamente diseñado. Hacían parte de la misma los datos de identidad, sexo, edad y síntomas clásicos de reflujo gastroesofágico (RGE), pirosis y regurgitación, tanto en frecuencia por semana, como duración. Se consideraron casos los individuos sin Helicobacter pylori a la histología gástrica (116 individuos). Aleatoriamente se seleccionaron 232 controles con presencia histológica de Helicobacter pylori. Métodos: a cada uno de los 348 pacientes incluidos en el estudio se les practicó una endoscopia digestiva alta. Biopsias para histopatología, coloración de hematoxilina y eosina y Giemsa: esófago distal (2), cardias (3), cuerpo gástrico m (4), antro gástrico (4), una de estas pruebas se utilizó para test rápido de ureasa. Análisis estadístico: se realizó análisis univariado y bivariado. Como medida de asociación se calculó la razón de disparidad (OR). Para establecer significancia estadística se utilizó la prueba de Chi2, valor alfa del 5 por ciento. Resultados: no hubo diferencias estadísticamente significativas entre los casos (Gl) y los controles (G2) para edad (p = 0.363) y sexo (p == 0.7). Se encontró una tendencia lineal inversa entre severidad de inflamación de la mucosa gástrica y la presencia de síntomas de RGE (Chi2 de tendencia = I 6.2, p = 0.00006) y evidencia histológica de esofagitis (Chi de tendencia 4.19, p = 0.04). La presencia de inflamación gástrica severa tuvo relación inversa con los síntomas de RGE (Chi2 = 5.9, p = 0.0/5, OR = 0.26, IC95 por ciento: 0.07- 0.92) J con esofagitis histológica (Chi 2 = 4.9, p = 0.025, OR = 0.30, IC 95 por ciento: 0.01- 1)...