Fisiología y fisiopatología de la distensión abdominal : gas intestinal /

Premi Extraordinari de Doctorat concedit pels programes de doctorat de la UAB per curs acadèmic 2017-2018Los trabajos que componen esta tesis doctoral están enfocados al estudio de la fisiología del gas intestinal. En nuestro primer trabajo determinamos el volumen de gas intestinal producido tras una comida rica en residuos fermentables como las alubias, con y sin lavado intestinal. Observamos una gran diferencia entre el volumen de gas intestinal evacuado con y sin lavado, sin lavado sólo se evacuaron una cuarta parte del volumen total producido, demostrando que la homeostasis del gas intestinal es un proceso altamente dinámico, donde una gran proporción del gas producido por la fermentación bacteriana de los residuos de la comida se absorbe rápidamente a la sangre y/o se metaboliza por microorganismos que consumen gas, y sólo una proporción relativamente modesta se elimina por el ano. Siguiendo en la línea del efecto de la dieta sobre la producción de gas intestinal, en el segundo trabajo realizamos varios experimentos combinando dieta alta y baja en residuos fermentables, con ayunas y tras una comida rica en residuos fermentables. Observamos un incremento en el volumen de gas intestinal producido en los experimentos con una precarga alta en residuos fermentables, con respecto a una precarga baja en residuos fermentables ambos en ayunas, demostrando que los residuos preexistentes en el colon producto de comidas previas ejercen efecto en la producción del gas intestinal. Tras una comida alta en residuos fermentables, en ambas precargas demostramos un incremento notable en la producción de gas intestinal, lo que es esperado. No obstante la producción de gas intestinal no fue tan diferente como se cabría esperar para las diferentes precargas, sugiriendo que la fermentación bacteriana es un proceso saturable. Nuestros resultados demuestran que la actividad metabólica de la microbiota intestinal aumenta notablemente durante las primeras horas tras la ingesta de sustratos fermentables no absorbibles, pero esta actividad persiste horas más tarde, aunque a un nivel más bajo que en la fase temprana, es decir la producción de gas intestinal en respuesta a una comida depende del contenido de residuos en el colon derivado de las comidas previas; ambos efectos son sumativos. Una proporción substancial de sujetos con trastornos intestinales funcionales, incluso en la población general, se quejan de síntomas que son comúnmente atribuidos al gas, tales como, distensión y flatulencia. Los nuevos conocimientos arrojados por los estudios presentes pueden ayudar a clarificar la dinámica del gas intestinal en relación a estos síntomas, tomando en consideración diferentes factores que pueden influir en la homeostasis del gas intestinal y tolerancia, tales como motilidad intestinal, tránsito, sensibilidad y actividad microbiotaThe works of this thesis are focused on the study of the physiology of intestinal gas. In our first experiment, we determine the volume of intestinal gas produced after a flatulogenic test meal, with and without wash-out. Observed a great difference between the volume of intestinal gas evacuated with and without wash-out, only a quarter of the total volume produced were evacuated. Our data indicate that intestinal gas homeostasis is a highly dynamic process. A large proportion of the gas produced by bacterial fermentation of meal residues appears to be rapidly absorbed into the blood and/or metabolized by gas-consuming microorganisms, and only a relatively modest proportion eliminated per anus. Following the line, in the second experiment the intestinal gas production was measured after 1 day low-flatulogenic diet and fast or test meal; or 1 day high-flatulogenic diet and fast or test meal. We observed an increase in the volume of intestinal gas produced in the experiments with high preload respect to a low preload both in fasting, showing that preexisting residues on colon exert effect in the production of intestinal gas. After a test meal in both preload demonstrate a great increase in gas production, what is expected, but the gas production rate after the test meal with the high-flatulogenic preload was not higher than with the low-flatulogenic preload, suggesting that gas production may be a saturable process. Show, that the metabolic activity of intestinal microbiota markedly increases during the first few hours after ingestion of non-absorbable, fermentable substrates, but this activity still persists hours later, albeit at a lower level than in the early phase, and demonstrates summation effects of fermentable foodstuffs on gas production. A substantial proportion of subjects with functional gut disorders, or even in the general population, complain of symptoms that are commonly attributed to gas, like distension and bloating. This new knowledge should contribute to elucidating the dynamic complex of the intestinal gas in relationship with these symptoms, take into consideration different factors that may influence gas homeostasis and tolerance, such as intestinal motility, transit, sensitivity,and microbiota activity

Clinical significance of small bowel manometry patterns suggestive of intestinal obstruction

Constipation; Intestinal manometry; Intestinal neuropathyRestrenyiment; Manometria intestinal; Neuropatia intestinalEstreñimiento; Manometría intestinal; Neuropatía intestinalIntroduction Minute rhythm and prolonged simultaneous contractions are patterns of postprandial small bowel contractile activity that historically have been considered as suggestive of mechanical intestinal obstruction; however, these patterns have been also encountered in patients with motility-like symptoms in the absence of bowel obstruction. The objective of this study was to determine the current diagnostic outcome of patients with these intestinal manometry patterns. Methods Retrospective study of patients with chronic digestive symptoms evaluated by intestinal manometry at our center between 2010 and 2018. Results The minute rhythm (MRP) or prolonged simultaneous contractions (PSC) postprandial patterns were detected in 61 of 488 patients (55 MRP and 6 PSC). Clinical work-up detected a previously non-diagnosed partial mechanical obstruction of the distal intestine in 10 (16%) and a systemic disorder causing intestinal neuropathy in 32 (53%). In the remaining 19 patients (31%, all with MRP), the origin of the contractile pattern was undetermined, but in 16, substantial fecal retention was detected within 7 days of the manometric procedure by abdominal imaging, and in 6 of them colonic cleansing completely normalized intestinal motility on a second manometry performed within 39 ± 30 days. Conclusion and Inference Currently, the most frequent origin of MRP and PSC encountered on small bowel manometry is intestinal neuropathy, while a previously undetected mechanical obstruction is rare. Still, in a substantial proportion of patients, no underlying disease can be identified, and in them, colonic fecal retention might play a role, because in a subgroup of these patients, manometry normalized after colonic cleansing. Hence, colonic preparation may be considered prior to intestinal manometry.This work was supported by the Instituto de Salud Carlos III and co-financed by the European Union (FEDER/FSE) [PI17/01794]; Spanish Ministry of Economy and Competitiveness (Dirección General de Investigación Científica y Técnica) [SAF 2016-76648-R]; Ciberehd is funded by the Instituto de Salud Carlos III. LA was supported by the Instituto de Salud Carlos III (CM20/00182)

Significado del patrón ritmo minuto en período postprandial en la manometría gastrointestinal

Objetivo: Determinar el significado del patrón ritmo minuto postprandial. Métodos: Se revisaron manometrías para el análisis de las alteraciones manométricas y posterior correlación con la clínica. Resultados: Los diagnósticos fueron: Trastorno motor 69, ritmo minuto 52, normales: 161. Clínicamente la presencia de crisis suboclusivas fue más frecuente en pacientes con ritmo minuto y trastorno motor que en pacientes con manometría normal, en cambio la alteración del ritmo deposicional fue más frecuente en pacientes con manometría normal. El dolor abdominal fue similar en todos. Conclusión: El ritmo minuto en ausencia de oclusión se podría considerar criterio de alteración neuropático.Objectiu: Determinar el significat del patró ritme minut postprandial. Mètodes: Es van revisar manometrías per a l'anàlisi de les alteracions manomètriques i posterior correlació amb la clínica. Resultats: Els diagnòstics van ser: Trastorn motor 69, ritme minut 52, normals: 161. Clínicament la presència de crisis suboclusivas va ser més freqüent en pacients amb ritme minut i trastorn motor que en pacients amb manometria normal, en canvi l'alteració del ritme deposicional va ser més freqüent en pacients amb manometria normal. El dolor abdominal va ser similar en tots. Conclusió: El ritme minut en absència d'oclusió es podria considerar criteri d'alteració neuropàtic

Clinical significance of small bowel manometry patterns suggestive of intestinal obstruction

Minute rhythm and prolonged simultaneous contractions are patterns of postprandial small bowel contractile activity that historically have been considered as suggestive of mechanical intestinal obstruction; however, these patterns have been also encountered in patients with motility-like symptoms in the absence of bowel obstruction. The objective of this study was to determine the current diagnostic outcome of patients with these intestinal manometry patterns. Retrospective study of patients with chronic digestive symptoms evaluated by intestinal manometry at our center between 2010 and 2018. The minute rhythm (MRP) or prolonged simultaneous contractions (PSC) postprandial patterns were detected in 61 of 488 patients (55 MRP and 6 PSC). Clinical work-up detected a previously non-diagnosed partial mechanical obstruction of the distal intestine in 10 (16%) and a systemic disorder causing intestinal neuropathy in 32 (53%). In the remaining 19 patients (31%, all with MRP), the origin of the contractile pattern was undetermined, but in 16, substantial fecal retention was detected within 7 days of the manometric procedure by abdominal imaging, and in 6 of them colonic cleansing completely normalized intestinal motility on a second manometry performed within 39 ± 30 days. Currently, the most frequent origin of MRP and PSC encountered on small bowel manometry is intestinal neuropathy, while a previously undetected mechanical obstruction is rare. Still, in a substantial proportion of patients, no underlying disease can be identified, and in them, colonic fecal retention might play a role, because in a subgroup of these patients, manometry normalized after colonic cleansing. Hence, colonic preparation may be considered prior to intestinal manometry. Minute rhythm (or clustered contractions) in postprandial small bowel manometry can be produced by intestinal neuropathy or mechanical occlusion, but in some patients, the minute rhythm pattern is associated with colonic fecal retention, and resolves after colonic cleansing. Hence, colonic preparation may be considered prior to intestinal manometry

Fisiología y fisiopatología de la distensión abdominal: Gas intestinal

Los trabajos que componen esta tesis doctoral están enfocados al estudio de la fisiología del gas intestinal. En nuestro primer trabajo determinamos el volumen de gas intestinal producido tras una comida rica en residuos fermentables como las alubias, con y sin lavado intestinal. Observamos una gran diferencia entre el volumen de gas intestinal evacuado con y sin lavado, sin lavado sólo se evacuaron una cuarta parte del volumen total producido, demostrando que la homeostasis del gas intestinal es un proceso altamente dinámico, donde una gran proporción del gas producido por la fermentación bacteriana de los residuos de la comida se absorbe rápidamente a la sangre y/o se metaboliza por microorganismos que consumen gas, y sólo una proporción relativamente modesta se elimina por el ano. Siguiendo en la línea del efecto de la dieta sobre la producción de gas intestinal, en el segundo trabajo realizamos varios experimentos combinando dieta alta y baja en residuos fermentables, con ayunas y tras una comida rica en residuos fermentables. Observamos un incremento en el volumen de gas intestinal producido en los experimentos con una precarga alta en residuos fermentables, con respecto a una precarga baja en residuos fermentables ambos en ayunas, demostrando que los residuos preexistentes en el colon producto de comidas previas ejercen efecto en la producción del gas intestinal. Tras una comida alta en residuos fermentables, en ambas precargas demostramos un incremento notable en la producción de gas intestinal, lo que es esperado. No obstante la producción de gas intestinal no fue tan diferente como se cabría esperar para las diferentes precargas, sugiriendo que la fermentación bacteriana es un proceso saturable. Nuestros resultados demuestran que la actividad metabólica de la microbiota intestinal aumenta notablemente durante las primeras horas tras la ingesta de sustratos fermentables no absorbibles, pero esta actividad persiste horas más tarde, aunque a un nivel más bajo que en la fase temprana, es decir la producción de gas intestinal en respuesta a una comida depende del contenido de residuos en el colon derivado de las comidas previas; ambos efectos son sumativos. Una proporción substancial de sujetos con trastornos intestinales funcionales, incluso en la población general, se quejan de síntomas que son comúnmente atribuidos al gas, tales como, distensión y flatulencia. Los nuevos conocimientos arrojados por los estudios presentes pueden ayudar a clarificar la dinámica del gas intestinal en relación a estos síntomas, tomando en consideración diferentes factores que pueden influir en la homeostasis del gas intestinal y tolerancia, tales como motilidad intestinal, tránsito, sensibilidad y actividad microbiota.The works of this thesis are focused on the study of the physiology of intestinal gas. In our first experiment, we determine the volume of intestinal gas produced after a flatulogenic test meal, with and without wash-out. Observed a great difference between the volume of intestinal gas evacuated with and without wash-out, only a quarter of the total volume produced were evacuated. Our data indicate that intestinal gas homeostasis is a highly dynamic process. A large proportion of the gas produced by bacterial fermentation of meal residues appears to be rapidly absorbed into the blood and/or metabolized by gas-consuming microorganisms, and only a relatively modest proportion eliminated per anus. Following the line, in the second experiment the intestinal gas production was measured after 1 day low-flatulogenic diet and fast or test meal; or 1 day high-flatulogenic diet and fast or test meal. We observed an increase in the volume of intestinal gas produced in the experiments with high preload respect to a low preload both in fasting, showing that preexisting residues on colon exert effect in the production of intestinal gas. After a test meal in both preload demonstrate a great increase in gas production, what is expected, but the gas production rate after the test meal with the high-flatulogenic preload was not higher than with the low-flatulogenic preload, suggesting that gas production may be a saturable process. Show, that the metabolic activity of intestinal microbiota markedly increases during the first few hours after ingestion of non-absorbable, fermentable substrates, but this activity still persists hours later, albeit at a lower level than in the early phase, and demonstrates summation effects of fermentable foodstuffs on gas production. A substantial proportion of subjects with functional gut disorders, or even in the general population, complain of symptoms that are commonly attributed to gas, like distension and bloating. This new knowledge should contribute to elucidating the dynamic complex of the intestinal gas in relationship with these symptoms, take into consideration different factors that may influence gas homeostasis and tolerance, such as intestinal motility, transit, sensitivity,and microbiota activity

Differential effects of western and mediterranean-type diets on gut microbiota : a metagenomics and metabolomics approach

Our aim was to determine the effect of diet on gut microbiota, digestive function and sensations, using an integrated clinical, metagenomics and metabolomics approach. We conducted a cross-over, randomised study on the effects of a Western-type diet versus a fibre-enriched Mediterranean diet. In 20 healthy men, each diet was administered for 2 weeks preceded by a 2-week washout diet. The following outcomes were recorded: (a) number of anal gas evacuations; (b) digestive sensations; (c) volume of gas evacuated after a probe meal; (d) colonic content by magnetic resonance imaging; (e) gut microbiota taxonomy and metabolic functions by shotgun sequencing of faecal samples; (f) urinary metabolites using untargeted metabolomics. As compared to a Western diet, the Mediterranean diet was associated with (i) higher number of anal gas evacuations, (ii) sensation of flatulence and borborygmi, (iii) larger volume of gas after the meal and (iv) larger colonic content. Despite the relatively little difference in microbiota composition between both diets, microbial metabolism differed substantially, as shown by urinary metabolite profiles and the abundance of microbial metabolic pathways. The effects of the diet were less evident in individuals with robust microbiotas (higher beta-diversity). To conclude, healthy individuals tolerate dietary changes with minor microbial modifications at the composition level but with remarkable variation in microbial metabolism

Colonic content assessment from MRI imaging using a semi-automatic approach

The analysis of the morphology and content of the gut is necessary in order to achieve a better understanding of its metabolic and functional activity. Magnetic resonance imaging (MRI) has become an important imaging technique since it is able to visualize soft tissues in an undisturbed bowel using no ionizing radiation. In the last few years, MRI of gastrointestinal function has advanced substantially. However, few studies have focused on the colon, because the analysis of colonic content is time consuming and cumbersome. This paper presents a semi-automatic segmentation tool for the quantitative assessment of the unprepared colon from MRI images. The techniques developed here have been crucial for a number of clinical experiments.Peer ReviewedPostprint (published version

High Resolution Esophageal Manometry in Patients with Chagas Disease: A Cross-Sectional Evaluation

<div><p>Introduction</p><p>Gastrointestinal involvement affects 30–40% of the patients with chronic Chagas disease. Esophageal symptoms appear once the structural damage is established. Little is known about the usefulness of high resolution manometry to early identification of esophageal involvement.</p><p>Method</p><p>We performed a cross-sectional study at the Vall d’Hebron University Hospital (Barcelona, Spain) between May 2011 and April 2012. Consecutive patients diagnosed with Chagas disease in the chronic phase were offered to participate. All patients underwent a structured questionnaire about digestive symptoms, a barium esophagogram (Rezende classification) and an esophageal high resolution manometry (HRM). A control group of patients with heartburn who underwent an esophageal HRM in our hospital was selected.</p><p>Results</p><p>62 out of 73 patients that were included in the study fulfilled the study protocol. The median age of the Chagas disease group (CG) was 37 (IQR 32–45) years, and 42 (67.7%) patients were female. Twenty-seven (43.5%) patients had esophageal symptoms, heartburn being the most frequent. Esophagogram was abnormal in 5 (8.77%). The esophageal HRM in the CG showed a pathological motility pattern in 14 patients (22.6%). All of them had minor disorders of the peristalsis (13 with ineffective esophageal motility and 1 with fragmented peristalsis). Hypotonic lower esophageal sphincter was found more frequently in the CG than in the control group (21% vs 3.3%; p<0.01). Upper esophageal sphincter was hypertonic in 22 (35.5%) and hypotonic in 1 patient. When comparing specific manometric parameters or patterns in the CG according to the presence of symptoms or esophagogram no statistically significant association were seen, except for distal latency.</p><p>Conclusion</p><p>The esophageal involvement measured by HRM in patients with chronic Chagas disease in our cohort is 22.6%. All the patients with esophageal alterations had minor disorders of the peristalsis. Symptoms and esophagogram results did not correlate with the HRM results.</p></div

A fermented milk product containing B. lactis CNCM i-2494 improves the tolerance of a plant-based diet in patients with disorders of gut-brain interactions

Healthy, plant-based diets, rich in fermentable residues, may induce gas-related symptoms. The aim of this exploratory study was to assess the effects of a fermented milk product, containing probiotics, on the tolerance of a healthy diet in patients with disorders of gut-brain interactions (DGBI), complaining of excessive flatulence. In an open design, a 3-day healthy, mostly plant-based diet was administered to patients with DGBI (52 included, 43 completed) before and at the end of 28 days of consumption of a fermented milk product (FMP) containing Bifidobacterium animalis subsp. lactis CNCM I-2494 and lactic acid bacteria. As compared to a habitual diet, the flatulogenic diet increased the perception of digestive symptoms (flatulence score 7.1 ± 1.6 vs. 5.8 ± 1.9; p < 0.05) and the daily number of anal gas evacuations (22.4 ± 12.5 vs. 16.5 ± 10.2; p < 0.0001). FMP consumption reduced the flatulence sensation score (by -1.6 ± 2.2; p < 0.05) and the daily number of anal gas evacuations (by -5.3 ± 8.2; p < 0.0001). FMP consumption did not significantly alter the overall gut microbiota composition, but some changes in the microbiota correlated with the observed clinical improvement. The consumption of a product containing B. lactis CNCM I-2494 improved the tolerance of a healthy diet in patients with DGBI, and this effect may be mediated, in part, by the metabolic activity of the microbiot