Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome.

BACKGROUND: Intestinal immune activation is involved in irritable bowel syndrome (IBS) pathophysiology. While most dietary approaches in IBS involve food avoidance, there are fewer indications on food supplementation. Palmithoylethanolamide, structurally related to the endocannabinoid anandamide, and polydatin are dietary compounds which act synergistically to reduce mast cell activation. AIM: To assess the effect on mast cell count and the efficacy of palmithoylethanolamide/polydatin in patients with IBS. METHODS: We conducted a pilot, 12-week, randomised, double-blind, placebo-controlled, multicentre study assessing the effect of palmithoylethanolamide/polydatin 200 mg/20 mg or placebo b.d. on low-grade immune activation, endocannabinoid system and symptoms in IBS patients. Biopsy samples, obtained at screening visit and at the end of the study, were analysed by immunohistochemistry, enzyme-linked immunoassay, liquid chromatography and Western blot. RESULTS: A total of 54 patients with IBS and 12 healthy controls were enrolled from five European centres. Compared with controls, IBS patients showed higher mucosal mast cell counts (3.2 ± 1.3 vs. 5.3 ± 2.7%, P = 0.013), reduced fatty acid amide oleoylethanolamide (12.7 ± 9.8 vs. 45.8 ± 55.6 pmol/mg, P = 0.002) and increased expression of cannabinoid receptor 2 (0.7 ± 0.1 vs. 1.0 ± 0.8, P = 0.012). The treatment did not significantly modify IBS biological profile, including mast cell count. Compared with placebo, palmithoylethanolamide/polydatin markedly improved abdominal pain severity (P < 0.05). CONCLUSIONS: The marked effect of the dietary supplement palmithoylethanolamide/polydatin on abdominal pain in patients with IBS suggests that this is a promising natural approach for pain management in this condition. Further studies are now required to elucidate the mechanism of action of palmithoylethanolamide/polydatin in IBS. ClinicalTrials.gov number, NCT01370720.

Cognitive and hedonic responses to meal ingestion correlate with changes in circulating metabolites.

BACKGROUND: We have previously shown that meal ingestion induces cognitive perception (sensations) with a hedonic dimension (well-being) that depends on the characteristics of the meal and the appropriateness of the digestive response. The aim of the present study is to identify metabolomic biomarkers of the cognitive response to meal ingestion. METHODS: In 18 healthy subjects, the response to a test meal (Edanec, 1 kcal/mL) ingested until maximum satiation (50 mL/min) was assessed. Perception measurements and blood samples were taken before, at the end of the meal, and 20 min after ingestion. The cognitive response and the hedonic dimension were measured on 10 cm scales. Metabolomic analysis was performed using nuclear magnetic resonance (NMR) spectroscopy and values of triglycerides, insulin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) were determined using conventional laboratory techniques. KEY RESULTS: Ingestion up to maximum satiation induced sensation of fullness and decreased digestive well-being. The total amount ingested by each subject correlated with the basal sensation of hunger, but not with other sensations or blood metabolite levels. Immediately after ingestion, satiation correlated with an increase in glucose (R = 0.49; p = 0.038) and valine levels (R = 0.48; p = 0.043). Twenty-minutes after finalizing ingestion, triglyceride levels had significantly increased which correlated with the recovery in well-being (R = 0.48; p = 0.046) and the decrease in desire to eat a food of choice (R = -0.56; p = 0.016). The increase in lipids inversely correlated with abdominal discomfort (R = -0.51; p = 0.032). CONCLUSIONS & INFERENCES: Cognitive and hedonic responses to meal ingestion correlate with changes in circulating metabolites, which may serve as objective biomarkers of perception.

The joint power of sex and stress to modulate brain-gut-microbiota axis and intestinal barrier homeostasis: implications for irritable bowel syndrome.

BACKGROUND: Intestinal homeostasis is a dynamic process that takes place at the interface between the lumen and the mucosa of the gastrointestinal tract, where a constant scrutiny for antigens and toxins derived from food and microorganisms is carried out by the vast gut-associated immune system. Intestinal homeostasis is preserved by the ability of the mucus layer and the mucosal barrier to keep the passage of small-sized and antigenic molecules across the epithelium highly selective. When combined and preserved, immune surveillance and barrier's selective permeability, the host capacity of preventing the development of intestinal inflammation is optimized, and viceversa. In addition, the brain-gut-microbiome axis, a multidirectional communication system that integrates distant and local regulatory networks through neural, immunological, metabolic, and hormonal signaling pathways, also regulates intestinal function. Dysfunction of the brain-gut-microbiome axis may induce the loss of gut mucosal homeostasis, leading to uncontrolled permeation of toxins and immunogenic particles, increasing the risk of appearance of intestinal inflammation, mucosal damage, and gut disorders. Irritable bowel syndrome is prevalent stress-sensitive gastrointestinal disorder that shows a female predominance. Interestingly, the role of stress, sex and gonadal hormones in the regulation of intestinal mucosal and the brain-gut-microbiome axis functioning is being increasingly recognized. PURPOSE: We aim to critically review the evidence linking sex, and stress to intestinal barrier and brain-gut-microbiome axis dysfunction and the implications for irritable bowel syndrome.

[Iron deficiency: not always blood losses]. / Ferropenia: no siempre son pérdidas.

UNLABELLED: Iron deficiency may be the only presenting sign of malabsorption due to the presence of intestinal villous atrophy. Once gastrointestinal blood losses have been excluded, intestinal malabsorption should be investigated. OBJECTIVES: To determine the utility of jejunal biopsy in the evaluation of iron deficiency due to a defective absorption and the different diseases that may cause malabsortive iron deficiency. METHODS: Seventy patients with iron deficiency (ferritin<25 ng/ml), referred to the Unitat de Proves Funcionals Digestives to perform a jejunal biopsy were included. Jejunal biopsy was obtained distal to Treitz with a Watson capsule. Histological changes were classified according to the criteria proposed by Marsh. RESULTS: Jejunal biopsy was performed in 66 patients. Histology was normal in 25, unespecific in 1, showed inflammatory infiltrate in 12, hyperplastic changes in 2 and atrophy in 25. In one patient showed intestinal giardiasis. The clinical diagnosis was celiac sprue in 21 patients (32%), aclorhydria in 7 (10.5%), bacterial overgrowth in 1 (1.5%), intestinal giardiasis in 1 (1.5%), menstrual blood loss in 1 (1.5%) and 35(53%) patients remained without a definitive diagnosis. CONCLUSIONS: Jejunal biopsy is useful in the evaluation of iron deficiency due to intestinal malabsorption and reveals intestinal abnormalities in a significant number of cases.

Ferropenia: no siempre son pérdidas / Iron deficiency: not always blood losses

La ferropenia puede ser la única manifestación de un síndrome malabsortivo, secundario a la presencia de una atrofia intestinal. Por ello, descartadas las pérdidas gastrointestinales, debería tenerse en cuenta esta posibilidad en el estudio de la ferropenia. Objetivos: Evaluar la utilidad de la biopsia yeyunal en el diagnóstico de la malabsorción intestinal como causa de ferropenia y analizar cuales son las causas de ferropenia malabsortiva. Método: Se han incluido 70 pacientes con ferropenia (ferritina < 25 ng/ml) remitidos a la Unitat de Proves Funcionals Digestives, para la valoración de una posible malabsorción intestinal mediante la realización de una biopsia yeyunal. La biopsia yeyunal se obtuvo distal al ángulo de Treitz mediante cápsula de Watson. Se clasificaron los resultados histológicos según los criterios de Marsh. Resultados: La biopsia yeyunal se realizó en 66 pacientes. Fue normal en 25 pacientes, inespecífica en 1, en 12 se evidenciaron lesiones grado 1 (infiltrado linfocitario), en 2 lesiones grado 2 (hiperplasia de criptas) y en 25 lesiones grado 3 (atrofia). En otro paciente se objetivó una giardiasis intestinal. El diagnóstico clínico de los pacientes incluídos fue de enfermedad celíaca en 21 (32 por ciento), aclorhidria en 7 (10,5 por ciento), sobrecrecimiento bacteriano en 1 (1,5 por ciento), giardiasis intestinal en otro (1,5 por ciento), pérdidas ginecológicas en otra (1,5 por ciento) y 35 (53 por ciento) quedaron sin diagnóstico definitivo. Conclusiones: La biopsia yeyunal es una prueba útil en el diagnóstico de malabsorción como causa de ferropenia, permitiendo poner de manifiesto la existencia de patología intestinal en un alto porcentaje de casos (AU)