Alimentación funcional para corregir desórdenes gastrointestinales asociados a trastornos del espectro autista: una revisión sistemática / Functional feeding to correct gastrointestinal disorders associated with autism spectrum disorders: a systematic review

Antecedentes: los trastornos gastrointestinales (TGI) son comorbilidades comunes en los pacientes con trastornos del espectro autista (TEA); los tratamientos con dietas libres de gluten y caseína (LGLC) o suplementos de prebióticos/probióticos podrían reducir la severidad de los TGI. Objetivo: integrar y discutir la evidencia sobre la efectividad de las terapias con dietas LGLC y suplementos de prebióticos/probióticos sobre los TGI en pacientes con TEA. Metodología: se utilizaron las guías para la publicación de revisiones sistemáticas y metaanálisis (PRISMA). Se analizaron las características de los participantes, las intervenciones dietéticas, la administración de suplementos de prebióticos/prebióticos, los efectos de las intervenciones sobre los TGI, el riesgo de sesgo de los estudios y la seguridad de los tratamientos. Resultados: se analizaron quince investigaciones; la prevalencia de los TGI entre los pacientes con TEA fue alta (58 %; rango, 27-83 %). En más del 20 % de los pacientes intervenidos con dietas LGLC o suplementos disminuyó la severidad de los TGI (principalmente estreñimiento, diarrea y dolor abdominal). Se reportaron aumentos en los conteos de bacterias benéficas y una disminución de la proporción de bacterias patógenas tras el uso de los suplementos. Sin embargo, todas estas investigaciones presentaron sesgos metodológicos importantes. Conclusiones: aunque se han encontrado reducciones en la frecuencia y severidad de algunos TGI, la efectividad de estos tratamientos aún no se ha comprobado. Dadas las diferencias metodológicas de las investigaciones, se justifica el diseño de estudios rigurosos para evaluar los efectos terapéuticos de estos tratamientos sobre la salud gastrointestinal en pacientes con TEA (AU)

Background: gastrointestinal disorders (GIDs) are common comorbidities in patients with autism spectrum disorders (ASD); treatments with gluten- and casein-free (LGLC) diets or prebiotic/probiotic supplements may reduce the severity of GIDs. Objective: to integrate and discuss the evidence on the effectiveness of LGLC diet therapies and prebiotic/probiotic supplements on GIDs in patients with ASD. Methodology: the guidelines for the publication of systematic reviews and meta-analyses (PRISMA) were used. Participant characteristics, dietary interventions, prebiotic/prebiotic supplementation, effects of interventions on GIDs, risk of bias, and safety of treatments were analyzed. Results: fifteen investigations were analyzed; the prevalence of GIDs among patients with ASD was high (58 %; range, 27-83 %). In more than 20 % of the patients managed with LGLC diets or supplements GID severity decreased (mainly constipation, diarrhea, and abdominal pain). Increases in the counts of beneficial bacteria and a decrease in the proportion of pathogenic bacteria were reported after supplement use. However, all these investigations had significant methodological biases. Conclusions: although reductions in the frequency and severity of some GIDs have been found, the effectiveness of these treatments has not been proven yet. Given the methodological differences in the investigations, the design of rigorous studies to evaluate the therapeutic effects of these treatments on gastrointestinal health in patients with ASD is warranted (AU)

A dynamic and integrated in vitro/ex vivo gastrointestinal model for the evaluation of the probability and severity of infection in humans by Salmonella spp. vehiculated in different matrices.

The lack of proper gastrointestinal models assessing the inter-strain virulence variability of foodborne pathogens and the effect of the vehicle (food matrix) affects the risk estimation. This research aimed to propose a dynamic and integrated in vitro/ex vivo gastrointestinal model to evaluate the probability and severity of infection of foodborne pathogens at different matrices. An everted gut sac was used to determine the adhesion and invasion of Salmonella enterica and tissue damage. S. Typhimurium ATCC 14028 was used as a representative bacterium, and two matrices (water and cheese) were used as vehicles. No differences (p > 0.05) in the probability of infection (Pinf) were found for intra-experimental repeatability. However, the Pinf of cheese-vehiculated S. Typhimurium was different compared to water- vehiculated S. Typhimurium, 7.2-fold higher. The histological analysis revealed Salmonella-induced tissue damage, compared with the control (p < 0.05). In silico proposed interactions between two major Salmonella outer membrane proteins (OmpA and Rck) and digested peptides from cheese casein showed high binding affinity and stability, suggesting a potential protective function from the food matrix. The results showed that the everted gut sac model is suitable to evaluate the inter-strain virulence variability, considering both physiological conditions and the effect of the food matrix.

Effect of the nixtamalization process on the protein bioaccessibility of white and red sorghum flours during in vitro gastrointestinal digestion.

Protein bioaccessibility is a major concern in sorghum (Sorghum bicolor L. Moench) due to potential interactions with tannins affecting its nutritional value. Technological treatments such as boiling or alkaline cooking have been proposed to address this problem by reducing tannin-protein interactions. This research aimed to evaluate the impact of nixtamalization in the protein bioaccessibility from two sorghum varieties (red and white sorghum) during in vitro gastrointestinal digestion. Nixtamalization increased protein bioaccessibility in the non-digestible fraction (NDF) (5.26 and 26.31% for red and white sorghum, respectively). However, cooking showed a higher permeation speed of protein from red sorghum flours at the end of the intestinal incubation (9.42%). The SDS-PAGE profile of the digested fraction (DF) at 90 min of intestinal incubation indicated that, for red sorghum, cooking allows the formation of α and γ-kafirins while nixtamalization increase α-kafirin release. Principal Components Analysis (PCA) showed the association between nixtamalization and dissociation of δα kafirin complexes and increased protein content in the digestible fraction. In silico interactions indicated the highest biding energies for (+)-catechin and kafirin fractions (ß-kafirin: -7.0 kcal/mol; γ-kafirin: -5.8 kcal/mol, and δ-kafirin: -6.8 kcal/mol), suggesting a minor influence of depolymerized proanthocyanidin fractions with sorghum proteins as a result of the nixtamalization process. In conclusion, nixtamalization increased the bioaccessibility of sorghum proteins, depolymerizing condensed tannins, and breaking protein-tannin complexes. Such technological process improves the nutrimental value of sorghum, supporting its inclusion in the human diet.

Effect of the in vitro gastrointestinal digestion on free-phenolic compounds and mono/oligosaccharides from Moringa oleifera leaves: Bioaccessibility, intestinal permeability and antioxidant capacity.

Moringa oleifera is a plant recognized for its compounds such as dietary fiber (oligosaccharides, amongst others) and polyphenols, with biological activities. These properties depend on bioactive compounds (BC) interactions with food matrix/digestion conditions, which have not been evaluated. Thus, the aim of this study was to evaluate the bioaccessibility, intestinal permeability and antioxidant capacity of BC (free-phenolic compounds (PC); and mono/oligosaccharides (MOS)) from Moringa oleifera leaves (ML) powder during in vitro gastrointestinal digestion. The gallic/caffeic acids, morin, kaempferol, mannose and stachyose showed the highest bioaccessibilities (~6-210%). The PC correlated with the antioxidant capacity (R2: 0.59-0.98, p < .05), whereas gallic/caffeic acids were the highest. The apparent permeability coefficients of bioactive compounds (0.62-36.65 × 10-4 cm/s) and water flux/glucose transport confirmed the model similarity to in vivo experiments. The results suggest that ML digestion dynamically modifies PC/MOS bioaccessibility/antioxidant capacity while most of them are not completely absorbed in the small intestine.

Fermented non-digestible fraction from combined nixtamalized corn (Zea mays L.)/cooked common bean (Phaseolus vulgaris L.) chips modulate anti-inflammatory markers on RAW 264.7 macrophages.

Chronic non-communicable diseases (NCDs) are low-level inflammation processes affected by several factors including diet. It has been reported that mixed whole grain and legume consumption, e.g. corn and common bean, might be a beneficial combination due to its content of bioactive compounds. A considerable amount would be retained in the non-digestible fraction (NDF), reaching the colon, where microbiota produce short-chain fatty acids (SCFAs) and phenolic compounds (PC) with known anti-inflammatory effect. The aim of this study was to estimate the anti-inflammatory potential of fermented-NDF of corn-bean chips (FNDFC) in RAW 264.7 macrophages. After 24 h, FNDFC produced SCFAs (0.156-0.222 mmol/l), inhibited nitric oxide production > 80% and H2O2 > 30%, up-regulated anti-inflammatory cytokines (I-TAC, TIMP-1) > 2-fold, and produced angiostatic and protective factors against vascular/tissue damage, and amelioration of tumor necrosis factor signalling and inflammatory bowel disease. These results confirm the anti-inflammatory potential derived from healthy corn-bean chips.

Physicochemical and nutraceutical properties of moringa (Moringa oleifera) leaves and their effects in an in vivo AOM/DSS-induced colorectal carcinogenesis model.

Moringa (Moringa oleifera) is a plant that has generated great interest in recent years because of its attributed medicinal properties. The aim of this study was to characterize the bioactive compounds of moringa leaves (MO) and evaluate their effect on a colorectal carcinogenesis model. Twenty-four male CD-1 mice were divided into 4 groups: Group 1 fed with basal diet (negative control/NC); Group 2 received AOM/DSS (positive control); Groups 3 and 4 were fed with basal diet supplemented with moringa leaves (2.5% w/w and 5% w/w, respectively) for 12weeks. Moringa leaves exhibited a high content of dietary fiber (~18.75%) and insoluble dietary fiber (2.29%). There were identified 9 phenolic compounds whereas the chlorogenic and ρ-coumaric acid showed the higher contents (44.23-63.34µg/g and 180.45-707.42µg/g, respectively). Moringa leaves decreased the activity of harmful fecal enzymes (ß-glucosidase, ß-glucuronidase, tryptophanase and urease up to 40%, 43%, 103% and 266%, respectively) as well tumors incidence in male CD1-mice (~50% with 5% w/v of moringa dose). These findings suggest that the bioactive compounds of moringa such as total dietary fiber and phenolic compounds may have chemopreventive capacity. This is the first study of the suppressive effect of moringa leaves in an in vivo model of AOM/DSS-induced colorectal carcinogenesis.

Bioaccessibility and antioxidant activity of free phenolic compounds and oligosaccharides from corn (Zea mays L.) and common bean (Phaseolus vulgaris L.) chips during in vitro gastrointestinal digestion and simulated colonic fermentation.

Corn (Zea mays L.) and common beans (Phaseolus vulgaris L.) are alternative suitable ingredients for snacks, because of their content of bioactive compounds such as phenolic compounds (PC) and oligosaccharides (OS). However, there is no information about the transformation of these compounds associated with food matrix during gastrointestinal digestion. Therefore, the objective of this work was to simulate the whole digestion process (mouth to colon) to estimate bioaccessibility and small intestine permeability of free PC and OS, and the antioxidant capacity of free PC. Digested nixtamalized corn-cooked common bean chips exhibited significant different quantities of free PC and OS, and higher antioxidant activity compared to methanolic extract. The free PC showed high values of apparent permeability coefficients (0.023-0.729×10-3), related with their absorption in the small intestine. Both free PC and OS were retained in the non-digestible fraction of chips (10.24-64.4%) and were able to reach the colon. Our results suggest the digestion potential to increase chip bioactive compounds and antioxidant activity. Additional studies are required to evaluate their in vivo effects.

The fermented non-digestible fraction of common bean (Phaseolus vulgaris L.) triggers cell cycle arrest and apoptosis in human colon adenocarcinoma cells.

Cancer is a leading cause of death worldwide with colorectal cancer (CRC) ranking as the third contributing to overall cancer mortality. Non-digestible compounds such as dietary fiber have been inversely associated with CRC in epidemiological in vivo and in vitro studies. In order to investigate the effect of fermentation products from a whole non-digestible fraction of common bean versus the short-chain fatty acid (SCFAs) on colon cancer cells, we evaluated the human gut microbiota fermented non-digestible fraction (hgm-FNDF) of cooked common bean (Phaseolus vulgaris L.) cultivar Negro 8025 and a synthetic mixture SCFAs, mimicking their concentration in the lethal concentration 50 (SCFA-LC50) of FNDF (hgm-FNDF-LC50), on the molecular changes in human colon adenocarcinoma cells (HT-29). Total mRNA from hgm-FNDF-LC50 and SCFA-LC50 treated HT-29 cells were used to perform qPCR arrays to determine the effect of the treatments on the transcriptional expression of 84 genes related to the p53-pathway. This study showed that both treatments inhibited cell proliferation in accordance with modulating RB1, CDC2, CDC25A, NFKB and E2F genes. Furthermore, we found an association between the induction of apoptosis and the modulation of APAF1, BID, CASP9, FASLG, TNFR10B and BCL2A genes. The results suggest a mechanism of action by which the fermentation of non-digestible compounds of common bean exert a beneficial effect better than the SCFA mixture by modulating the expression of antiproliferative and pro-apoptotic genes in HT-29 cells to a greater extent, supporting previous results on cell behavior, probably due to the participation of other compounds, such as phenolic fatty acids derivatives and biopetides.

Fermented nondigestible fraction from common bean (Phaseolus vulgaris L.) cultivar Negro 8025 modulates HT-29 cell behavior.

The aim of the study was to evaluate the effect of a fermented nondigestible fraction (FNDF) of cooked bean (Phaseolus vulgaris L.) cultivar Negro 8025 on human colon adenocarcinoma HT-29 cell survival. Negro 8025 was chosen for in vitro fermentation based on comparison of chemical composition with 2 other cultivars: Azufrado Higuera and Pinto Durango. Negro 8025 had 58% total dietary fiber, 27% resistant starch, and 20 mg of (+)-catechin equivalents per gram of sample. Short-chain fatty acids (SCFAs) production and pH of the medium were measured after fermentation as indicators of colon protection through induced arrest on cell culture and apoptosis. Butyrate and pH of FNDF of Negro 8025 were higher than the control fermented raffinose extract. The FNDF inhibited HT-29 cell survival in a time- and concentration-dependent manner. The lethal concentration 50 (LC(50)) was 13.63% FNDF (equivalent to 7.36, 0.33, and 3.31 mmol of acetic, propionic, and butyric acids, respectively). DNA fragmentation, an apoptosis indicator, was detected by the TdT-mediated dUTP nick end labeling method in cells treated with the LC(50)-FNDF and a synthetic mixture of SCFAs mimicking LC(50)-FNDF. Our results suggest that common bean is a reliable source of fermentable substrates in colon, producing compounds with potential chemoprotective effect on HT-29 colon adenocarcinoma cells, so it may present an effective alternative to mitigate colon cancer development.

Chemical composition and in vitro polysaccharide fermentation of different beans (Phaseolus vulgaris L.).

The composition of bioactives including polysaccharide yield and resistant starch (RS) content of 4 raw and cooked bean (Phaseolus vulgaris L.) cultivars was evaluated. Polysaccharide was fermented in vitro by incubation with human gut flora under anaerobic conditions and short-chain fatty acids (SCFAs) production was compared at 6, 12, and 24 h by gas chromatography. Polysaccharide and soluble fiber contents increased upon cooking with stachyose as the major oligosaccharide. Cooked bean of cultivar Bayo Madero had the highest yield of polysaccharides (55%) and resistant starch (37%), followed by those of Negro 8025 (48% and 32%, respectively). Acetate was the most abundant SCFAs formed in all bean varieties. The concentration of SCFAs was cultivar-dependent; Bayo Madero and Negro 8025 displayed the highest concentration of butyrate (15 mmol/L), while Azufrado Higuera had the lowest and highest concentrations of acetate (39 mmol/L) and propionate (14 mmol/L), respectively. The results suggest that the common bean is an excellent source of polysaccharides that can be fermented in the colon and produce SCFAs, compounds previously reported to exert health benefits.