Fitoquímicos: una nueva clase de prebióticos / Phytochemicals: a new class of prebiotics

RESUMEN La microbiota intestinal (MI) es considerada como un nuevo blanco para la prevención y manejo nutricional de las alteraciones inflamatorias y metabólicas asociadas a las enfermedades crónicas no-transmisibles. Los prebióticos son principalmente fibras solubles cuyo consumo favorece el crecimiento de poblaciones bacterianas beneficiosas de la MI e impacta favorablemente la salud del consumidor. Esta revisión presenta a los fitoquímicos dietarios, que incluyen a más de 8.000 compuestos, como una nueva clase de prebióticos debido a su capacidad de estimular poblaciones de Lactobacillus, Bifidobacterium, Akkermansia y de bacterias productoras de butirato en el colon, a expensa de bacterias potencialmente dañinas como C. histolyticum. Además, los fitoquímicos son transformados por la MI en múltiples metabolitos que ejercen actividades biológicas a veces más potentes que la molécula inicial de la cual provienen. Individuos con distintos metabotipos han sido descritos de acuerdo a su capacidad de responder al consumo de isoflavonas, lignanos o elagitaninos, dependiendo de la presencia en su MI de bacterias capaces de transformar dichos polifenoles en equol, enterolactona/enterodiol y urolitinas, respectivamente, los cuales exhiben actividades biológicas. Valerolactonas y ácidos aromáticos también son producidos por la MI a través del metabolismo de las proantocianidinas. El efecto prebiótico de los fitoquímicos contribuiría a explicar los efectos saludables del consumo de frutas y verduras ricos en fitoquímicos.

ABSTRACT Intestinal microbiota (IM) is considered as a new target for the prevention and nutritional management of inflammatory and metabolic alterations associated with non-transmissible chronic diseases. Prebiotics are mainly soluble fibers whose consumption favors the growth of beneficial bacterial populations of the IM and positively impacts health. This review discusses dietary phytochemicals, which include more than 8,000 compounds, as a new class of prebiotics due to its ability to stimulate populations of Lactobacillus, Bifidobacterium, Akkermansia and butyrate producing bacteria in the colon at the expense of potentially harmful bacteria, such as C. histolyticum. In addition, phytochemicals are transformed by IM into a great array of metabolites exerting biological activities and are sometimes more potent than the initial molecule from which they are derived. Individuals with different metabotypes have been described according to their ability to respond to the consumption of isoflavones, lignans or ellagitannins, depending on the presence in their IM of bacteria capable of transforming these polyphenols into equol, enterolactone/enterodiol and urolithins, respectively, which exhibit biological activities. Valerolactones and aromatic acids are also produced by the IM through proanthocyanidin metabolism. The prebiotic effect of phytochemicals would help to explain the healthy effects associated with the consumption of fruits and vegetables rich in phytochemicals.

Las alteraciones de la microbiota intestinal en la patogenia del hígado graso no alcohólico / Alterations of the intestinal microbiota in the pathogenesis of nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is currently considered in Chile and worldwide, as the main cause of cirrhosis and liver transplantation. It is therefore one of the main public health objectives for reducing its prevalence. In last years, it was suggested that the intestinal microbiota (IM) might contribute to the pathophysiology of NAFLD, as well as in the progression toward nonalcoholic steatohepatitis (NASH) and cirrhosis. It is known that changes in the composition of IM are associated with alterations in intestinal permeability and the production of inflammatory metabolites. These alterations are part of the pathophysiological mechanisms leading to the development of NASH. However studies on MI in patients with NAFLD and NASH in Chile are scarce. Through a research grant, recently awarded at the Hospital Clínico Universidad de Chile, we aim to confirm and characterize the intestinal dysbiosis associated with NAFLD in Chilean patients and to establish the relationship between the changes in microbial composition with the progression of liver damage. The description of these alterations represents an opportunity to explore new therapeutic approaches for future interventions. In effect, through the restoration of an intestinal microbial environment towards homeostasis in these patients, we expect to reverse or improve the progression of damage provoked by this disease. (AU)

El papel de la microbiota intestinal en el desarrollo de la obesidad y de la diabetes de tipo-2 / The role of intestinal microbiota in the development of obesity and type-2 diabetes

The intestinal microbiota (IM) is a complex consortium including a great number of bacteria, fungi, yeasts, virus and phages. The harmonic crosstalk between the IM, the epithelia barrier and the local immune system determine gut homeostasis in the healthy subject. The IM plays a key role in regulating energy harvest, energy expenditure, fat storage and food intake in the host. Increasing evidence suggests that bacterial composition, functional genes and metabolic activities of the IM are altered in the subjects with obesity or type-2 diabetes (T2D). It appears that dietary fat is also an important factor which affects the IM composition as well as the gut barrier function and the plasma levels of LPS. This metabolic endotoxemia would contribute to the development of systemic low grade inflammation, insulin resistance and T2D. The development of dietary (prebiotics, probiotics) and therapeutic (antibiotics, microbiota transplantation) tools to reestablish the homeostasis of the IM constitute interesting new strategies for the prevention or management of obesity and T2D...

Trabajos de Investigación Increase of plasma fatty acids without changes in n-6/n-3-PUFA ratio in asymptomatic obese subjects / Aumento de las concentraciones plasmáticas de ácidos grasos sin cambio en el ratio de n-6/n-3 PUFA en sujetos obesos asintomáticos

Obesity is associated with a low grade inflammation which contributes to the development of insulin resistance and diabetes. The aim of this study was to assess the total saturated (SFAs), monounsaturated (MUFAs) and polyunsaturated fatty acids (PUFAs) in plasma from asymptomatic obese subjects and to determine the arachidonic/eicosapentanoic acid ratio [ARA/EPA] as a marker of inflammation, and its eventual association with ultrasensitive CRP. Fourteen obese (34.4 ± 11.1y.; BMI: 36.0 ± 4,5 kg/m2) and 12 normal-weight (30.6 ± 7.8y.; BMI: 23,6± 2,4 kg/m2) subjects were recruited and their plasma fatty acids were determined by gas chromatography. usCRP was higher in the obese subjects (p=0,01) and correlates with their body fat content. The percentages of SFAs, MUFAs, PUFAs were not affected in the obese subjects but their concentrations were increased, compared with the control group. However, no differences in the long chain PUFAs (DHA and EPA) concentrations or in the plasmatic ARA/EPA ratio were observed in these subjects. These observations do not support a relation between the ARA/EPA ratio and the presence of low grade inflammation evaluated by plasma usCRP in this group of asymptomatic obese subjects.

La obesidad está asociada con una inflamación de bajo grado que contribuye al desarrollo de la insulino-resistencia y de la diabetes. El objetivo de este estudio fue evaluar las concentraciones plasmáticas de ácidos grasos saturados (AGS), monoinsaturados (AGMI) y poliinsaturados (AGPI) en sujetos obesos asintomáticos y determinar el ratio ácido araquidónico/ácido eicosapentanoico [ARA/EPA] como un posible marcador de inflamación, con su eventual asociación con los niveles de proteína C reactiva ultrasensible (PCRus). Se reclutaron 14 sujetos obesos (34,4 ± 11.1 años; índice de masa corporal: 36,0 ± 4,5 kg/m2) y 12 normopeso (30,6 ± 7.8 años; índice de masa corporal: 23,6 ± 2,4 kg/m2); las concentraciones plasmáticas de ácidos grasos fueron determinados por cromatografía de gases. Los niveles de PCRus fueron más elevadas en los sujetos obesos (p=0,01) y correlacionaron con el contenido de grasa corporal. Los porcentajes relativos de AGS, AGMI, AGPI no se vieron afectados en los sujetos obesos, pero sus concentraciones plasmáticas se incrementaron en comparación con el grupo control. Sin embargo, no se observaron diferencias en las concentraciones de PUFAs de cadena larga (DHA, EPA y ARA) ni en el ratio ARA/EPA en los sujetos obesos. Estas observaciones no apoyan el uso del ratio ARA/EPA como un marcador de inflamación de bajo grado evaluada por PCRus en este grupo de sujetos obesos asintomáticos.

Utilización de suplementos nutricionales para el manejo del sobrepeso y obesidad: una revisión de la evidencia / Use of dietary supplements for the management of overweight and obesity: a review of the evidence

Simultaneously to the rapid increase of overweight and obesity a great number of products oriented to weight loss have emerged in the market. The aim of this study was to evaluate the scientific evidence supporting the use of three products designed for weight loss available in Chile: a lipidic emulsion that stimulates ileal brake, a protease inhibitor and an amylase inhibitor. The results indicate that the amylase and protease inhibitors efficiently inhibit the respective enzymatic activities in vitro; however, they do not affect weight control in clinical trials carried out in normal weight as well as in obese subjects. Thus, there is not enough evidence supporting the use of these products for weight control. On the other hand, the results concerning the lipidic emulsion are conflicting and more studies are needed to confirm its possible effect on weight control.

Paralelamente al rápido aumento de la prevalencia de sobrepeso y obesidad han surgido en el mercado múltiples productos que prometen estimular la pérdida de peso sin modificar la dieta y estilo de vida de los individuos. El objetivo de este trabajo es evaluar la evidencia científica que apoye el uso de tres productos disponibles en Chile para el control ponderal y la reducción de sobrepeso y obesidad: una emulsión lipídica que estimula el freno ileal, un inhibidor de proteasa y un inhibidor de amilasa. Los resultados indican que el inhibidor de amilasa y el inhibidor de proteasa, si bien parecen funcionar in vitro, no muestran ningún efecto sobre el control ponderal en los ensayos clínicos realizados tanto en sujetos normopeso como en obesos. El nivel de evidencia que apoya el uso de estos productos para el control ponderal es por lo tanto insuficiente. En caso de la emulsión lipídica, los resultados son conflictivos y más estudios son necesarios para confirmar su eventual efecto sobre el control del peso corporal.

Identification of Lactobacillus spp. in colostrum from Chilean mothers

The biodiversity of Lactobacillus spp. in colostrum samples from 116 Chilean mothers was analyzed by PCR and 16S rDNA sequencing. Lactobacilli were isolated in 55.3% of the samples, with concentrations of 3.33 ± 0.55 (log CFU/ml). The predominant species were L. plantarum (64%), L. fermentum (16%) and L. pentosus (9%). 28% of the isolated strains were resistant to gastric pH and bile salts, suggesting that they could be used as probiotics.

Se analizó la biodiversidad de especies de Lactobacillus en muestras de calostro de 116 madres chilenas mediante PCR y secuenciación del rDNA 16S. Se aislaron lactobacilos en 55,3% de las muestras, con concentraciones de 3,33 ± 0,55 (log UFC / ml). Las especies predominantes fueron L. plantarum (64%), L. fermentum (16%) y L. pentosus (9%). 28% de las cepas aisladas fueron resistentes a pH gástrico y a las sales biliares, lo que sugiere que podrían ser utilizados como probióticos.

Efecto de un producto lácteo con probióticos y prebióticos sobre la función digestiva de sujetos sanos y constipados / Effect of a milk product containing probiotics and prebiotics on the digestive function of healthy and constipated subjects

Constipation is a complex disorder, which affects an important part of the population and results in an increase of gastrointestinal symptoms and in lower stool frequency. The addition of soluble fibers (prebiotics) and probiotic in foodstuffs has been proposed as a useful tool to improve digestive wellbeing of affected individuals. The aim of this study was to evaluate the effect of the daily consumption of Minishot, a milk drink with prebiotics (inulin I polydextrose) and probiotics (Bifidobacterium lactis BB12), on the digestive comfort of healthy and constipated subjects. We conducted a randomized, controlled, double blind clinical trial in 33 healthy subjects and 64 constipated subjects (< 3 stools I week). Subjects underwent a one-week observation period followed by two periods of two weeks of consumption of Minishot or placebo, separated between them by a two-week washout period. The volunteers recorded daily in a table the presence and severity of distracters and digestive symptoms and the number and consistency of stools. Neither Minishot nor the placebo affected the digestive wellbeing or the stool frequency and consistency in the control subjects. In the constipated subjects, both consumption of Minishot and the placebo improved digestive comfort and stool frequency. However, compared with the placebo, Minishot significantly decreased the frequency of hard stools and the proportion of subjects emitting them, and increased the frequency of normal stools.

La constipación es un trastorno complejo que afecta una parte importante de la población. El consumo de prebióticos y probióticos ha sido propuesta como una herramienta para mejorar el bienestar digestivo de las personas afectadas. El objetivo del estudio fue evaluar el efecto del consumo diario de una bebida láctea con inulina/polidextrosa y Bifidobacterium lactis Bbl2, Minishot, sobre el bienestar digestivo de sujetos sanos o constipados. Se realizó un ensayo clínico randomizado, controlado y en doble ciego en 33 sujetos sanos y 64 sujetos constipados (< 3 deposiciones / semana). Después de una semana de observación, cada sujeto tuvo 2 periodos de 2 semanas de consumo de Minishot o del placebo, espaciados entre si por 2 semanas de reposo. Los voluntarios registraron diariamente la presencia e intensidad de síntomas digestivos y el número y consistencia de deposiciones. El consumo de Minishot no afecto en forma importante el bienestar digestivo de los sujetos sanos ni alteró la frecuencia y consistencia de sus deposiciones. En los sujetos constipados, tanto el consumo de Minishot como del placebo mejoraron el bienestar digestivo y la frecuencia de deposición. Comparado con el placebo, el consumo de Minishot disminuyó significativamente la frecuencia de deposiciones muy duras y la proporción de sujetos emitiéndolas, y aumento la frecuencia de deposiciones normales/blandas y la proporción de sujetos emitiéndolas.

La microbiota intestinal: Un nuevo actor en el desarrollo de la obesidad / The association of intestinal microbiota with obesity

Intestinal microbiota (IM) plays a role in the development of obesity and its associated low grade inflammation. Bacterial colonization of the gastrointestinal tract of germ free mice (without microbiota) increases by 60 percent their fat mass, alters their fasting glucose and insulin levels, triples their hepatic triglycerides and induces adipocyte hypertrophy. IM favors fat storage in adipocytes through the inhibition of Fiaf (Fasting Induced Adipocyte Factor), an inhibitor of lipoprotein lipase. Compared with normal weight subjects, the IM from obese exhibits a higher proportion of Firmicutes/Bacteroidetes and is more efficient in extracting energy from foodstuffs. The loss of bodyweight by a hypocaloric diet reverts the proportion of bacteria to that of lean subjects. The intake of a high fat diet also alters the IM, affecting intestinal barrier function and favoring endotoxinemia. These events increase oxidative and pro-inflammatory processes in plasma and peripheral tissues and increment the risk of insulin resistance. Such events are reverted by the administration of pre-biotics which stimulate the growth of Bifdobacterium and Lactobacillus species in the colon, reestablishing the gut homeostasis. Interestingly, products resulting from the fermentation of prebiotics stimulate the differentiation of enteroendocrine cells and the release of glucagon like peptide 1 and peptide YY, that have insulin like and anorexigenic activities, thus contributing to body weight equilibrium.

Algunas verdades sobre el café / Some trues concerning coffee

El café es una de las bebidas más consumidas a nivel mundial, debido a sus propiedades organolépticas y a su capacidad de mantener a los individuos en estado de alerta. No obstante, su consumo se asocia frecuentemente con efectos negativos sobre la salud. Este artículo revisa la información más reciente acerca de la relación entre el consumo de café y la salud. Varios estudios epidemiológicos desarrollados en la última década muestran en forma consistente que el consumo de café se asocia a un menor riesgo de diabetes tipo-2, daño hepático y enfermedades neurodegenerativas como el Parkinson. Los mecanismos que podrían dar cuenta de estas observaciones aún no se comprenden completamente pero se podrían relacionar con el perfil específico de antioxidantes del café y con las altas concentraciones de éstos, en particular de ácido clorogénico.

Efecto de un extracto seco de boldo sobre el tránsito intestinal oro-cecal en voluntarios sanos / Effect of a dry boldo extract on oro cecal intestinal transit time in healthy volunteers

Background: Boldo (peumus boldus Molina) is a widely used medicinal plant. However, its physiological effects are not well known. Recent studies in animals showed that certain components of boldo relax smooth muscle and prolong intestinal transit. Aim: to assess the effects of a dry boldo extract on oro cecal transit time in normal humans. Subjects and methods: twelve volunteers received 2.5 g of a dry boldo extract or a placebo (glucose) during 2 successive periods of 4 days. On the fourth day, 20 g of lactulose were administered and breath hydrogen was collected every 15 min. Oro cecal transit time was defined as the time in which breath hydrogen increased by 20 ppm over the fasting level. Results: oro cecal transit time was larger after dry boldo extract administration, compared to placebo (112.5ñ15.4 and 87ñ11.8 min respectively, paired t p<0.05). Conclusions: dry boldo extract prolongs oro cecal transit time, a possible explanation for its medicinal use