Gut microbiome and anti-viral immunity in COVID-19.

SARS-CoV-2 mainly affects the respiratory system, but the gastrointestinal tract is also a target. Prolonged gut disorders, in COVID-19 patients, were correlated with decreased richness and diversity of the gut microbiota, immune deregulation and delayed viral clearance. Although there are no definitive conclusions, ample evidence would suggest that the gut microbiome composition and function play a role in COVID-19 progression. Microbiome modulation strategies for population stratification and management of COVID-19 infection are under investigation, representing an area of interest in the ongoing pandemic. In this review, we present the existing data related to the interaction between gut microbes and the host's immune response to SARS-CoV-2 and discuss the implications for current disease management and readiness to face future pandemics.

Incidencia de nefropatía por contraste en pacientes sometidos a tomografía computarizada: ¿qué factores la condicionan? / Factors affecting the incidence of contrast-induced nephropathy in patients undergoing computed tomography

Objetivo: Analizar la incidencia de nefropatía por contraste en una cohorte de pacientes sometidos a tomografía computarizada (TC) con contraste yodado intravenoso. Valorar los resultados de la nefroprotección con N-acetilcisteína. Pacientes y métodos: Estudio observacional prospectivo, entre los meses de marzo y julio de 2016. Los pacientes seleccionados tenían programada una TC. Se incluyeron los primeros 5 pacientes de cada día, que aceptaban participar y firmaban el consentimiento informado. Se registraron antecedentes cardiovasculares, tratamientos crónicos e indicación de la TC. Se determinó la creatinina y la urea en sangre pre-TC y pos-TC. El filtrado glomerular se determinó por MDRD-4 (Modification of Diet in Renal Disease). Respecto al contraste, se analizó tipo y dosis. Se registró el uso de N-acetilcisteína anterior a la TC. Estadística: SPSS 15.0(R) utilizando comparación de medias y proporciones. Significación: p < 0,05. Resultados: No se detectó ninguna NC en 202 pacientes estudiados. Datos globales: edad: 63,92 ± 12 años (rango 22-87); 57,4% varones; 21,8% diabéticos; 39,6% hipertensos; 176 pacientes tenían MDRD4 ≥ 60 ml/min/1,73 m2 (89,45 ± 14, rango 62,36-134,14) y 26 MDRD4 < 60 ml/min/1,73 m2 (45,38 ± 11, rango 9,16-58,90). La principal indicación de TC fue oncológica (81,2%). El único contraste administrado fue iopamidol, en dosis de 107,83 ± 11 ml (rango 70-140). El intervalo de días entre analíticas fue de 4,06 ± 1 días. Solo en 13 pacientes se administró N-acetilcisteína: en 9 con MDRD < 60 ml/min/1,73 m2 y en 4 con MDRD4 > 60 ml/min/1,73 m2 (p = 0,000). Conclusiones: La incidencia de NC es no significativa en la cohorte estudiada con un filtrado glomerular superior a 30 ml/min/1,73 m2: la realización de TC de forma "programada", utilizando un contraste yodado "no iónico" en dosis relativamente baja, es un factor que quizás explique estos resultados favorables

Objective: To analyze the incidence of contrast-induced nephropathy in a cohort of patients undergoing computed tomography (CT) with intravenous iodinated contrast material. To evaluate the efficacy of N-acetylcysteine in preventing contrast-induced nephropathy. Patients and methods: This prospective observational study was carried out in the months comprising March 2016 through July 2016. We selected the first five patients scheduled to undergo CT examination each day who agreed to participate and signed the informed consent form. We recorded patients' cardiovascular histories, chronic treatments, and indications for the CT examination. We measured blood levels of creatinine and urea before and after the CT examination. We used the Modification of Diet in Renal Disease (MDRD-4) equation to estimate the glomerular filtration rate. We analyzed the type and dose of contrast material. We recorded whether N-acetylcysteine was administered before the CT examination. We used SPSS 15.0(R) to compare means and proportions. Statistical significance was set at p < 0.05. Results: No incidents of contrast-induced nephropathy were detected in any of the 202 patients included [mean age, 63.92 ± 12 years (range 22-87); 57.4% male; 21.8% diabetic; 39.6% hypertensive; 87.1% had MDRD4 ≥ 60 ml/min/1.73 m2 (89.45 ± 14, range 62.36-134.14) and 12.9% had MDRD4 < 60 ml/min/1.73 m2 (45.38 ± 11, range 9.16-58.90)]. The most common indication for CT examinations was oncologic (81.2%). The only contrast agent administered was iopamidol; the mean dose was 107.83 ± 11 ml (range 70-140). The mean interval between pre-CT and post-CT laboratory tests was 4.06 ± 1 days. Only 13 patients received N-acetylcysteine; 9 of these had MDRD < 60 ml/min/1.73 m2 and 4 had MDRD4 ≥ 60 ml/min/1.73 m2 (p = 0.000). Conclusions: The incidence of contrast-induced nephropathy was not significant in patients with glomerular filtration rates greater than 30 ml/min/1.73 m2: these favorable results might be due to analyzing only scheduled examinations and to using relatively low doses of a "nonionic" iodinated contrast agent

Factors affecting the incidence of contrast-induced nephropathy in patients undergoing computed tomography. / Incidencia de nefropatía por contraste en pacientes sometidos a tomografía computarizada: ¿qué factores la condicionan?

OBJECTIVE: To analyze the incidence of contrast-induced nephropathy in a cohort of patients undergoing computed tomography (CT) with intravenous iodinated contrast material. To evaluate the efficacy of N-acetylcysteine in preventing contrast-induced nephropathy. PATIENTS AND METHODS: This prospective observational study was carried out in the months comprising March 2016 through July 2016. We selected the first five patients scheduled to undergo CT examination each day who agreed to participate and signed the informed consent form. We recorded patients' cardiovascular histories, chronic treatments, and indications for the CT examination. We measured blood levels of creatinine and urea before and after the CT examination. We used the Modification of Diet in Renal Disease (MDRD-4) equation to estimate the glomerular filtration rate. We analyzed the type and dose of contrast material. We recorded whether N-acetylcysteine was administered before the CT examination. We used SPSS 15.0® to compare means and proportions. Statistical significance was set at p < 0.05. RESULTS: No incidents of contrast-induced nephropathy were detected in any of the 202 patients included [mean age, 63.92 ± 12 years (range 22-87); 57.4% male; 21.8% diabetic; 39.6% hypertensive; 87.1% had MDRD4 ≥ 60 ml/min/1.73 m2 (89.45 ± 14, range 62.36-134.14) and 12.9% had MDRD4 < 60 ml/min/1.73 m2 (45.38 ± 11, range 9.16-58.90)]. The most common indication for CT examinations was oncologic (81.2%). The only contrast agent administered was iopamidol; the mean dose was 107.83 ± 11 ml (range 70-140). The mean interval between pre-CT and post-CT laboratory tests was 4.06 ± 1 days. Only 13 patients received N-acetylcysteine; 9 of these had MDRD < 60 ml/min/1.73 m2 and 4 had MDRD4 ≥ 60 ml/min/1.73 m2 (p = 0.000). CONCLUSIONS: The incidence of contrast-induced nephropathy was not significant in patients with glomerular filtration rates greater than 30 ml/min/1.73 m2: these favorable results might be due to analyzing only scheduled examinations and to using relatively low doses of a "nonionic" iodinated contrast agent.

Microbiota in obesity: interactions with enteroendocrine, immune and central nervous systems.

Western diets, with high consumption of simple sugars and saturated fats, contribute to the rise in the prevalence of obesity. It now seems clear that high-fat diets cause obesity, at least in part, by modifying the composition and function of the microorganisms that colonize in the gastrointestinal tract, the microbiota. The exact pathways by which intestinal microbiota contribute to obesity remain largely unknown. High-fat diet-induced alterations in intestinal microbiota have been suggested to increase energy extraction, intestinal permeability and systemic inflammation while decreasing the capability to generate obesity-suppressing short-chain fatty acids. Moreover, by increasing systemic inflammation, microglial activation and affecting vagal nerve activity, 'obese microbiota' indirectly influence hypothalamic gene expression and promote overeating. Because the potential of intestinal microbiota to induce obesity has been recognized, multiple ways to modify its composition and function are being investigated to provide novel preventive and therapeutic strategies against diet-induced obesity.

Bifidobacterium CECT 7765 modulates early stress-induced immune, neuroendocrine and behavioral alterations in mice.

Emerging evidence suggests that there is a window of opportunity within the early developmental period, when microbiota-based interventions could play a major role in modulating the gut-brain axis and, thereby, in preventing mood disorders. This study aims at evaluating the effects and mode of action of Bifidobacterium pseudocatenulatum CECT 7765 in a murine model of chronic stress induced by maternal separation (MS). C57Bl/6J male breast-fed pups were divided into four groups, which were subjected or not to MS and supplemented with placebo or B. pseudocatenulatum CECT7765 until postnatal period (P) 21 and followed-up until P41. Behavioral tests were performed and neuroendocrine parameters were analyzed including corticosterone, cytokine/chemokine concentrations and neurotransmitters. Microbiota was also analyzed in stools by 16S rRNA gene sequencing. B. pseudocatenulatum CECT 7765 administration attenuated some aspects of the excessive MS-induced stress response of the hypothalamic-pituitary-adrenal (HPA) axis, particularly corticosterone production at baseline and in response to subsequent acute stress in adulthood. B. pseudocatenulatum CECT 7765 also down-regulated MS-induced intestinal inflammation (reducing interferon gamma [IFN-γ]) and intestinal hypercatecholaminergic activity (reducing dopamine [DA] and adrenaline [A] concentrations) at P21. These effects have a long-term impact on the central nervous system (CNS) of adult mice since MS mice fed B. pseudocatenulatum CECT 7765 showed lower anxiety levels than placebo-fed MS mice, as well as normal neurotransmitter levels in the hypothalamus. The anti-inflammatory effect of B. pseudocatenulatum CECT 7765 seemed to be related to an improvement in glucocorticoid sensitivity in mesenteric lymph node immunocompetent cells at P21. The administration of B. pseudocatenulatum CECT 7765 to MS animals also reversed intestinal dysbiosis affecting the proportions of ten Operational Taxonomic Units (OTUs) at P21, which could partly explain the restoration of immune, neuroendocrine and behavioral alterations caused by stress in early and later life. In summary, we show that B. pseudocatenulatum CECT 7765 is able to beneficially modulate the consequences of chronic stress on the HPA response produced by MS during infancy with long-lasting effects in adulthood, via modulation of the intestinal neurotransmitter and cytokine network with short and long-term consequences in brain biochemistry and behavior.

Microbiota and host determinants of behavioural phenotype in maternally separated mice.

Early-life stress is a determinant of vulnerability to a variety of disorders that include dysfunction of the brain and gut. Here we exploit a model of early-life stress, maternal separation (MS) in mice, to investigate the role of the intestinal microbiota in the development of impaired gut function and altered behaviour later in life. Using germ-free and specific pathogen-free mice, we demonstrate that MS alters the hypothalamic-pituitary-adrenal axis and colonic cholinergic neural regulation in a microbiota-independent fashion. However, microbiota is required for the induction of anxiety-like behaviour and behavioural despair. Colonization of adult germ-free MS and control mice with the same microbiota produces distinct microbial profiles, which are associated with altered behaviour in MS, but not in control mice. These results indicate that MS-induced changes in host physiology lead to intestinal dysbiosis, which is a critical determinant of the abnormal behaviour that characterizes this model of early-life stress.

Aspectos de la información preoperatoria relacionada con la ansiedad del paciente programado para cirugía / Preoperative aspects of information related to patient anxiety scheduled for surgery

Introducción: La ansiedad preoperatoria es un evento frecuente que depende de múltiples factores. Uno de ellos es la información previa que recibe el paciente, que debe de ser sencilla, inteligible y fidedigna. El objetivo de este estudio es establecer la relación entre el grado de información del procedimiento quirúrgico y el nivel de ansiedad preoperatoria en los pacientes programados para cirugía. Material y métodos: Estudio descriptivo transversal de 99 pacientes seleccionados aleatoriamente, programados para intervención quirúrgica en el Hospital Royo Villanova, del sector I de Zaragoza. Se valoró el nivel de ansiedad preoperatoria y el grado de información previa mediante la escala APAIS y se utilizó la escala STAI-AE en algunos de los pacientes, para comprobar la veracidad de la escala APAIS. El análisis estadístico se realizó mediante el programa SPSS v.21.0, aplicando la prueba de Chi-cuadrado, el test Anova y la prueba no paramétrica de Kruskal Wallis para estudiar la asociación entre las distintas preguntas y el grado de ansiedad. Para valorar la asociación de las dos escalas se empleó el test de Correlación de Pearson. Resultados: Las variables de: nivel educativo, tipo de cirugía, especialidad e intervención quirúrgica previa, no muestran una significación estadística (p<0,05) respecto a la variable de nivel de ansiedad. Se ha evidenciado que existe asociación entre el grado de información y el nivel de ansiedad. Conclusiones: Los datos que muestra el presente estudio refuerzan la hipótesis de que los pacientes que creen necesitar más conocimientos sobre el procedimiento quirúrgico presentan niveles de ansiedad mayores que los pacientes que creen necesitar menos (AU)

Background: Preoperative anxiety is a frequent event that depends on multiple factors. One is the prior information to the patient, which must be simple, understandable and reliable. The aim of this study is to establish the relationship between the degree of information of the surgical procedure and the level of preoperative anxiety in patients scheduled for surgery. Material and methods: Cross-sectional study of 99 randomly selected patients scheduled for surgery at the Hospital Royo Villanova (sector I at Zaragoza). APAIS and STAI-AE scales were used to assess the preoperative anxiety level and the degree of prior information. The statistical analysis was performed using SPSS v.21.0, with the Chi-square test, ANOVA test and the nonparametric Kruskal Wallis to study the association between the different questions and the degree of anxiety. To assess the association of the two scales Pearson correlation test was used. Results: The educational level, type of surgery, previous surgery, specialty and previous surgery variables do not show statistical significance (p <0.05) compared to the anxiety level variable. It has been shown that there is an association between the degree of information and level of anxiety. Conclusions: The data shown in the present study support the hypothesis that patients who believe they need more knowledge about the surgical procedure have higher anxiety levels than patients who believe they need less (AU)

The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease.

OBJECTIVE: Intestinal dysbiosis has been associated with coeliac disease (CD), but whether the alterations are cause or consequence of the disease is unknown. This study investigated whether the human leukocyte antigen (HLA)-DQ2 genotype is an independent factor influencing the early gut microbiota composition of healthy infants at family risk of CD. DESIGN: As part of a larger prospective study, a subset (n=22) of exclusively breastfed and vaginally delivered infants with either high genetic risk (HLA-DQ2 carriers) or low genetic risk (non-HLA-DQ2/8 carriers) of developing CD were selected from a cohort of healthy infants with at least one first-degree relative with CD. Infant faecal microbiota was analysed by 16S rRNA gene pyrosequencing and real time quantitative PCR. RESULTS: Infants with a high genetic risk had significantly higher proportions of Firmicutes and Proteobacteria and lower proportions of Actinobacteria compared with low-risk infants. At genus level, high-risk infants had significantly less Bifidobacterium and unclassified Bifidobacteriaceae proportions and more Corynebacterium, Gemella, Clostridium sensu stricto, unclassified Clostridiaceae, unclassified Enterobacteriaceae and Raoultella proportions. Quantitative real time PCR also revealed lower numbers of Bifidobacterium species in infants with high genetic risk than in those with low genetic risk. In high-risk infants negative correlations were identified between Bifidobacterium species and several genera of Proteobacteria (Escherichia/Shigella) and Firmicutes (Clostridium). CONCLUSIONS: The genotype of infants at family risk of developing CD, carrying the HLA-DQ2 haplotypes, influences the early gut microbiota composition. This finding suggests that a specific disease-biased host genotype may also select for the first gut colonisers and could contribute to determining disease risk.

Impaired responses to gliadin and gut microbes of immune cells from mice with altered stress-related behavior and premature immune senescence.

Stress is associated with impaired communication between the nervous and immune systems leading to immunosenescence and increased disease risk. We investigated whether leukocytes from mice with altered stress-related behavior and premature immunosenescence, as well as from chronologically aged mice differently responded ex vivo to celiac disease (CD) triggers (gliadin) and intestinal bacteria by ELISA and flow cytometry and differed in microbiota composition. We found that altered stress-related behavior and premature immunosenescence led to alterations in T lymphocytes and cytokine release of immune cells basally and in response to peptic fragments of gliadin and commensal and pathogenic bacteria, possibly increasing susceptibility to CD in adulthood.

Hepatic molecular responses to Bifidobacterium pseudocatenulatum CECT 7765 in a mouse model of diet-induced obesity.

BACKGROUND AND AIMS: Bifidobacterium pseudocatenulatum CECT 7765 moderates body weight gain and metabolic parameters in high-fat diet-(HFD)-fed mice but, the mechanisms of action are not yet understood. To further understand the effects of this bacterial strain, we have investigated the molecular changes in the liver of mice fed a HFD and supplemented with the bacteria. METHODS AND RESULTS: Gene expression and protein levels were measured in the liver of C57BL/6 male mice following sub-chronic consumption of a HFD and B. pseudocatenulatum CECT 7765. Our results show that the consumption of this bacterial strain modulated the expression of key genes involved in the regulation of energy metabolism and transport of lipids that were affected by the HFD.B. pseudocatenulatum CECT 7765 significantly counteracted the effects caused by the HFD on the fatty acid transporter CD36, the transcription regulator of lipid biosynthesis EGR1 and the regulators of glucose metabolism, IGFBP2 and PPP1R3B, both at the mRNA and protein levels. The bacterial strain slightly induced the transcript levels of PNPLA2, a lipase that hydrolyses triglycerides in lipid droplets. In the standard diet (SD)-fed mice, the administration of B. pseudocatenulatum CECT 7765 donwregulated the expression of INSIG1 and HMGCR critically involved in the regulation of cholesterol levels. CONCLUSION: B. pseudocatenulatum CECT 7765 modified the expression of key regulators of fatty acid and cholesterol metabolism and transport, lipid levels and glucose levels in the liver which supports the beneficial metabolic effects of this bacterial strain.

Modulation of phenotypic and functional maturation of dendritic cells by intestinal bacteria and gliadin: relevance for celiac disease.

DC maturation and functions are influenced by microbial and environmental stimuli, which could contribute to immune dysfunction. Here, we have investigated the role of enterobacteria (Escherichia coli CBL2 and Shigella CBD8) isolated from CD patients, bifidobacteria (Bifidobacterium longum CECT 7347 and Bifidobacterium bifidum CECT 7365), and gliadins on phenotypic and functional features of MDDCs and in coculture with Caco-2 cells. The ultimate goal of our study is to understand the roles played by specific components of the gut microbiota in CD. Enterobacteria induced marked alterations in MDDC morphology, inducing podosome dissolution and dendrites, and activated MDDC adhesion and spreading. Enterobacteria also induced inflammatory cytokine production (IFN-γ, TNF-α, and IL-12), partially resembling the gliadin-induced Th1-type cytokine profile. B. longum CECT 7347 and B. bifidum CECT 7365 induced minor MDDC morphological changes and activated adhesion and spreading and inflammatory cytokine production to a lesser extent compared with enterobacteria. B. longum CECT 7347 also induced lower CD86 and CD40 expression on MDDCs than the two enterobacteria. The aforementioned bifidobacterial strain also reduced gliadin-induced IFN-γ production and increased IL-10 secretion when both stimuli were combined. Similar trends were detected for MDDCs cocultured with Caco-2 cells. B. longum CECT 7347 reversed the gliadin-reduced ZO-1 expression in Caco-2 cells. Thus, our results suggest that specific components of the gut microbiota may influence phenotypic and functional maturation of DCs differently and their interactions with epithelial cells. This could ultimately define the role of DCs in CD progression.

Discerning the role of Bacteroides fragilis in celiac disease pathogenesis.

Celiac disease (CD) is associated with intestinal dysbiosis, which can theoretically lead to dysfunctions in host-microbe interactions and contribute to the disease. In the present study, possible differences in Bacteroides spp. and their pathogenic features between CD patients and controls were investigated. Bacteroides clones (n = 274) were isolated, identified, and screened for the presence of the virulence genes (bft and mpII) coding for metalloproteases. The proteolytic activity of selected Bacteroides fragilis strains was evaluated by zymography and, after gastrointestinal digestion of gliadin, by high-pressure liquid chromatography/electrospray ionization/tandem mass spectrometry. The effects of B. fragilis strains on Caco-2 cell culture permeability and inflammatory response to digested gliadin were determined. B. fragilis was more frequently identified in CD patients than in healthy controls, in contrast to Bacteroides ovatus. B. fragilis clones carrying virulence genes coding for metalloproteases were more abundant in CD patients than in controls. B. fragilis strains, representing the isolated clones and carrying metalloprotease genes, showed gelatinase activity and exerted the strongest adverse effects on the integrity of the Caco-2 cell monolayer. All B. fragilis strains also showed gliadin-hydrolyzing activity, and some of them generated immunogenic peptides that preserved or increased inflammatory cytokine production (tumor necrosis factor alpha) and showed increased ability to permeate through Caco-2 cell cultures. These findings suggest that increased abundance of B. fragilis strains with metalloprotease activities could play a role in CD pathogenesis, although further in vivo studies are required to support this hypothesis.

La Autoridad Europea de Seguridad Alimentaria (EFSA) como órgano de asesoramiento científico en seguridad alimentaria y nutrición / The European Food Safety Authority (EFSA) as organ of scientific advice in food safety and nutrition

La Autoridad Europea de Seguridad Alimentaria (EFSA) constituye, actualmente, la pieza clave del análisis de riesgos asociados a la cadena alimentaria en Europa. En este contexto, la EFSA se encarga de proporcionar asesoramiento científico, de forma independiente de los Estados miembros y la Comisión Europea, y de comunicar los riesgos existentes o emergentes. La EFSA cubre todos los aspectos de la seguridad alimentaria, la nutrición humana, la salud y el bienestar animal, así como la salud y la protección de las plantas. Para ello, existen diversos paneles científicos especializados en diversas áreas del conocimiento, una comisión científica y varios directorados. En particular, el Panel de Nutrición, Productos Dietéticos y Alergias(NDA) se ocupa de los temas relacionados con la nutrición, como la evaluación de las solicitudes de alegaciones nutricionales y de propiedades saludables de los alimentos y de nuevos alimentos, el establecimiento de valores de referencia de ingesta, las alergias alimentarias y las fórmulas infantiles. El resultado de la labor de evaluación y asesoramiento de la EFSA se traduce en opiniones científicas y otras publicaciones. El asesoramiento de la EFSA constituye la base de la legislación europea, así como del desarrollo de políticas nutricionales, la identificación de aspectos clave para la salud pública relacionados con la dieta, y el desarrollo de programas de educación para el mantenimiento de una dieta saludable(AU)

The European Food Safety Authority (EFSA) is the cornerstone of the risk assessment related to the food chain in Europe. In this context, EFSA provides scientific advice independently from the Member States and the European Commission and communicate the existing and emerging risks. EFSA covers all aspects related to food and feed safety, human nutrition, animal health and well-being, and plant health and protection. To do so, there are different scientific panels specialized in diverse scientific areas, a scientific commission that coordinate their tasks and several directorates. In particular, the Panel on Nutrition, Dietetic Products and Allergies (NDA) deals with issues related to human nutrition, such as the evaluations of applications of nutritional and health claims made on foods and novel foods, the establishment of population reference intakes, food allergy and infant formula. The results of the scientific assessments are translated into scientific opinions and other documents. EFSA’s advice provides a sound foundation for European legislation and for the development of nutritional policies, setting diet-related public health targets and developing educational programs on healthy diets(AU)

Immunostimulatory effect of faecal Bifidobacterium species of breast-fed and formula-fed infants in a peripheral blood mononuclear cell/Caco-2 co-culture system.

Bifidobacterium spp. typical of the human intestinal microbiota are believed to influence the balance of immune responses in the intestinal mucosa. The aim of the present study was to investigate the effect of different bifidobacterial species and their mixtures in in vitro experiments with peripheral blood mononuclear cells (PBMC) and Caco-2 cells. Bifidobacterium adolescentis, B. angulatum, B. breve, B. catenulatum, B. infantis, B. longum and two combinations of these bifidobacteria simulating the species composition found in faecal samples from breast-fed (BF) and formula-fed (FF) infants were used. The levels of several cytokines were measured by direct stimulation of PBMC and by stimulation of a Caco-2/PBMC co-culture with bifidobacteria. B. catenulatum and B. breve were the strongest enhancers of interferon-γ (IFN-γ) production by direct stimulation of PBMC. B. longum was the highest inducer of IL-10 and the lowest TNF-α stimulus. In the Caco-2/PBMC system, B. breve was the highest inducer of IL-8 production by Caco-2 cells, significantly different from B. infantis, B. adolescentis and the FF mixture (P < 0·05). IFN-γ produced by PBMC stimulated with the BF mixture (containing 22 % B. breve, compared with 7 % in the FF mixture) was significantly higher compared with B. adolescentis, B. infantis and B. longum. B. adolescentis also inhibited IFN-γ production compared with the FF mixture and B. longum. The proportion of different Bifidobacterium strains seems to be an important determinant of the cytokine balance in the simulated intestinal environment studied. B. breve and the combination of the Bifidobacterium species typically found in the microbiota of BF infants have shown the most significant effects.

Dietary glycosaminoglycans interfere in bacterial adhesion and gliadin-induced pro-inflammatory response in intestinal epithelial (Caco-2) cells.

Dietary components may have an important role in maintaining a balanced gut microbiota composition. Celiac disease is an autoimmune enteropathy caused by gliadins, and has been associated with a reduced proportion of Bifidobacterium in gut microbiota. This study evaluates the influence of glycosaminoglycans (GAGs) on bacterial adhesion and their contribution in the gliadins-induced inflammatory response. The adhesion of potential probiotic (Bifidobacterium longum CECT 7347 and Bifidobacterium bifidum CECT 7365), commensal (Escherichia coli and Bacteroides fragilis) and pathogenic (Salmonella enterica CECT 443 and Listeria monocytogenes CECT 935) bacteria to mucin and Caco-2 cell cultures was determined. Gliadins were subjected to in vitro digestion (pepsin/pancreatin-bile), with/out GAGs, and the presence or not of cell suspensions of B. longum (10(8) CFU/ml). B. longum, E. coli, and L. monocytogenes, markedly interact with the high-sulphur-containing fraction of GAGs. The GAGs reduced the gliadins-mediated production of interleukin-1ß, but not tumour necrosis factor-α. The results suggest that GAGs may ameliorate gliadin-induced inflammatory response, though they also slightly interfere with the action of B. longum.

Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women.

Obesity is associated with complications during pregnancy and increased health risks in the newborn. The objective of the present study was to establish possible relationships between gut microbiota, body weight, weight gain and biochemical parameters in pregnant women. Fifty pregnant women were classified according to their BMI in normal-weight (n 34) and overweight (n 16) groups. Gut microbiota composition was analysed by quantitative real-time PCR in faeces and biochemical parameters in plasma at 24 weeks of pregnancy. Reduced numbers of Bifidobacterium and Bacteroides and increased numbers of Staphylococcus, Enterobacteriaceae and Escherichia coli were detected in overweight compared with normal-weight pregnant women. E. coli numbers were higher in women with excessive weight gain than in women with normal weight gain during pregnancy, while Bifidobacterium and Akkermansia muciniphila showed an opposite trend. In the whole population, increased total bacteria and Staphylococcus numbers were related to increased plasma cholesterol levels. Increased Bacteroides numbers were related to increased HDL-cholesterol and folic acid levels, and reduced TAG levels. Increased Bifidobacterium numbers were related to increased folic acid levels. Increased Enterobacteriaceae and E. coli numbers were related to increased ferritin and reduced transferrin, while Bifidobacterium levels showed the opposite trend. Therefore, gut microbiota composition is related to body weight, weight gain and metabolic biomarkers during pregnancy, which might be of relevance to the management of the health of women and infants.

Bifidobacteria inhibit the inflammatory response induced by gliadins in intestinal epithelial cells via modifications of toxic peptide generation during digestion.

Celiac disease (CD) is a chronic enteropathy triggered by intake of gliadin, the toxic component of gluten. This study aims at evaluating the capacity of different Bifidobacterium strains to counteract the inflammatory effects of gliadin-derived peptides in intestinal epithelial (Caco-2) cells. A commercial extract of several gliadin (Gld) types (alpha, beta, gamma, [symbol: see text] ) was subjected to in vitro gastrointestinal digestion (pepsin at pH 3, pancreatin-bile at pH 6), inoculated or not with cell suspensions (10(8) colony forming units/ml) of either B. animalis IATA-A2, B. longum IATA-ES1, or B. bifidum IATA-ES2, in a bicameral system. The generated gliadin-derived peptides were identified by reverse phase-HPLC-ESI-MS/MS. Caco-2 cell cultures were exposed to the different gliadin peptide digestions (0.25 mg protein/ml), and the mRNA expression of nuclear factor kappa-B (NF-kappaB), tumor necrosis factor alpha (TNF-alpha), and chemokine CXCR3 receptor were analyzed by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in stimulated cells. The production of the pro-inflammatory markers NF-kappaB p50, TNF-alpha, and IL-1beta (interleukine 1beta) by Caco-2 cells was also determined by ELISA. The peptides from gliadin digestions inoculated with bifidobacteria did not exhibit the toxic amino acid sequences identified in those noninoculated (alpha/beta-Gld [158-164] and alpha/beta-Gld [122-141]). The RT-PCR analysis evidenced a down-regulation in mRNA expression of pro-inflammatory biomarkers. Consistent with these results the production of NF-kappaB, TNF-alpha, and IL-1beta was reduced (18.2-22.4%, 28.0-64.8%, and abolished, respectively) in cell cultures exposed to gliadin digestions inoculated with bifidobacteria. Therefore, bifidobacteria change the gliadin-derived peptide pattern and, thereby, attenuate their pro-inflammatory effects on Caco-2 cells.

Pivotal Advance: Bifidobacteria and Gram-negative bacteria differentially influence immune responses in the proinflammatory milieu of celiac disease.

CD is a chronic inflammatory disorder of the small intestine that presents in genetically predisposed individuals following gluten consumption. In this study, the effects of Bifidobacterium (Bifidobacterium bifidum IATA-ES2 and Bifidobacterium longum ATCC15707) and Gram-negative bacteria (Bacteroides fragilis DSM2451, Escherichia coli CBL2, and Shigella CBD8 isolated from CD patients), alone and in the presence of CD triggers (gliadins and/or IFN-gamma) on surface marker expression and cytokine production by PBMCs, were determined. These effects were also evaluated in cocultures of PBMCs and Caco-2 cells. The Gram-negative bacteria induced higher secretion of Th1-type proinflammatory cytokines (IL-12 and/or IFN-gamma) than the Bifidobacterium strains. Shigella CBD8 and E. coli CBL2 up-regulated mainly HLA-DR and CD40 expression involved in Th1 activation, and Bifidobacterium strains up-regulated CD83 expression. Specific interactions among the studied bacteria, gliadins, and IFN-gamma, which favored the CD immune features, were also detected. Therefore, intestinal bacteria could be additional factors that regulate the ability of monocytes recruited to the mucosa to respond to gliadins and IFN-gamma in CD patients, influencing the course of the disease.

Interactions of gut microbiota with functional food components and nutraceuticals.

The human gut is populated by an array of bacterial species, which develop important metabolic and immune functions, with a marked effect on the nutritional and health status of the host. Dietary component also play beneficial roles beyond basic nutrition, leading to the development of the functional food concept and nutraceuticals. Prebiotics, polyunsaturated fatty acids (PUFAs) and phytochemicals are the most well characterized dietary bioactive compounds. The beneficial effects of prebiotics mainly relay on their influence on the gut microbiota composition and their ability to generate fermentation products (short-chain fatty acids) with diverse biological roles. PUFAs include the omega-3 and omega-6 fatty acids, whose balance may influence diverse aspects of immunity and metabolism. Moreover, interactions between PUFAs and components of the gut microbiota may also influence their biological roles. Phytochemicals are bioactive non-nutrient plant compounds, which have raised interest because of their potential effects as antioxidants, antiestrogenics, anti-inflammatory, immunomodulatory, and anticarcinogenics. However, the bioavailability and effects of polyphenols greatly depend on their transformation by components of the gut microbiota. Phytochemicals and their metabolic products may also inhibit pathogenic bacteria while stimulate the growth of beneficial bacteria, exerting prebiotic-like effects. Therefore, the intestinal microbiota is both a target for nutritional intervention and a factor influencing the biological activity of other food compounds acquired orally. This review focuses on the reciprocal interactions between the gut microbiota and functional food components, and the consequences of these interactions on human health.

Interplay between human leukocyte antigen genes and the microbial colonization process of the newborn intestine.

Coeliac disease (CD) development involves genetic (HLA-DQ2/DQ8) and environmental factors. Herein, the influence of the HLA-DQ genotype on the gut colonization process of breast-fed children was determined. A cohort of 20 newborns, with at least one first-degree relative with CD, were classified according to their HLA-DQ genotype into high, intermediate and low genetic risk groups, showing 24-28%, 7-8% and less than 1% probability to develop CD, respectively. Faecal microbiota was analysed at 7 days, 1 and 4 months of children's age by fluorescence in situ hybridization. When considering all data, Gram-negative bacteria and Bacteroides-Prevotella group proportions were higher (P<0.05) in the high than in the intermediate and low genetic risk groups. E. coli, Streptococcus-Lactococcus, E. rectale-C. coccoides, sulphate-reducing bacteria, C. lituseburense and C. histolyticum group proportions were also significantly higher (P<0.05) in the high than in the low genetic risk group. Correlations between these bacterial groups and the genetic risk were also detected (P<0.05). In addition, the number and type of CD relative seemed to influence (P<0.050) these bacterial proportions in children at CD risk. At 4 months of age, similar relationships were established between the high genetic risk to develop CD and the proportions of Streptococcus-Lactococcus (P<0.05), E. rectale-C. coccoides (P<0.05), C. lituseburense (P<0.05), C. histolyticum (P<0.05), Bacteroides-Prevotella (P<0.10) groups and total Gram-negative bacteria (P<0.05). The results suggest a relationship between HLA-DQ genes and the gut microbial colonization process that could lead to a change in the way this disorder is investigated.