Esther Nova

Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios

Genetic variability in the FADS1-FADS2 gene cluster [encoding delta-5 (D5D) and delta-6 (D6D) desaturases] has been associated with plasma long-chain PUFA (LCPUFA) and lipid levels in adults. To better understand these relationships, we further characterized the association between FADS1-FADS2 genetic variability and D5D and D6D activities in adolescents. Thirteen single nucleotide polymorphisms (SNPs) were genotyped in 1,144 European adolescents (mean ± SD age: 14.7 ± 1.4 y). Serum phospholipid fatty acid levels were analyzed using gas chromatography. D5D and D6D activities were estimated from the C20:4n-6/C20:3n-6 and C20:3n-6/C18:2n-6 ratios, respectively. Minor alleles of nine SNPs were associated with higher 18:2n-6 levels (1.9E-18 ≤ P ≤ 6.1E-5), lower C20:4n-6 levels (7.1E-69 ≤ P ≤ 1.2E-12), and lower D5D activity (7.2E-44 ≤ P ≤ 4.4E-5). All haplotypes carrying the rs174546 minor allele were associated with lower D5D activity, suggesting that this SNP is in linkage disequilibrium with a functional SNP within FADS1. In contrast, only the rs968567 minor allele was associated with higher D6D activity (P = 1.5E-6). This finding agrees with an earlier in vitro study showing that the minor allele of rs968567 is associated with a higher FADS2 promoter activity. These results suggest that rare alleles of several SNPs in the FADS gene cluster are associated with higher D6D activity and lower D5D activity in European adolescents.

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.

Moderate alcohol consumption and the immune system: A review

Increasing evidence suggests that light to moderate amounts of polyphenol-rich alcoholic beverages like wine or beer could have health benefits. Scientists have long debated the effects of alcohol on immune function, showing on the one hand, that high doses of alcohol consumption can directly suppress a wide range of immune responses, and that alcohol abuse is associated with an increased incidence of a number of infectious diseases. On the other hand, moderate alcohol consumption seems to have a beneficial impact on the immune system compared to alcohol abuse or abstinence. Therefore, the link between alcohol consumption, immune response, as well as infectious and inflammatory processes remains not completely understood. With this in mind, it is important to realise that other factors, unrelated or indirectly related to immune function, like drinking patterns, beverage type, amount of alcohol, or gender differences, will affect the influence that alcohol consumption may have on the immune system. This review summarises published data describing the effects that light to moderate amounts of polyphenol-rich beverages like wine or beer seem to have on immunity in healthy adults.

The adaptive response of the immune system to the particular malnutrition of eating disorders

Despite the seriously undernourished state of patients with anorexia nervosa (AN) and bulimia nervosa (BN), controversial findings have been published regarding some aspects of the immune system that are otherwise impaired in more typical types of malnutrition, such as protein-energy malnutrition. In general, adaptation processes seem to occur enabling immune function to be preserved during long periods of the illness. However, cell-mediated immunity is usually altered in AN and BN as reflected by lymphocyte subset counts and the response to delayed hypersensitivity tests. Regarding the helper/cytotoxic T cell ratio (CD4:CD8), an immunological marker of the nutritional status, the results of our studies on AN and BN patients showed that the duration of the eating disorder and the time when appropriate treatment is achieved are likely contributors to the alteration of this ratio. Despite these findings, it has been repeatedly pointed out that anorexic patients seem to be free of common viral infections at least until the most advanced stages of debilitation. Some hypotheses that could explain the lack of infection symptoms are reviewed. Cytokines and the altered acute phase response to infection, as well as cortisol and leptin, are considered to be potential factors involved in the adaptation processes occurring in these syndromes. Further progress in the knowledge of the psychoneuroendocrine–immune interactions established in AN and BN will be relevant to the understanding of the aetiology and maintenance mechanisms of these pathologies.

Influence of Environmental and Genetic Factors Linked to Celiac Disease Risk on Infant Gut Colonization by Bacteroides Species

ABSTRACT Celiac disease (CD) is an immune-mediated enteropathy involving genetic and environmental factors whose interaction might influence disease risk. The aim of this study was to determine the effects of milk-feeding practices and the HLA-DQ genotype on intestinal colonization of Bacteroides species in infants at risk of CD development. This study included 75 full-term newborns with at least one first-degree relative suffering from CD. Infants were classified according to milk-feeding practice (breast-feeding or formula feeding) and HLA-DQ genotype (high or low genetic risk). Stools were analyzed at 7 days, 1 month, and 4 months by PCR and denaturing gradient gel electrophoresis (DGGE). The Bacteroides species diversity index was higher in formula-fed infants than in breast-fed infants. Breast-fed infants showed a higher prevalence of Bacteroides uniformis at 1 and 4 months of age, while formula-fed infants had a higher prevalence of B. intestinalis at all sampling times, of B. caccae at 7 days and 4 months, and of B. plebeius at 4 months. Infants with high genetic risk showed a higher prevalence of B. vulgatus, while those with low genetic risk showed a higher prevalence of B. ovatus, B. plebeius, and B. uniformis. Among breast-fed infants, the prevalence of B. uniformis was higher in those with low genetic risk than in those with high genetic risk. Among formula-fed infants, the prevalence of B. ovatus and B. plebeius was increased in those with low genetic risk, while the prevalence of B. vulgatus was higher in those with high genetic risk. The results indicate that both the type of milk feeding and the HLA-DQ genotype influence the colonization process of Bacteroides species, and possibly the disease risk.

Immunomodulatory effects of probiotics in different stages of life

The immunomodulatory properties of lactic acid bacteria (LAB) and foods containing them (e.g., fermented milks) is a topic currently under investigation. Individuals could potentially benefit from the inclusion of LAB in the diet at different times during the life cycle. One of the most accepted specific uses of probiotic bacteria is the prevention of atopic eczema in infants with family history of the disease who receive the probiotic bacteria early, through supplementation of the gestating mother and orally after birth. Immune enhancing effects have also been suggested to be beneficial in diarrhoea treatment, especially in children infected with rotavirus and in malnourished patients, infants and adolescents, whose capacity to produce IFN-gamma can be increased after LAB-containing yoghurt intake. Regarding young people and adults, investigations have been conducted exploring the immunomodulation by LAB in subjects under stressful situations, in the prevention of urinary tract infections in fertile women and in the treatment of allergy. However, the beneficial effects of probiotics in these conditions remain controversial and the scientific evidence provided so far is not considered to be conclusive. The elderly population has been the focus of investigations aimed at identifying the capacity of probiotics to counteract the immunosenescence process by increasing phagocytic and natural killer (NK) cell activities and to protect against infection. The mechanisms involved in the different effects attributed to LAB remain to be clarified. Moreover, considering that the immunomodulatory properties are strain-specific, defining the optimal dose of a certain bacteria or combination of bacteria strains and the duration of treatment for a desired effect in a target population group is essential in order to substantiate health claims.

Lifestyle-related determinants of inflammation in adolescence

Inflammatory processes are involved in the pathogenesis of the most common chronic non-communicable diseases and may also play an important initiating role in their development. Only recently have inflammatory markers been included in epidemiological studies focusing on nutritional status, body composition and physical activity. We are just starting to understand how different lifestyles can determine basal levels of inflammatory biomarkers in early ages. This review aims to summarise what is known about the relationships between lifestyle-related determinants (focusing on overweight, physical activity and dietary habits) and inflammatory markers in apparently healthy young populations. Obesity is the most widely studied determinant. Several large-scale studies have now demonstrated that healthy young subjects with more body fat or higher BMI have moderately higher concentrations of inflammatory markers than their leaner peers, supporting the idea that obesity should be considered as a state of chronic low-grade inflammation. Less data is available to allow us to elucidate how physical activity/fitness or dietary patterns may have a direct effect on inflammation in apparently healthy, disease-free young populations.

Immune development and intestinal microbiota in celiac disease

Celiac disease (CD) is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. The etiology of this disorder is complex, involving both environmental and genetic factors. The major genetic risk factor for CD is represented by HLA-DQ genes, which account for approximately 40% of the genetic risk; however, only a small percentage of carriers develop the disease. Gluten is the main environmental factor responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Epidemiological and clinical data suggest that environmental factors other than gluten might play a role in disease development, including early feeding practices (e.g., breast milk versus formula and duration of breastfeeding), infections, and alterations in the intestinal microbiota composition. Herein, we review what is known about the influence of dietary factors, exposure to infectious agents, and intestinal microbiota composition, particularly in early life, on the risk of developing CD, as well as the possible dietary strategies to induce or increase gluten tolerance.

Changes in the Immune System after Moderate Beer Consumption

Background/Aim: Epidemiological studies have suggested that moderate alcohol consumption is associated with lower morbidity. However, intervention studies are needed to elucidate mechanisms involved. This study was aimed to determine the effects of moderate beer consumption on the immune function of healthy adults, taking into account gender differences. Methods: After a 30-day alcohol abstinence period, 57 healthy volunteers consumed a moderate intake of beer (330 ml for women and 660 ml for men) for 30 days. Total leukocyte and lymphocyte counts; absolute values of T-lymphocyte CD3+, CD4+, and CD8+ subsets; delayed-hypersensitivity skin response (DHSR); absolute values of B lymphocytes (CD19+) and serum immunoglobulin concentrations (IgG, IgA, and IgM); and cytokine production (IL-2, IL-4, IL-6, IL-10, IFN-γ, and TNF-α) were evaluated following the abstinence and alcohol consumption periods. Results: After moderate beer consumption CD3+ cells increased only in women (p < 0.05). IgG, IgM, and IgA concentrations, as well as IL-2, IL-4, IL-10, and IFN-γ cytokine production increased while IFN-γ/IL-10 ratio decreased in both men and women (p < 0.05). The rest of the immunological parameters analyzed remained unchanged. Conclusion: Moderate beer consumption produced an immunomodulatory effect in a healthy adult Spanish population; this effect appears to be more relevant in women than in men.

Potential health benefits of moderate alcohol consumption: current perspectives in research

The benefits of moderate amounts of alcohol for a better health and longer life expectancy compared with abstinence have been suggested by the findings of numerous studies. However, controversies have emerged regarding the influence of confounding factors and the systematic errors that might have been inadvertently disregarded in the early studies. This review includes a description of the findings of those research studies published in the last 5 years on the effects of moderate alcohol consumption on all-cause mortality, CVD and inflammation, the immune system, insulin sensitivity, non-alcoholic fatty liver disease (NAFLD) and cancer. Promising evidences exist from both animal studies and human clinical trials regarding intermediate end-points of CHD and insulin sensitivity, such as HDL, adiponectin or fibrinogen. However, controversies and inconsistent findings exist regarding many of these diseases and related functions and biomarkers. Further research and human randomised-controlled trials with adequate standardisation of the study conditions are necessary in order to draw a comparison between studies, establish the causal effect of moderate alcohol intake on disease protection and reach consensus on the circumstances that allow the recommendation of moderate alcohol habitual intakes as a strategy for health maintenance.