Modulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver by probiotics

The potential for the positive manipulation of the gut microbiome through the introduction of beneficial microbes, as also known as probiotics, is currently an active area of investigation. The FAO/WHO define probiotics as live microorganisms that confer a health benefit to the host when administered in adequate amounts. However, dead bacteria and bacterial molecular components may also exhibit probiotic properties. The results of clinical studies have demonstrated the clinical potential of probiotics in many pathologies, such as allergic diseases, diarrhea, inflammatory bowel disease and viral infection. Several mechanisms have been proposed to explain the beneficial effects of probiotics, most of which involve gene expression regulation in specific tissues, particularly the intestine and liver. Therefore, the modulation of gene expression mediated by probiotics is an important issue that warrants further investigation. In the present paper, we performed a systematic review of the probiotic-mediated modulation of gene expression that is associated with the immune system and inflammation. Between January 1990 to February 2014, PubMed was searched for articles that were published in English using the MeSH terms “probiotics' and 'gene expression' combined with “intestines', 'liver', 'enterocytes', 'antigen-presenting cells', 'dendritic cells', 'immune system', and 'inflammation'. Two hundred and five original articles matching these criteria were initially selected, although only those articles that included specific gene expression results (77) were later considered for this review and separated into three major topics: the regulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver. Particular strains of Bifidobacteria, Lactobacilli, Escherichia coli, Propionibacterium, Bacillus and Saccharomyces influence the gene expression of mucins, Toll-like receptors, caspases, nuclear factor-κB, and interleukins and lead mainly to an anti-inflammatory response in cultured enterocytes. In addition, the interaction of commensal bacteria and probiotics with the surface of antigen-presenting cells in vitro results in the downregulation of pro-inflammatory genes that are linked to inflammatory signaling pathways, whereas other anti-inflammatory genes are upregulated. The effects of probiotics have been extensively investigated in animal models ranging from fish to mice, rats and piglets. These bacteria induce a tolerogenic and hyporesponsive immune response in which many genes that are related to the immune system, in particular those genes expressing anti-inflammatory cytokines, are upregulated. By contrast, information related to gene expression in human intestinal cells mediated by the action of probiotics is scarce. There is a need for further clinical studies that evaluate the mechanism of action of probiotics both in healthy humans and in patients with chronic diseases. These types of clinical studies are necessary for addressing the influence of these microorganisms in gene expression for different pathways, particularly those that are associated with the immune response, and to better understand the role that probiotics might have in the prevention and treatment of disease.

The effects of a 20-week exercise program on blood-circulating biomarkers related to brain health in overweight or obese children:The ActiveBrains project

Background:Emerging research supports the idea that exercise positively affects neurodevelopment.However,the mechanisms linking exercise with brain health are largely unknown.We aimed to investigate the effect of exercise on(a)blood biomarkers selected based on previous evidence(brainderived neurotrophic factor,β-hydroxybutyrate(BHB),cathepsin B(CTSB),kynurenine,fibroblast growth factor 21(FGF21),soluble vascular cell adhesion molecule-1(sVCAM-1));and(b)a panel of 92 neurology-related proteins(discovery analysis).We also investigated whether changes in these biomarkers mediate the effects of exercise on brain health(hippocampal structure and function,cognitive performance,and mental health).Methods:We randomized 81 overweight/obese children(10.1±1.1 years,41%girls)into 2 groups:either 20 weeks of aerobic plus resistance exercise or control.Candidate biomarkers were assessed using enzyme-linked immunosorbent assay(ELISA)for kynurenine,FGF21,and CTSB;colorimetry forβ-hydroxybutyrate;and XMap for brain-derived neurotrophic factor and soluble vascular cell adhesion molecule-1.The92 neurology-related proteins were analyzed by an antibody-based proteomic analysis.Results:Our intervention had no significant effect on candidate biomarkers(all p>0.05).In the discovery analysis,a reduction in circulating macrophage scavenger receptor type-I was observed(standardized differences between groups=-0.3,p=0.001).This effect was validated using ELISA methods(standardized difference=-0.3,p=0.01).None of the biomarkers mediated the effects of exercise on brain health.Conclusions:Our study does not support a chronic effect of exercise on candidate biomarkers.We observed that while chronic exercise reduced the levels of macrophage scavenger receptor type-Ⅰ,it did not mediate the effects of exercise on brain health.Future studies should explore the implications of this novel biomarker for overall health.

Serum levels of the novel adipokine isthmin-1 are associated with obesity in pubertal boys

Objectives To evaluate whether there is an association between the serum levels of the novel insulin-like adipokine isthmin-1(ISM1)and obesity-related phenotypes in a population of Spanish children and to investigate the plausible molecular alterations behind the alteration of the serum levels of this protein in children with obesity.Methods The study population is a sub-cohort of the PUBMEP research project,consisting of a cross-sectional population of 119 pubertal children with overweight(17 boys,19 girls),obesity(20 boys,25 girls),and normal weight(17 boys,21 girls).All subjects were classified into experimental groups according to their sex,obesity,and insulin resistance(IR)status.They were counted anthropometry,glucose and lipid metabolism,inflammation and cardiovascular biomarkers as well as isthmin-1(ISM1)serum levels.This population was intended as a discovery population to elucidate the relationship between obesity and ISM1 levels in children.Furthermore,the study population had blood whole-genome DNA methylation examined,allowing deepening into the obesity–ISM1 molecular relationship.Results Higher serum ISM1 levels were observed in boys with obesity than in normal weight(P=0.004)and overweight(P=0.007)boys.ISM1 serum levels were positively associated with body mass index(BMI)Z-score(P=0.005)and fat mass(P=0.058)and negatively associated with myeloperoxidase(MPO)(P=0.043)in boys.Although we did not find associations between ISM1 serum levels and metabolic outcomes in girls,which may indicate a putative sexual dimorphism,fat mass was positively associated in all children,including boys and girls(P=0.011).DNA methylation levels in two-enhancer-related CpG sites of ISM1(cg03304641 and cg14269097)were associated with serum levels of ISM1 in children.Conclusions ISM1 is associated with obesity in boys at the pubertal stage,elucidating how this protein might be of special relevance as a new biomarker of obesity in children.Further studies including a longitudinal design during puberty are needed.