The impact of probiotic supplementation during pregnancy on DNA methylation of obesity-related genes in mothers and their children.

PURPOSE: Dietary supplementation with probiotics during pregnancy has been suggested to decrease the risk for obesity in women after delivery and to minimize excessive weight gain in their children. Epigenetic DNA methylation has been proposed to impact on gene activity, thereby providing a plausible molecular mechanism for a broad range of biological processes and diseases. This pilot study aimed to evaluate whether probiotic supplementation during pregnancy could modify the DNA methylation status of the promoters of obesity and weight gain-related genes in mothers and their children. METHODS: A sample of 15 pregnant women was taken from a prospective, randomized mother and infant nutrition and probiotic study. Seven women received the probiotic supplementation and eight served as controls. The women's and their children's DNA methylation status of obesity (623 genes) and weight gain-related (433) gene promoters were analyzed from blood samples at the mean of 9.8 months (range 6.1-12.7 months) postpartum. RESULTS: Probiotic supplementation led to significantly decreased levels of DNA methylation in 37 gene promoters and increased levels of DNA methylation in one gene promoter in women. In their children, 68 gene promoters were significantly affected consistently with a lower level of DNA methylation in the probiotic group. CONCLUSIONS: On the basis of our pilot study, we suggest that probiotic supplementation during pregnancy may affect the DNA methylation status of certain promoters of obesity and weight gain-related genes both in mothers and their children, thereby providing a potential mechanism for long-lasting health effects.

The impact of dietary counselling during pregnancy on vitamin intake and status of women and their children.

We aimed here to assess the impact of dietary counselling during pregnancy on dietary intake of vitamins and the vitamin status of women and their children. At the first trimester of pregnancy, 89 women from allergic families were randomized to a control group (n = 45) or to receive individual dietary counselling (n = 44). Women's vitamin intakes and serum concentrations were analyzed during and after pregnancy. Further, vitamin concentrations were measured from breast milk and infant serum at one month of age. The study is registered as clinical study (NCT00167000; section 3, http://www.clinicaltrials.gov ). Dietary counselling resulted in a higher intake of beta-carotene and vitamin E compared to controls. Further, in women lower serum beta-carotene and higher colostrum vitamin A concentrations were found in the intervention group compared to controls. Dietary counselling during pregnancy improves women's vitamin intakes but does not provide unambiguous effects on vitamin status of women or children.

Weight status and dietary intake determine serum leptin concentrations in pregnant and lactating women and their infants.

Leptin regulates energy homeostasis and immune and metabolic functions. Highly elevated leptin concentrations during pregnancy may be associated with aberrations in maternal metabolism and long-term health consequences both in women and children. The objective of the present study was to evaluate whether dietary counselling, probiotic supplementation, maternal characteristics or dietary intake during pregnancy has an impact on serum leptin concentrations in women, cord blood or in children. A total of 256 pregnant women were randomised to a control group (n 85) or to receive dietary counselling with probiotics (n 85) or placebo (n 86). Dietary counselling aimed at affecting the type of fat used and to increase the amount of fibre in the women's diet. Women's dietary intake and serum leptin concentrations were analysed at the first and third trimesters of pregnancy and at 1 month postpartum. Furthermore, leptin concentrations were measured from the cord blood and from children's serum at 1 and 6 months of age. Weight status and dietary composition were the key determinants of leptin concentrations. Specifically, high dietary fibre and low SFA intakes were related to low serum leptin concentrations in women. Female sex and birth weight were associated with higher infant leptin, whereas cord blood leptin was additionally affected by maternal leptin concentration and protein intake. Probiotics or dietary counselling did not affect leptin concentrations. Weight control to recommended levels and modification of diet towards higher fibre and lower SFA intakes during pregnancy may through leptin concentrations provide health benefits to both women and children.

Expression of microbiota, Toll-like receptors, and their regulators in the small intestinal mucosa in celiac disease.

OBJECTIVES: Less than one-tenth of the carriers of the risk genes HLA-DQ2 or HLA-DQ8 develop celiac disease, suggesting that other genetic and environmental factors are important in the pathogenesis. The role of gut microbiota has been addressed previously with inconsistent findings. Our aim was to evaluate microbiota, its receptors (Toll-like receptors [TLRs]), and regulators of the TLRs in the small intestinal mucosa in celiac disease. METHODS: Microbiota was analyzed by quantitative polymerase chain reaction (total bacteria and 10 bacterial group- and species-specific primers) and gene expression of interleukin-8 (IL-8), TLR2, TLR3, TLR4, TLR5, TLR9, and regulators of TLRs, Toll-interacting protein (TOLLIP), and single immunoglobulin IL-1R-related molecule, by relative quantitative reverse transcription-polymerase chain reaction in 10 children with celiac disease (untreated celiacs), 9 children with normal small intestinal mucosa (controls), and 6 adults with celiac disease with normal small intestinal mucosa after following a gluten-free diet (treated celiacs). RESULTS: Small intestinal microbiota was comparable among controls, untreated celiacs, and treated celiacs. Expression of IL-8 mRNA, a marker of intestinal inflammation, was significantly increased in untreated celiacs as compared with treated celiacs (P=0.002) and controls (P=0.001). Expression of TLR-2 mRNA was significantly decreased in untreated (P=0.001) and treated (P=0.03) celiacs, whereas expression of TLR-9 mRNA was increased in untreated celiacs (P=0.001) as compared with controls. Expression of TOLLIP mRNA was downregulated in untreated celiacs as compared with controls (P=0.02). CONCLUSIONS: Altered gene expression of TLR2, TLR9, and TOLLIP in small intestinal biopsies in celiac disease suggests that microbiota-associated factors may be important in the development of the disease.

Dietary sucrose intake is related to serum leptin concentration in overweight pregnant women.

BACKGROUND: Overweight, characterized by low-degree systemic inflammation, predisposes women to impaired glucose metabolism during pregnancy. Adipokine leptin participates in the regulation of energy balance and immune action. AIMS OF THE STUDY: Objective of the study was to evaluate if aberrations in glucose metabolism during pregnancy are related to leptin concentration and whether serum leptin concentration is affected by diet composition. SUBJECTS AND METHODS: Normal-weight (n = 61) and overweight or obese (BMI > 25, n = 42) pregnant women visited study clinic at third trimester of pregnancy and one month postpartum. Serum fasting leptin and insulin as well as plasma glucose concentrations were measured, insulin resistance (HOMA) and sensitivity (QUICKI) calculated, and dietary intake from food records determined. RESULTS: In overweight women leptin concentration was significantly higher both in pregnancy, 45.27 (95% CI 39.40-51.14) ng/ml, and postpartum, 31.84 (27.38-36.30) ng/ml, than in normal-weight women, 31.09 (95% CI 27.80-34.37) ng/ml and 16.23 (13.93-18.53) ng/ml, respectively. Equally, blood glucose concentration during pregnancy was higher, 4.82 (4.67-4.97)mmol/l, and insulin concentration, 15.34 (12.00-18.68) mU/l, more pronounced in overweight compared to normal-weight women, 4.51 (4.42-4.61) mmol/l and 8.28 (7.21-9.36) mU/l, respectively. Significantly higher HOMA and lower QUICKI were also detected in overweight compared to normal-weight women. At third trimester of pregnancy, leptin concentration correlated positively with insulin concentration in normal-weight (r = 0.561, P = 0.002) and overweight women (r = 0.736, P < 0.001), as well as with HOMA (r = 0.568, P = 0.002 and r = 0.731, P < 0.001, respectively) whereas negative association was found with QUICKI in normal-weight (r = -0.484, P = 0.011) and overweight women (r = -0.711, P < 0.001). Importantly, serum leptin concentration was affected by dietary sucrose intake both as quantitatively (r = 0.424, P = 0.009) and relative to energy intake (r = 0.408, P = 0.012) in overweight but not in normal-weight pregnant women. CONCLUSIONS: Overweight-related elevation in serum leptin is associated with impaired regulation of glucose metabolism during pregnancy. The novel finding that dietary sucrose intake is related to serum leptin concentration is in line with the current dietary recommendations to overweight pregnant women with impaired glucose metabolism advising the lower intake of sucrose during pregnancy.

Aetiology and pathogenesis of reactive arthritis: role of non-antigen-presenting effects of HLA-B27.

Spondyloarthropathies are inflammatory diseases closely associated with human leukocyte antigen (HLA)-B27 by unknown mechanisms. One of these diseases is reactive arthritis (ReA), which is typically triggered by Gram-negative bacteria, which have lipopolysaccharide as an integral component of their outer membrane. Several findings in vivo and in vitro obtained from patients with ReA and from different model systems suggest that HLA-B27 modulates the interaction between ReA-triggering bacteria and immune cells by a mechanism unrelated to the antigen presentation function of HLA-B27. In this review we piece together a jigsaw puzzle from the new information obtained from the non-antigen-presenting effects of HLA-B27.