Perinatal exposure to titanium dioxide (TiO
), as a foodborne particle, may influence the intestinal barrier function and the susceptibility to develop inflammatory bowel disease (IBD) later in life. ...Here, we investigate the impact of perinatal foodborne TiO
exposure on the intestinal mucosal function and the susceptibility to develop IBD-associated colitis. Pregnant and lactating mother mice were exposed to TiO
until pups weaning and the gut microbiota and intestinal barrier function of their offspring was assessed at day 30 post-birth (weaning) and at adult age (50 days). Epigenetic marks was studied by DNA methylation profile measuring the level of 5-methyl-2'-deoxycytosine (5-Me-dC) in DNA from colic epithelial cells. The susceptibility to develop IBD has been monitored using dextran-sulfate sodium (DSS)-induced colitis model. Germ-free mice were used to define whether microbial transfer influence the mucosal homeostasis and subsequent exacerbation of DSS-induced colitis.
In pregnant and lactating mice, foodborne TiO
was able to translocate across the host barriers including gut, placenta and mammary gland to reach embryos and pups, respectively. This passage modified the chemical element composition of foetus, and spleen and liver of mothers and their offspring. We showed that perinatal exposure to TiO
early in life alters the gut microbiota composition, increases the intestinal epithelial permeability and enhances the colonic cytokines and myosin light chain kinase expression. Moreover, perinatal exposure to TiO
also modifies the abilities of intestinal stem cells to survive, grow and generate a functional epithelium. Maternal TiO
exposure increases the susceptibility of offspring mice to develop severe DSS-induced colitis later in life. Finally, transfer of TiO
-induced microbiota dysbiosis to pregnant germ-free mice affects the homeostasis of the intestinal mucosal barrier early in life and confers an increased susceptibility to develop colitis in adult offspring.
Our findings indicate that foodborne TiO
consumption during the perinatal period has negative long-lasting consequences on the development of the intestinal mucosal barrier toward higher colitis susceptibility. This demonstrates to which extent environmental factors influence the microbial-host interplay and impact the long-term mucosal homeostasis.
The association between alcoholism and the Taq1 “A” and “B” polymorphic alleles at the DRD2 gene and 48‐bp tandem repeat in exon 3 of dopamine D4 receptor (DRD4) gene in 42 unrelated Slavic‐surnamed ...patients and 76 normal controls was examined. The frequency of the A1 allele was higher in alcoholic patients and in alcoholic patients with a family history of alcoholism than in controls (χ2= 3.45, p < 0.001 and χ2= 3.97, p < 0.001, respectively). Moreover, the frequency of the A1 allele was higher in alcoholics with a family history of alcoholism than in alcoholics without a family history (χ2= 3.33, p < 0.001).The results of association analysis for both the Taq1 “B” and DRD4 alleles were negative for alcoholics in general, subgroups of alcoholics and normal controls. However, the 7‐repeat allele (DRD4*7R) of DRD4 gene occurred at significantly higher frequency in alcoholics with a family history of alcoholism compared with those without a family history (χ2= 3.42, p < 0.01).The results indicate that the A1 allele of the DRD2 gene is associated with susceptibility to alcoholism in general.The A1 allele, as well as the DRD4*7R allele, is significantly prevalent among alcoholics with a family history, in comparison with alcoholics without a family history, reflecting different roles of genetic factors in development of alcoholism.
