Intestinal epithelial dopamine receptor signaling drives sex-specific disease exacerbation in a mouse model of multiple sclerosis.

Although the gut microbiota can influence central nervous system (CNS) autoimmune diseases, the contribution of the intestinal epithelium to CNS autoimmunity is less clear. Here, we showed that intestinal epithelial dopamine D2 receptors (IEC DRD2) promoted sex-specific disease progression in an animal model of multiple sclerosis. Female mice lacking Drd2 selectively in intestinal epithelial cells showed a blunted inflammatory response in the CNS and reduced disease progression. In contrast, overexpression or activation of IEC DRD2 by phenylethylamine administration exacerbated disease severity. This was accompanied by altered lysozyme expression and gut microbiota composition, including reduced abundance of Lactobacillus species. Furthermore, treatment with N2-acetyl-L-lysine, a metabolite derived from Lactobacillus, suppressed microglial activation and neurodegeneration. Taken together, our study indicates that IEC DRD2 hyperactivity impacts gut microbial abundances and increases susceptibility to CNS autoimmune diseases in a female-biased manner, opening up future avenues for sex-specific interventions of CNS autoimmune diseases.

Characteristics of polycyclic aromatic hydrocarbons in PM2.5 emitted from different cooking activities in China.

Nineteen polycyclic aromatic hydrocarbons (PAHs) in PM2.5 emitted from five different cooking activities were characterized, and their influencing factors were determined. The total quantified particle-bounded PAH concentrations (ΣPAHs) in the airs from the cooking activities were 4.2-36.5-fold higher than those in corresponding backgrounds. The highest ΣPAHs were seen in cafeteria frying (783 ± 499 ng/m3), followed by meat roasting (420 ± 191 ng/m3), fish roasting (210 ± 105 ng/m3), snack-street boiling (202 ± 230 ng/m3), and cafeteria boiling (150 ± 65 ng/m3). The main influencing factors on the PAH emissions were cooking methods, fat contents in raw materials, and oil consumptions. Four- to six-ringed PAHs had the highest contributions to the ΣPAHs (avg. 87.5%). Diagnostic ratios of individual PAH were similar between the two charbroiling and other three conventional Chinese cooking methods, respectively, demonstrating the dominance of cooking methods in the PAH emissions. Remarkably high benzo(b)fluoranthene/benzo(k)fluoranthene (BbF/BkF) ratio (8.31) was seen in the snack-street boiling, attributed to the coal combustion as cooking fuel. Both fluoranthene/(fluoranthene + pyrene) [FLT/(FLT + PYR)] and benzo(a)anthracene/(benzo(a)anthracene + chrysene) [BaA/(BaA + CHR)] ratios were higher for the oil-based cooking than those from the water-based ones. In addition, two ratios of indeno(1,2,3-cd)pyrene/(indeno(1,2,3-cd)pyrene + benzo(g,h,i)perylene) [IPY/(IPY + BPE)] and benzo(a)pyrene/(benzo(a)pyrene + benzo(g,h,i)perylene) [BaP/(BaP + BPE)] were higher for two charbroiling than the three conventional Chinese cooking methods. The characterization work in this study is particularly important since cooking is a potential contributor of atmospheric PAHs in urban China. Carcinogenic potencies of PAHs were assessed by comparison with the air quality guideline and health risk estimation. The BaP and BaP equivalent were higher for the oil-based than the water-based cooking activities.