Impact of the combination of diet with environment exposures on an eczema mouse model

Background: The dietary habits and environmental factors have been proved to contribute to the progression of eczema. The objective of the study is to investigate the impact and mechanism of the combined stimulation of diet and environmental exposures on the initiation and development of eczema.

Methods: The BALB/c mice were fed with high fat and high sugar diet (HFHSD) and placed in an artificial climate box with a dampness and heat (DH) environment of 35 °C and humidity of 95 % for 8 h every day, and then 1 % and 1.5 % 2, 4-dinitrochlorobenzene (DNCB) solutions were used to sensitize for 3 days and stimulate the dorsal skin of the mice 14 times. A variety of indicators and parameters pertaining to general indications, histopathological assessment of the skin, immune and inflammatory responses, and oxidative stress, etc. were evaluated and analyzed. Finally, 16S rRNA Sequencing was employed to identify the changes of intestinal flora from the cecal contents.

Results: Compared with DNCB alone group, combination with DH, HFHSD and DNCB significantly increased mice body weight and rectal temperature, but decreased food and water intakes, and grip strength. The addition of DH and HFHSD considerably enhanced the clinical scoring of eczema, the number of scratches, the thicknesses of the epidermis and dermis, and the infiltration of mast cells at the site of the dorsal lesion compared to DNCB alone group, indicating that DH + HFHSD worsens the dorsal lesions in the DNCB-induced eczema mice. Meanwhile, the elevation of the spleen index, the increases of Th1/Th2 cells ratio, the decreases of Th17/Treg cells ratio, and the changes of mRNA expression of different T-cell subsets-related cytokines in skin lesions indicated that DH and HFHSD exacerbated the immune imbalance of Th1/Th2 and Th17/Treg in DNCB-induced eczema. Furthermore, the upregulation of inflammatory factors IL-6 and IL-8 expression in the dorsal skin are further increased by the co-stimulation of DH and HFHSD, which were related with the changes of oxidative stress (SOD and MDA). Importantly, gut microbiota was found to be associated with the worsening of eczema by the stimulation of DH + HFHSD. DH plus HFHSD can decrease the relative abundance of Firmicutes and Actinobacteria, which are positively related with Th1/Th2 ratio.

Conclusions: In conclusion, this study established a mouse model of eczema that mimics patients living in DH environments and consuming high-calorie diets, and firstly proved that the mechanism by which co-stimulation of DH and HFHSD exacerbate DNCB-induced eczema involving the imbalance of Th1/Th2 and Th17/Treg cell subtypes, the increase of inflammation factors expression, the exacerbation of oxidative stress and the changes of gut flora composition. This study offers novel treatment strategy for eczema through interfering diet and environment, and provides an appropriate animal model for eczema research.

Balance of Th1/Th2 and Th17/Treg; Dampness and heat environment (DH); Eczema; Gut microbiota; High fat and high sugar diet (HFHSD); Mouse model.