DataSheet1_Modulation of the Gut Microbiota by Sihocheonggan-Tang Shapes the Immune Responses of Atopic Dermatitis.docx

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by complex immune dysregulation and closely related to the gut microbiome. The present study investigated the microbiome-mediated effect of Sihocheonggan-Tang (SHCGT) on AD-like symptoms induced by 2,4-dinitrochlorobenzene (DNCB) in BALB/c mice. DNCB was applied regularly to the ear and dorsal skin of BALB/c mice, and SHCGT was administered orally daily for 2 weeks. The composition of the gut microbiota was analyzed using 16S rRNA sequencing, and the effect of gut microbiome-derived metabolites, specifically short-chain fatty acids (SCFAs), was evaluated in tumor necrosis factor-alpha (TNF-α)- and interferon-gamma (IFN-γ)-treated HaCaT cells. SHCGT alleviated DNCB-induced symptoms of AD and the immune response to AD by decreasing the plasma immunoglobulin E level and splenic interleukin-4, interleukin-10, TNF-α, and IFN-γ levels. The gut microbiome composition and the damaged gut epithelial barrier in mice with AD were also significantly altered by SHCGT, and the reduced SCFA levels therein were elevated. We found that SFCAs directly inhibited the mRNA expression of IL-6 and ICAM-1 in TNF-α- and INF-γ-treated HaCaT cells. The finding that SHCGT regulates the gut microbiome and improves DNCB-induced AD in mice suggests that this herbal medicine has therapeutic potential in patients with AD.

特应性皮炎（Atopic Dermatitis, AD）是一种以复杂免疫失调为特征的慢性炎症性皮肤病，且与肠道微生物组密切相关。本研究探讨了Sihocheonggan-Tang（SHCGT）对2,4-二硝基氯苯（2,4-dinitrochlorobenzene, DNCB）诱导的BALB/c小鼠AD样症状的肠道菌群介导作用。研究人员定期将DNCB涂抹于BALB/c小鼠的耳部及背部皮肤，并每日灌胃给予SHCGT，持续2周。采用16S rRNA测序分析肠道菌群组成，并在经肿瘤坏死因子-α（tumor necrosis factor-alpha, TNF-α）和干扰素-γ（interferon-gamma, IFN-γ）处理的HaCaT细胞中，评估了肠道菌群衍生代谢物——尤其是短链脂肪酸（short-chain fatty acids, SCFAs）——的作用效果。SHCGT可通过降低血浆免疫球蛋白E水平以及脾脏中白细胞介素-4、白细胞介素-10、TNF-α及IFN-γ的水平，缓解DNCB诱导的AD症状及AD相关免疫应答。此外，SHCGT还可显著改变AD小鼠的肠道菌群组成与受损的肠道上皮屏障，并提升其体内原本降低的SCFA水平。本研究发现，SCFAs可直接抑制经TNF-α和IFN-γ处理的HaCaT细胞中白细胞介素-6（interleukin-6, IL-6）及细胞间黏附分子-1（intercellular adhesion molecule 1, ICAM-1）的mRNA表达。上述研究结果表明，SHCGT可调控肠道菌群并改善小鼠体内DNCB诱导的AD，提示该草药制剂对AD患者具有治疗潜力。