Modulation of the Gut Microbiota by Sihocheonggan-Tang Shapes the Immune Responses of Atopic Dermatitis

Abstract

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.

Neuroprotection of cannabidiol in epileptic rats: Gut microbiome and metabolome sequencing

“…Hence, we hypothesized that CBD might be involved in regulating the metabolic function of the gut microbiota of epileptic rats. Furthermore, the composition of the gut microbiome and the levels of IL-10, IL-4, and TNF-α were altered in mice after drug intervention, and regulation of SCFAs, microbial metabolites, could affect the expression of IL-6 ( 49 ). Combined with the above analysis, we could speculate that the gut microbiome is involved in the process of CBD alleviating epilepsy, which might be mediated by microbial metabolites regulating inflammatory factors.…”

The role of short-chain fatty acids in inflammatory skin diseases

“…Consistent with the above findings, mice exhibiting AD-like symptoms induced with transdermal injection of 2,4-dinitrochlorobenzene have lower SCFA levels compared to the healthy littermates. Furthermore, the symptoms of AD in these mice are relieved after treatment, and the SCFA levels are normalized ( Chun et al, 2021 ). These findings underscore the role of the SCFAs as signaling molecules of the gut-skin axis.…”

“…These inflammatory keratinocytes involve in the pathophysiology of AD. SFCAs markedly reduce IL-6 and ICAM-1 mRNA levels in human keratinocytes (HaCaT cells) stimulated with TNF-α and INF-γ in vitro ( Chun et al, 2021 ) ( Figure 1 ). In addition, butyrate also inhibits the inflammatory phenotype of cultured human keratinocytes by inducing acetylation of histone H3 lysine 9 (AcH3K9) ( Meijer et al, 2010 ; Traisaeng et al, 2019 ).…”

“…Recent studies have shown that the gut microbiome is an important factor influencing host immunity, inflammation and metabolism ( Yao et al, 2022 ). The gut-skin axis is a fairly recent concept that refers to the bidirectional relationship between the gut microbiome and skin, and an increasing body of evidence suggests that changes in the gut microbiome is related with skin inflammation ( Kim et al, 2020 ; Chun et al, 2021 ). The gut and the skin are both highly innervated and vascularized organs, and harbor numerous resident microorganisms with similar functions ( O’Neill et al, 2016 ).…”

Tremella fuciformis polysaccharides alleviate induced atopic dermatitis in mice by regulating immune response and gut microbiota

“…Gut microbes may play a role in the development of AD by regulating the immune system through interactions between the microbes and the host, and in particular, alterations in the gut microbiota affect immune system homeostasis by altering the production of metabolites. Several studies have demonstrated that the development of AD can be prevented by modulating the intestinal flora and metabolites ( Fang et al, 2020 ; Kim et al, 2020 ; Chun et al, 2021 ).…”