Atopic dermatitis and gut microbiota

Atopic dermatitis (AD), also known as atopic eczema or eczema, is clinically characterized by dry skin, eczema-like rashes, and severe itching. It is a common chronic and recurrent inflammatory skin disease. Atopy refers to an allergic constitution, so some patients often have accompanying symptoms such as allergic asthma and allergic rhinitis, which significantly affect their quality of daily life. Atopic dermatitis is most prevalent in infancy and can persist into adolescence and even adulthood. With the increase in industrialization worldwide, the incidence of atopic dermatitis is also rising. A 2013 epidemiological survey in China showed that the prevalence of atopic dermatitis among children aged 1-7 years was 12.94%. Scholars such as Davies summarized multiple studies published in 2015, finding that the global prevalence of atopic dermatitis in childhood is 7.89%, and individuals with atopic dermatitis are four times more likely to have allergic rhinitis and asthma compared to the general population.

1. Pathogenesis of Atopic Dermatitis

The etiology of atopic dermatitis is multifactorial, with genetic, environmental, dietary, and emotional factors potentially leading to its onset. The pathogenesis mainly includes two biological pathways: barrier dysfunction and immune response. When the integrity of the skin is compromised, susceptibility to allergens and pathogens increases. Antigens penetrate the skin and activate antigen-presenting cells, inducing CD4+ T cells to differentiate into helper T cells and regulatory T cells, promoting the development of atopic dermatitis. During the acute inflammatory phase, a Th2-type immune response predominates, which gradually shifts to a Th1-type immune response during the chronic phase. Regulatory T cells utilize various molecular mechanisms to inhibit the antigenic action of antigen-presenting cells under inflammatory conditions, maintaining the stability of the immune system. Immune imbalance plays a key role in the inflammatory response of atopic dermatitis, especially the imbalance in Th1/Th2 differentiation leading to abnormal cytokine secretion. The inflammatory response in atopic dermatitis is primarily Th2/Th22-dominant, while Th1 and Th17 immune responses regulate the development and progression of atopic dermatitis.

2. Characteristics of Gut Microbiota in Atopic Dermatitis Patients

Numerous studies have shown that the diversity of gut microbiota is negatively correlated with the onset and progression of atopic dermatitis, with dysbiosis being particularly evident in moderate to severe patients. Compared to healthy individuals, atopic dermatitis patients have an increased proportion of Fusobacterium, Clostridium difficile, Escherichia coli, and Staphylococcus aureus in their gut environment, while the proportion of Bifidobacterium and Bacteroides is reduced. Additionally, patients with severe atopic dermatitis have fewer bacteria producing propionate and butyrate in their intestines, resulting in lower biodiversity. Propionate and butyrate, as short-chain fatty acids (SCFAs), have anti-inflammatory and immune-regulating effects.

3. Pathways of Gut Microbiota Influence

1. Immune Pathway

It is well known that probiotics, prebiotics, and synbiotics influence host immune cell function by altering the composition and distribution of gut microbiota. Through various interactions with antigen-presenting cells such as macrophages, dendritic cells, and epithelial cells, depending on the specific probiotic strains supplemented, they can activate immune signals by producing IL-12, IL-18, and TNF-α, or trigger immune tolerance by producing anti-inflammatory cytokines (e.g., IL-10 and TGF-β). In an environment rich in IL-10 and TGF-β cytokines, dendritic cells and macrophages can promote the increase of induced regulatory T cells. A meta-analysis showed that probiotics can effectively reduce the atopic dermatitis score index in children aged 1-18 years and in Asian children with atopic dermatitis. Lactobacillus, fermented milk bacteria, and probiotic mixtures can lower the atopic dermatitis score index in affected children, while Lactobacillus rhamnosus GG and Lactobacillus plantarum have no effect on the disease course of atopic dermatitis patients.

2. Metabolite Pathway

Gut microbes and their metabolites can alter intestinal mucosal permeability, affecting skin barrier function as they enter the circulatory system. In mouse experiments, phenols produced by gut bacteria were found to accumulate in the skin through circulation, downregulating the expression of keratin 10 and interfering with the differentiation of keratinocytes, thereby affecting epidermal differentiation and skin barrier function. Additionally, clinical trials have shown that individuals lacking sufficient probiotic intake have elevated levels of free p-cresol in their serum and reduced skin hydration capacity. Short-chain fatty acids produced by gut microbes play an important role in the treatment of inflammatory diseases, with propionate promoting the production of macrophages and dendritic cell precursors, enhancing phagocytic capacity, and inhibiting the differentiation of naive T cells into Th2 cells, preventing allergic inflammation. Another clinical trial indicated that after supplementing with the Bifidobacterium strain LKM512, the concentration of kynurenic acid, a metabolite of tryptophan, significantly increased in the feces of atopic dermatitis patients, leading to reduced skin itching and improved quality of life. Kynurenic acid has mucosal protective and immune-regulating effects. Furthermore, the intake of Bifidobacterium LKM512 promotes the increased production of short-chain fatty acids, especially butyrate, in the patients' intestines, inducing the production of Th1 cytokines and promoting the recovery of intestinal mucosal barrier function.

3. Neuroendocrine Regulatory Pathway

Many data indicate that the itching associated with atopic dermatitis is related to genetic, environmental, and psychological factors. In the skin, the nervous and immune systems interact bidirectionally through neuroactive substances (neuropeptides and neurotransmitters) released by skin nerves and immune cells. The gut microbiome can regulate the gut-skin axis through direct and indirect pathways. Studies have found that feeding mice with Lactobacillus significantly alleviates stress-induced hair loss and neurodermatitis, confirming a connection between the gut, skin, and nervous systems. Numerous animal experiments have shown that stress and the activity of the hypothalamic-pituitary-adrenal axis can affect the composition of gut microbiota. For example, mice exposed to chronic psychosocial stress have a higher relative abundance of Bacteroides in their cecum, while the abundance of Clostridium decreases, along with increased levels of interleukin-6 and chemokine CCL2. Moreover, under stress conditions, the adrenal axis regulates cortisol secretion, which can alter the composition of gut microbiota and affect local and systemic immune cells in the gut, as well as change intestinal permeability and barrier function. This also alters the levels of neuroendocrine molecules in circulation, such as tryptamine and serotonin, improving skin barrier function and alleviating skin inflammation.

References:

Pei Yue, Mo Xiumei, Ping Ruiyue, Zeng Jianbo, Zhang Yu, Li Hongyi. Research progress on the correlation between atopic dermatitis and intestinal and skin microbiota. Journal of Chinese Integrative Medicine and Dermatology.

Zhang Jie, Zheng Xiaocao, Cao Xianwei. The correlation between atopic dermatitis and gut microbiome. Journal of Chinese Leprosy and Dermatology.

Che Dandan, Di Zhenghong. Progress in the treatment of atopic dermatitis. Medical Review 1006-2084(2019)18-3634-07.

Note: This article is for informational purposes only and should not be considered medical guidance.