Disordered development of gut microbiome interferes with the establishment of the gut ecosystem during early childhood with atopic dermatitis

Abstract

The gut microbiome influences the development of allergic diseases during early childhood. However, there is a lack of comprehensive understanding of microbiome-host crosstalk. Here, we analyzed the influence of gut microbiome dynamics in early childhood on atopic dermatitis (AD) and the potential interactions between host and microbiome that control this homeostasis. We analyzed the gut microbiome in 346 fecal samples (6–36 months; 112 non-AD, 110 mild AD, and 124 moderate to severe AD) from the Longitudinal Cohort for Childhood Origin of Asthma and Allergic Disease birth cohort. The microbiome-host interactions were analyzed in animal and in vitro cell assays. Although the gut microbiome maturated with age in both AD and non-AD groups, its development was disordered in the AD group. Disordered colonization of short-chain fatty acids (SCFA) producers along with age led to abnormal SCFA production and increased IgE levels. A butyrate deficiency and downregulation of GPR109A and PPAR-γ genes were detected in AD-induced mice. Insufficient butyrate decreases the oxygen consumption rate of host cells, which can release oxygen to the gut and perturb the gut microbiome. The disordered gut microbiome development could aggravate balanced microbiome-host interactions, including immune responses during early childhood with AD.

Bacterial Metabolites: A Link between Gut Microbiota and Dermatological Diseases

“…Interestingly, there is ample evidence that AD is characterized by gut dysbiosis, especially the depletion of butyrate-producing bacteria [ 35 , 36 , 37 , 38 ]. The reduction in butyrate-producing Bacteroides fragilis has been found to correlate with increased total IgE, egg-IgE, and milk-IgE [ 38 ]. Moreover, the microbiota in AD produce fewer SCFAs, particularly propionate and butyrate, which have been assessed in fecal samples [ 38 , 39 ].…”

“…The reduction in butyrate-producing Bacteroides fragilis has been found to correlate with increased total IgE, egg-IgE, and milk-IgE [ 38 ]. Moreover, the microbiota in AD produce fewer SCFAs, particularly propionate and butyrate, which have been assessed in fecal samples [ 38 , 39 ]. Reduced exposure to SCFAs early in life may be one of the factors responsible for the development and course of the disease, which seems to confirm the work of Roduit et al They found that in a one-year-old pediatric population, a lower fecal level of propionate and butyrate was associated with a markedly higher prevalence of atopic diseases diagnosed at the age of 6 [ 40 ].…”

Obesity and the microbiome in atopic dermatitis: Therapeutic implications for PPAR-γ agonists

“…The gut microbiome has been compared between infants with and without AD. Facultative anaerobes predominate during the first 6–12 months of life prior to colonization with obligate anaerobes ( 44 ). Notably, the anaerobe Akkermansia muciniphila was only detected in healthy infants and their mothers, suggesting it may correlate with protection against AD ( 45 ).…”

“…Notably, the anaerobe Akkermansia muciniphila was only detected in healthy infants and their mothers, suggesting it may correlate with protection against AD ( 45 ). Breast feeding may account for some of the microbiota differences between AD and non-AD infants ( 44 ). In the second year of life, moderate to severe AD was associated with a higher abundance of facultative anaerobes compared to healthy controls.…”

Lactobacillus for the treatment and prevention of atopic dermatitis: Clinical and experimental evidence

“…In addition, healthy gut flora has a protective effect against food allergies ( Méndez et al., 2021 ). Disturbances of the intestinal microbiome in early infancy worsen immune dysfunction in children with AD ( Lee et al., 2022 ). In addition, a study showed that transplanting fecal microbiota to restore gut ecology provides a new method for treating AD ( Kim et al., 2021 ).…”