Delayed Gut Colonization Shapes Future Allergic Responses in a Murine Model of Atopic Dermatitis

Abstract

Epidemiological studies have long reported that perturbations of the childhood microbiome increase the risk of developing allergies, but a causal relationship with atopic dermatitis remains unclear. Here we colonized germ-free mice at birth or at one or eight week-of-age to investigate the role of prenatal and early postnatal microbial exposure on development of oxozolone-induced dermatitis later in life. We demonstrate that only one week delayed microbial colonization increased IgE levels and the total histological score of the inflamed ear compared to mice colonized throughout life. In parallel, several pro-inflammatory cytokines and chemokines were upregulated in the ear tissue demonstrating an enhanced immunological response following delayed postnatal colonization of the gut. In contrast, sensitivity to oxazolone-induced dermatitis was unaffected by the presence of a maternal microbiota during gestation. Mice colonized at eight week-of-age failed to colonize Rikenellaceae, a group of bacteria previously associated with a high-responding phenotype, and did not develop an immunological response to the same extent as the early colonized mice despite pronounced histopathological manifestations. The study provides proof-of-principle that the first intestinal colonizers of mice pups are crucial for the development of oxazolone-induced dermatitis later in life, and that the status of the maternal microbiota during pregnancy has no influence on the offspring’s allergic immune response. This highlights an important window of opportunity following birth for microbiota-mediated interventions to prevent atopic responses later in life. How long such a window is open may vary between mice and humans considering species differences in the ontogeny of the immune system.

D-galactose Intake Alleviates Atopic Dermatitis in Mice by Modulating Intestinal Microbiota

“…However, to clarify the function of Alphaproteobacteria and Deltaproteobacteria in the gut microbiota, further studies are needed. At the family level, Arildsen et al ( 38 ) reported that mice that failed to colonize Rikenellaceae were associated with a high-responding phenotype of oxazolone-induced dermatitis. In our results, D-galactose intake increased the abundance of Rikenellaceae in contrast to the PBS intake in DNCB-induced AD model, which is consistent with the previous report.…”

The role of nutrition, food allergies, and gut dysbiosis in immune-mediated inflammatory skin disease: a narrative review

“…Thirty-two studies were eligible and therefore included: 13 narrative reviews [1,3,4 ▪ ,5,6 ▪ ,7 ▪ ,8–10,11 ▪ ,12,13 ▪ ,14 ▪ ], 4 meta-analyses (MA) [15,16 ▪▪ ,17 ▪▪ ,18], 3 randomized controlled trials (RCTs) [19,20 ▪▪ ,21], 2 retrospective case control studies [22,23], 2 retrospective cohort studies [24 ▪▪ ,25], 2 prospective cohort studies [26 ▪▪ ,27 ▪▪ ], 2 animal studies [28,29], 1 prospective cross-sectional study [30 ▪▪ ], 1 systematic review [31], 1 case control study [32 ▪ ], and 1 genome-wide association study (GWAS) [33 ▪▪ ]. The data found that nutrition, microbiome, and gut dysbiosis play a significant role in the development and progression of various inflammatory and immune-related skin conditions, such as psoriasis, AD, HS, and alopecia areata (AA).…”

“…One recent study investigated the role of prenatal and early postnatal microbial exposure on the development of skin allergies later in life using germ-free mice [29]. The results showed that only a one-week delay in microbial colonization after birth increased inflammation and IgE levels in the skin, while the presence of a maternal microbiota during pregnancy had no effect on the offspring's allergic immune response to the skin.…”

Skin microbiota of oxazolone-induced contact hypersensitivity mouse model

“…Studies on colitis models either describe the gut microbiome on a community level or not at all, although one study describes the microbiome on the family level [50][51][52][53]. With OXAinduced atopic dermatitis models, most studies explore the gut microbiome, and one study explores the skin microbiome [13][14][15][16]. In the study examining the skin microbiome of an OXA-induced atopic dermatitis model by [16], OXA treatment resulted in somewhat similar effects on the microbiota.…”

“…Commensal microbes are known to protect from pathogens, and suggested to inhibit allergic sensitisation and inflammatory responses [10,11], whereas unfavourable shifts in the microbiome are associated with certain skin diseases [9,12]. In previous studies with skin models using OXA, most studies describe the OXA-induced changes in gut microbiome [13][14][15], and only one study describes the skin microbiome [16]. Therefore, not much is known about the effect of contact dermatitis on the skin microbiome, or the effect of OXA on microbiome in general.…”