Impact of the early-life skin microbiota on the development of canine atopic dermatitis in a high-risk breed birth cohort

Abstract

Canine atopic dermatitis (CAD) is a prevalent inflammatory skin disease of dogs worldwide. Certain breeds such as the West Highland White Terriers (WHWT) are predisposed to suffer from CAD. Microbial dysbiosis is known to play a significant role in the pathogenesis of the disease, which is similar to its human counterpart, atopic dermatitis (AD). To date, no large cohort-study has been conducted in a predisposed dog breed to study the impact of the early-life microbiota on the development of CAD, as well as the possible implication of factors such as hygiene and access to the outdoors. in this study skin samples of 143 WHWT, including 109 puppies up to three weeks old and 34 parent dogs, from 17 breeders, were subjected to 16S rRNA gene and ITS2 amplicon sequencing to disclose the bacterial and fungal oral and skin microbiota, respectively. The oral samples served as a control group to confirm differences between haired and mucosal surfaces. The cutaneous microbiota differed between sample sites and age of the dogs. The season of sampling, geographical origin as well as hygiene status of the household and the access to the outdoors shaped the skin microbiota of the puppies significantly. However, we found that the individual early-life microbiota did not predispose for the later development of CAD. Among the inflammatory skin diseases occurring in dogs, canine atopic dermatitis (CAD) is prevalent with up to 10% of dogs affected worldwide 1,2. CAD is a genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features associated with IgE antibodies most commonly directed against environmental allergens 3. Across species, similarities in the clinical manifestations of atopic dermatitis have been observed and the disease is becoming more common 4. In contrast to humans who may develop respiratory signs, dogs usually remain in the cutaneous stage of the disease 5. Nevertheless, CAD is frequently discussed as a model for human atopic dermatitis (AD). AD has a strong genetic component 6 , but its occurrence seems to be increasing in recent years due to environmental factors 2. Among the discussions about protective and risk factors, the hygiene hypothesis 7 has been prominent for many years. It speculates that early microbial exposure reduces the risk for developing allergies and, consequently, the improvement of hygiene may explain a rise in allergic diseases. This hypothesis has been

Atopic dermatitis in West Highland white terriers – Part III: early life peripheral blood regulatory T cells are reduced in atopic dermatitis

“…on the skin 46 . The most abundant genera of the early‐life skin microbiome described in our previous study 32 were not associated with the Treg cell levels in either healthy or allergic dogs except for a significant positive correlation between the relative abundance of Lachnospiraceae on the skin and the percentage of CD4 + CD25 + Foxp3 + Treg cells from allergic dogs. Genera belonging to Lachnospiraceae have been positively associated with egg allergy in children 47 .…”

“…canis ‐specific IgG levels above the cut‐off level of the test, which was determined in a previous study 21 . In our previous study in the same birth cohort, we determined Streptococcus , Lachnospiraceae family unclassified genus and Acinetobacter as the most abundant bacterial genera of the early‐life skin microbiome 32 . The Spearman’s rank correlation coefficient indicated that there was a moderate, yet significantly positive association between the relative abundance of Lachnospiraceae and the percentage of CD4 + CD25 + Foxp3 + cells in puppies that became allergic ( r = 0.568, P = 0.017) (Figure 3), and not in nonallergic puppies (Table 1).…”

“…Skin microbiota samples of 3‐month‐old puppies were obtained and processed as described previously 32 . The samples were subjected to 16S rRNA gene amplicon sequencing to disclose the bacterial skin microbiota and bioinformatic analysis was performed as described previously 32 …”

“…We prospectively studied a subgroup of dogs participating in a birth cohort, aiming at investigating the natural history of AD and the influencing early-life factors, as described in detail elsewhere. 31,32 Briefly, within 18 months from June 2014, 107 WHWT puppies from 29 litters and 17 breeders were recruited. All breeders, and subsequently the new owners, signed a written informed consent before participating in the study, which was approved by the the Committee on Animal Experimentation [Kantonale Tierversuchskommission (r-KTVK)] of the Canton of Zurich Department of Health ZH199/201/4, no.…”

A case of canine blepharoconjunctivitis associated with atopic dermatitis

“…Canine atopic dermatitis is a common inflammatory skin disorder in genetically exposed dogs associated with IgE antibodies to allergens [5,6]. Pruritus is most common clinical signs of atopic dermatitis and has the characteristics of relapse [7][8][9].…”