Antibiotics-Induced Dysbiosis of Intestinal Microbiota Aggravates Atopic Dermatitis in Mice by Altered Short-Chain Fatty Acids

Abstract

PurposeAlterations in the intestinal microbiota in early life affects the development of atopic dermatitis (AD) in humans. This study aimed to further investigate the effects of gut dysbiosis in early life in an ovalbumin (OVA)-induced mouse model of AD.MethodsThe AD mouse model was developed by serial OVA sensitization and mice were treated with an antibiotic cocktail in their drinking water for 2 weeks before primary sensitization. Probiotics (Lactobacillus rhamnosus, 1 × 109 CFU) or 100 µL of fresh fecal supernatant were orally administered daily from 1 week before the first sensitization until the end of the study.ResultsThe AD mice which received antibiotics had significantly aggravated phenotypes, including clinical score, transepidermal water loss, and histopathology, compared to those treated with healthy feces or probiotics. Total systemic immunoglobulin E production and skin interleukin (IL) 4 levels were significantly increased in the antibiotic-treated mice compared to the other groups. Antibiotic treatment also increased the levels of IL17 and group 3 innate lymphoid cells (ILC3) in the gut and significantly suppressed the production of short-chain fatty acids (SCFAs) and decreased the number FOXP3+ cells.ConclusionsOur results suggest that the status of the gut microbiota in early life in the mouse may play a crucial role in AD development through intestinal SCFA production through regulate the numbers of CD4+IL17+/CD4+FOXP3+ regulatory T cells and ILC3s.

Advances and novel developments in environmental influences on the development of atopic diseases

“…In mice models of atopic dermatitis, antibiotic use was associated with significantly aggravated phenotypes, including clinical score, transepidermal water loss, and histopathology, compared to those treated with healthy feces or probiotics. 91 Timing, dose, and frequency of antibiotics in prenatal and infant populations have also been associated with the development of childhood allergies and asthma. 92,93 Short chain fatty acids (SCFAs) which are fermentation end products of insoluble fibers by intestinal microorganisms have been implicated in the maintenance of epithelial integrity and IgA production.…”

“…Antibiotic usage has been documented to perturb the gut flora of individuals, which places them at an increased risk for the development of allergies and asthma. In mice models of atopic dermatitis, antibiotic use was associated with significantly aggravated phenotypes, including clinical score, transepidermal water loss, and histopathology, compared to those treated with healthy feces or probiotics 91 . Timing, dose, and frequency of antibiotics in prenatal and infant populations have also been associated with the development of childhood allergies and asthma 92,93 .…”

“…Short chain fatty acids (SCFAs) which are fermentation end products of insoluble fibers by intestinal microorganisms have been implicated in the maintenance of epithelial integrity and IgA production 94 . Antibiotics‐induced dysbiosis of intestinal microbiota has been shown to increase severity of atopic dermatitis in mice through alterations in SCFA’s and decreases in the number of Foxp3⁺ T regulatory cells 91 …”

NLR and Intestinal Dysbiosis-Associated Inflammatory Illness: Drivers or Dampers?

“…The intestinal microbiota influences host metabolism ( 16 ), immune system ( 17 , 18 ), gut microbicide mechanisms ( 19 ), and maintains the intestinal barrier ( 20 ). Many studies show that environmental factors, such as the use of antibiotics ( 21 , 22 ), diet ( 23 ) and stress ( 24 ) can alter the intestinal microbiota, increasing pathobiontic bacteria at the expense of commensal bacteria, a process known as dysbiosis ( 25 ). Gut dysbiosis contributes to the development of several autoimmune, inflammatory and metabolic diseases, such as rheumatoid arthritis (RA), inflammatory bowel diseases (IBD), and diabetes mellitus ( 26 , 27 ).…”

Important Role of Immunological Responses to Environmental Exposure in the Development of Allergic Asthma

“…Antibiotic exposure during maternal pregnancy or early life 67 68 69 70 71 and cesarean delivery 57 72 73 can increase the prevalence of asthma in children by affecting the gut microbiota and other mechanisms. Anti-parasitic therapy is also shown to be associated with increased prevalence of asthma.…”