Role of functional food with gut modulatory potential in atopic dermatitis

• Main Author: Lee, Ying Hui
• Other Authors: Thirumaran s/o Thanabalu
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2024
• Subjects: Medicine, Health and Life Sciences; Gut microbiota; Atopic dermatitis; Antioxidant dietary fiber
• Online Access: https://hdl.handle.net/10356/173995
• Institution: Nanyang Technological University

Atopic dermatitis (AD) is a common paediatric skin disease with no satisfactory therapy despite increasing prevalence of the disease. AD is characterized by dysbiosis of gut and skin microbiota. Emerging evidence indicates that manipulation of gut microbiota using functional foods including probiotics and prebiotics can alleviate the AD clinical symptoms. Prebiotics can rebalance the microbial communities by providing a nutrient-rich gut environment for the beneficial commensals to thrive, thus prebiotics supplementation is considered a promising approach for successful modulation of gut microbiota to prevent as well as to treat AD patients. Two murine AD models were successfully generated with hallmarks of human AD including epidermal thickening, mast cells accumulation in skin lesions and a significant increase of total serum immunoglobulin (Ig)E obtained following the onset of AD. The first AD model (N-WASPK5KOi) was generated through postnatal deletion of Neural-Wiskott Aldrich Syndrome Protein (N-WASP) in mice keratinocytes using tamoxifen (TAM)-inducible expression of Cre. The onset of AD starting between 5 to 9 weeks after TAM induction. In the second model, AD was induced in BALB/c mice by repeated topical applications of 2,4-dinitrofluorobenzene (DNFB) to the dorsal skin and ear. We have shown that this DNFB-induced AD model can be reliably generated with three epicutaneous DNFB applications over a two weeks period. Because of its high reproducibility and predictability of AD-like symptoms, relative low cost and shorter time in AD development, DNFB-induced AD mice were chosen as murine AD model for prebiotics intervention study. Next, we demonstrated that olive-derived antioxidant dietary fiber (OADF), a by-product of olive oil production caused significant improvement of AD-like symptoms; reduced serum levels of immunoglobulin (Ig)E, interleukin (IL)-1β, IL-6, CXCL1 and increased serum levels of IL-10. DNFB-induced AD mice had gut microbiota dysbiosis compared with that of healthy controls. We also found that OADF supplementation in AD mice restored gut microbiota balance and increased butyrate production. This change in the gut has implication for the skin through IL-10 mediated anti-inflammatory effects clearly visible in the downregulation of AD-related immune response. In vitro characterization of OADF fermentation profiles by human gut microbiota using SHIME further confirmed its strong butyrate-stimulating effects and also showed its capability to reduce the production of branched SCFA and extend beneficial saccharolytic fermentation towards more distal part of the colon. All together these findings highlight the importance of the gut-skin axis for the AD dietary therapeutic agents and suggest that OADF can be an effective functional food or nutraceutical ingredient for AD patients through beneficially affecting gut microbiota of the host.