Jeong-Hyun Kim1, Seung-Hwa Lee1, Mi-Jin Kang2, Sun-Goo Hwang3, Yoon Mee Park1, Bong-Soo Kim4, So-Yeon Lee5, Shin Ah Kim6, Min Jee Park7, Kun Baek Song5, Eom Ji Choi5, Sungsu Jung8, Soo-Jong Hong5. 1. Department of Medicine, University of Ulsan College of Medicine, Seoul, Korea. 2. Humidifier Disinfectant Health Center, Asan Medical Center, Seoul, Korea. 3. Department of Environment and Applied Plant Science, Sangji University, Wonju, Korea. 4. Department of Life Science, Multidisciplinary Genome Institute, Hallym University, Chuncheon, Korea. 5. Department of Pediatrics, Childhood Asthma Atopy Center, Humidifier Disinfectant Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 6. Asan Medical Center, Humidifier Disinfectant Health Center, Seoul, Korea. 7. Department of Pediatrics, Uijeongbu Eulji Medical Center, Uijeongbu, Korea. 8. Department of Pediatrics, Pusan National University Yangsan Hospital, Yangsan, Korea.
Abstract
BACKGROUND: Gut microbiota dysbiosis is linked to the development and responses of the immune system and can play an important role in the onset of allergic diseases including atopic dermatitis (AD). This study investigated the association between host genetics and the gut microbiota in AD. METHODS: A global gene expression profiling of the gut epithelial colonocytes, genetic variations analysis, and the gut microbial composition analysis were performed. RESULTS: This study identified the upregulation of PTGR2 (p = .028), a gene involved in prostaglandin catalysis and inflammatory responses, as a potential risk factor for AD. In subsequent fine mapping analysis using 17 single nucleotide polymorphisms (SNPs) of PTGR2 in 864 Korean subjects (420 AD patients and 444 unaffected controls), several SNPs and haplotypes showed significant associations with AD and its SCORing AD (SCORAD) values (p = .002). To investigate host-microbial interactions, further gut microbiota data and genotypes were obtained from an independent cohort of 176 subjects (91 AD patients and 85 controls). From correlation analysis, a significantly negative association between SNP and Bifidobacterium abundance was observed in AD patients (p = .005). In additional observations of PTGR2-associated downstream molecules, NRF2 (p = .004) and several antioxidant genes (GSTT1, GCLC, GPX1; p < .05) showed significantly reduced expression in AD patients. CONCLUSIONS: Our current findings suggest that the interaction between PTGR2 dysregulated expression and a Bifidobacterium abundance affects a higher risk of AD and a more severe onset.
BACKGROUND: Gut microbiota dysbiosis is linked to the development and responses of the immune system and can play an important role in the onset of allergic diseases including atopic dermatitis (AD). This study investigated the association between host genetics and the gut microbiota in AD. METHODS: A global gene expression profiling of the gut epithelial colonocytes, genetic variations analysis, and the gut microbial composition analysis were performed. RESULTS: This study identified the upregulation of PTGR2 (p = .028), a gene involved in prostaglandin catalysis and inflammatory responses, as a potential risk factor for AD. In subsequent fine mapping analysis using 17 single nucleotide polymorphisms (SNPs) of PTGR2 in 864 Korean subjects (420 AD patients and 444 unaffected controls), several SNPs and haplotypes showed significant associations with AD and its SCORing AD (SCORAD) values (p = .002). To investigate host-microbial interactions, further gut microbiota data and genotypes were obtained from an independent cohort of 176 subjects (91 AD patients and 85 controls). From correlation analysis, a significantly negative association between SNP and Bifidobacterium abundance was observed in AD patients (p = .005). In additional observations of PTGR2-associated downstream molecules, NRF2 (p = .004) and several antioxidant genes (GSTT1, GCLC, GPX1; p < .05) showed significantly reduced expression in AD patients. CONCLUSIONS: Our current findings suggest that the interaction between PTGR2 dysregulated expression and a Bifidobacterium abundance affects a higher risk of AD and a more severe onset.