Association of breast milk-derived arachidonic acid-induced infant gut dysbiosis with the onset of atopic dermatitis.

Abstract

OBJECTIVE

The specific breast milk-derived metabolites that mediate host-microbiota interactions and contribute to the onset of atopic dermatitis (AD) remain unknown and require further investigation.

DESIGN

We enrolled 250 mother-infant pairs and collected 978 longitudinal faecal samples from infants from birth to 6 months of age, along with 243 maternal faecal samples for metagenomics. Concurrently, 239 corresponding breast milk samples were analysed for metabolomics. Animal and cellular experiments were conducted to validate the bioinformatics findings.

RESULTS

The clinical findings suggested that a decrease in daily breastfeeding duration was associated with a reduced incidence of AD. This observation inspired us to investigate the effects of breast milk-derived fatty acids. We found that high concentrations of arachidonic acid (AA), but not eicosapentaenoic acid (EPA) or docosahexaenoic acid, induced gut dysbiosis in infants. Further investigation revealed that four specific bacteria degraded mannan into mannose, consequently enhancing the mannan-dependent biosynthesis of O-antigen and lipopolysaccharide. Correlation analysis confirmed that in infants with AD, the abundance of Escherichia coli under high AA concentrations was positively correlated with some microbial pathways (eg, 'GDP-mannose-derived O-antigen and lipopolysaccharide biosynthesis'). These findings are consistent with those of the animal studies. Additionally, AA, but not EPA, disrupted the ratio of CD4/CD8 cells, increased skin lesion area and enhanced the proportion of peripheral Th2 cells. It also promoted IgE secretion and the biosynthesis of prostaglandins and leukotrienes in BALB/c mice fed AA following ovalbumin immunostimulation. Moreover, AA significantly increased IL-4 secretion in HaCaT cells costimulated with TNF-α and INF-γ.

CONCLUSIONS

This study demonstrates that AA is intimately linked to the onset of AD via gut dysbiosis.

Authors

Jiang, Suhua,Cai, Mengyun,Li, Dingru,Chen, Xiangping,Chen, Xiaoqian,Huang, Qitao,Zhong, Caimei,Zheng, Xiufeng,Zhou, Dan,Chen, Zhiyan,Zhang, Lin,Ching, Jessica Yl,Chen, Ailing,Lu, Shaoxia,Zhang, Lifang,Hu, Ling,Liao, Yan,Li, Ying,He, Zhihua,Wu, Jingjing,Huo, Huiyi,Liang, Yongqi,Li, Wanwen,Zou, Yanli,Luo, Wei,Ng, Siew C,Chan, Francis Kl,Chen, Xia,Deng, Yuhua

Published Date 2024 Jul 30

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