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.
Competing Interests: Competing interests: FKLC is Board Member of CUHK Medical Centre. He is a cofounder, non-executive Board Chairman and non-executive scientific advisor, Chief Medical Officer and shareholder of GenieBiome. He receives patent royalties through his affiliated institutions. He has received fees as an advisor and honoraria as a speaker for Eisai Co., AstraZeneca, Pfizer, Takeda Pharmaceutical Co. and Takeda (China) Holdings Co. SCN has served as an advisory board member for Pfizer, Ferring, Janssen and Abbvie and received honoraria as a speaker for Ferring, Tillotts, Menarini, Janssen, Abbvie and Takeda. SCN has received research grants through her affiliated institutions from Olympus, Ferring and Abbvie. SCN is a founder member, non-executive director, non-executive scientific advisor and shareholder of GenieBiome. SCN receives patent royalties through her affiliated institutions. FKLC, SCN and LinZ are named inventors of patent applications held by the CUHK and MagIC that cover the therapeutic and diagnostic use of microbiome.
(© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)
Processing Request
No Comments.