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
Department of paediatrics, The First People's Hospital of Foshan, Foshan, People's Republic of China.
Institute of translational medicine, The First People's Hospital of Foshan, Foshan, People's Republic of China.
Gut. 2024 Dec 10;74(1):45-57. doi: 10.1136/gutjnl-2024-332407.
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.
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.
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 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.
This study demonstrates that AA is intimately linked to the onset of AD via gut dysbiosis.
介导宿主与微生物群相互作用并导致特应性皮炎（AD）发病的母乳特异性代谢物仍不清楚，需要进一步研究。
我们招募了250对母婴，收集了978份从出生到6个月大婴儿的纵向粪便样本，以及243份母亲粪便样本用于宏基因组学研究。同时，对239份相应的母乳样本进行代谢组学分析。进行动物和细胞实验以验证生物信息学研究结果。
临床研究结果表明，每日母乳喂养时间的减少与AD发病率的降低有关。这一观察结果促使我们研究母乳衍生脂肪酸的作用。我们发现，高浓度的花生四烯酸（AA），而非二十碳五烯酸（EPA）或二十二碳六烯酸，会导致婴儿肠道菌群失调。进一步研究表明，四种特定细菌将甘露聚糖降解为甘露糖，从而增强了O抗原和脂多糖的甘露聚糖依赖性生物合成。相关性分析证实，在患有AD的婴儿中，高AA浓度下 的丰度与一些微生物途径（如“GDP-甘露糖衍生的O抗原和脂多糖生物合成”）呈正相关。这些发现与动物研究结果一致。此外，AA而非EPA破坏了CD4/CD8细胞的比例，增加了皮肤病变面积并提高了外周Th2细胞的比例。在卵清蛋白免疫刺激后喂食AA的BALB/c小鼠中，它还促进了IgE分泌以及前列腺素和白三烯的生物合成。此外，AA在与TNF-α和INF-γ共同刺激的HaCaT细胞中显著增加了IL-4的分泌。
本研究表明，AA通过肠道菌群失调与AD的发病密切相关。
