Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
J Immunol Res. 2023 Jul 29;2023:9603576. doi: 10.1155/2023/9603576. eCollection 2023.
Studies suggest that early-life gut microbiota composition and intestinal short-chain fatty acids (SCFAs) are linked to future asthma susceptibility. Furthermore, infancy offers a critical time window to modulate the microbiota and associated metabolites through diet-microbe interactions to promote infant health. Human milk oligosaccharides (HMOs), nondigestible carbohydrates abundant in breast milk, are prebiotics selectively metabolized by gut microbiota that consequently modify microbiome composition and SCFA production.
Using a house dust mite mouse model of allergy, we investigated the impacts of early oral treatment of pups with biologically relevant doses of 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL), two of the most abundant HMOs in human milk, in amelioration of allergic airway disease severity.
We found that administration of 2'-FL and 6'-SL during early life reduced lung histopathology scores, circulating IgE, cytokine levels, and inflammatory cell infiltration, all hallmark symptoms of allergic asthma. HMO supplementation also increased the relative abundance of intestinal and , known SCFA producers within the gut. Indeed, we detected increased SCFA concentrations in both the intestine and blood of adult mice who received HMOs prior to weaning.
We propose a model in which orally administered HMOs delivered during early life shift the microbiota toward increased production of SCFAs, which dampens the allergic immune responses behind allergy and asthma. Overall, these data suggest the potential for HMO supplementation to protect infants against asthma development later in life, with possible benefits against additional atopic diseases such as eczema and food allergies.
研究表明，生命早期的肠道微生物群落组成和肠道短链脂肪酸（SCFAs）与未来的哮喘易感性有关。此外，婴儿期是通过饮食-微生物相互作用调节微生物群和相关代谢物，促进婴儿健康的关键时期。人乳低聚糖（HMOs）是母乳中丰富的不可消化碳水化合物，是肠道微生物选择性代谢的益生元，从而改变微生物群落组成和 SCFA 产生。
我们使用屋尘螨过敏小鼠模型，研究了早期口服给予 2'-岩藻糖基乳糖（2'-FL）和 6'-唾液酸乳糖（6'-SL）等两种母乳中最丰富的 HMO 生物相关剂量，对改善过敏气道疾病严重程度的影响。
我们发现，生命早期给予 2'-FL 和 6'-SL 可降低肺组织病理学评分、循环 IgE、细胞因子水平和炎症细胞浸润，这些都是过敏哮喘的标志性症状。HMO 补充还增加了肠道中已知的 SCFA 产生菌和的相对丰度。事实上，我们在接受 HMO 补充的成年小鼠的肠道和血液中都检测到 SCFA 浓度增加。
我们提出了一个模型，即生命早期口服给予 HMO 可促使微生物群落向增加 SCFA 产生的方向转变，从而抑制过敏和哮喘背后的过敏免疫反应。总体而言，这些数据表明 HMO 补充有可能保护婴儿免受日后哮喘的发生，并且可能对湿疹和食物过敏等其他特应性疾病有好处。
