Dogra Shaillay Kumar, Martin Francois-Pierre, Donnicola Dominique, Julita Monique, Berger Bernard, Sprenger Norbert
Nestlé Institute of Health Sciences, Société des Produits Nestlé S.A., 1000 Lausanne 26, Switzerland.
Microorganisms. 2021 Sep 12;9(9):1939. doi: 10.3390/microorganisms9091939.
(1) Background: Human milk oligosaccharides (HMOs) may support immune protection, partly via their action on the early-life gut microbiota. Exploratory findings of a randomized placebo-controlled trial associated 2'fucosyllactose (2'FL) and lacto-N-neotetraose (LNnT) formula feeding with reduced risk for reported bronchitis and lower respiratory tract illnesses (LRTI), as well as changes in gut microbiota composition. We sought to identify putative gut microbial mechanisms linked with these clinical observations. (2) Methods: We used stool microbiota composition, metabolites including organic acids and gut health markers in several machine-learning-based classification tools related prospectively to experiencing reported bronchitis or LRTI, as compared to no reported respiratory illness. We performed preclinical epithelial barrier function modelling to add mechanistic insight to these clinical observations. (3) Results: Among the main features discriminant for infants who did not experience any reported bronchitis ( = 80/106) or LRTI ( = 70/103) were the 2-HMO formula containing 2'FL and LNnT, higher acetate, fucosylated glycans and , as well as lower succinate, butyrate, propionate and 5-aminovalerate, along with Carnobacteriaceae members and . Acetate correlated with several species. By univariate analysis, infants experiencing no bronchitis or LRTI, compared with those who did, showed higher acetate ( < 0.007) and subsp. ( ≤ 0.03). In vitro experiments demonstrate that 2'FL, LNnT and lacto-N-tetraose (LNT) stimulated subsp. (ATCC15697) metabolic activity. Metabolites in spent culture media, primarily due to acetate, supported epithelial barrier protection. (4) Conclusions: An early-life gut ecology characterized by -species-driven metabolic changes partly explains the observed clinical outcomes of reduced risk for bronchitis and LRTI in infants fed a formula with HMOs. (Trial registry number NCT01715246.).
(1) 背景：人乳寡糖（HMOs）可能部分通过对早期肠道微生物群的作用来支持免疫保护。一项随机安慰剂对照试验的探索性结果表明，喂养含有2'-岩藻糖基乳糖（2'FL）和乳糖-N-新四糖（LNnT）的配方奶粉与报告的支气管炎和下呼吸道疾病（LRTI）风险降低以及肠道微生物群组成的变化有关。我们试图确定与这些临床观察结果相关的假定肠道微生物机制。(2) 方法：我们使用粪便微生物群组成、包括有机酸在内的代谢物以及肠道健康标志物，在几种基于机器学习的分类工具中，前瞻性地比较了报告有支气管炎或LRTI的婴儿与未报告有呼吸道疾病的婴儿。我们进行了临床前上皮屏障功能建模，以增加对这些临床观察结果的机制性理解。(3) 结果：对于未报告有任何支气管炎（n = 80/106）或LRTI（n = 70/103）的婴儿，主要的判别特征包括含有2'FL和LNnT的2-HMO配方奶粉、较高的乙酸盐、岩藻糖基化聚糖和[具体物质未明确]，以及较低的琥珀酸盐、丁酸盐、丙酸盐和5-氨基戊酸盐，还有肉杆菌科成员和[具体物质未明确]。乙酸盐与几种[具体菌种未明确]相关。通过单变量分析，未经历支气管炎或LRTI的婴儿与经历过的婴儿相比，乙酸盐含量更高（P < 0.007），[具体菌种未明确]亚种[具体物质未明确]含量更高（P ≤ 0.03）。体外实验表明，2'FL、LNnT和乳糖-N-四糖（LNT）刺激了[具体菌种未明确]亚种[具体物质未明确]（ATCC15697）的代谢活性。消耗培养基中的代谢物，主要是由于乙酸盐，支持上皮屏障保护。(4) 结论：以[具体菌种未明确]驱动的代谢变化为特征的早期肠道生态，部分解释了在喂养含HMOs配方奶粉的婴儿中观察到的支气管炎和LRTI风险降低的临床结果。（试验注册号NCT01715246。）
