PDF(Pubmed)
Abstract：
Observational evidence suggests that human milk oligosaccharides (HMOs) promote the growth of commensal bacteria in early life and adulthood. However, the mechanisms by which HMOs benefit health through modulation of gut microbial homeostasis remain largely unknown. 2\'-fucosyllactose (2\'-FL) is the most abundant oligosaccharide in human milk and contributes to the essential health benefits associated with human milk consumption. Here, we investigated how 2\'-FL prevents colitis in adulthood through its effects on the gut microbial community. We found that the gut microbiota from adult mice that consumed 2\'-FL exhibited an increase in abundance of several health-associated genera, including Bifidobacterium and Lactobacillus. The 2\'-FL-modulated gut microbial community exerted preventive effects on colitis in adult mice. By using Bifidobacterium infantis as a 2\'-FL-consuming bacterial model, exploratory metabolomics revealed novel 2\'-FL-enriched secretory metabolites by Bifidobacterium infantis, including pantothenol. Importantly, pantothenate significantly protected the intestinal barrier against oxidative stress and mitigated colitis in adult mice. Furthermore, microbial metabolic pathway analysis identified 26 dysregulated metabolic pathways in fecal microbiota from patients with ulcerative colitis, which were significantly regulated by 2\'-FL treatment in adult mice, indicating that 2\'-FL has the potential to rectify dysregulated microbial metabolism in colitis. These findings support the contribution of the 2\'-FL-shaped gut microbial community and bacterial metabolite production to the protection of intestinal integrity and prevention of intestinal inflammation in adulthood.IMPORTANCEAt present, neither basic research nor clinical studies have revealed the exact biological functions or mechanisms of action of individual oligosaccharides during development or in adulthood. Thus, it remains largely unknown whether human milk oligosaccharides could serve as effective therapeutics for gastrointestinal-related diseases. Results from the present study uncover 2\'-FL-driven alterations in bacterial metabolism and identify novel B. infantis-secreted metabolites following the consumption of 2\'-FL, including pantothenol. This work further demonstrates a previously unrecognized role of pantothenate in significantly protecting the intestinal barrier against oxidative stress and mitigating colitis in adult mice. Remarkably, 2\'-FL-enhanced bacterial metabolic pathways are found to be dysregulated in the fecal microbiota of ulcerative colitis patients. These novel metabolic pathways underlying the bioactivities of 2\'-FL may lay a foundation for applying individual oligosaccharides for prophylactic intervention for diseases associated with impaired intestinal homeostasis.
摘要：
观察证据表明，人乳寡糖（HMO）在生命早期和成年期促进共生细菌的生长。然而,HMO通过调节肠道微生物稳态而有益于健康的机制仍然未知。2'-岩藻糖基乳糖（2'-FL）是人乳中最丰富的低聚糖，有助于与人乳消费相关的基本健康益处。这里,我们调查了2'-FL如何通过其对肠道微生物群落的影响来预防成年期结肠炎。我们发现，来自消耗2'-FL的成年小鼠的肠道微生物群表现出几个健康相关属的丰度增加，包括双歧杆菌和乳杆菌。2'-FL调节的肠道微生物群落对成年小鼠结肠炎具有预防作用。通过使用婴儿双歧杆菌作为2'-FL消耗细菌模型，探索性代谢组学揭示了婴儿双歧杆菌新的富含2'-FL的分泌代谢产物，包括泛醇.重要的是,泛酸在成年小鼠中显著保护肠屏障抵抗氧化应激并减轻结肠炎。此外，微生物代谢途径分析确定了溃疡性结肠炎患者粪便微生物群中26个失调的代谢途径，在成年小鼠中受到2'-FL处理的显着调节，表明2'-FL具有纠正结肠炎中微生物代谢失调的潜力。这些发现支持2'-FL形肠道微生物群落和细菌代谢物产生对保护肠道完整性和预防成年期肠道炎症的贡献。重要的是，目前，基础研究和临床研究都没有揭示个体寡糖在发育或成年期的确切生物学功能或作用机制。因此，人乳寡糖是否可以作为胃肠道相关疾病的有效治疗药物仍是未知的。本研究的结果揭示了2'-FL驱动的细菌代谢变化，并在消耗2'-FL后鉴定了新的婴儿芽孢杆菌分泌的代谢产物，包括泛醇.这项工作进一步证明了泛酸在显著保护肠屏障抵抗氧化应激和减轻成年小鼠结肠炎中的先前未被认识到的作用。值得注意的是,发现2'-FL增强的细菌代谢途径在溃疡性结肠炎患者的粪便微生物群中失调。2'-FL生物活性的这些新的代谢途径可能为应用个体寡糖预防性干预与肠道稳态受损相关的疾病奠定基础。
