Wang Wenli, An Qin, Zou Yunxia, Meng Qingyong, Zhang Yali
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
The International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201400, China.
Nutrients. 2025 Jul 7;17(13):2248. doi: 10.3390/nu17132248.
BACKGROUND/OBJECTIVES: The establishment of early gut microbiota is crucial for host health. Lactoferrin (LF), which is present in breast milk, positively impacts gut microbiota composition. However, the effect of lactation LF on the establishment and composition of early gut microbiota in different disease models in adulthood remains unclear.
Lactation-LF-deficient mice were established using systemically LF-knocked-out maternal mice. This study assessed the maturity of the gut microbiota in LF feeding-deficient mice in relation to age and changes in the gut microbiota in adult high-fat diet (HFD)-induced obesity, dextran sodium sulfate (DSS)-induced acute colitis, and chronic unpredictable mild stress (CUMS)-induced depression models.
Compared to LF intake during lactation, LF deficiency during lactation increased the abundance of potentially pathogenic bacteria in the gut, resulting in abnormal microbial maturation. LF intake during lactation aggravated gut microbiota dysbiosis induced via HFD, DSS, and CUMS in adulthood and may change the function of , , , , , and . Comparing the different models revealed that bacteria that were jointly upregulated via HFD and DSS exhibited increased levels of inflammation and oxidation. LF deficiency during lactation may weaken the association between an HFD and inflammatory bowel disease (IBD). The changing trends in many gut microbes caused by DSS and HFD were opposite to those that changed with age.
Lactoferrin deficiency increases the abundance of potential pathogens and disrupts microbial maturation. This lack of LF exacerbates dysbiosis in models of obesity, colitis, and depression. Regulating the gut microbiota according to the rules of microbial succession during the maturation process of gut microbiota may improve gut microbiota dysbiosis in patients with obesity and IBD.
背景/目的：早期肠道微生物群的建立对宿主健康至关重要。母乳中存在的乳铁蛋白（LF）对肠道微生物群的组成有积极影响。然而，哺乳期LF对成年期不同疾病模型中早期肠道微生物群的建立和组成的影响仍不清楚。
使用全身性敲除LF的母鼠建立哺乳期LF缺陷小鼠。本研究评估了LF喂养缺陷小鼠肠道微生物群的成熟度与年龄的关系，以及成年高脂饮食（HFD）诱导的肥胖、葡聚糖硫酸钠（DSS）诱导的急性结肠炎和慢性不可预测轻度应激（CUMS）诱导的抑郁模型中肠道微生物群的变化。
与哺乳期摄入LF相比，哺乳期LF缺乏会增加肠道中潜在病原菌的丰度，导致微生物成熟异常。哺乳期摄入LF会加重成年期由HFD、DSS和CUMS诱导的肠道微生物群失调，并可能改变 、 、 、 、 和 的功能。比较不同模型发现，通过HFD和DSS共同上调的细菌表现出炎症和氧化水平增加。哺乳期LF缺乏可能会削弱HFD与炎症性肠病（IBD）之间的关联。DSS和HFD引起的许多肠道微生物的变化趋势与随年龄变化的趋势相反。
乳铁蛋白缺乏会增加潜在病原体的丰度并破坏微生物成熟。LF的这种缺乏会加剧肥胖、结肠炎和抑郁症模型中的失调。根据肠道微生物群成熟过程中的微生物演替规律调节肠道微生物群，可能会改善肥胖和IBD患者的肠道微生物群失调。
