College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
College of Biological Sciences, China Agricultural University, Beijing, China.
BMC Biol. 2023 Oct 31;21(1):242. doi: 10.1186/s12915-023-01748-2.
Lactoferrin is an active protein in breast milk that plays an important role in the growth and development of infants and is implicated as a neuroprotective agent. The incidence of depression is currently increasing, and it is unclear whether the lack of lactoferrin during lactation affects the incidence of depressive-like behavior in adulthood.
Lack of lactoferrin feeding during lactation affected the barrier and innate immune functions of the intestine, disrupted the intestinal microflora, and led to neuroimmune dysfunction and neurodevelopmental delay in the hippocampus. When exposed to external stimulation, adult lactoferrin feeding-deficient mice presented with worse depression-like symptoms; the mechanisms involved were activation of the LPS-TLR4 signalling pathway in the intestine and hippocampus, reduced BDNF-CREB signaling pathway in hippocampus, increased abundance of depression-related bacteria, and decreased abundance of beneficial bacteria.
Overall, our findings reveal that lactoferrin feeding deficient during lactation can increase the risk of depressive-like behavior in adults. The mechanism is related to the regulatory effect of lactoferrin on the development of the "microbial-intestinal-brain" axis.
乳铁蛋白是母乳中的一种活性蛋白，在婴儿的生长发育中起着重要作用，并被认为是一种神经保护剂。目前，抑郁症的发病率正在上升，尚不清楚哺乳期缺乏乳铁蛋白是否会影响成年后患抑郁样行为的发生率。
哺乳期缺乏乳铁蛋白喂养会影响肠道的屏障和固有免疫功能，破坏肠道微生物群，导致海马的神经免疫功能障碍和神经发育迟缓。当受到外界刺激时，成年期缺乏乳铁蛋白喂养的小鼠表现出更严重的抑郁样症状；涉及的机制包括肠道和海马中 LPS-TLR4 信号通路的激活、海马中 BDNF-CREB 信号通路的减少、与抑郁相关的细菌丰度增加和有益细菌丰度减少。
总之，我们的研究结果表明，哺乳期缺乏乳铁蛋白喂养会增加成年后患抑郁样行为的风险。其机制与乳铁蛋白对“微生物-肠道-大脑”轴发育的调节作用有关。
