Division of Pediatric Nephrology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
Nutrients. 2024 Aug 8;16(16):2607. doi: 10.3390/nu16162607.
Lactoferrin, a glycoprotein derived from breastmilk, is recognized for its health benefits in infants and children; however, its protective effects when administered during gestation and lactation against offspring hypertension remain unclear. This study aimed to investigate whether maternal lactoferrin supplementation could prevent hypertension in offspring born to mothers with chronic kidney disease (CKD), with a focus on nitric oxide (NO), renin-angiotensin system (RAS) regulation, and alterations in gut microbiota and short-chain fatty acids (SCFAs). Prior to pregnancy, female rats were subjected to a 0.5% adenine diet for 3 weeks to induce CKD. During pregnancy and lactation, pregnant rats received one of four diets: normal chow, 0.5% adenine diet, 10% lactoferrin diet, or adenine diet supplemented with lactoferrin. Male offspring were euthanized at 12 weeks of age (n = 8 per group). Supplementation with lactoferrin during gestation and lactation prevented hypertension in adult offspring induced by a maternal adenine diet. The maternal adenine diet caused a decrease in the index of NO availability, which was restored by 67% with maternal LF supplementation. Additionally, LF was related to the regulation of the RAS, as evidenced by a reduced renal expression of renin and the angiotensin II type 1 receptor. Combined maternal adenine and LF diets altered beta diversity, shifted the offspring's gut microbiota, decreased propionate levels, and reduced the renal expression of SCFA receptors. The beneficial effects of lactoferrin are likely mediated through enhanced NO availability, rebalancing the RAS, and alterations in gut microbiota composition and SCFAs. Our findings suggest that maternal lactoferrin supplementation improves hypertension in offspring in a model of adenine-induced CKD, bringing us closer to potentially translating lactoferrin supplementation clinically for children born to mothers with CKD.
乳铁蛋白是一种源自母乳的糖蛋白，其在婴儿和儿童中的健康益处已得到认可；然而，其在妊娠和哺乳期给予时对后代高血压的保护作用尚不清楚。本研究旨在探讨母体乳铁蛋白补充是否可以预防患有慢性肾病（CKD）的母亲所生后代的高血压，重点关注一氧化氮（NO）、肾素-血管紧张素系统（RAS）调节以及肠道微生物群和短链脂肪酸（SCFA）的变化。在怀孕前，雌性大鼠接受 0.5%腺嘌呤饮食 3 周以诱导 CKD。在妊娠和哺乳期，怀孕的大鼠接受以下四种饮食中的一种：普通饲料、0.5%腺嘌呤饮食、10%乳铁蛋白饮食或腺嘌呤饮食加乳铁蛋白补充。雄性后代在 12 周龄时安乐死（每组 8 只）。在妊娠和哺乳期补充乳铁蛋白可预防由母体腺嘌呤饮食引起的成年后代高血压。母体腺嘌呤饮食导致 NO 可用性指数下降，母体 LF 补充使其恢复了 67%。此外，LF 与 RAS 的调节有关，这表现在肾素和血管紧张素 II 型 1 受体的表达减少。母体腺嘌呤和 LF 饮食的联合改变了 beta 多样性，改变了后代的肠道微生物群，降低了丙酸盐水平，并减少了 SCFA 受体的肾脏表达。乳铁蛋白的有益作用可能是通过增加 NO 的可用性、重新平衡 RAS 以及改变肠道微生物群组成和 SCFAs 来介导的。我们的研究结果表明，在腺嘌呤诱导的 CKD 模型中，母体乳铁蛋白补充可改善后代的高血压，这使我们更接近于潜在地将乳铁蛋白补充剂临床应用于患有 CKD 的母亲所生的儿童。
