Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.
College of Medicine, Chang Gung University, Taoyuan 330, Taiwan.
Nutrients. 2022 Aug 21;14(16):3435. doi: 10.3390/nu14163435.
Emerging evidence supports that early-life disturbance of gut microbiota has an impact on adult disease in later life. Offspring hypertension can be programmed by maternal chronic kidney disease (CKD). Conversely, perinatal use of gut microbiota-targeted therapy has been implemented to reverse programming processes and prevent hypertension. Short-chain fatty acids (SCFAs), the major gut microbiota-derived metabolites, can be applied as postbiotics. Propionate, one of predominant SCFAs, has been shown to have antihypertensive property. We examined whether perinatal propionate supplementation can prevent offspring hypertension induced by maternal CKD. CKD was induced by chow supplemented with 0.5% adenine for 3 weeks before pregnancy. Propionate (P) was supplemented at 200 mmol/L in drinking water during pregnancy and lactation. Male offspring were divided into four groups ( = 7-8/group): control, CKD, control+propionate (CP), and CKD+propionate (CKDP). Maternal CKD-induced offspring hypertension was reversed by perinatal propionate supplementation. The protective effects of perinatal propionate treatment were related to increased propionate-generating bacteria spp. and plasma propionate level, increased expression of renal G protein-coupled receptor 41 (GPR41, a SCFA receptor), augmentation of α-diversity, and shifts in gut microbiota composition. In summary, our results highlight that maternal CKD-induced offspring hypertension can be prevented by the use of gut microbial metabolite SCFAs in early life, which could shed light on the prevention of the current hypertension pandemic.
新出现的证据表明，生命早期肠道微生物群的紊乱会对以后的成年疾病产生影响。母体慢性肾脏病 (CKD) 可导致后代高血压。相反，已经采用了针对肠道微生物群的治疗方法来逆转编程过程并预防高血压。短链脂肪酸 (SCFA) 是主要的肠道微生物群衍生代谢物，可以作为后生元应用。丙酸是主要的 SCFA 之一，已被证明具有降压作用。我们研究了围产期补充丙酸是否可以预防母体 CKD 引起的后代高血压。在怀孕前，用含 0.5%腺嘌呤的饮食喂养 3 周来诱导 CKD。在怀孕和哺乳期，将丙酸 (P) 以 200mmol/L 的浓度添加到饮用水中。雄性后代分为四组（每组 7-8 只）：对照组、CKD 组、对照组+丙酸 (CP 组) 和 CKD+丙酸 (CKDP 组)。围产期补充丙酸可逆转母体 CKD 引起的后代高血压。围产期丙酸治疗的保护作用与产生丙酸的细菌 spp. 和血浆丙酸水平升高、肾脏 G 蛋白偶联受体 41（GPR41，一种 SCFA 受体）表达增加、α-多样性增加以及肠道微生物群组成的变化有关。总之，我们的结果强调了生命早期使用肠道微生物代谢物 SCFA 可以预防母体 CKD 引起的后代高血压，这可能为当前高血压流行的预防提供新的思路。
