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The short-chain fatty acids butyrate and propionate protect against inflammation-induced activation of mediators involved in active labor: implications for preterm birth.
Molecular Human Reproduction ( IF 4 ) Pub Date : 2020-04-01 , DOI: 10.1093/molehr/gaaa025
Hope Eveline Carter Moylan 1 , Caitlyn Nguyen-Ngo 1 , Ratana Lim 1, 2 , Martha Lappas 1, 2
Affiliation  

Spontaneous preterm birth is a global health issue affecting up to 20% of pregnancies and leaves a legacy of neurodevelopmental complications. Inflammation has been implicated in a significant proportion of preterm births, where pro-inflammatory insults trigger production of additional pro-inflammatory and pro-labor mediators. Thus, novel therapeutics that can target inflammation may be a novel avenue for preventing preterm birth and improving adverse fetal outcomes. Short-chain fatty acids (SCFAs), such as butyrate and propionate, are dietary metabolites produced by bacterial fermentation of fiber in the gut. SCFAs are known to possess anti-inflammatory properties and have been found to function through G-coupled-receptors and histone deacetylases. Therefore, this study aimed to investigate the effect of SCFAs on pro-inflammatory and pro-labor mediators in an in vitro model of preterm birth. Primary human cells isolated from myometrium and fetal membranes (decidua, amnion mesenchymal and amnion epithelial cells) were stimulated with the pro-inflammatory cytokines tumor necrosis factor alpha (TNF) or interleukin 1B (IL1B). The SCFAs butyrate and propionate suppressed inflammation-induced expression of pro-inflammatory cytokines and chemokines, adhesion molecules, the uterotonic prostaglandin PGF2alpha and enzymes involved in remodeling of myometrium and degradation of the fetal membranes. Notably, propionate and butyrate also suppressed inflammation-induced prostaglandin signaling and myometrial cell contraction. These effects appear to be mediated through suppression of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation. These results suggest that the SCFAs may be able to prevent myometrial contractions and rupture of membranes. Further in vivo studies are warranted to identify the efficacy of SCFAs as a novel anti-inflammatory therapeutic to prevent inflammation-induced spontaneous preterm birth.

中文翻译:

短链脂肪酸丁酸和丙酸可防止炎症诱导的活跃分娩介质激活:对早产的影响。

自发性早产是一个全球性的健康问题,影响多达 20% 的怀孕并留下神经发育并发症的遗留问题。炎症与很大比例的早产有关,其中促炎性损伤会引发额外的促炎和促分娩介质的产生。因此,针对炎症的新型疗法可能是预防早产和改善不良胎儿结局的新途径。短链脂肪酸 (SCFA),例如丁酸和丙酸,是由肠道中的纤维细菌发酵产生的膳食代谢物。已知 SCFA 具有抗炎特性,并且已发现通过 G 偶联受体和组蛋白脱乙酰酶发挥作用。所以,早产体外模型。从子宫肌层和胎膜(蜕膜、羊膜间充质和羊膜上皮细胞)分离的原代人类细胞用促炎细胞因子肿瘤坏死因子 α (TNF) 或白细胞介素 1B (IL1B) 刺激。SCFAs 丁酸盐和丙酸盐抑制炎症诱导的促炎细胞因子和趋化因子、粘附分子、子宫收缩前列腺素 PGF 2alpha 的表达和参与子宫肌层重塑和胎膜降解的酶。值得注意的是,丙酸盐和丁酸盐还抑制了炎症诱导的前列腺素信号传导和子宫肌层细胞收缩。这些作用似乎是通过抑制核因子 kappa B (NF-κB) 和丝裂原活化蛋白激酶 (MAPK) 激活来介导的。这些结果表明短链脂肪酸可能能够防止子宫​​肌层收缩和膜破裂。需要进一步的体内研究来确定 SCFA 作为一种新型抗炎疗法的功效,以防止炎症引起的自发性早产。
更新日期:2020-04-01
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