Maternal obese-type gut microbiota differentially impact cognition, anxiety and compulsive behavior in male and female offspring in mice.
Maternal obese-type gut microbiota differentially impact cognition, anxiety and compulsive behavior in male and female offspring in mice.
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DOI：
10.1371/journal.pone.0175577
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Berthoud HR
中科院分区：
文献类型：
--
作者：
Bruce-Keller AJ;Fernandez-Kim SO;Townsend RL;Kruger C;Carmouche R;Newman S;Salbaum JM;Berthoud HR
众所周知，母亲肥胖会使后代易患代谢和神经发育异常。虽然这些现象背后的机制尚不清楚，但高脂肪饮食会显著改变肠道微生物群，而肠道微生物群会影响生理功能。为了确定母体饮食诱导的肠道生态失调是否会破坏后代的神经行为功能，我们将高脂肪饮食（HFD）或对照低脂肪饮食相关（CD）肠道微生物群移植到常规饲养的雌性小鼠中。然后繁殖雄性小鼠，并跟踪雄性和雌性后代的行为表型。虽然母体行为不受影响，但HFD母鼠的新生儿在母体分离后的发声比CD母鼠的幼崽少。此外，与CD母鼠的雄性后代相比，HFD母鼠的断奶雄性后代在探索、认知和刻板/强迫行为方面存在显著和选择性破坏;而HFD母鼠的雌性后代体重和肥胖增加。16 S宏基因组分析证实了在CD和HFD母鼠中建立了不同的微生物群，在整个妊娠和哺乳期间改变了多样性和分类学分布。同样，与CD母鼠相比，HFD母鼠的后代以及雄性与雌性相比，肠道微生物多样性和分布也发生了显著变化。对差异代表类群的行为表现的回归分析表明，减少代表性的厚壁菌门的特定成员预测男性后代的行为下降。总的来说，这些数据确定高脂肪饮食诱导的母体生态失调足以以性别特异性方式破坏小鼠后代的行为功能。因此，这些数据加强了母体饮食和后代神经编程之间的重要联系，并表明肠道生态失调可能将不健康的现代饮食与神经发育和儿童疾病的患病率增加联系起来。
Maternal obesity is known to predispose offspring to metabolic and neurodevelopmental abnormalities. While the mechanisms underlying these phenomena are unclear, high fat diets dramatically alter intestinal microbiota, and gut microbiota can impact physiological function. To determine if maternal diet-induced gut dysbiosis can disrupt offspring neurobehavioral function, we transplanted high fat diet- (HFD) or control low fat diet-associated (CD) gut microbiota to conventionally-housed female mice. Recipient mice were then bred and the behavioral phenotype of male and female offspring was tracked. While maternal behavior was unaffected, neonatal offspring from HFD dams vocalized less upon maternal separation than pups from CD dams. Furthermore, weaned male offspring from HFD dams had significant and selective disruptions in exploratory, cognitive, and stereotypical/compulsive behavior compared to male offspring from CD dams; while female offspring from HFD dams had increases in body weight and adiposity. 16S metagenomic analyses confirmed establishment of divergent microbiota in CD and HFD dams, with alterations in diversity and taxonomic distribution throughout pregnancy and lactation. Likewise, significant alterations in gut microbial diversity and distribution were noted in offspring from HFD dams compared to CD dams, and in males compared to females. Regression analyses of behavioral performance against differentially represented taxa suggest that decreased representation of specific members of the Firmicutes phylum predict behavioral decline in male offspring. Collectively, these data establish that high fat diet-induced maternal dysbiosis is sufficient to disrupt behavioral function in murine offspring in a sex-specific manner. Thus these data reinforce the essential link between maternal diet and neurologic programming in offspring and suggest that intestinal dysbiosis could link unhealthy modern diets to the increased prevalence of neurodevelopmental and childhood disorders.