Myelin as a regulator of development of the microbiota-gut-brain axis.
Myelin as a regulator of development of the microbiota-gut-brain axis.
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DOI：
10.1016/j.bbi.2020.11.001
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Gareau MG
中科院分区：
文献类型：
--
作者：
Keogh CE;Kim DHJ;Pusceddu MM;Knotts TA;Rabasa G;Sladek JA;Hsieh MT;Honeycutt M;Brust-Mascher I;Barboza M;Gareau MG
外周和中枢神经系统的髓鞘形成对调节运动、感觉和认知功能至关重要。由于髓鞘形成在生命早期迅速发生，早期定植期间新生儿肠道生态失调可能通过调节免疫反应和神经元分化而改变正确的髓鞘形成。尽管儿童普遍使用抗生素（Abx），但新生儿Abx诱导的生态失调对微生物群、肠、脑（MGB）轴的发育（包括髓鞘形成和行为）的影响尚不清楚。我们假设新生儿abx诱导的生态失调失调失调了宿主与微生物的相互作用，损害了大脑中的髓鞘形成，并改变了MGB轴。新生C57BL/6小鼠从出生后第7天（P7）至断奶（P23），每天口服Abx鸡尾酒（新霉素、万古霉素、氨苄西林）或水（载药），诱导肠道生态失调。在成年小鼠（6-8周）中进行行为（认知；焦虑样行为）、微生物群测序和qPCR（回肠、结肠、海马和前额叶皮层[PFC]）。新生儿服用Abx导致成年期肠道生态失调、肠道生理受损、细菌代谢物紊乱和行为改变（认知缺陷和焦虑行为）。在abx处理的小鼠PFC区，髓磷脂相关基因（Mag、Mog、Mbp、Mobp、Plp）和转录因子（Sox10、Myrf）的表达显著增加。免疫荧光成像和western blot分析证实髓鞘形成增加，表明与成年期假对照组相比，新生abx治疗小鼠的MBP、SOX10和MYRF表达增加。最后，在完成Abx治疗后给予短链脂肪酸丁酸盐恢复肠道生理、行为和髓鞘损伤，表明肠道微生物群在介导这些作用中起关键作用。综上所述，我们确定了新生儿Abx给药对MGB轴的长期影响，特别是对PFC区域的髓磷脂调节，可能导致认知功能受损，细菌代谢物可有效逆转这种改变的表型。
Myelination in the peripheral and central nervous systems is critical in regulating motor, sensory, and cognitive functions. As myelination occurs rapidly during early life, neonatal gut dysbiosis during early colonization can potentially alter proper myelination by dysregulating immune responses and neuronal differentiation. Despite common usage of antibiotics (Abx) in children, the impact of neonatal Abx-induced dysbiosis on the development of microbiota, gut, brain (MGB) axis, including myelination and behavior, is unknown. We hypothesized that neonatal Abx-induced dysbiosis dysregulates host-microbe interactions, impairing myelination in the brain, and altering the MGB axis. Neonatal C57BL/6 mice were orally gavaged daily with an Abx cocktail (neomycin, vancomycin, ampicillin) or water (vehicle) from postnatal day 7 (P7) until weaning (P23) to induce gut dysbiosis. Behavior (cognition; anxiety-like behavior), microbiota sequencing, and qPCR (ileum, colon, hippocampus and pre-frontal cortex [PFC]) were performed in adult mice (6–8 weeks). Neonatal Abx administration led to intestinal dysbiosis in adulthood, impaired intestinal physiology, coupled with perturbations of bacterial metabolites and behavioral alterations (cognitive deficits and anxiolytic behavior). Expression of myelin-related genes (Mag, Mog, Mbp, Mobp, Plp) and transcription factors (Sox10, Myrf) important for oligodendrocytes were significantly increased in the PFC region of Abx-treated mice. Increased myelination was confirmed by immunofluorescence imaging and western blot analysis, demonstrating increased expression of MBP, SOX10 and MYRF in neonatally Abx-treated mice compared to sham controls in adulthood. Finally, administration of the short chain fatty acid butyrate following completion of the Abx treatment restored intestinal physiology, behavior, and myelination impairments, suggesting a critical role for the gut microbiota in mediating these effects. Taken together, we identified a long-lasting impact of neonatal Abx administration on the MGB axis, specifically on myelin regulation in the PFC region, potentially contributing to impaired cognitive function and bacterial metabolites are effective in reversing this altered phenotype.
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影响因子：
7.3
作者：
Arrieta MC;Stiemsma LT;Amenyogbe N;Brown EM;Finlay B
通讯作者：
Finlay B
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
3.5
作者：
Clark, RE;West, AN;Squire, LR
通讯作者：
Squire, LR
DOI：
10.1177/0148607113486809
发表时间：
2013-11
期刊：
JPEN. Journal of parenteral and enteral nutrition
影响因子：
--
作者：
Cresci G;Nagy LE;Ganapathy V
通讯作者：
Ganapathy V
影响因子：
6.6
作者：
BENES, FM
通讯作者：
BENES, FM