Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut-Brain Axis.
Human-Derived Bifidobacterium dentium Modulates the Mammalian Serotonergic System and Gut-Brain Axis.
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DOI：
10.1016/j.jcmgh.2020.08.002
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发表时间：
2021
影响因子：
7.2
通讯作者：
Versalovic J
中科院分区：
文献类型：
--
作者：
Engevik MA;Luck B;Visuthranukul C;Ihekweazu FD;Engevik AC;Shi Z;Danhof HA;Chang-Graham AL;Hall A;Endres BT;Haidacher SJ;Horvath TD;Haag AM;Devaraj S;Garey KW;Britton RA;Hyser JM;Shroyer NF;Versalovic J
人体肠道微生物区系可以调节肠嗜铬细胞产生5-羟色胺。然而，微生物诱导的5-羟色胺信号转导机制还不是很清楚。用无菌培养液、活的双歧杆菌、热灭活的B牙或活的卵形杆菌处理成年无菌小鼠。用小鼠和人的肠样组织研究B牙本质代谢物对肠嗜铬细胞释放5-羟色胺的影响。用质谱仪测定体内、体外短链脂肪酸和5-羟色胺的含量。用定量聚合酶链式反应和免疫组织化学方法检测色氨酸羟化酶、短链脂肪酸受体2、5-羟色胺受体和5-羟色胺再摄取转运体的表达。RNA原位杂交检测5-羟色胺受体在脑内的表达，大理石埋藏实验评价5-羟色胺受体依赖行为。B牙本质单一相关的小鼠表现出粪便醋酸盐的增加。这一发现与肠道5-羟色胺浓度升高和5-羟色胺受体2a、4和5-羟色胺转运体表达增加相一致。这些影响在B卵子处理的小鼠中是不存在的。醋酸盐和B牙本质分泌物的应用可刺激小鼠和人的肠小体释放5-羟色胺。脑组织原位杂交还显示，与无菌对照组相比，B牙本质处理组小鼠海马区5-羟色胺受体2a的表达显著增加。在功能上，B牙本质的定植正常化物种--以前被证明与5-羟色胺受体2a有关的典型的重复和焦虑样行为。这些数据表明，B牙质和细菌代谢物醋酸酯能够调节多种宿主组织中5-羟色胺能系统的关键成分，并与成人行为的功能变化有关。
The human gut microbiota can regulate production of serotonin (5-hydroxytryptamine [5-HT]) from enterochromaffin cells. However, the mechanisms underlying microbial-induced serotonin signaling are not well understood. Adult germ-free mice were treated with sterile media, live Bifidobacterium dentium, heat-killed B dentium, or live Bacteroides ovatus. Mouse and human enteroids were used to assess the effects of B dentium metabolites on 5-HT release from enterochromaffin cells. In vitro and in vivo short-chain fatty acids and 5-HT levels were assessed by mass spectrometry. Expression of tryptophan hydroxylase, short-chain fatty acid receptor free fatty acid receptor 2, 5-HT receptors, and the 5-HT re-uptake transporter (serotonin transporter) were assessed by quantitative polymerase chain reaction and immunostaining. RNA in situ hybridization assessed 5-HT–receptor expression in the brain, and 5-HT–receptor–dependent behavior was evaluated using the marble burying test. B dentium mono-associated mice showed increased fecal acetate. This finding corresponded with increased intestinal 5-HT concentrations and increased expression of 5-HT receptors 2a, 4, and serotonin transporter. These effects were absent in B ovatus-treated mice. Application of acetate and B dentium–secreted products stimulated 5-HT release in mouse and human enteroids. In situ hybridization of brain tissue also showed significantly increased hippocampal expression of 5-HT–receptor 2a in B dentium–treated mice relative to germ-free controls. Functionally, B dentium colonization normalized species-typical repetitive and anxiety-like behaviors previously shown to be linked to 5-HT–receptor 2a. These data suggest that B dentium, and the bacterial metabolite acetate, are capable of regulating key components of the serotonergic system in multiple host tissues, and are associated with a functional change in adult behavior.
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DOI：
10.1016/j.jpba.2017.01.044
发表时间：
2017-05-10
影响因子：
3.4
作者：
Chan, James Chun Yip;Kioh, Dorinda Yan Qin;Chan, Eric Chun Yong
通讯作者：
Chan, Eric Chun Yong
影响因子：
64.8
作者：
Apelqvist, Å;Li, H;Edlund, H
通讯作者：
Edlund, H
影响因子：
4.8
作者：
Brown, AJ;Goldsworthy, SM;Dowell, SJ
通讯作者：
Dowell, SJ
影响因子：
5
作者：
BROEKKAMP, CL;RIJK, HW;LLOYD, KL
通讯作者：
LLOYD, KL
DOI：
10.1152/ajpgi.90375.2008
发表时间：
2008-12-01
影响因子：
4.5
作者：
Bertrand, Paul P.;Hu, Xiaoya;Bertrand, Rebecca L.
通讯作者：
Bertrand, Rebecca L.