Degroote Stéphanie, Hunting Darel J, Baccarelli Andrea A, Takser Larissa
Faculté de Médecine et Sciences de la Santé, Université de Sherbrooke, 3001 12e Avenue Nord, Sherbrooke, QC J1H 5H3, Canada.
Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02115, United States.
Prog Neuropsychopharmacol Biol Psychiatry. 2016 Nov 3;71:76-82. doi: 10.1016/j.pnpbp.2016.06.010. Epub 2016 Jun 21.
A growing body of evidence indicates that gut microbiota characteristics may be closely related to mental dysfunctions. However, no studies have investigated fetal brain development in relation to the maternal gut microbiota, despite the extensive use of antibiotics in obstetric practice.
To determine how periconceptional exposure to SuccinylSulfaThiazole (SST), a non-absorbable antibiotic, can affect behavior in rat offspring. This antibiotic drug has previously been shown to substantially perturb the gut microbiota in rats following a 28-day exposure.
Female Wistar rats were divided in two groups: control, or exposed during one month before breeding until gestational day 15 to a diet containing 1% SST. We administered behavioral tests to offspring, i.e., open field (post-natal day 20), social interactions (P25), marble burying (P30), elevated plus maze (P35), and prepulse inhibition of the acoustic startle reflex (sensory gating) (P45).
Both male and female offspring exposed peri-conceptionally to SST showed reduced social interactions, with a decrease of about half in time spent in social interactions compared to controls, reduced exploration of the open arm by 20% in the elevated plus maze test indicating increased anxiety and altered sensorimotor gating, with a 1.5-2-fold decrease in startle inhibition.
Maternal periconceptional exposure to SST provokes alterations in offspring behavior in the absence of maternal infection. Because we administered SST, a non-absorbable antibiotic, only to the dam, we conclude that these neurobehavioral alterations in the offspring are related to maternal gut microbiota alterations.
越来越多的证据表明,肠道微生物群特征可能与精神功能障碍密切相关。然而,尽管产科实践中广泛使用抗生素,但尚无研究调查与母体肠道微生物群相关的胎儿大脑发育情况。
确定孕前接触不可吸收抗生素琥珀磺胺噻唑(SST)如何影响大鼠后代的行为。此前已证明,这种抗生素在暴露28天后会显著扰乱大鼠的肠道微生物群。
将雌性Wistar大鼠分为两组:对照组,或在交配前1个月至妊娠第15天期间接触含1% SST的饮食。我们对后代进行了行为测试,即旷场试验(出生后第20天)、社交互动试验(出生后第25天)、埋大理石试验(出生后第30天)、高架十字迷宫试验(出生后第35天)以及听觉惊吓反射的前脉冲抑制试验(感觉门控)(出生后第45天)。
孕前接触SST的雄性和雌性后代均表现出社交互动减少,与对照组相比,社交互动时间减少约一半,在高架十字迷宫试验中,对开放臂的探索减少20%,表明焦虑增加且感觉运动门控改变,惊吓抑制降低1.5至2倍。
在无母体感染的情况下,母体孕前接触SST会引发后代行为改变。由于我们仅对母鼠施用了不可吸收的抗生素SST,因此我们得出结论,后代的这些神经行为改变与母体肠道微生物群改变有关。