Regulation of gut luminal serotonin by commensal microbiota in mice.

Regulation of gut luminal serotonin by commensal microbiota in mice.
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DOI:
10.1371/journal.pone.0180745
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发表时间:
2017
期刊:
影响因子:
3.7
通讯作者:
Sudo N
Sudo N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hata T;Asano Y;Yoshihara K;Kimura-Todani T;Miyata N;Zhang XT;Takakura S;Aiba Y;Koga Y;Sudo N

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肠腔血清素(5-羟色胺:5-HT)有助于几种胃肠道功能,如蠕动反射。5-HT从肠嗜铬(EC)细胞释放,以响应许多刺激,包括来自肠道微生物群的信号。然而,肠道微生物群调节肠腔中5-HT水平的具体机制尚未阐明。我们以前的工作与gnotobiotic小鼠表明,游离的儿茶酚胺可以产生的共轭的儿茶酚胺的解共轭,因此,我们推测,解共轭的细菌酶可能是肠道微生物可以产生游离的5-HT在肠腔的机制之一。在这项研究中,我们使用无菌(GF)小鼠和无特定病原体(SPF)粪便植物群(EX-GF)感染的无菌小鼠来验证这一假设。GF小鼠盲肠和结肠腔中的5-HT水平显著低于EX-GF小鼠。此外,这些水平在暴露于SPF微生物群后仅3天内迅速增加。在EX-GF小鼠中,大部分5-HT为非结合的游离形式,而在GF小鼠中发现约50%的5-HT为结合形式。这些结果进一步支持了目前的观点,即肠道微生物群在促进具有生物活性的游离5-HT的产生方面起着至关重要的作用。葡萄糖醛酸苷结合的5-HT通过细菌酶解结合可能是导致肠腔中游离5-HT产生的机制之一。
Gut lumen serotonin (5-hydroxytryptamine: 5-HT) contributes to several gastrointestinal functions such as peristaltic reflexes. 5-HT is released from enterochromaffin (EC) cells in response to a number of stimuli, including signals from the gut microbiota. However, the specific mechanism by which the gut microbiota regulates 5-HT levels in the gut lumen has not yet been clarified. Our previous work with gnotobiotic mice showed that free catecholamines can be produced by the deconjugation of conjugated catecholamines; hence, we speculated that deconjugation by bacterial enzymes may be one of the mechanisms whereby gut microbes can produce free 5-HT in the gut lumen. In this study, we tested this hypothesis using germ-free (GF) mice and gnotobiotic mice recolonized with specific pathogen-free (SPF) fecal flora (EX-GF). The 5-HT levels in the lumens of the cecum and colon were significantly lower in the GF mice than in the EX-GF mice. Moreover, these levels were rapidly increased, within only 3 days after exposure to SPF microbiota. The majority of 5-HT was in an unconjugated, free form in the EX-GF mice, whereas approximately 50% of the 5-HT was found in the conjugated form in the GF mice. These results further support the current view that the gut microbiota plays a crucial role in promoting the production of biologically active, free 5-HT. The deconjugation of glucuronide-conjugated 5-HT by bacterial enzymes is likely one of the mechanisms contributing to free 5-HT production in the gut lumen.
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