Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells
Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells
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DOI：
10.1096/fj.14-259598
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发表时间：
2015-04-01
期刊：
影响因子：
4.8
通讯作者：
Kashyap, Purna C.
中科院分区：
文献类型：
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作者：
Reigstad, Christopher S.;Salmonson, Charles E.;Kashyap, Purna C.
肠道微生物群的改变已经在几种胃肠（GI）运动改变的疾病中得到描述，并且人们对肠道微生物群在调节GI功能中的作用的认识正在增加。血清素[5-羟色胺（5-HT）]是胃肠道运动和分泌的关键调节因子。为了确定肠道微生物、结肠收缩性和宿主血清素能基因表达之间的关系，我们评估了无菌（GF）或人源化（HM;前GF定植有人类肠道微生物群）的小鼠。5-HT缩短GF和HM结肠的收缩持续时间。来自HM和常规饲养（CR）小鼠的微生物群显著增加了结肠mRNA Tph 1 [（色氨酸羟化酶）1，粘膜5-HT合成的速率限制; P < 0.01]和嗜铬粒蛋白A（神经内分泌; P < 0.01），对单胺氧化酶A（5-羟色胺催化剂），5-羟色胺受体5-HT 4或小鼠5-羟色胺转运蛋白没有影响。HM和CR小鼠的结肠Tph 1蛋白（P < 0.05）和5-HT浓度也增加（GF，17 +/- 3 ng/mg; HM，25 +/- 2 ng/mg; CR，35 +/- 3 ng/mg; P < 0.05）。肠嗜铬（EC）细胞数量（产生5-HT的细胞）不变。短链脂肪酸（SCFA）促进BON细胞（人EC细胞模型）中的TPH 1转录。因此，通过SCFA起作用的肠道微生物群是肠道5-HT产生和体内平衡的重要决定因素。
Gut microbiota alterations have been described in several diseases with altered gastrointestinal (GI) motility, and awareness is increasing regarding the role of the gut microbiome in modulating GI function. Serotonin [5-hydroxytryptamine (5-HT)] is a key regulator of GI motility and secretion. To determine the relationship among gut microbes, colonic contractility, and host serotonergic gene expression, we evaluated mice that were germ-free (GF) or humanized (HM; ex-GF colonized with human gutmicrobiota). 5-HT reduced contractile duration in both GF and HM colons. Microbiota from HM and conventionally raised (CR) mice significantly increased colonic mRNAs Tph1 [(tryptophan hydroxylase) 1, rate limiting for mucosal 5-HT synthesis; P < 0.01] and chromogranin A (neuroendocrine secretion; P < 0.01), with no effect on monoamine oxidase A (serotonin catabolism), serotonin receptor 5-HT4, or mouse serotonin transporter. HM and CR mice also had increased colonic Tph1 protein (P < 0.05) and 5-HT concentrations (GF, 17 +/- 3 ng/mg; HM, 25 +/- 2 ng/mg; and CR, 35 +/- 3 ng/mg; P < 0.05). Enterochromaffin (EC) cell numbers (cells producing 5-HT) were unchanged. Short-chain fatty acids (SCFAs) promoted TPH1 transcription in BON cells (human EC cell model). Thus, gut microbiota acting through SCFAs are important determinants of enteric 5-HT production and homeostasis.