Oral Administration of Penicillin or Streptomycin May Alter Serum Serotonin Level and Intestinal Motility via Different Mechanisms.
Oral Administration of Penicillin or Streptomycin May Alter Serum Serotonin Level and Intestinal Motility via Different Mechanisms.
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口服青霉素或链霉素可能通过不同机制改变血清血清素水平和肠道蠕动
DOI：
10.3389/fphys.2020.605982
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发表时间：
2020
影响因子：
4
通讯作者：
Rong W
中科院分区：
文献类型：
--
作者：
Zhu C;Gong H;Luo P;Dong L;Zhang G;Shi X;Rong W
背景/目的肠嗜铬细胞（Enterochromaffin cells， EC）是肠内分泌细胞中最大的细胞群，根据胃肠道（GIT）的机械和化学信号释放血清素（5-HT）。EC细胞如何对改变的微生物群作出反应，如由于抗生素治疗，仍然知之甚少。我们假设起搏器通道HCN2可能有助于EC细胞功能的调节及其对抗生素引起的肠道菌群变化的反应。方法小鼠分别给予青霉素或链霉素或两者同时给予饮水，连续10 d。采用气相色谱-质谱法检测青霉素或链霉素治疗后盲肠短链脂肪酸（SCFAs）谱的变化。测定血清5-HT含量、全肠运输时间、粪便含水量、盲肠重量及盲肠黏膜HCN2、TPH1的表达。伊伐布雷定（一种HCN通道阻滞剂）用于探索HCN2在青霉素诱导的5-羟色胺可利用性和肠蠕动变化中的作用。结果在肠上皮细胞上检测到HCN2免疫荧光。青霉素和链霉素均能显著降低盲肠中scfa总量，其中青霉素治疗组的丁酸盐、异丁酸盐和异戊酸盐水平比链霉素组降低得更大。青霉素组小鼠HCN2表达增加，链霉素组小鼠TPH1表达增加。抗生素组小鼠盲肠变大变重，血清5-羟色胺水平升高，粪便含水量增加。此外，青霉素治疗小鼠肠道转运时间延长。腹腔注射伊伐布雷定可减弱青霉素对血清5-HT水平、盲肠大小和重量、肠蠕动和粪便含水量的影响。结论口服青霉素对肠道菌群结构的破坏可显著提高血清5-HT水平，抑制肠道蠕动，至少部分是通过上调HCN2的表达来实现的。口服链霉素可能通过上调TPH1的表达，从而增加5-HT的合成，从而改变5-HT的可利用性。不同抗生素对肠道菌群组成的影响可能通过不同机制调节5-羟色胺的可利用性和肠道蠕动。
Background/Aims Enterochromaffin cells (EC cells) constitute the largest population of enteroendocrine cells and release serotonin (5-HT) in response to mechanical and chemical cues of the gastrointestinal tract (GIT). How EC cells respond to altered microbiota such as due to antibiotic treatments remain poorly understood. We hypothesized that the pacemaker channel HCN2 might contribute to the regulation of EC cells functions and their responses to antibiotics-induced changes in intestinal flora. Methods Mice were given either penicillin or streptomycin or both in drinking water for 10 consecutive days. The changes in the profile of short chain fatty acids (SCFAs) in the cecum following penicillin or streptomycin treatments were tested by GC-MS. Serum 5-HT content, whole intestinal transit time, fecal water content, cecum weight and expression of HCN2 and TPH1 in cecal mucosa were measured. Ivabradine (a HCN channels blocker) was used to explore the role of HCN2 in penicillin-induced changes in 5-HT availability and intestinal motility. Results HCN2 immunofluorescence was detected on intestinal EC cells. Both penicillin and streptomycin caused significant reduction in total SCFAs in the cecum, with the penicillin-treated group showing greater reductions in butyrate, isobutyrate and isovalerate levels than the streptomycin group. The expression of HCN2 was increased in the mice treated with penicillin, whereas TPH1 expression was increased in the mice treated with streptomycin. Mice treated with antibiotics all had larger and heavier cecum, elevated serum 5-HT level and increased fecal water content. Besides, mice treated with penicillin had prolonged intestinal transit time. Intraperitoneal injection of Ivabradine attenuated the effect of penicillin on serum 5-HT level, cecum size and weight, intestinal motility, and fecal water content. Conclusion Disruptions of the intestinal flora structure due to oral administration of penicillin may significantly increase serum 5-HT level and inhibit intestinal motility, at least partially through up-regulating the expression of HCN2. Oral administration of streptomycin may alter 5-HT availability by up-regulating TPH1 expression thus increasing synthesis of 5-HT. Alterations of intestinal flora composition due to exposure to different antibiotics may regulate 5-HT availability and intestinal motility through different mechanisms.
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肠粘蛋白5-HT细胞 - GLP-1和肠道微生物代谢产物的主要靶标。
影响因子：
8.1
作者：
Lund ML;Egerod KL;Engelstoft MS;Dmytriyeva O;Theodorsson E;Patel BA;Schwartz TW
通讯作者：
Schwartz TW
影响因子：
11.1
作者：
Golubeva AV;Joyce SA;Moloney G;Burokas A;Sherwin E;Arboleya S;Flynn I;Khochanskiy D;Moya-Pérez A;Peterson V;Rea K;Murphy K;Makarova O;Buravkov S;Hyland NP;Stanton C;Clarke G;Gahan CGM;Dinan TG;Cryan JF
通讯作者：
Cryan JF
影响因子：
--
作者：
Frye RE;Rose S;Slattery J;MacFabe DF
通讯作者：
MacFabe DF
影响因子：
4.8
作者：
Brown, AJ;Goldsworthy, SM;Dowell, SJ
通讯作者：
Dowell, SJ
影响因子：
4.2
作者：
de la Batie, Caroline Dejean;Barbier, Valerie;Ouss, Lisa
通讯作者：
Ouss, Lisa