Regulation of Enteroendocrine Cell Networks by the Major Human Gut Symbiont Bacteroides thetaiotaomicron.
Regulation of Enteroendocrine Cell Networks by the Major Human Gut Symbiont Bacteroides thetaiotaomicron.
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DOI：
10.3389/fmicb.2020.575595
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发表时间：
2020
影响因子：
5.2
通讯作者：
Carding SR
中科院分区：
文献类型：
--
作者：
Modasia A;Parker A;Jones E;Stentz R;Brion A;Goldson A;Defernez M;Wileman T;Ashley Blackshaw L;Carding SR
肠道微生物在维持宿主生理功能方面具有重要作用，但它们对上皮化学感受性肠内分泌细胞（EEC）的影响尚不清楚。我们研究了普遍存在的肠道细菌多形拟杆菌（Bt）及其主要发酵产物乙酸盐、丙酸盐和琥珀酸盐（APS）在小鼠胃肠道（GIT）中形成EEC网络的作用。在无特定病原体（SPF）、无菌（GF）小鼠、Bt或罗伊氏乳杆菌（Lr）常规化的GF小鼠以及给予APS的GF小鼠中，通过荧光免疫组织化学评估了胃肠道沿着组织中EEC群体的分布和数量。同时，我们还评估了这些研究中使用肠隐窝来源的上皮单层培养物的适用性。GF小鼠上调其EEC网络，在一般EEC标志物嗜铬粒蛋白A（ChrA）表达、产生嗜铬粒蛋白的肠嗜铬细胞的数量以及产生胰高血糖素的K细胞和L细胞方面，血清胰高血糖素样肽-1（GLP-1）水平相应增加。Bt常规化使EEC数量恢复到SPF小鼠的水平，具有区域特异性;对ChrA和L细胞的影响主要在小肠中，对K细胞和EC细胞的影响在结肠中最明显。相比之下，Lr没有恢复常规GF小鼠的EEC网络。对来自整个小肠的分泌性上皮细胞单层培养物的分析表明，肠单层是可变的，并且可能排除GIP表达细胞，不能准确反映体内观察到的EEC细胞组成。关于Bt对EECs的作用机制，用Bt定殖GF小鼠导致乙酸盐、丙酸盐和琥珀酸盐（APS）在盲肠和结肠中的产生和积累，当以生理浓度通过饮用水给予GF小鼠10天时，其在很大程度上模拟了Bt在GF小鼠中的作用。停用APS后，某些EEC的变化保持不变，在某些情况下，变化大于APS治疗期间的变化。这些数据提供了微生物群影响GIT不同区域调节EEC网络的证据，其中单一微生物Bt概括了其在可能依赖于其发酵产物的过程中的作用。
Gut microbes have critical roles in maintaining host physiology, but their effects on epithelial chemosensory enteroendocrine cells (EEC) remain unclear. We investigated the role that the ubiquitous commensal gut bacterium Bacteriodes thetaiotaomicron (Bt) and its major fermentation products, acetate, propionate, and succinate (APS) have in shaping EEC networks in the murine gastrointestinal tract (GIT). The distribution and numbers of EEC populations were assessed in tissues along the GIT by fluorescent immunohistochemistry in specific pathogen free (SPF), germfree (GF) mice, GF mice conventionalized by Bt or Lactobacillus reuteri (Lr), and GF mice administered APS. In parallel, we also assessed the suitability of using intestinal crypt-derived epithelial monolayer cultures for these studies. GF mice up-regulated their EEC network, in terms of a general EEC marker chromogranin A (ChrA) expression, numbers of serotonin-producing enterochromaffin cells, and both hormone-producing K- and L-cells, with a corresponding increase in serum glucagon-like peptide-1 (GLP-1) levels. Bt conventionalization restored EEC numbers to levels in SPF mice with regional specificity; the effects on ChrA and L-cells were mainly in the small intestine, the effects on K-cells and EC cells were most apparent in the colon. By contrast, Lr did not restore EEC networks in conventionalized GF mice. Analysis of secretory epithelial cell monolayer cultures from whole small intestine showed that intestinal monolayers are variable and with the possible exclusion of GIP expressing cells, did not accurately reflect the EEC cell makeup seen in vivo. Regarding the mechanism of action of Bt on EECs, colonization of GF mice with Bt led to the production and accumulation of acetate, propionate and succinate (APS) in the caecum and colon, which when administered at physiological concentrations to GF mice via their drinking water for 10 days mimicked to a large extent the effects of Bt in GF mice. After withdrawal of APS, the changes in some EEC were maintained and, in some cases, were greater than during APS treatment. This data provides evidence of microbiota influences on regulating EEC networks in different regions of the GIT, with a single microbe, Bt, recapitulating its role in a process that may be dependent upon its fermentation products.
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影响因子：
4.8
作者：
Habib, Abdella M.;Richards, Paul;Gribble, Fiona M.
通讯作者：
Gribble, Fiona M.
影响因子：
64.5
作者：
Beumer, Joep;Puschhof, Jens;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
56.9
作者：
Bry, L;Falk, PG;Gordon, JI
通讯作者：
Gordon, JI
L细胞转录组的微生物调节。
影响因子：
4.6
作者：
Arora T;Akrami R;Pais R;Bergqvist L;Johansson BR;Schwartz TW;Reimann F;Gribble FM;Bäckhed F
通讯作者：
Bäckhed F
影响因子：
4.8
作者：
Egerod, Kristoffer L.;Engelstoft, Maja S.;Schwartz, Thue W.
通讯作者：
Schwartz, Thue W.