L cells are an important class of enteroendocrine cells secreting hormones such as glucagon like peptide-1 and peptide YY that have several metabolic and physiological effects. The gut is home to trillions of bacteria affecting host physiology, but there has been limited understanding about how the microbiota affects gene expression in L cells. Thus, we rederived the reporter mouse strain, GLU-Venus expressing yellow fluorescent protein under the control of the proglucagon gene, as germ-free (GF). L_pos cells from ileum and colon of GF and conventionally raised (CONV-R) GLU-Venus mice were isolated and subjected to transcriptomic profiling. We observed that the microbiota exerted major effects on ileal L cells. Gene Ontology enrichment analysis revealed that microbiota suppressed biological processes related to vesicle localization and synaptic vesicle cycling in L_pos cells from ileum. This finding was corroborated by electron microscopy of L_pos cells showing reduced numbers of vesicles as well as by demonstrating decreased intracellular GLP-1 content in primary cultures from ileum of CONV-R compared with GF GLU-Venus mice. By analysing L_pos cells following colonization of GF mice we observed that the greatest transcriptional regulation was evident within 1 day of colonization. Thus, the microbiota has a rapid and pronounced effect on the L cell transcriptome, predominantly in the ileum.

中文翻译：

---

L细胞转录组的微生物调控。

L细胞是一类重要的肠内分泌细胞，分泌激素如胰高血糖素肽1和肽YY，具有多种代谢和生理作用。肠道是数以万亿计影响宿主生理的细菌的家园，但人们对微生物群如何影响 L 细胞中的基因表达的了解有限。因此，我们将报告小鼠品系、在胰高血糖素原基因控制下表达黄色荧光蛋白的 GLU-Venus 重新衍生为无菌 (GF)。位置_{_}来自回肠和结肠的 GF 细胞和常规培养的 (CONV-R) GLU-Venus 小鼠被分离出来并进行转录组分析。我们观察到微生物群对回肠 L 细胞产生重大影响。基因本体富集分析表明，微生物群抑制了回肠 L _pos细胞中与囊泡定位和突触囊泡循环相关的生物学过程。_{与 GF GLU-Venus 小鼠相比，L pos}细胞的电子显微镜证实了这一发现，显示囊泡数量减少，并且证明来自 CONV-R 回肠的原代培养物中细胞内 GLP-1 含量降低。通过分析 L _posGF 小鼠定殖后的细胞，我们观察到最大的转录调节在定殖后 1 天内很明显。因此，微生物群对主要在回肠的 L 细胞转录组具有快速而显着的影响。