Schalich Kasey, Rajagopala Seesandra, Das Suman, O'Connell Ryan, Yan Fang
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States.
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
Front Microbiol. 2023 Jan 4;13:1051310. doi: 10.3389/fmicb.2022.1051310. eCollection 2022.
Intestinal epithelial cells (IECs) provide the frontline responses to the gut microbiota for maintaining intestinal homeostasis. Our previous work revealed that IEC-derived components promote the beneficial effects of a commensal and probiotic bacterium, GG (LGG). This study aimed to elucidate the regulatory effects of IEC-derived components on LGG at the molecular level.
Differential gene expression in LGG cultured with IEC-derived components at the timepoint between the exponential and stationary phase was studied by RNA sequencing and functional analysis.
The transcriptomic profile of LGG cultured with IEC-derived components was significantly different from that of control LGG, with 231 genes were significantly upregulated and 235 genes significantly down regulated (FDR <0.05). The Clusters of Orthologous Groups (COGs) and Gene Ontology (GO) analysis demonstrated that the predominant genes enriched by IEC-derived components are involved in nutrient acquisition, including transporters for amino acids, metals, and sugars, biosynthesis of amino acids, and in the biosynthesis of cell membrane and cell wall, including biosynthesis of fatty acid and lipoteichoic acid. In addition, genes associated with cell division and translation are upregulated by IEC-derived components. The outcome of the increased transcription of these genes is supported by the result that IEC-derived components significantly promoted LGG growth. The main repressed genes are associated with the metabolism of amino acids, purines, carbohydrates, glycerophospholipid, and transcription, which may reflect regulation of metabolic mechanisms in response to the availability of nutrients in bacteria.
These results provide mechanistic insight into the interactions between the gut microbiota and the host.
肠道上皮细胞（IECs）对肠道微生物群做出一线反应以维持肠道稳态。我们之前的研究表明，IECs衍生成分可促进共生益生菌GG（LGG）的有益作用。本研究旨在阐明IECs衍生成分在分子水平上对LGG的调节作用。
通过RNA测序和功能分析研究了在指数期和稳定期之间的时间点用IECs衍生成分培养的LGG中的差异基因表达。
用IECs衍生成分培养的LGG的转录组谱与对照LGG的转录组谱显著不同，有231个基因显著上调，235个基因显著下调（FDR<0.05）。直系同源基因簇（COGs）和基因本体论（GO）分析表明，IECs衍生成分富集的主要基因参与营养获取，包括氨基酸、金属和糖的转运蛋白、氨基酸的生物合成，以及细胞膜和细胞壁的生物合成，包括脂肪酸和脂磷壁酸的生物合成。此外，与细胞分裂和翻译相关的基因被IECs衍生成分上调。这些基因转录增加的结果得到了IECs衍生成分显著促进LGG生长这一结果的支持。主要被抑制的基因与氨基酸、嘌呤、碳水化合物、甘油磷脂的代谢以及转录有关，这可能反映了细菌对营养物质可用性的代谢机制调节。
这些结果为肠道微生物群与宿主之间的相互作用提供了机制性见解。
