發(fā)布者：抗性基因網(wǎng) 時(shí)間：2023-06-14 瀏覽量：627
摘要
? ? ? 癌癥（CRC）患者腸道微生物群的分類組成發(fā)生了變化，這是一種新發(fā)現(xiàn)的疾病背后的驅(qū)動(dòng)力，但其活性卻被忽視了。我們通過元轉(zhuǎn)錄組和16S rRNA基因（rDNA）測序?qū)RC腸道中的活性微生物分類組成進(jìn)行了初步研究。我們揭示了CRC（n?=?10） 和控制（n?=?10） 過度活躍和休眠物種的群落，因?yàn)榛顒?dòng)的變化往往與豐度無關(guān)。引人注目的是，患病的腸道顯著影響了丁酸產(chǎn)生菌、臨床相關(guān)ESKAPE、口服和腸桿菌科病原體的轉(zhuǎn)錄。對(duì)抗生素（AB）耐藥性基因的重點(diǎn)分析表明，CRC和對(duì)照微生物群都表現(xiàn)出多藥耐藥性表型，包括ESKAPE物種。然而，幾個(gè)AB家族的絕大多數(shù)AB抗性決定因素在CRC腸道中上調(diào)。我們發(fā)現(xiàn)，環(huán)境腸道因素以主要依賴于健康的方式調(diào)節(jié)體外有氧CRC微生物群的AB抗性基因表達(dá)，特別是酸壓、滲透壓和氧化壓。這與這些隊(duì)列的元轉(zhuǎn)錄組分析一致，而滲透壓和氧化壓誘導(dǎo)了不同的調(diào)節(jié)反應(yīng)。這項(xiàng)工作為CRC中活性微生物的組織提供了新的見解，并揭示了功能相關(guān)群體活性的顯著調(diào)節(jié)，以及AB抗性基因在微生物組范圍內(nèi)的意外上調(diào)，以應(yīng)對(duì)癌性腸道的環(huán)境變化。
ABSTRACT
Taxonomic composition of the gut microbiota in colorectal cancer (CRC) patients is altered, a newly recognized driving force behind the disease, the activity of which has been overlooked. We conducted a pilot study on active microbial taxonomic composition in the CRC gut via metatranscriptome and 16S rRNA gene (rDNA) sequencing. We revealed sub-populations in CRC (n?=?10) and control (n?=?10) cohorts of over-active and dormant species, as changes in activity were often independent from abundance. Strikingly, the diseased gut significantly influenced transcription of butyrate producing bacteria, clinically relevant ESKAPE, oral, and Enterobacteriaceae pathogens. A focused analysis of antibiotic (AB) resistance genes showed that both CRC and control microbiota displayed a multidrug resistant phenotype, including ESKAPE species. However, a significant majority of AB resistance determinants of several AB families were upregulated in the CRC gut. We found that environmental gut factors regulated AB resistance gene expression in vitro of aerobic CRC microbiota, specifically acid, osmotic, and oxidative pressures in a predominantly health-dependent manner. This was consistent with metatranscriptome analysis of these cohorts, while osmotic and oxidative pressures induced differentially regulated responses. This work provides novel insights into the organization of active microbes in CRC, and reveals significant regulation of functionally related group activity, and unexpected microbiome-wide upregulation of AB resistance genes in response to environmental changes of the cancerous gut.
https://journals.asm.org/doi/full/10.1128/msphere.00626-22