摘要
      癌症（CRC）患者肠道微生物群的分类组成发生了变化，这是一种新发现的疾病背后的驱动力，但其活性却被忽视了。我们通过元转录组和16S rRNA基因（rDNA）测序对CRC肠道中的活性微生物分类组成进行了初步研究。我们揭示了CRC（n = 10） 和控制（n = 10） 过度活跃和休眠物种的群落，因为活动的变化往往与丰度无关。引人注目的是，患病的肠道显著影响了丁酸产生菌、临床相关ESKAPE、口服和肠杆菌科病原体的转录。对抗生素（AB）耐药性基因的重点分析表明，CRC和对照微生物群都表现出多药耐药性表型，包括ESKAPE物种。然而，几个AB家族的绝大多数AB抗性决定因素在CRC肠道中上调。我们发现，环境肠道因素以主要依赖于健康的方式调节体外有氧CRC微生物群的AB抗性基因表达，特别是酸压、渗透压和氧化压。这与这些队列的元转录组分析一致，而渗透压和氧化压诱导了不同的调节反应。这项工作为CRC中活性微生物的组织提供了新的见解，并揭示了功能相关群体活性的显著调节，以及AB抗性基因在微生物组范围内的意外上调，以应对癌性肠道的环境变化。
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