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Abstract：
Extensive research has explored the role of gut microbiota in colorectal cancer (CRC). Nonetheless, metatranscriptomic studies investigating the in situ functional implications of host-microbe interactions in CRC are scarce. Therefore, we characterized the influence of CRC core pathogens and biofilms on the tumor microenvironment (TME) in 40 CRC, paired normal, and healthy tissue biopsies using fluorescence in situ hybridization (FISH) and dual-RNA sequencing. FISH revealed that Fusobacterium spp. was associated with increased bacterial biomass and inflammatory response in CRC samples. Dual-RNA sequencing demonstrated increased expression of pro-inflammatory cytokines, defensins, matrix-metalloproteases, and immunomodulatory factors in CRC samples with high bacterial activity. In addition, bacterial activity correlated with the infiltration of several immune cell subtypes, including M2 macrophages and regulatory T-cells in CRC samples. Specifically, Bacteroides fragilis and Fusobacterium nucleatum correlated with the infiltration of neutrophils and CD4+ T-cells, respectively. The collective bacterial activity/biomass appeared to exert a more significant influence on the TME than core pathogens, underscoring the intricate interplay between gut microbiota and CRC. These results emphasize how biofilms and core pathogens shape the immune phenotype and TME in CRC while highlighting the need to extend the bacterial scope beyond CRC pathogens to advance our understanding and identify treatment targets.
摘要：
广泛的研究已经探索了肠道微生物群在结直肠癌（CRC）中的作用。尽管如此，研究CRC中宿主-微生物相互作用的原位功能影响的meta转录组研究很少。因此,我们在40例CRC中表征了CRC核心病原体和生物膜对肿瘤微环境（TME）的影响，配对正常，和使用荧光原位杂交（FISH）和双RNA测序的健康组织活检。FISH显示梭杆菌属。与CRC样本中细菌生物量和炎症反应增加有关。双RNA测序显示促炎细胞因子的表达增加，防御素,基质金属蛋白酶，和免疫调节因子在CRC样品中具有高细菌活性。此外,细菌活性与几种免疫细胞亚型的浸润相关，包括CRC样品中的M2巨噬细胞和调节性T细胞。具体来说,脆弱拟杆菌和核梭杆菌属与中性粒细胞和CD4+T细胞浸润相关，分别。集体细菌活性/生物量似乎对TME的影响比核心病原体更显著。强调肠道微生物群和CRC之间复杂的相互作用。这些结果强调了生物膜和核心病原体如何塑造CRC中的免疫表型和TME，同时强调需要将细菌范围扩展到CRC病原体之外，以促进我们的理解和确定治疗靶标。
