The gut microbiota has been recognized as an important determinant in the initiation and progression of colorectal cancer (CRC), with recent studies shining light on the molecular mechanisms that may contribute to the interactions between microbes and the CRC microenvironment. Despite the increasing wealth of associations being established in the field, proving causality remains challenging. Obstacles include the high variability of the microbiome and its context, both across individuals and across time. Additionally, there is a lack of large and representative cohort studies with long-term follow-up and/or appropriate sampling methods for studying the mucosal microbiome. Finally, most studies focus on CRC, whereas interactions between host and bacteria in early events in carcinogenesis remain elusive, reinforced by the heterogeneity of CRC development. Here, we discuss these current most prominent obstacles, the recent developments, and research needs.

肠道微生物群已被认为是结直肠癌 (CRC) 发生和进展的重要决定因素，最近的研究揭示了可能有助于微生物与结直肠癌微环境之间相互作用的分子机制。尽管该领域建立的关联越来越丰富，但证明因果关系仍然具有挑战性。障碍包括微生物组及其背景在个体和时间上的高度变异性。此外，缺乏大规模且具有代表性的队列研究，以及长期随访和/或适当的采样方法来研究粘膜微生物组。最后，大多数研究都集中在结直肠癌上，而在致癌过程的早期事件中宿主和细菌之间的相互作用仍然难以捉摸，而结直肠癌发展的异质性又强化了这一点。在这里，我们讨论这些当前最突出的障碍、最新进展和研究需求。