LAUSR

Simple Summary Although alterations of intestinal bacterial microbiota have been admitted as playing one of the most important roles in colorectal carcinogenesis, the links between microbiota compositional changes and premalignant colorectal polyps have still not been fully examined. Furthermore, there is a lack of knowledge in terms of defining the precise differences and the correct interpretation of tissue-derived and stool-based bacterial dysbiosis in patients with precancerous colorectal lesions. Thus, this systematic review aims, firstly, to assess whether and how the tissue-derived intestinal microbiota structure differs from the bacterial dysbiosis in fecal samples of patients with simple, advanced colorectal adenoma and carcinoma in situ, and, secondly, to propose the correct selection of each matrix in order to increase sampling accuracy and applicability in future microbiota studies and clinical practice. Abstract Alterations in gut microbiota play a pivotal role in the adenoma-carcinoma sequence. However, there is still a notable lack of the correct implementation of tissue and fecal sampling in the setting of human gut microbiota examination. This study aimed to review the literature and to consolidate the current evidence on the use of mucosa and a stool-based matrix investigating human gut microbiota changes in precancerous colorectal lesions. A systematic review of papers from 2012 until November 2022 published on the PubMed and Web of Science databases was conducted. The majority of the included studies have significantly associated gut microbial dysbiosis with premalignant polyps in the colorectum. Although methodological differences hampered the precise fecal and tissue-derived dysbiosis comparison, the analysis revealed several common characteristics in stool-based and fecal-derived gut microbiota structures in patients with colorectal polyps: simple or advanced adenomas, serrated lesions, and carcinomas in situ. The mucosal samples considered were more relevant for the evaluation of microbiota’s pathophysiological involvement in CR carcinogenesis, while non-invasive stool sampling could be beneficial for early CRC detection strategies in the future. Further studies are required to identify and validate mucosa-associated and luminal colorectal microbial patterns and their role in CRC carcinogenesis, as well as in the clinical setting of human microbiota studies.