He Fuhai, Huang Xiaoliang, Wang Zhen, Qin Mingjian, Chen Chuanbin, Huang Zigui, Wu Yongzhi, Huang Yongqi, Tang Binzhe, Long Chenyan, Mo Xianwei, Tang Weizhong, Liu Jungang
Department of Gastrointestinal Surgery, Division of Colorectal and Anal Surgery, Guangxi Medical University Cancer Hospital, Nanning, People's Republic of China.
Mol Carcinog. 2025 Mar;64(3):526-542. doi: 10.1002/mc.23863. Epub 2024 Dec 18.
This study aims to determine whether gender is a factor in the interplay between the human intestinal flora and colorectal cancer (CRC), ultimately providing new evidence for the clinical prediction and management of CRC in different genders. In this study, we included 186 untreated CRC patients, and classified them into two groups based on pathological staging: Groups Ⅰ-Ⅱ and Groups Ⅲ-Ⅳ, with male and female groups within each group. We collected preoperative fecal samples from these patients and performed 16S rRNA gene sequencing to analyze their intestinal flora. In the CRC Stages I-II cohort, the gut microbiota of the female group exhibited greater diversity and abundance compared to the male group, with a total of 13 gut microbiota demonstrating significant disparities. Notably, s__Parabacteroides gordonii, s__Bacteroides faecis, and s__Bacteroides nordii were found to be more prevalent in the female group relative to the male group. Within the CRC Stages III-IV cohort, 51 gut microbiota exhibited significant differences between the genders. In the immunocyte composition of fecal samples from patients with CRC, a higher proportion of naive B cells is observed in the male group as compared to the female group. In female CRC patients within the CRC Stages III-IV cohort, Actinomyces exhibited a significant negative correlation with activated dendritic cells, CD4+ memory T cells, and eosinophils. In male CRC patients within the CRC Stages III-IV cohort, Actinomyces demonstrated a significant positive correlation with naive B cells and a significant positive correlation with immune activation genes TNFRSF25 and TMIGD2. In female CRC patients within the CRC Stages III-IV cohort, Actinomyces showed a significant negative correlation with activated dendritic cells, CD4+ memory T cells, and eosinophils, and a significant positive correlation with immune activation genes TNFSF13B, LTA, KLRK1, and CXCL12. In the CRC Stages I-II group, the female group's intestinal flora is more diverse and richer than the male group. In the CRC Stages III-IV group, there are a total of 51 different intestinal flora in both the male and female groups. We also found that Actinomyces affects the occurrence and development of CRC in the male and female groups through different pathways. The results show that the intestinal flora differs between male and female CRC patients and is closely associated with cancer development.
本研究旨在确定性别是否是人类肠道菌群与结直肠癌(CRC)相互作用中的一个因素,最终为不同性别的CRC临床预测和管理提供新证据。在本研究中,我们纳入了186例未经治疗的CRC患者,并根据病理分期将他们分为两组:Ⅰ-Ⅱ期组和Ⅲ-Ⅳ期组,每组再分为男性组和女性组。我们收集了这些患者的术前粪便样本,并进行16S rRNA基因测序以分析其肠道菌群。在CRCⅠ-Ⅱ期队列中,女性组的肠道微生物群与男性组相比表现出更高的多样性和丰度,共有13种肠道微生物群存在显著差异。值得注意的是,相对于男性组,戈登拟杆菌、粪拟杆菌和诺氏拟杆菌在女性组中更为普遍。在CRCⅢ-Ⅳ期队列中,51种肠道微生物群在性别之间存在显著差异。在CRC患者粪便样本的免疫细胞组成中,男性组中幼稚B细胞的比例高于女性组。在CRCⅢ-Ⅳ期队列的女性CRC患者中,放线菌与活化树突状细胞、CD4+记忆T细胞和嗜酸性粒细胞呈显著负相关。在CRCⅢ-Ⅳ期队列的男性CRC患者中,放线菌与幼稚B细胞呈显著正相关,与免疫激活基因TNFRSF25和TMIGD2呈显著正相关。在CRCⅢ-Ⅳ期队列的女性CRC患者中,放线菌与活化树突状细胞、CD4+记忆T细胞和嗜酸性粒细胞呈显著负相关,与免疫激活基因TNFSF13B、LTA、KLRK1和CXCL12呈显著正相关。在CRCⅠ-Ⅱ期组中,女性组的肠道菌群比男性组更多样化和丰富。在CRCⅢ-Ⅳ期组中,男性和女性组共有51种不同的肠道菌群。我们还发现放线菌通过不同途径影响男性和女性组中CRC的发生和发展。结果表明,男性和女性CRC患者的肠道菌群不同,且与癌症发展密切相关。