Pan Si-Yuan, Zhou Cheng-Bei, Deng Jia-Wen, Zhou Yi-Lu, Liu Zhu-Hui, Fang Jing-Yuan
Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Institute of Digestive Disease, Shanghai, China.
J Gastroenterol Hepatol. 2024 May;39(5):868-879. doi: 10.1111/jgh.16462. Epub 2024 Jan 14.
Patients with cholelithiasis (CL) or cholecystectomy (CE) would have more chances of getting colorectal adenoma (CRA) or cancer (CRC). We aimed to figure out the effects of gut microbiota and bile acid on colorectal neoplasm in CL and CE patients.
This was a retrospective observational study that recruited 514 volunteers, including 199 people with normal gallbladders (normal), 152 CL, and 163 CE patients. Discovery cohort was established to explore the difference in gut microbiota through 16S rRNA and metagenomics sequencing. Validation cohort aimed to verify the results through quantitative polymerase chain reaction (qPCR).
Significant enrichment of Escherichia coli was found in patients with cholelithiasis or cholecystectomy both in the discovery cohort (16S rRNA sequencing, P = 0.013, P = 0.042; metagenomics sequencing, P = 0.026) and validation cohort (P < 0.0001, P < 0.0001). Pks E. coli was found enriched in CL and CE patients through qPCR (in discovery cohort: P = 0.018; in validation cohort: P < 0.0001, P < 0.0001). The differences in bile acid metabolism were found both through Tax4Fun analysis of 16S rRNA sequencing (Ko00120, primary bile acid biosynthesis, P = 0.014; Ko00121, secondary bile acid biosynthesis, P = 0.010) and through metagenomics sequencing (map 00121, P = 0.026). The elevation of serum total bile acid of CE patients was also found in validation cohort (P < 0.0001). The level of serum total bile acid was associated with the relative abundance of pks E. coli (r = 0.1895, P = 0.0012).
E. coli, especially pks species, was enriched in CL and CE patients. Pks E. coli and bile acid metabolism were found associated with CRA and CRC in people after cholecystectomy.
胆石症（CL）或胆囊切除术（CE）患者患结直肠腺瘤（CRA）或癌（CRC）的几率更高。我们旨在探究肠道微生物群和胆汁酸对CL和CE患者结直肠肿瘤的影响。
这是一项回顾性观察研究，招募了514名志愿者，包括199名胆囊正常者（正常组）、152名CL患者和163名CE患者。建立发现队列，通过16S rRNA和宏基因组测序探索肠道微生物群的差异。验证队列旨在通过定量聚合酶链反应（qPCR）验证结果。
在发现队列（16S rRNA测序，P = 0.013，P = 0.042；宏基因组测序，P = 0.026）和验证队列（P < 0.0001，P < 0.0001）中，胆石症或胆囊切除术患者的大肠杆菌均有显著富集。通过qPCR发现产志贺毒素大肠杆菌在CL和CE患者中富集（在发现队列中：P = 0.018；在验证队列中：P < 0.0001，P < 0.0001）。通过对16S rRNA测序的Tax4Fun分析（Ko00120，初级胆汁酸生物合成，P = 0.014；Ko00121，次级胆汁酸生物合成，P = 0.010）和宏基因组测序（map 00121，P = 0.026）均发现胆汁酸代谢存在差异。在验证队列中也发现CE患者血清总胆汁酸升高（P < 0.0001）。血清总胆汁酸水平与产志贺毒素大肠杆菌的相对丰度相关（r = 0.1895，P = 0.0012）。
CL和CE患者中大肠杆菌，尤其是产志贺毒素菌株富集。发现胆囊切除术后人群中产志贺毒素大肠杆菌和胆汁酸代谢与CRA和CRC相关。
