Hepato-pancreato-biliary
Abhinav Seth, Resident Physician: General Surgery
General surgery Resident
Department of Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
Iowa city, Iowa, United States
Carlos HF Chan, MD, PhD
Associate Professor
Department of Surgery, University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
Zhong-Liao Fang, Doctor
Staff Physician
Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, Guangxi, United States
Brooks jackson, Doctor
Professor, Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City
University of Iowa Hospital & Clinics, United States
Zhi-Hua Jiang, Doctor
Staff
Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, Guangxi, China, Guangxi, China (People's Republic)
Xu Wei Lu, Doctor
Staff Physician
People's Hospital of Heng Zhou city, Guangxi, China
HenZhou, Guangxi, China (People's Republic)
Ming Yong Liang, Doctor
Staff Physician
Hengzhou Center for Disease Prevention and Control, Hengzhou city, Guangxi, China
Henghou, China (People's Republic)
Wen Qian Tang, Doctor
Staff Physician
Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, Guangxi, China
Nanning, Guangxi, China (People's Republic)
Introduction: Clonorchis sinensis (CS), a parasitic infection after consuming raw freshwater fishes in southeastern Asia, is associated with the development of cholangiocarcinoma (CCA) since they reside within the biliary system. Emerging evidence suggests CS plays a role in the development of hepatocellular carcinoma (HCC) although the underlying mechanism is poorly understood. We hypothesize CS infection leads to a dysbiosis of gut microbiome and promotes liver carcinogenesis.
Methods:
Methods: Stool and blood samples were collected from patients with CCA/HCC and healthy subjects in a CS-endemic region of Guangxi, China. CS and hepatitis B virus (HBV) infection were determined by stool microscopy and serum HBV surface antigen. Gut microbiome (N=10/group) was determined by 16S ribosomal RNA sequencing methods. Microbial diversity was determined by Shannon and Chao1 indices and ANOSIM analysis. MetaStat analysis was performed to identify microbial changes at the phylum and genus levels.
Results:
Results: Among HBV- subjects, alpha diversity was reduced in CS+ subjects by Chao1 index (505 in CS- Healthy vs. 387 in CS+ Healthy vs. 389 in CS+ CCA, one-way ANOVA P=0.008). Among HBV+ subjects, alpha diversity was not different between CS- and CS+ subjects but reduced in HCC vs. healthy subjects (466 in CS- Healthy vs. 375 in CS- HCC, P=0.07; 487 in CS+ Healthy vs. 386 in CS+ HCC, P=0.02). While beta diversity was reduced in cancer vs. healthy subjects regardless of HBV/CS status in ANOSIM analysis (R=0.166-0.856, P< 0.01), CS infection reduced beta diversity in HBV- healthy subjects (R=0.170, P=0.026). While Bacteroidota, Synergistota, and Desulfobacterota were enriched in cancer vs. healthy subjects (Fig. 1), no phylum was enriched in CS+ vs. CS- subjects. However, 48 and 14 genera were different between CS- vs. CS+ in HBV- and HBV+ healthy subjects, respectively; 5 were in common (Acidaminococcus and Oxalobacter enriched in CS+ subjects, Anaerocolumna, Ruminiclostridium and Harryflintia in CS- subjects). 25, 73 and 12 genera were different between cancer and healthy subjects based on their infection status: HBV+CS-, HBV+CS+, and HBV-CS+, respectively. Adlercreutzia, Bacteroides and Leptotrichia were enriched in HCC patients. Enterorhabdus, Prevotellaceae UCG-001, Rikenella, Candidatus Stoquefichus, and Turicibacter were reduced in HCC patients.
Conclusions:
Conclusions: CS infection decreases microbial diversities in HBV- subjects. Both CS infection and liver cancers are associated with dysbiosis of gut microbiome, which plays an important role in liver carcinogenesis and response to anti-cancer therapy.