Gut microbiota composition in chemotherapy and targeted therapy of patients with metastatic colorectal cancer

Yen-Cheng Chen; Chia-Hsien Chuang; Zhi-Feng Miao; Kwan-Ling Yip; Chung-Jung Liu; Ling-Hui Li; Deng-Chyang Wu; Tian Lu Cheng; Chung-Yen Lin; Jaw-Yuan Wang

doi:10.3389/fonc.2022.955313

Gut microbiota composition in chemotherapy and targeted therapy of patients with metastatic colorectal cancer

Front Oncol. 2022 Sep 23:12:955313. doi: 10.3389/fonc.2022.955313. eCollection 2022.

Authors

Yen-Cheng Chen^{1

2}, Chia-Hsien Chuang³, Zhi-Feng Miao¹, Kwan-Ling Yip¹, Chung-Jung Liu⁴, Ling-Hui Li⁵, Deng-Chyang Wu^{6

7}, Tian Lu Cheng⁶, Chung-Yen Lin³, Jaw-Yuan Wang^{1

2

8

9

10

11}

Affiliations

¹ Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
² Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
³ Institute of Information Science, Academia Sinica, Taipei, Taiwan.
⁴ Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
⁵ Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
⁶ Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁷ Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁸ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁹ Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹⁰ Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹¹ Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan.

Abstract

Studies have reported the effects of the gut microbiota on colorectal cancer (CRC) chemotherapy, but few studies have investigated the association between gut microbiota and targeted therapy. This study investigated the role of the gut microbiota in the treatment outcomes of patients with metastatic CRC (mCRC). We enrolled 110 patients with mCRC and treated them with standard cancer therapy. Stool samples were collected before administering a combination of chemotherapy and targeted therapy. Patients who had a progressive disease (PD) or partial response (PR) for at least 12 cycles of therapy were included in the study. We further divided these patients into anti-epidermal growth factor receptor (cetuximab) and anti-vascular endothelial growth factor (bevacizumab) subgroups. The gut microbiota of the PR group and bevacizumab-PR subgroup exhibited significantly higher α-diversity. The β-diversity of bacterial species significantly differed between the bevacizumab-PR and bevacizumab-PD groups (P = 0.029). Klebsiella quasipneumoniae exhibited the greatest fold change in abundance in the PD group than in the PR group. Lactobacillus and Bifidobacterium species exhibited higher abundance in the PD group. The abundance of Fusobacterium nucleatum was approximately 32 times higher in the PD group than in the PR group. A higher gut microbiota diversity was associated with more favorable treatment outcomes in the patients with mCRC. Bacterial species analysis of stool samples yielded heterogenous results. K. quasipneumoniae exhibited the greatest fold change in abundance among all bacterial species in the PD group. This result warrants further investigation especially in a Taiwanese population.

Keywords: Bifidobacterium species; Fusobacterium nucleatum; Klebsiella quasipneumoniae; Lactobacillus species; metastatic colorectal cancer; targeted therapy.