Disordered Gut Microbiota in Colorectal Tumor-Bearing Mice Altered Serum Metabolome Related to Fufangchangtai

Mengmeng Cai; Ya Xiao; Zhibing Lin; Jinmiao Lu; Xiaoyu Wang; Sajid Ur Rahman; Shilan Zhu; Xiaoyu Chen; Jialin Gu; Yuzhu Ma; Zhaoguo Chen; Jiege Huo

doi:10.3389/fphar.2022.889181

Disordered Gut Microbiota in Colorectal Tumor-Bearing Mice Altered Serum Metabolome Related to Fufangchangtai

Front Pharmacol. 2022 May 26:13:889181. doi: 10.3389/fphar.2022.889181. eCollection 2022.

Authors

Mengmeng Cai^{1

2

3}, Ya Xiao^{1

2}, Zhibing Lin⁴, Jinmiao Lu^{3

5}, Xiaoyu Wang⁴, Sajid Ur Rahman^{3

6}, Shilan Zhu^{3

5}, Xiaoyu Chen^{3

5}, Jialin Gu^{1

2}, Yuzhu Ma^{1

2}, Zhaoguo Chen³, Jiege Huo^{1

2}

Affiliations

¹ Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
² Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China.
³ Key Laboratory of Animal Parasitology of Ministry of Agriculture, Laboratory of Quality and Safety Risk Assessment for Animal Products on Biohazards (Shanghai) of Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
⁴ School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.
⁵ South China Agricultural University, Guangzhou, China.
⁶ College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.

Abstract

Purpose: This study aimed to investigate the relationship between gut microbiota (GM) and serum metabolism using antineoplastic Fufangchangtai (FFCT) as the model prescription in the treatment of colorectal cancer (CRC). Methods: Tumor-bearing mice and normal mice were administered different doses of FFCT. The tumor volume of tumor-bearing mice was observed. The levels of CD4⁺ and CD8⁺ T cells in the blood, spleen, and tumor of mice were determined using a flow cytometer. The bacterial microbiota in stool samples from mice and the serum metabolomics of FFCT-treated mice and fecal microbiota transplantation mice were detected using 16s RNA sequencing and liquid chromatography-mass spectrometry (LC/MS), respectively. Results: The tumor volume of mice showed no significant decrease after FFCT intervention. The levels of CD4⁺ and CD8⁺T lymphocytes showed a significant increase under the intervention of FFCT. GM of colorectal tumor-bearing mice and healthy mice were determined, and the diversity and abundance of Firmicutes, Deferribacteres, Bacteroidetes, and Proteobacteria were significantly different between the two groups. Furthermore, we found that the levels of matrine, isogingerenone B, and armillaripin were significantly decreased in tumor-bearing mice after FFCT intervention, indicating that the tumor-induced dysbiosis of gut bacteria may affect the absorption and metabolism of FFCT. Under the intervention of FFCT, serum metabolism of mice transplanted with feces from CRC patients showed less metabolites related to FFCT than that from healthy people, indicating that GM could be a single factor affecting the metabolism of FFCT. Furthermore, we found that different doses of FFCT-treated mice had higher abundance of Roseburia, Turicibacter, and Flexispira than that in the non-intervention control group. Firmicutes and Bacteroidetes in FFCT-treated groups showed a similar trend compared to the healthy group, indicating that FFCT might correct the intestinal microenvironment by modulating gut microbiota in colorectal tumor-bearing mice. Conclusion: The dysbiosis of GM in tumor-bearing mice reduced the serum metabolites related to FFCT, and FFCT could correct the disordered GM of colorectal tumor-bearing mice to exert efficacy.

Keywords: Fufangchangtai; colorectal cancer; gut microbiota; serum metabolome; traditional Chinese medicine.