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  3. Integrated microbiome and metabolome analysis reveals synergistic efficacy of basil polysaccharide and gefitinib in lung cancer through modulation of gut microbiota and fecal metabolites

Integrated microbiome and metabolome analysis reveals synergistic efficacy of basil polysaccharide and gefitinib in lung cancer through modulation of gut microbiota and fecal metabolites

  • Int J Biol Macromol. 2024 Nov;281(Pt 2):135992. doi: 10.1016/j.ijbiomac.2024.135992.
Bing Feng 1,  Yanjing Lu 2,  Bowen Zhang 2,  Ying Zhu 1,  Zuqing Su 1,  Lipeng Tang 1,  Laijun Yang 3,  Tong Wang 2,  Chunxia He 4,  Chutian Li 5,  Jie Zhao 5,  Xirun Zheng 5,  Guangjuan Zheng 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
  • 2 State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
  • 3 Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
  • 4 State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
  • 5 Department of Pathology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China.
  • 6 State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Department of Pharmacology of Traditional Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Department of Pathology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China. Electronic address: zhengguangjuan@gzucm.edu.cn.
PMID: 39414535 DOI: 10.1016/j.ijbiomac.2024.135992
Abstract

Emerging evidence suggests that gut microbiota and its metabolites significantly influence the effectiveness of EGFR-TKIs (e.g., gefitinib, erlotinib) in lung Cancer treatment. Plant Polysaccharides can interact with gut microbiota, leading to changes in the host-microbe metabolome that may affect drug metabolism and therapeutic outcomes. Our previous research demonstrated the efficacy of basil polysaccharide (BPS) in treating various cancers by regulating hypoxic microenvironment and inhibiting epithelial-mesenchymal transition process. However, the potential impact of BPS on gut microbiota has not been thoroughly explored. In this study, we employed an immunodeficient gefitinib-resistant xenograft mouse model to explore whether BPS enhances the antitumor effects of gefitinib. A multi-omics approach, including 16S rDNA amplicon Sequencing and LC-MS, was used to elucidate these synergistic effects. Our findings indicate that BPS can enhance tumor responsiveness to gefitinib by modulating the gut microbiota and its metabolites through multiple metabolic pathways. These changes in gut microbiota and metabolites could potentially affect Cancer related signaling pathway and lung resistance-related protein, which are pivotal in determining the efficacy of EGFR-TKIs in Cancer treatment.

Keywords

Basil polysaccharide; EGFR-TKIs; Gefitinib; Gut microbiota; Lung cancer; Metabolites.

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