Gut microbiome and serum short-chain fatty acids are associated with responses to chemo- or targeted therapies in Chinese patients with lung cancer
BackgroundThe association between gut microbes and short-chain fatty acids (SCFAs) and therapeutic responses of patients with lung cancer (LC) receiving therapy remains unknown.MethodsFecal and serum samples were prospectively collected from patients with LC, classified as responders, if they presen...
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| Format: | Article |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1165360/full |
| _version_ | 1797777448157315072 |
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| author | Huan-Huan Chen Huan-Huan Chen Huan-Huan Chen Huan-Huan Chen Qi-Jun Wu Qi-Jun Wu Qi-Jun Wu Tie-Ning Zhang Tie-Ning Zhang Tie-Ning Zhang Tie-Ning Zhang Yu-Hong Zhao Yu-Hong Zhao Yu-Hong Zhao |
| author_facet | Huan-Huan Chen Huan-Huan Chen Huan-Huan Chen Huan-Huan Chen Qi-Jun Wu Qi-Jun Wu Qi-Jun Wu Tie-Ning Zhang Tie-Ning Zhang Tie-Ning Zhang Tie-Ning Zhang Yu-Hong Zhao Yu-Hong Zhao Yu-Hong Zhao |
| author_sort | Huan-Huan Chen |
| collection | DOAJ |
| description | BackgroundThe association between gut microbes and short-chain fatty acids (SCFAs) and therapeutic responses of patients with lung cancer (LC) receiving therapy remains unknown.MethodsFecal and serum samples were prospectively collected from patients with LC, classified as responders, if they presented durable clinical benefits, and non-responders, if not. The composition of gut microbes was analyzed using 16S ribosomal DNA sequencing. Serum SCFA concentrations were detected using gas chromatography. Cell proliferation, migration, invasion, cell cycle, and apoptosis assays were performed on isobutyric acid-treated A549 cells. Reverse transcription-quantitative PCR, Western blotting, immunocytochemistry, and immunofluorescence staining experiments have been performed to investigate the expression of associated genes or proteins.ResultsNon-responders harbored higher microbiome α-diversity but lower β-diversity compared with responders. Compared to the patients with low α-diversity, those with high α-diversity showed significantly shorter progression-free survival. Additionally, β-diversity has also been observed between these two groups. Specifically, Parasutterella, Clostridiaceae, and Prevotella_7 were more abundant among responders, whereas Bacteroides_stercoris and Christensenellaceae_R-7_group were more abundant in non-responders. The serum SCFA (especially acetate and isobutyrate) levels tended to be higher in responders. Isobutyric acid inhibited the proliferation, migration, and invasion of A549 cells by inducing apoptosis and G1/S arrest while upregulating the expression of GPR41, GPR43, and GPR5C and downregulating that of PAR1, and increasing the activity of histone acetyltransferases.ConclusionWe revealed the influence of gut microbiota and SCFAs on the therapeutic responses in patients with LC and the anti-tumor effect of isobutyric acid, indicating their potential use as therapeutic targets. |
| first_indexed | 2024-03-12T23:04:05Z |
| format | Article |
| id | doaj.art-d47dc968b76844cd8233ffcf731b697a |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-03-12T23:04:05Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-d47dc968b76844cd8233ffcf731b697a2023-07-19T06:13:21ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-07-011410.3389/fmicb.2023.11653601165360Gut microbiome and serum short-chain fatty acids are associated with responses to chemo- or targeted therapies in Chinese patients with lung cancerHuan-Huan Chen0Huan-Huan Chen1Huan-Huan Chen2Huan-Huan Chen3Qi-Jun Wu4Qi-Jun Wu5Qi-Jun Wu6Tie-Ning Zhang7Tie-Ning Zhang8Tie-Ning Zhang9Tie-Ning Zhang10Yu-Hong Zhao11Yu-Hong Zhao12Yu-Hong Zhao13Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, ChinaClinical Research Center, Shengjing Hospital of China Medical University, Shenyang, ChinaKey Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, ChinaClinical Research Center, Shengjing Hospital of China Medical University, Shenyang, ChinaKey Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, ChinaClinical Research Center, Shengjing Hospital of China Medical University, Shenyang, ChinaKey Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, ChinaClinical Research Center, Shengjing Hospital of China Medical University, Shenyang, ChinaKey Laboratory of Precision Medical Research on Major Chronic Disease, Shengjing Hospital of China Medical University, Shenyang, ChinaBackgroundThe association between gut microbes and short-chain fatty acids (SCFAs) and therapeutic responses of patients with lung cancer (LC) receiving therapy remains unknown.MethodsFecal and serum samples were prospectively collected from patients with LC, classified as responders, if they presented durable clinical benefits, and non-responders, if not. The composition of gut microbes was analyzed using 16S ribosomal DNA sequencing. Serum SCFA concentrations were detected using gas chromatography. Cell proliferation, migration, invasion, cell cycle, and apoptosis assays were performed on isobutyric acid-treated A549 cells. Reverse transcription-quantitative PCR, Western blotting, immunocytochemistry, and immunofluorescence staining experiments have been performed to investigate the expression of associated genes or proteins.ResultsNon-responders harbored higher microbiome α-diversity but lower β-diversity compared with responders. Compared to the patients with low α-diversity, those with high α-diversity showed significantly shorter progression-free survival. Additionally, β-diversity has also been observed between these two groups. Specifically, Parasutterella, Clostridiaceae, and Prevotella_7 were more abundant among responders, whereas Bacteroides_stercoris and Christensenellaceae_R-7_group were more abundant in non-responders. The serum SCFA (especially acetate and isobutyrate) levels tended to be higher in responders. Isobutyric acid inhibited the proliferation, migration, and invasion of A549 cells by inducing apoptosis and G1/S arrest while upregulating the expression of GPR41, GPR43, and GPR5C and downregulating that of PAR1, and increasing the activity of histone acetyltransferases.ConclusionWe revealed the influence of gut microbiota and SCFAs on the therapeutic responses in patients with LC and the anti-tumor effect of isobutyric acid, indicating their potential use as therapeutic targets.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1165360/fulllung cancergut microbiomeshort-chain fatty acidchemotherapytargeted therapy |
| spellingShingle | Huan-Huan Chen Huan-Huan Chen Huan-Huan Chen Huan-Huan Chen Qi-Jun Wu Qi-Jun Wu Qi-Jun Wu Tie-Ning Zhang Tie-Ning Zhang Tie-Ning Zhang Tie-Ning Zhang Yu-Hong Zhao Yu-Hong Zhao Yu-Hong Zhao Gut microbiome and serum short-chain fatty acids are associated with responses to chemo- or targeted therapies in Chinese patients with lung cancer Frontiers in Microbiology lung cancer gut microbiome short-chain fatty acid chemotherapy targeted therapy |
| title | Gut microbiome and serum short-chain fatty acids are associated with responses to chemo- or targeted therapies in Chinese patients with lung cancer |
| title_full | Gut microbiome and serum short-chain fatty acids are associated with responses to chemo- or targeted therapies in Chinese patients with lung cancer |
| title_fullStr | Gut microbiome and serum short-chain fatty acids are associated with responses to chemo- or targeted therapies in Chinese patients with lung cancer |
| title_full_unstemmed | Gut microbiome and serum short-chain fatty acids are associated with responses to chemo- or targeted therapies in Chinese patients with lung cancer |
| title_short | Gut microbiome and serum short-chain fatty acids are associated with responses to chemo- or targeted therapies in Chinese patients with lung cancer |
| title_sort | gut microbiome and serum short chain fatty acids are associated with responses to chemo or targeted therapies in chinese patients with lung cancer |
| topic | lung cancer gut microbiome short-chain fatty acid chemotherapy targeted therapy |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1165360/full |
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