Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acids
Baicalin is a small molecule medication used to treat hepatitis. Our research group discovered that administering baicalin orally to mice following fecal microbiota transplantation from patients resistant to ICIs supported anti-PD-1 activity. However, the precise mechanisms behind this effect are pr...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661823003894 |
| _version_ | 1797398672547250176 |
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| author | Zhang Yu Liu Xiaojia Zhao Wei Zhang Jian Wang Aiting Wang Jing Yang Lin Cao Bangwei Yan Dan |
| author_facet | Zhang Yu Liu Xiaojia Zhao Wei Zhang Jian Wang Aiting Wang Jing Yang Lin Cao Bangwei Yan Dan |
| author_sort | Zhang Yu |
| collection | DOAJ |
| description | Baicalin is a small molecule medication used to treat hepatitis. Our research group discovered that administering baicalin orally to mice following fecal microbiota transplantation from patients resistant to ICIs supported anti-PD-1 activity. However, the precise mechanisms behind this effect are presently unknown. In this present study, ATB-treated C57BL/6 J mice received FMT from patients with advanced NSCLC amenable to αPD-1. Additionally, subcutaneous LLC cells were injected into the mice. Baicalin oral gavage and αPD-1 injection were administered to the mice on days 3 and 9 after tumour inoculation. 16 S rRNA, metabolomics, and flow cytometry were utilized to clarify the mechanisms of baicalin's relief of immunosuppression. The results indicated that oral administration of baicalin enriched bacteria such as Akkermansia and Clostridia_UCG-014, resulted in an increase in SCFAs, which improved the ratio of PD-1+ (CD8+ T cell/Treg) and promoted the levels of IFN-γ+ CD8+ T cells and TNF-α+ CD8+ T cells within the tumour microenvironment. In conclusion, baicalin regulates the metabolites of the gut microbiota to improve the PD-1+ (CD8+ T cell/Treg) balance and circumvent anti-PD-1 resistance. This is achieved through the regulation of short-chain fatty acids. |
| first_indexed | 2024-03-09T01:28:57Z |
| format | Article |
| id | doaj.art-0473dc27c61343ecbe8de695ad3c24b0 |
| institution | Directory Open Access Journal |
| issn | 1096-1186 |
| language | English |
| last_indexed | 2024-03-09T01:28:57Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj.art-0473dc27c61343ecbe8de695ad3c24b02023-12-10T06:13:52ZengElsevierPharmacological Research1096-11862024-01-01199107033Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acidsZhang Yu0Liu Xiaojia1Zhao Wei2Zhang Jian3Wang Aiting4Wang Jing5Yang Lin6Cao Bangwei7Yan Dan8Beijing Institute of Clinical Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaBeijing Institute of Clinical Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaBeijing Institute of Clinical Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaCollege of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaBeijing Institute of Clinical Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaDepartment of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, ChinaNational Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaDepartment of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; Corresponding authors.Beijing Institute of Clinical Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; Corresponding authors.Baicalin is a small molecule medication used to treat hepatitis. Our research group discovered that administering baicalin orally to mice following fecal microbiota transplantation from patients resistant to ICIs supported anti-PD-1 activity. However, the precise mechanisms behind this effect are presently unknown. In this present study, ATB-treated C57BL/6 J mice received FMT from patients with advanced NSCLC amenable to αPD-1. Additionally, subcutaneous LLC cells were injected into the mice. Baicalin oral gavage and αPD-1 injection were administered to the mice on days 3 and 9 after tumour inoculation. 16 S rRNA, metabolomics, and flow cytometry were utilized to clarify the mechanisms of baicalin's relief of immunosuppression. The results indicated that oral administration of baicalin enriched bacteria such as Akkermansia and Clostridia_UCG-014, resulted in an increase in SCFAs, which improved the ratio of PD-1+ (CD8+ T cell/Treg) and promoted the levels of IFN-γ+ CD8+ T cells and TNF-α+ CD8+ T cells within the tumour microenvironment. In conclusion, baicalin regulates the metabolites of the gut microbiota to improve the PD-1+ (CD8+ T cell/Treg) balance and circumvent anti-PD-1 resistance. This is achieved through the regulation of short-chain fatty acids.http://www.sciencedirect.com/science/article/pii/S1043661823003894Gut microbiotaBaicalinPD-1 monoclonal antibodyShort-chain fatty acids (SCFAs) |
| spellingShingle | Zhang Yu Liu Xiaojia Zhao Wei Zhang Jian Wang Aiting Wang Jing Yang Lin Cao Bangwei Yan Dan Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acids Pharmacological Research Gut microbiota Baicalin PD-1 monoclonal antibody Short-chain fatty acids (SCFAs) |
| title | Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acids |
| title_full | Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acids |
| title_fullStr | Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acids |
| title_full_unstemmed | Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acids |
| title_short | Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acids |
| title_sort | baicalin circumvents anti pd 1 resistance by regulating the gut microbiota metabolite short chain fatty acids |
| topic | Gut microbiota Baicalin PD-1 monoclonal antibody Short-chain fatty acids (SCFAs) |
| url | http://www.sciencedirect.com/science/article/pii/S1043661823003894 |
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