Immune checkpoint blockade therapy with anti-PD-1 monoclonal antibody (mAb) is a treatment for colorectal cancer (CRC). However, some patients remain unresponsive to PD-1 blockade. The gut microbiota has been linked to immunotherapy resistance through unclear mechanisms. We found that patients with metastatic CRC who fail to respond to immunotherapy had a greater abundance of Fusobacterium nucleatum and increased succinic acid. Fecal microbiota transfer from responders with low F. nucleatum, but not F. nucleatum-high non-responders, conferred sensitivity to anti-PD-1 mAb in mice. Mechanistically, F. nucleatum-derived succinic acid suppressed the cGAS-interferon-β pathway, consequently dampening the antitumor response by limiting CD8 T cell trafficking to the tumor microenvironment (TME) in vivo. Treatment with the antibiotic metronidazole reduced intestinal F. nucleatum abundance, thereby decreasing serum succinic acid levels and resensitizing tumors to immunotherapy in vivo. These findings indicate that F. nucleatum and succinic acid induce tumor resistance to immunotherapy, offering insights into microbiota-metabolite-immune crosstalk in CRC.
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http://dx.doi.org/10.1016/j.chom.2023.04.010 | DOI Listing |
Gut Microbes
December 2025
Beijing Institute of Clinical Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus; however, many patients respond poorly to this drug in clinical practice. The potential involvement of microbiota-mediated intestinal immunity and related signals in metformin responsiveness has not been previously investigated. In this study, we successfully constructed a humanized mouse model by fecal transplantation of the gut microbiota from clinical metformin-treated - responders and non-responders, and reproduced the difference in clinical phenotypes of responsiveness to metformin.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Department of Chemistry, Suleyman Demirel University, Faculty of Arts and Science, 32260 Isparta, Turkey.
Poly(lactic) (PLA) is a biodegradable material obtained from renewable resources and is recognized as a safe biopolymer by the Food and Drug Administration. PLA expresses excellent mechanical and moldability attributes nonetheless poor elasticity/functionality limits its widespread utilization. One approach to compensate for this is chemical surface modification through free radical grafting with small organic molecules like maleic anhydride (MA).
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
State Key Laboratory of Fine Chemicals, Laboratory of Advanced Materials and Catalytic Engineering, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China.
The industrial advancement of downstream products resulting from the directed hydrogenation of maleic anhydride is hindered by the limitations related to the activity and stability of catalysts. The development of nonprecious metal intermetallic compounds, in which active sites are adjustable in the local structures and electronic properties embedded within a distinct framework, holds immense potential in enhancing catalytic efficacy and stability. Herein, we report that nickel-based silicides catalysts, RNiSi (R = Ca, La, and Y), afford high efficiency in the selective hydrogenation of maleic anhydride.
View Article and Find Full Text PDFMol Pharm
January 2025
Department of Industrial and Molecular Pharmaceutics, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United States.
Lumefantrine (LMF) is a low-solubility antimalarial drug that cures acute, uncomplicated malaria. It exerts its pharmacological effects against erythrocytic stages of spp. and prevents malaria pathogens from producing nucleic acid and protein, thereby eliminating the parasites.
View Article and Find Full Text PDFEng Life Sci
January 2025
Mechanical and Process Engineering RPTU Kaiserslautern-Landau Kaiserslautern Germany.
Bioelectrochemical systems (BESs) offer a sustainable method for chemical production, including the enhanced production of succinic acid. By combining fermentation with BES, it could be possible to achieve sustainable succinic acid production and CO fixation using . In literature, the potential application of BES is commonly associated with increased succinate yields, as it is expected to enhance the availability of NADH, thereby influencing the intracellular nicotinamide adenine dinucleotide (NADH/NAD) balance.
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