Fusobacterium nucleatum-associated metabolites in disease pathogenesis: from cancer to immunotherapy
8 affiliations
- 1Faculty of Allied Medical Sciences, Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University
- 2Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University)
- 3Department of General Medicine, IMS and SUM Hospital, Siksha ‘O’ Anusandhan (Deemed to be University)
- 4College of Pharmacy, Alnoor University
- 5Department of General Medicine, Sharda University
- 6Department of Nutrition and Dietetics, Chandigarh University
- 7Centre for Research Impact and Outcome, Chitkara University
- 8Department of Pharmacy, College of Pharmacy, The Islamic University
Abstract
Fusobacterium , especially Fusobacterium nucleatum , has emerged as a metabolically active pathobiont that can affect host physiology and disease pathogenesis. Through its ability to produce and regulate various metabolites, Fusobacterium can shape immune response, cellular metabolism, and disease progression. Short-chain fatty acids (SCFAs), being part of Fusobacterium -associated metabolic changes observed during disease, are involved in microbial cross-feeding and can affect neutrophil recruitment and inflammatory signaling through free fatty acid receptors. In the case of colorectal cancer (CRC), Fusobacterium -derived metabolites can impact tumor and immune cell phenotype via a number of mechanisms, including aryl hydrocarbon receptor (AhR) activation via indole derivatives, inflammatory and metabolic signaling via hydrogen sulfide, as well as an increase in Glucose transporter 1 (GLUT1) expression, lactate production, and histone lactylation via formate-related metabolites. Besides, F. nucleatum can reshape tumor-cell metabolism, including cholesterol biosynthesis through miR-130a-3p-mediated inhibition of AMP-activated protein kinase (AMPK) signaling, whereas butyrate has been reported to counteract this metabolic phenotype in experimental CRC models. In addition, F. nucleatum -associated succinate has been shown to suppress cGAS–Interferon beta (IFN-β) signaling, thereby reducing antitumor immune activation, impairing CD8 ⁺ T-cell trafficking, and promoting immune escape and resistance to anti-Programmed Cell Death Protein 1 (PD-1) therapy. The present review provides an overview of current understanding of the biological roles of Fusobacterium -derived metabolites, focusing on SCFAs, succinate, indole derivatives, hydrogen sulfide, and formate-related metabolites.
Related
- Molecular Mechanisms of the Gut-Liver-Placenta Axis in Intrahepatic Cholestasis of Pregnancy: Microbiota-Associated Pathogenesis and Next-Generation Therapeutic Strategies.
- Microbiota-Associated Metabolites as Biomarkers and Therapeutic Opportunities in Inflammatory Bowel Disease
- Crosstalk between gut microbiota-associated metabolites and adaptive immunity in cholecystitis: a conceptual mechanistic framework and potential therapeutic implications
- Small-Intestinal Motility Interrelates With Fecal Microbiota, Metabolites and Metabolic Tissue Gene Expression in Metabolic Dysfunction-Associated Steatotic Liver Disease
- Regimen-Dependent Anti-Cytokine and Immune-Checkpoint Autoantibodies Are Associated with Immunotherapy Toxicity and Response in Melanoma
BibTeX
@article{farah2026fusobacterium,
title = {{Fusobacterium nucleatum-associated metabolites in disease pathogenesis: from cancer to immunotherapy}},
author = {Husni Farah and G. PadmaPriya and Samir Sahoo and Bahjat Alhasso and Shrey Kumar Srivastav and Anju Rani and Ritesh Singh and Ahmed Hassan Khdyr},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1996310},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1996310/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Fusobacterium nucleatum-associated metabolites in disease pathogenesis: from cancer to immunotherapy
AU - Husni Farah
AU - G. PadmaPriya
AU - Samir Sahoo
AU - Bahjat Alhasso
AU - Shrey Kumar Srivastav
AU - Anju Rani
AU - Ritesh Singh
AU - Ahmed Hassan Khdyr
PY - 2026
DA - 2026/10/26
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1996310
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1996310/full
AB - Fusobacterium , especially Fusobacterium nucleatum , has emerged as a metabolically active pathobiont that can affect host physiology and disease pathogenesis. Through its ability to produce and regulate various metabolites, Fusobacterium can shape immune response, cellular metabolism, and disease progression. Short-chain fatty acids (SCFAs), being part of Fusobacterium -associated metabolic changes observed during disease, are involved in microbial cross-feeding and can affect neutrophil recruitment and inflammatory signaling through free fatty acid receptors. In the case of colorectal cancer (CRC), Fusobacterium -derived metabolites can impact tumor and immune cell phenotype via a number of mechanisms, including aryl hydrocarbon receptor (AhR) activation via indole derivatives, inflammatory and metabolic signaling via hydrogen sulfide, as well as an increase in Glucose transporter 1 (GLUT1) expression, lactate production, and histone lactylation via formate-related metabolites. Besides, F. nucleatum can reshape tumor-cell metabolism, including cholesterol biosynthesis through miR-130a-3p-mediated inhibition of AMP-activated protein kinase (AMPK) signaling, whereas butyrate has been reported to counteract this metabolic phenotype in experimental CRC models. In addition, F. nucleatum -associated succinate has been shown to suppress cGAS–Interferon beta (IFN-β) signaling, thereby reducing antitumor immune activation, impairing CD8 ⁺ T-cell trafficking, and promoting immune escape and resistance to anti-Programmed Cell Death Protein 1 (PD-1) therapy. The present review provides an overview of current understanding of the biological roles of Fusobacterium -derived metabolites, focusing on SCFAs, succinate, indole derivatives, hydrogen sulfide, and formate-related metabolites.
SN - 1664-302X
ER -