What question did this study set out to answer?

This research aims to explore how a low-fiber diet influences lung tumor development through gut microbiota and immune cell interactions.

May 20, 2026

B111-02 Low-Fiber Diet Promotes Lung Tumorigenesis via Gut Microbiota-Dependent Expansion of Myeloid-Derived Suppressor Cells and Metabolite Dysregulation

Key Points

This research aims to explore how a low-fiber diet influences lung tumor development through gut microbiota and immune cell interactions.
Used a lung adenocarcinoma model inducing tumors with intranasal Adeno-Cre.
Mice were divided into groups receiving low-fiber or high-fiber diets with precise compositions.
Examined the effects of dietary manipulation on tumor burden, immune profiling, and metabolomic changes.
Low-fiber diet increased lung tumor burden and reduced survival in mice, correlating with enhanced MDSC and immune dysregulation.
Antibiotic treatment mitigating microbiota resulted in reduced tumor progression, underscoring microbiome's role in cancer.
Metabolomic analysis revealed elevated serine and fructose linked to pro-inflammatory responses and tumor-promoting inflammation.

Abstract

Abstract Introduction Lung cancer remains the leading cause of cancer-related mortality worldwide. Recent studies implicate the gut microbiome as a systemic modulator of immunity and cancer progression. Given prior links between dietary fiber to immune modulation, this study investigates the gut-lung axis, focusing on low-fiber diet-mediated lung tumorigenesis. We explore mechanisms involving myeloid-derived suppressor cells (MDSCs) and dysregulated metabolites. Methods Using the inducible KrasLSL-G12D; Trp53flox/flox; Msh2flox/flox (KPM) lung adenocarcinoma model, lung tumorigenesis was induced via intranasal Adeno-Cre. Mice were fed one of two precisely formulated, isocaloric, and isobulking diets: a Low-Fiber diet (containing 8% non-fermentable cellulose, 0% soluble inulin) and a High-Fiber diet (containing 8% non-fermentable cellulose and 15% soluble inulin). Diets were administered prophylactically or therapeutically. Microbiome dependence was assessed using broad-spectrum antibiotics treatment. Lung tumor burden was quantified by digital histopathology, while immune profiling, plasma metabolomics, and systemic cytokine analyses characterized diet-related changes. Anti-Gr1 MDSC depletion was assessed to explore immunological effects on tumor growth. Results Low-fiber diet significantly increased lung tumor burden and reduced survival in both early and established disease settings. Antibiotic-mediated microbiome depletion mitigated tumor progression, demonstrating microbiota involvement. Immune profiling revealed marked expansion of lung MDSCs (CD11b+Gr1+) and monocytes (CD11b+Ly6C+CX3CR1+) in low-fiber-fed mice, alongside elevated systemic IL-6, IL-17A, and TNF-α levels. Adaptive immunity showed increased pro-inflammatory Th17 and γδT17 cells, with minimal changes in Th1 and Treg populations. Metabolomic analysis identified elevated plasma serine and fructose associated with tumor-promoting inflammation and immunosuppression. MDSCs depletion reduced lung tumor burden and enhanced CD8+ cytotoxic T-cell activity (CD107a) (Figure 1). Conclusion This study unveils a novel immunometabolic axis linking a low-fiber diet to gut microbiota-mediated lung tumorigenesis through MDSCs expansion and metabolite dysregulation. Targeting dietary patterns and gut microbiota composition may offer preventative strategies for lung cancer, especially in high-risk populations. Results further suggest potential avenues for improving immune checkpoint inhibitor responsiveness through metabolic interventions. This abstract is funded by: R37

Mark Helpful

Bookmark

Relay