Gut microbiome metabolites in lung cancer: The emerging importance of short-chain fatty acids

Area of Science:

• Microbiome research
• Cancer biology
• Metabolic pathways

Background:

• Short-chain fatty acids (SCFAs) are microbial metabolites of dietary fiber.
• SCFAs are increasingly recognized for their significant roles in lung cancer progression and therapeutic responses.

Purpose of the Study:

• To elucidate the multifaceted roles of SCFAs in lung cancer.
• To explore SCFA-mediated mechanisms influencing tumor growth, apoptosis, angiogenesis, and epithelial-mesenchymal transition.
• To investigate SCFA's impact on the efficacy and toxicity of cancer treatments, including immunotherapy and conventional therapies.

Main Methods:

• Review of existing literature on SCFA production by gut microbiota.
• Analysis of SCFA mechanisms, including histone deacetylase inhibition, G-protein-coupled receptor activation, and metabolic reprogramming.
• Examination of SCFA's influence on direct antitumor effects and modulation of systemic immunity and mucosal barrier integrity.

Main Results:

• SCFAs exhibit direct antitumor activities, suppressing tumor growth and angiogenesis while promoting apoptosis.
• SCFAs enhance immunotherapy efficacy and mitigate chemotherapy/radiotherapy toxicity by preserving mucosal barriers and immune homeostasis.
• The function of butyrate, a key SCFA, is dualistic, offering protection but potentially inducing multidrug resistance in specific contexts.

Conclusions:

• SCFAs are critical mediators of microbiome-host interactions relevant to lung cancer.
• Reconciling the opposing effects of SCFAs, particularly butyrate, is essential for translating microbiome-based interventions.
• SCFAs represent promising metabolic co-adjuvants to enhance lung cancer therapy efficacy and reduce side effects.