Short chain fatty acids: key regulators of the local and systemic immune response in inflammatory diseases and infections
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Updated: Aug 5, 2025

Author Spotlight: Gut Microbiome-Lung Tissue Communication Through Short-Chain Fatty Acid Analysis
Published on: June 21, 2024
Lisa-Marie Ney1, Maximilian Wipplinger1, Martha Grossmann1
1Institute of Biochemistry II, Jena University Hospital, Kastanienallee 1, 07747 Jena, Germany.
Abstract:
The human intestinal microbiome substantially affects human health and resistance to infections in its dynamic composition and varying release of microbial-derived metabolites. Short-chain fatty acids (SCFA) produced by commensal bacteria through fermentation of indigestible fibres are considered key regulators in orchestrating the host immune response to microbial colonization by regulating phagocytosis, chemokine and central signalling pathways of cell growth and apoptosis, thereby shaping the composition and functionality of the intestinal epithelial barrier. Although research of the last decades provided valuable insight into the pleiotropic functions of SCFAs and their capability to maintain human health, mechanistic details on how SCFAs act across different cell types and other organs are not fully understood. In this review, we provide an overview of the various functions of SCFAs in regulating cellular metabolism, emphasizing the orchestration of the immune response along the gut-brain, the gut-lung and the gut-liver axes. We discuss their potential pharmacological use in inflammatory diseases and infections and highlight new options of relevant human three-dimensional organ models to investigate and validate their biological functions in more detail.
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