Linking Short-Chain Fatty Acids to Systemic Homeostasis: Mechanisms, Therapeutic Potential, and Future Directions

Short-chain fatty acids (SCFAs), pivotal metabolites derived from microbial fermentation of dietary fiber, serve as critical modulators of glucose and lipid metabolism. Dysregulation of SCFA levels, often stemming from inadequate fiber intake or dysbiosis of SCFA-producing microbiota, correlates wit...

Full description

Saved in:
Bibliographic Details
Main Authors: Yueru Zhao, Jing Chen, Yunlong Qin, Jinguo Yuan, Zixian Yu, Rui Ma, Fude Liu, Jin Zhao
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Journal of Nutrition and Metabolism
Online Access:http://dx.doi.org/10.1155/jnme/8870958
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849240243685818368
author Yueru Zhao
Jing Chen
Yunlong Qin
Jinguo Yuan
Zixian Yu
Rui Ma
Fude Liu
Jin Zhao
author_facet Yueru Zhao
Jing Chen
Yunlong Qin
Jinguo Yuan
Zixian Yu
Rui Ma
Fude Liu
Jin Zhao
author_sort Yueru Zhao
collection DOAJ
description Short-chain fatty acids (SCFAs), pivotal metabolites derived from microbial fermentation of dietary fiber, serve as critical modulators of glucose and lipid metabolism. Dysregulation of SCFA levels, often stemming from inadequate fiber intake or dysbiosis of SCFA-producing microbiota, correlates with heightened susceptibility to diverse pathologies, including autoimmune disorders, metabolic syndromes, and malignancies. Emerging evidence underscores the pleiotropic roles of SCFAs in orchestrating gut and systemic homeostasis, positioning them as novel therapeutic candidates for immune dysregulation, inflammatory conditions, and transplant rejection. This review synthesizes current knowledge on SCFA biosynthesis, absorption dynamics, and their multifaceted regulatory mechanisms, spanning epigenetic modulation, G protein–coupled receptor (GPR) signaling, and immune cell crosstalk. We further elucidate their therapeutic potential in clinical contexts, emphasizing their capacity to recalibrate immune responses, suppress chronic inflammation, and mitigate oncogenesis. By integrating recent advances in microbiome research and translational applications, this work highlights the imperative for precision interventions targeting SCFA pathways to bridge the gap between microbial ecology and clinical innovation.
format Article
id doaj-art-b86c240fa6b7440fa6f85012a576bccf
institution Kabale University
issn 2090-0732
language English
publishDate 2025-01-01
publisher Wiley
record_format Article
series Journal of Nutrition and Metabolism
spelling doaj-art-b86c240fa6b7440fa6f85012a576bccf2025-08-20T04:00:40ZengWileyJournal of Nutrition and Metabolism2090-07322025-01-01202510.1155/jnme/8870958Linking Short-Chain Fatty Acids to Systemic Homeostasis: Mechanisms, Therapeutic Potential, and Future DirectionsYueru Zhao0Jing Chen1Yunlong Qin2Jinguo Yuan3Zixian Yu4Rui Ma5Fude Liu6Jin Zhao7School of Clinical MedicineDepartment of NeurosurgeryDepartment of NephrologyDepartment of NephrologyDepartment of NephrologyDepartment of GeriatricsDepartment of NeurologyDepartment of NephrologyShort-chain fatty acids (SCFAs), pivotal metabolites derived from microbial fermentation of dietary fiber, serve as critical modulators of glucose and lipid metabolism. Dysregulation of SCFA levels, often stemming from inadequate fiber intake or dysbiosis of SCFA-producing microbiota, correlates with heightened susceptibility to diverse pathologies, including autoimmune disorders, metabolic syndromes, and malignancies. Emerging evidence underscores the pleiotropic roles of SCFAs in orchestrating gut and systemic homeostasis, positioning them as novel therapeutic candidates for immune dysregulation, inflammatory conditions, and transplant rejection. This review synthesizes current knowledge on SCFA biosynthesis, absorption dynamics, and their multifaceted regulatory mechanisms, spanning epigenetic modulation, G protein–coupled receptor (GPR) signaling, and immune cell crosstalk. We further elucidate their therapeutic potential in clinical contexts, emphasizing their capacity to recalibrate immune responses, suppress chronic inflammation, and mitigate oncogenesis. By integrating recent advances in microbiome research and translational applications, this work highlights the imperative for precision interventions targeting SCFA pathways to bridge the gap between microbial ecology and clinical innovation.http://dx.doi.org/10.1155/jnme/8870958
spellingShingle Yueru Zhao
Jing Chen
Yunlong Qin
Jinguo Yuan
Zixian Yu
Rui Ma
Fude Liu
Jin Zhao
Linking Short-Chain Fatty Acids to Systemic Homeostasis: Mechanisms, Therapeutic Potential, and Future Directions
Journal of Nutrition and Metabolism
title Linking Short-Chain Fatty Acids to Systemic Homeostasis: Mechanisms, Therapeutic Potential, and Future Directions
title_full Linking Short-Chain Fatty Acids to Systemic Homeostasis: Mechanisms, Therapeutic Potential, and Future Directions
title_fullStr Linking Short-Chain Fatty Acids to Systemic Homeostasis: Mechanisms, Therapeutic Potential, and Future Directions
title_full_unstemmed Linking Short-Chain Fatty Acids to Systemic Homeostasis: Mechanisms, Therapeutic Potential, and Future Directions
title_short Linking Short-Chain Fatty Acids to Systemic Homeostasis: Mechanisms, Therapeutic Potential, and Future Directions
title_sort linking short chain fatty acids to systemic homeostasis mechanisms therapeutic potential and future directions
url http://dx.doi.org/10.1155/jnme/8870958
work_keys_str_mv AT yueruzhao linkingshortchainfattyacidstosystemichomeostasismechanismstherapeuticpotentialandfuturedirections
AT jingchen linkingshortchainfattyacidstosystemichomeostasismechanismstherapeuticpotentialandfuturedirections
AT yunlongqin linkingshortchainfattyacidstosystemichomeostasismechanismstherapeuticpotentialandfuturedirections
AT jinguoyuan linkingshortchainfattyacidstosystemichomeostasismechanismstherapeuticpotentialandfuturedirections
AT zixianyu linkingshortchainfattyacidstosystemichomeostasismechanismstherapeuticpotentialandfuturedirections
AT ruima linkingshortchainfattyacidstosystemichomeostasismechanismstherapeuticpotentialandfuturedirections
AT fudeliu linkingshortchainfattyacidstosystemichomeostasismechanismstherapeuticpotentialandfuturedirections
AT jinzhao linkingshortchainfattyacidstosystemichomeostasismechanismstherapeuticpotentialandfuturedirections