Gut-Derived Indole-3-Propionic Acid Protects Against
Neuroinflammation After Traumatic Brain Injury Through the NLRP3
Signaling Pathway
Yue Zhao1, Lu Zhou1,
Xiuxiu Xu1,
Jiexin Zou2, Kai Hu2 and Lijuan Quan*1
1Department
of Rehabilitation, The 1st affiliated hospital,
Jiangxi Medical
College, Nanchang University, Nanchang, China; 2Animal
Center of Core Facility for Biomedical Science, Nanchang University
*Corresponding author:
ndyfy01461@ncu.edu.cn
Abstract
Traumatic brain injury (TBI) poses a significant threat to human and veterinary
health, with secondary neuroinflammation driven by the gut-brain axis
exacerbating brain damage. This study aimed to investigate the role of gut
microbiota-derived indole-3-propionic acid (IPA) in mitigating neuroinflammation
following traumatic brain injury (TBI) and to elucidate its mechanism. TBI
models were established using controlled rotational acceleration. Gut microbiota
composition and serum metabolites were analyzed via 16S rRNA sequencing and
untargeted metabolomics. Fecal microbiota transplantation (FMT) from TBI rats to
antibiotic-treated healthy rats was performed to validate microbiota-dependent
effects. IPA was orally administered post-TBI and neuroinflammation was assessed
by immunofluorescence, qRT-PCR and proteomics. Our results demonstrate that TBI
induces dysbiosis of gut commensals (e.g., Alistipes, Allobaculum) and reduces
serum IPA levels. Supplementation with IPA suppressed microglial activation and
NLRP3 inflammasome signaling, highlighting its therapeutic potential for
neuroinflammatory disorders. These findings reveal a novel gut-microbiota-neuroinflammation
axis, supporting IPA-based interventions for TBI management in both humans and
companion animals.
To Cite This Article:
Zhao Y, Zhou
L,
Xu
X,
Zou J, Hu K and Quan
L,
2025. Gut-Derived Indole-3-Propionic
Acid Protects Against Neuroinflammation After Traumatic Brain Injury Through the
NLRP3 Signaling Pathway. Pak Vet J. http://dx.doi.org/10.29261/pakvetj/2025.173