Indole-3-propionic acid alleviates ischemic brain injury in a mouse middle cerebral artery occlusion model

Xie, Yong; Zou, Xiaoxiong; Han, Jianbang; Zhang, Zhongfei; Feng, Zhiming; Ouyang, Qian; Hua, Shiting; Liu, Zhizheng; Liu, Cong; Cai, Yanling; Zou, Yuxiao; Tang, Yanping; Jiang, Xiaodan

doi:10.1016/j.expneurol.2022.114081

Cited by 32 publications

(22 citation statements)

References 50 publications

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“…The latest experimental studies show that indole-3-propionic acid treatment ameliorated the middle cerebral artery occlusion-induced alterations of the gut microbiome structure, specifically reshaping the microbial community composition in mice with middle cerebral artery occlusion to resemble that in the mice from the control group, with an increase in the abundance of probiotics and a decrease in the abundance of harmful bacteria. Indole-3-propionic acid repaired the integrity of the intestinal barrier and regulated the activities of regulatory T cells (Tregs) and Th17 cells in the gut-associated lymphoid tissue 33 . In our study, by analyzing the biosynthesis process of phenylalanine, tyrosine and tryptophan, it was found that indole was at a low expression level in patients with sepsis.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics-based study of potential biomarkers of sepsis

Yang

Chen

2023

Sci Rep

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The purpose of our study was to explore potential characteristic biomarkers in patients with sepsis. Peripheral blood specimens from sepsis patients and normal human volunteers were processed by liquid chromatography-mass spectrometry-based analysis. Outlier data were excluded by principal component analysis and orthogonal partial least squares-discriminant analysis using the metabolomics R software package metaX and MetaboAnalyst 5.0 (https://www.metaboanalyst.ca/home.xhtml) online analysis software, and differential metabolite counts were identified by using volcano and heatmaps. The obtained differential metabolites were combined with KEGG (Kyoto Gene and Kyoto Encyclopedia) analysis to screen out potential core differential metabolites, and ROC curves were drawn to analyze the changes in serum metabolites in sepsis patients and to explore the potential value of the metabolites in the diagnosis of sepsis patients. By metabolomic analysis, nine differential metabolites were screened for their significance in guiding the diagnosis and differential diagnosis of sepsis namely: 3-phenyl lactic acid, N-phenylacetylglutamine, phenylethylamine, traumatin, xanthine, methyl jasmonate, indole, l-tryptophan and 1107116. In this study, nine metabolites were finally screened based on metabolomic analysis and used as potential characteristic biomarkers for the diagnosis of sepsis.

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Section: Discussionmentioning

confidence: 99%

Metabolomics-based study of potential biomarkers of sepsis

Yang

Chen

2023

Sci Rep

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“…Decreased IPA production causes hyperactivation of microglia leading to excessive pruning of neuronal synapses (Wang, Chen, Luo, et al, 2023). Experimental brain ischemia reduces IPA levels in serum (Ganesh et al, 2023;Xie et al, 2022) and brain of aged mice (Ganesh et al, 2023), while administration of IPA after ischemia is protective (Ganesh et al, 2023;Xie et al, 2022). However, the AhR pathway is thought to cause brain damage after stroke (Cuartero et al, 2014).…”

Section: Peripheral Factors Impacting Microglial Activitymentioning

confidence: 99%

Role of microglia in stroke

Planas

2024

Glia

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Microglia play key roles in the post‐ischemic inflammatory response and damaged tissue removal reacting rapidly to the disturbances caused by ischemia and working to restore the lost homeostasis. However, the modified environment, encompassing ionic imbalances, disruption of crucial neuron–microglia interactions, spreading depolarization, and generation of danger signals from necrotic neurons, induce morphological and phenotypic shifts in microglia. This leads them to adopt a proinflammatory profile and heighten their phagocytic activity. From day three post‐ischemia, macrophages infiltrate the necrotic core while microglia amass at the periphery. Further, inflammation prompts a metabolic shift favoring glycolysis, the pentose‐phosphate shunt, and lipid synthesis. These shifts, combined with phagocytic lipid intake, drive lipid droplet biogenesis, fuel anabolism, and enable microglia proliferation. Proliferating microglia release trophic factors contributing to protection and repair. However, some microglia accumulate lipids persistently and transform into dysfunctional and potentially harmful foam cells. Studies also showed microglia that either display impaired apoptotic cell clearance, or eliminate synapses, viable neurons, or endothelial cells. Yet, it will be essential to elucidate the viability of engulfed cells, the features of the local environment, the extent of tissue damage, and the temporal sequence. Ischemia provides a rich variety of region‐ and injury‐dependent stimuli for microglia, evolving with time and generating distinct microglia phenotypes including those exhibiting proinflammatory or dysfunctional traits and others showing pro‐repair features. Accurate profiling of microglia phenotypes, alongside with a more precise understanding of the associated post‐ischemic tissue conditions, is a necessary step to serve as the potential foundation for focused interventions in human stroke.

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“…Indole-3-propionic acid (IPA), a tryptophan (Trp) catabolic product produced by intestinal flora, is reduced in the serum of MCAO mice. Significant increases in the number of Th17 and significant decreases in the number of Treg in tMCAO-induced Peyer’s patches and intestine-associated lymphoid tissues were reversed by exogenous supplementation of IPA [ 105 ]. Short-chain fatty acids (SCFAs) are produced by bacteria when they metabolize non-digestible fibers in the intestine and act to stabilize the intestine by activating G protein-coupled receptors and inhibiting histone deacetylases [ 119 ].…”

Section: Targeting Th17 Cells and Il-17a In Treatment Of Ischemic Strokementioning

confidence: 99%

Th17 Cells and IL-17A in Ischemic Stroke

Wang,

Gao,

Yuan

et al. 2023

Mol Neurobiol

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The neurological injury and repair mechanisms after ischemic stroke are complex. The inflammatory response is present throughout stroke onset and functional recovery, in which CD4 + T helper(Th) cells play a non-negligible role. Th17 cells, differentiated from CD4 + Th cells, are regulated by various extracellular signals, transcription factors, RNA, and post-translational modifications. Th17 cells specifically produce interleukin-17A(IL-17A), which has been reported to have pro-inflammatory effects in many studies. Recently, experimental researches showed that Th17 cells and IL-17A play an important role in promoting stroke pathogenesis (atherosclerosis), inducing secondary damage after stroke, and regulating post-stroke repair. This makes Th17 and IL-17A a possible target for the treatment of stroke. In this paper, we review the mechanism of action of Th17 cells and IL-17A in ischemic stroke and the progress of research on targeted therapy.

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Indole-3-propionic acid alleviates ischemic brain injury in a mouse middle cerebral artery occlusion model

Cited by 32 publications

References 50 publications

Metabolomics-based study of potential biomarkers of sepsis

Metabolomics-based study of potential biomarkers of sepsis

Role of microglia in stroke

Th17 Cells and IL-17A in Ischemic Stroke

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