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Extensive Summary of the Important Roles of Indole Propionic Acid, a Gut Microbial Metabolite in Host Health and Disease - PubMed

  • ️Sat Jan 01 2022

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Extensive Summary of the Important Roles of Indole Propionic Acid, a Gut Microbial Metabolite in Host Health and Disease

Hui Jiang et al. Nutrients. 2022.

Abstract

Increasing evidence suggests that metabolites produced by the gut microbiota play a crucial role in host-microbe interactions. Dietary tryptophan ingested by the host enters the gut, where indole-like metabolites such as indole propionic acid (IPA) are produced under deamination by commensal bacteria. Here, we summarize the IPA-producing bacteria, dietary patterns on IPA content, and functional roles of IPA in various diseases. IPA can not only stimulate the expression of tight junction (TJ) proteins to enhance gut barrier function and inhibit the penetration of toxic factors, but also modulate the immune system to exert anti-inflammatory and antioxidant effects to synergistically regulate body physiology. Moreover, IPA can act on target organs through blood circulation to form the gut-organ axis, which helps maintain systemic homeostasis. IPA shows great potential for the diagnosis and treatment of various clinical diseases, such as NAFLD, Alzheimer's disease, and breast cancer. However, the therapeutic effect of IPA depends on dose, target organ, or time. In future studies, further work should be performed to explore the effects and mechanisms of IPA on host health and disease to further improve the existing treatment program.

Keywords: gut barrier; gut microbiota; gut–organ axis; indole propionic acid; tryptophan.

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Conflict of interest statement

The authors declare that they have no competing interest.

Figures

Figure 1
Figure 1

Metabolic process of dietary tryptophan converted to IPA by gut microbiota. The active enzymes required for this process are indicated above the arrow, and the genes encoding these enzymes in C. sporogenes are shown below. The enzymatic activity of AAT has been demonstrated in C. sporogenes cells, but so far, the gene encoding this enzyme has not been identified. AAT: Aromatic amino acid aminotransferase, ACD: Acyl-CoA dehydrogenase, ILD: Indolelactate dehydratase, ILDH: Indolelactate dehydrogenase. The ball-and-stick models of the molecules involved in the figure were drawn using ChemDraw (

https://www.chemdraw.com.cn/

(accessed on 16 June 2022)) and chem3D (

https://www.wavemetrics.com/project/Chem3D

(accessed on 16 June 2022)).

Figure 2
Figure 2

Biological functions of IPA through various gut–organ axes. Blood circulation enables IPA to act on various target organs, regulating host disease and health through biological mechanisms as shown. Aβ: Amyloid β-protein, BBB: Blood–brain barrier, eNOS: endothelial nitric oxide synthase, GLP-1: Glucagon-like peptide-1, HFD: High-fat diet, IBD: Inflammatory bowel disease, IFN-I: Type I interferons, IS: Indoxyl sulfate, LPS: Lipopolysaccharide, NTM: Non-Mycobacterium tuberculosis, PXR: Pregnane X receptor, ROS: Reactive oxygen species, TJ: Tight junction, TB: Tuberculosis.

Figure 3
Figure 3

Summary of IPA production and functions. Red upward arrows indicate promotion, and blue downward arrows indicate inhibition. The dashed line indicates that further experimental verification is required. IPA: indole propionic acid, Trp: tryptophan, EAE: experimental autoimmune encephalomyelitis, T2DM: type 2 diabetes mellitus, NAFLD: Non-alcoholic fatty liver disease, CKD: chronic kidney disease, AHR: aryl hydrocarbon receptor, PXR: pregnane X receptor, ROS: reactive oxygen species, Tj: tight junction.

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