Microbiota-derived tryptophan metabolites in vascular inflammation and cardiovascular disease

Paeslack, Nadja; Mimmler, Maximilian; Becker, Stefanie; Gao, Zhenling; Khuu, My Phung; Mann, Amrit; Malinarich, Frano; Regen, Tommy; Reinhardt, Carsten

doi:10.1007/s00726-022-03161-5

Cited by 62 publications

(44 citation statements)

References 172 publications

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“…Indoxyl sulfate could promote vascular inflammation, whereas indole-3-propionic acid and indole-3-aldehyde had protective roles. Increasing evidence shows the protective role of microbiota-derived indole derivatives in blood pressure regulation and hypertension [ 164 ].…”

Section: Trp Metabolites From Gut Microbiota and Immune-associated Di...mentioning

confidence: 99%

Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

Gao

Yang

2022

Cells

129

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Tryptophan is an essential amino acid from dietary proteins. It can be metabolized into different metabolites in both the gut microbiota and tissue cells. Tryptophan metabolites such as indole-3-lactate (ILA), indole-3-acrylate (IAC), indole-3-propionate (IPA), indole-3-aldehyde (IAID), indoleacetic acid (IAA), indole-3-acetaldehyde and Kyn can be produced by intestinal microorganisms through direct Trp transformation and also, partly, the kynurenine (Kyn) pathway. These metabolites play a critical role in maintaining the homeostasis of the gut and systematic immunity and also potentially affect the occurrence and development of diseases such as inflammatory bowel diseases, tumors, obesity and metabolic syndrome, diseases in the nervous system, infectious diseases, vascular inflammation and cardiovascular diseases and hepatic fibrosis. They can not only promote the differentiation and function of anti-inflammatory macrophages, Treg cells, CD4+CD8αα+ regulatory cells, IL-10+ and/or IL-35+B regulatory cells but also IL-22-producing innate lymphoid cells 3 (ILC3), which are involved in maintaining the gut mucosal homeostasis. These findings have important consequences in the immunotherapy against tumor and other immune-associated diseases. We will summarize here the recent advances in understanding the generation and regulation of tryptophan metabolites in the gut microbiota, the role of gut microbiota-derived tryptophan metabolites in different immune cells, the occurrence and development of diseases and immunotherapy against immune-associated diseases.

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Section: Trp Metabolites From Gut Microbiota and Immune-associated Di...mentioning

confidence: 99%

Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

Gao

Yang

2022

Cells

129

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“…In recent years, accumulating evidence from translational research has highlighted the significant role of the gut microbiota and its metabolites in shaping the cardiovascular and cardiometabolic phenotypes. In particular, combined metagenomic and metabolomic approaches have contributed to our understanding of how intestinal microbial metabolism of dietary nutrients impact metabolic pathways and cardiovascular disease risk ( 1 , 2 ).…”

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confidence: 99%

Editorial: Impact of the gut microbiota on cardiovascular medicine

et al. 2022

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“…This suggests that ILA from microbial metabolism may affect immune function via activating the receptor signaling pathway. IPA has direct anti-inflammatory regulation effects on the immune cells via increasing IL-10 production or decreasing pro-inflammatory tumor necrosis factor expression [ 46 ]. As one of the ligands for AHR, type I interferons were produced in the central nervous system in combination with tryptophan metabolites such as IPA and IAld to activate AHR signaling in astrocytes and suppressed central nervous inflammation [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Limosilactobacillus reuteri Attenuates Atopic Dermatitis via Changes in Gut Bacteria and Indole Derivatives from Tryptophan Metabolism

Fang

Pan

Wang

et al. 2022

IJMS

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Gut bacteria are closely associated with the development of atopic dermatitis (AD) due to their immunoregulatory function. Indole derivatives, produced by gut bacteria metabolizing tryptophan, are ligands to activate the aryl hydrocarbon receptor (AHR), which plays a critical role in attenuating AD symptoms. Limosilactobacillus reuteri, a producer of indole derivatives, regulates mucosal immunity via activating the AHR signaling pathway. However, the effective substance and mechanism of L. reuteri in the amelioration of AD remain to be elucidated. In this research, we found that L. reuteri DYNDL22M62 significantly improved AD-like symptoms in mice by suppressing IgE levels and the expressions of thymic stromal lymphopoietin (TSLP), IL-4, and IL-5. L. reuteri DYNDL22M62 induced an increase in the production of indole lactic acid (ILA) and indole propionic acid (IPA) via targeted tryptophan metabolic analysis and the expression of AHR in mice. Furthermore, L. reuteri DYNDL22M62 increased the proportions of Romboutsia and Ruminococcaceae NK4A214 group, which were positively related to ILA, but decreased Dubosiella, which was negatively related to IPA. Collectively, L. reuteri DYNDL22M62 with the role of modulating gut bacteria and the production of indole derivatives may attenuate AD via activating AHR in mice.

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Microbiota-derived tryptophan metabolites in vascular inflammation and cardiovascular disease

Cited by 62 publications

References 172 publications

Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

Editorial: Impact of the gut microbiota on cardiovascular medicine

Limosilactobacillus reuteri Attenuates Atopic Dermatitis via Changes in Gut Bacteria and Indole Derivatives from Tryptophan Metabolism

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