Interactive relationship between Trp metabolites and gut microbiota: The impact on human pathology of disease

Khoshnevisan, Kamyar; Chehrehgosha, Maryam; Conant, Melissa; Meftah, Amir Mohammad; Baharifar, Hadi; Ejtahed, Hanieh‐Sadat; Gholami, Morteza; Sharifi, Farshad; Maleki, Hassan; Larijani, Bagher; Khorramizadeh, Mohammad Reza

doi:10.1111/jam.15533

Cited by 7 publications

(3 citation statements)

References 116 publications

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“…Trp metabolism in the gut microbiota has been reviewed by multiple papers [ 1 , 23 , 24 , 25 ]. The degradation of dietary proteins leads to the release of Trp, which is converted into various metabolites by the gut microbiota, such as indole, indole-3-acid-acetic (IAA), indole-3-propionic acid (IPA), indoleacrylic acid (IA), indole-3-aldehyde (IAld), tryptamine, indoleethanol (IE), indole-3-acetaldehyde (IAAld) and 3-methylindole (skatole), or catalyzed to produce Kyn and downstream metabolites such as 3-hydroxyanthranilic acid (3-HAA) and 3-hydroxykynurenine (3H-Kyn) [ 1 , 23 , 24 ] ( Figure 1 and Table 1 ).…”

Section: Trp Metabolism In Gut Microbiotamentioning

confidence: 99%

Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

Gao

Yang

2022

Cells

155

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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 Metabolism In Gut Microbiotamentioning

confidence: 99%

Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

Gao

Yang

2022

Cells

155

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“…After undergoing liver metabolism, they pass through the inferior vena cava to reach the heart to enter the systemic circulation. Non-nutrient substances can be transformed and detoxi ed in the liver and then eliminated from the body [18,19]. Nicotinamide participates in energy metabolism.…”

Section: Effects Of Ascending and Descending Medicine On Livermentioning

confidence: 99%

Systemic metabolomics characterization of the ascending and descending property

Liu

Zhou

et al. 2023

Preprint

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Background According to the theory of TCM, ascending medicine has the effects of elevating yang, raising drooping, and inducing sweating. Descending medicine has the effects of relieving dyspnea and hiccup, stopping reflux, and calming nerves. In conclusion, the ascending/descending properties of TCM serve as a guide for the use of TCMs in clinical practice. However, at present, there are few studies on the ascending/descending properties of TCM. This study aimed to compare the effects of 6 ascending and 8 descending medicine on the main organs (heart, liver, lung, spleen, and kidney) of normal rats, characterizing the ascending and descending properties. Methods The orgain samples of all experiment group were analyzed based on ultra performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-Q/TOFMS). Then, to character the ascending and descending properties, the effects of 6 ascending and 8 descending medicine on the main organs (heart, liver, lung, spleen, and kidney) of normal rats were compared. Results The systemic metabolomics results indicated that linoleic acid metabolism and arginine and proline metabolism were the major differential pathways affected by ascending/descending medicine in the heart; nicotinic acid and nicotinamide metabolism, glutamic acid and glutathione metabolism, and L-carnitine metabolism were the major differential pathways affected by ascending/descending medicine in the liver; tryptophan metabolism, phenylalanine metabolism, and pyroglutamic acid and glutamic acid metabolism were the major differential pathways affected by ascending/descending medicine in the lung; tryptophan metabolism, phenylalanine metabolism, and glutamic acid metabolism were the major differential pathways affected by ascending/descending medicine in the kidney; and glutamic acid and glutamine metabolism were the major differential pathway affected by ascending/descending medicine in the spleen. Conclusions Ascending medicine exhibited positive effects on nerve stimulation, immunity, and reproductive function by promoting energy metabolism in the heart and liver, whereas descending medicine had the opposite effect. Descending medicine exhibited a positive effect on diuresis by promoting blood circulation, whereas ascending medicine had the opposite effect. Both descending medicine and ascending medicine intervened with pulmonary inflammation, but the underlying mechanisms may be different. This study demonstrated that systemic metabolomics technology can be used for the characterization of traditional Chinese medicine properties.

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“…Gut microbes are known to produce kynurenine and kynurenine derivatives [ 75 ]. Fecal samples of NASH patients have lower L-tryptophan and higher kynurenine [ 76 ].…”

Section: Icrobial Metabolites On Metabolic-associated Fatty Liver Dis...mentioning

confidence: 99%

Roles of gut microbes in metabolic-associated fatty liver disease

Chen

2023

Tzu Chi Medical Journal

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Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease. Gut dysbiosis is considered a significant contributing factor in disease development. Increased intestinal permeability can be induced by gut dysbiosis, followed by the entry of lipopolysaccharide into circulation to reach peripheral tissue and result in chronic inflammation. We reviewed how microbial metabolites push host physiology toward MAFLD, including short-chain fatty acids (SCFAs), bile acids, and tryptophan metabolites. The effects of SCFAs are generally reported as anti-inflammatory and can improve intestinal barrier function and restore gut microbiota. Gut microbes can influence intestinal barrier function through SCFAs produced by fermentative bacteria, especially butyrate and propionate producers. This is achieved through the activation of free fatty acid sensing receptors. Bile is directly involved in lipid absorption. Gut microbes can alter bile acid composition by bile salt hydrolase-producing bacteria and bacterial hydroxysteroid dehydrogenase-producing bacteria. These bile acids can affect host physiology by activating farnesoid X receptor Takeda G protein-coupled receptor 5. Gut microbes can also induce MAFLD-associated symptoms by producing tryptophan metabolites kynurenine, serotonin, and indole-3-propionate. A summary of bacterial genera involved in SCFAs production, bile acid transformation, and tryptophan metabolism is provided. Many bacteria have demonstrated efficacy in alleviating MAFLD in animal models and are potential therapeutic candidates for MAFLD.

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Interactive relationship between Trp metabolites and gut microbiota: The impact on human pathology of disease

Cited by 7 publications

References 116 publications

Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

Systemic metabolomics characterization of the ascending and descending property

Roles of gut microbes in metabolic-associated fatty liver disease

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