Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

Teunis, Charlotte; Nieuwdorp, Max; Hanssen, Nordin M.J.

doi:10.3390/metabo12060514

Cited by 59 publications

(37 citation statements)

References 121 publications

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“…The gut microbiome influences liver diseases. Interactions between Trp metabolism, the gut microbiome and the immune system can be potential drivers of non-alcoholic fatty liver disease [ 165 ]. Indole-3-propionic acid, a gut-derived Trp metabolite, is associated with hepatic fibrosis [ 166 ].…”

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

156

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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

156

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“…Both tryptophan and 5-hydroxytryptophan (5-HTP) are used in the biosynthesis of 5-HT. Roughly 90% of dietary tryptophan is used in the kynurenine pathway, a process that competes with the synthetic pathway of 5-HT [ 12 , 13 ]. Unlike tryptophan, 5-HTP freely crosses the BBB and increases the 5-HT levels in the brain to exert an antidepressant effect [ 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Promoting Effect and Potential Mechanism of Lactobacillus pentosus LPQ1-Produced Active Compounds on the Secretion of 5-Hydroxytryptophan

Zeng

Song

Zhang

et al. 2022

Foods

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5-hydroxytryptophan (5-HTP) is an important substance thought to improve depression. It has been shown that Lactobacillus can promote the secretion of 5-HTP in the body and thus ameliorate depression-like behavior in mice. However, the mechanism by which Lactobacillus promotes the secretion of 5-HTP is unclear. In this study, we investigated the promoting effect and mechanism of Lactobacillus, isolated from Chinese fermented foods, on the secretion of 5-HTP. The results showed that Lactobacillus (L.) pentosus LPQ1 exhibited the strongest 5-HTP secretion-promoting effect ((9.44 ± 0.69)-fold), which was dependent on the mixture of compounds secreted by L. pentosus LPQ1 (termed SLPQ1). In addition, the results of the RNA sequencing (RNA-seq) and quantitative real-time polymerase chain reaction (qRT-PCR) analyses indicated that SLPQ1 alters the TNF and oxidative phosphorylation signaling pathways. Moreover, the SLPQ1 ultrafiltration fraction (>10 kDa) showed a similar 5-HTP promoting effect as SLPQ1. Furthermore, reverse-phase liquid chromatography-tandem mass spectrometry (RPLC-MS/MS) identified 29 compounds of >10 kDa in SLPQ1, including DUF488 domain-containing protein, BspA family leucine-rich repeat surface protein, and 30S ribosomal protein S5, which together accounted for up to 62.51%. This study reports new findings on the mechanism by which L. pentosus LPQ1 promotes 5-HTP production in some cell lines in vitro.

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“…The intestinal flora plays an important role in controlling the host's energy metabolism. The intestinal flora fermentatively degrades polysaccharides in the body to provide energy for the host [ 37 ]. Polysaccharides can be digested and decomposed into SCFAs by intestinal flora, such as Clostridium butyricum .…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Shengmaiyin in Myocardial Hypertrophy-Induced Rats: A Genomic Analysis by 16S rDNA

Ming

Kan

Liu³

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. The gut-cardiac axis theory provides new insights into the complex mechanisms of cardiac hypertrophy and provides new therapeutic targets. Cardiac hypertrophy is a risk factor for heart failure. Shengmaiyin (SMY) is a traditional Chinese medicine formula with clear effects in the treatment and prevention of cardiac hypertrophy, but the mechanism by which it improves cardiac hypertrophy is still unclear. Therefore, this study aimed to investigate the protective effect and mechanism of SMY on isoproterenol (ISO)-induced myocardial hypertrophy in rats. Methods. First, various pharmacodynamic methods were used to evaluate the therapeutic effect of SMY on ISO-induced myocardial hypertrophy in rats. Then, 16S rDNA amplicon sequencing technology was used to study the effect of SMY on the intestinal flora of rats with myocardial hypertrophy. Finally, the mechanism underlying the effect of SMY on cardiac hypertrophy was predicted by bioinformatics network analysis and verified by Western blotting. Results. SMY increased ejection fraction (EF%) and left ventricular fractional shortening (FS%), ameliorated myocardial cell injury and fibrosis, regulated blood lipids and energy metabolism, and decreased cardiac hypertrophy marker gene expression. The gut microbiota of ISO-induced myocardial hypertrophy rats were significantly changed, while SMY effectively ameliorated the dysbiosis of the intestinal flora in rats with myocardial hypertrophy, especially Prevotella 9, Lactobacillus, and Clostridium. Mechanistic studies have shown that the anticardiac hypertrophy effect of SMY is related to the inhibition of the expression of HIF1α/PPAR signalling pathway-related proteins. Conclusion. SMY significantly improves cardiac function, relieves myocardial cell fibrosis and necrosis, resists cardiac hypertrophy, improves blood lipid metabolism and energy metabolism, regulates intestinal microbial disturbance, and protects the heart.

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Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

Cited by 59 publications

References 121 publications

Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

Promoting Effect and Potential Mechanism of Lactobacillus pentosus LPQ1-Produced Active Compounds on the Secretion of 5-Hydroxytryptophan

Protective Effect of Shengmaiyin in Myocardial Hypertrophy-Induced Rats: A Genomic Analysis by 16S rDNA

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