Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

Su, Xiaomin; Gao, Yuan; Yang, Rongcun

doi:10.3390/cells11152296

Cited by 155 publications

(78 citation statements)

References 177 publications

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“…Since IDO1 substrates include several indole derivatives produced by bacteria, the kynurenine pathway may represent a critical evolutionary development to detoxify and destroy chemicals not produced by the host organism. This would be consistent with the expression of AHR and their activation by kynurenine or kynurenic acid leading to the activation of catabolic cytochrome oxidases as well as the expression of transcription factors such as FoxP3 and RORγt which define the differentiation of Treg and Th17 cells respectively ( Omenetti and Pizarro, 2015 ; Morris et al, 2017 ; Su et al, 2022 ). The Th17 cells concentrated in the intestinal walls and Peyer’s patches could exert a profound influence on host immunity ( Bhaumik and Basu, 2017 ; Cheng et al, 2019 ; Chen and Tang, 2021 ), modulated by dietary and microbial tryptophan and anthranilic acid.…”

Section: Dietary and Microbial Influencessupporting

confidence: 70%

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

et al. 2022

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Two of the molecular families closely associated with mediating communication between the brain and immune system are cytokines and the kynurenine metabolites of tryptophan. Both groups regulate neuron and glial activity in the central nervous system (CNS) and leukocyte function in the immune system, although neither group alone completely explains neuroimmune function, disease occurrence or severity. This essay suggests that the two families perform complementary functions generating an integrated network. The kynurenine pathway determines overall neuronal excitability and plasticity by modulating glutamate receptors and GPR35 activity across the CNS, and regulates general features of immune cell status, surveillance and tolerance which often involves the Aryl Hydrocarbon Receptor (AHR). Equally, cytokines and chemokines define and regulate specific populations of neurons, glia or immune system leukocytes, generating more specific responses within restricted CNS regions or leukocyte populations. In addition, as there is a much larger variety of these compounds, their homing properties enable the superimposition of dynamic variations of cell activity upon local, spatially limited, cell populations. This would in principle allow the targeting of potential treatments to restricted regions of the CNS. The proposed synergistic interface of ‘tonic’ kynurenine pathway affecting baseline activity and the superimposed ‘phasic’ cytokine system would constitute an integrated network explaining some features of neuroimmune communication. The concept would broaden the scope for the development of new treatments for disorders involving both the CNS and immune systems, with safer and more effective agents targeted to specific CNS regions.

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Section: Dietary and Microbial Influencessupporting

confidence: 70%

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

et al. 2022

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“…Although the specific microorganism profile in patients with MS is not yet known, it seems likely that these patients have a different microbiota composition (dysbiosis), when compared to patients without MS ( Figure 1 ). This different milieu, including different bacterial metabolites, may regulate inflammation and immunity, as well as the metabolic homeostasis [ 18 ]. The recognition of the microbiome impact on metabolism is recent and yet to be elucidated.…”

Section: Metabolic Syndrome and Microbiotamentioning

confidence: 99%

“…Concerning microbiota metabolites, Xiaomin and colleagues [ 18 ] summarized current knowledge on the role of gut microbiota-derived tryptophan metabolites in the development of several diseases, including MS. Tryptophan is an essential amino acid, obtained from dietary proteins, and its metabolites, such as such as indole-3-lactate, indole-3-acrylate, indole-3-propionate, indole-3-aldehyde, indoleacetic acid, indole-3-acetaldehyde, and kynurenine (Kyn), can be produced by multiple taxa resident in the gut microbiota, and may have a role in MS pathogenesis. The metabolites can promote the differentiation and function of anti-inflammatory cells (such as anti-inflammatory macrophages and Treg cells) and are involved in maintaining the gut mucosal homeostasis [ 18 ]. Namely, blood levels of specific tryptophan metabolites are lower in patients with type 2 diabetes, when compared to the lean controls [ 17 , 26 ].…”

Section: Metabolic Syndrome and Microbiotamentioning

confidence: 99%

Microbiota Modulation in Patients with Metabolic Syndrome

2022

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Metabolic syndrome (MS) comprises a vast range of metabolic dysfunctions, which can be associated to cardiovascular disease risk factors. MS is reaching pandemic levels worldwide and it currently affects around 25% in the adult population of developed countries. The definition states for the diagnosis of MS may be clear, but it is also relevant to interpret the patient data and realize whether similar criteria were used by different clinicians. The different criteria explain, at least in part, the controversies on the theme. Several studies are presently focusing on the microbiota changes according to the components of MS. It is widely accepted that the gut microbiota is a regulator of metabolic homeostasis, being the gut microbiome in MS described as dysbiotic and certain taxonomic groups associated to metabolic changes. Probiotics, and more recently synbiotics, arise as promising therapeutic alternatives that can mitigate some metabolic disturbances, namely by correcting the microbiome and bringing homeostasis to the gut. The most recent studies were revised and the promising results and perspectives revealed in this review.

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“…It also acts as a ligand for endogenous tryptophan metabolites, such as KYN and cinnabarinic acid (CA; Neavin et al, 2018;Shinde and McGaha, 2018). Exogenous substances, such as food, activate AHR signaling, which acts on epithelial renewal, barrier integrity, and immune cells [Th17 cells, intrinsic lymphocytes, macrophages, dendritic cells (DCs), and neutrophils] to maintain intestinal homeostasis (Lamas et al, 2018) (Su et al, 2022). About 1%-2% of ingested tryptophan is converted to 5-hydroxytryptamine (5-HT)/serotonin by the 5-HT pathway.…”

Section: Tryptophan Metabolic Pathwaymentioning

confidence: 99%

Modulation of adipose tissue metabolism by microbial-derived metabolites

et al. 2022

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Obesity and its complications, including type 2 diabetes, cardiovascular disease, and certain cancers, have posed a significant burden on health and healthcare systems over the years due to their high prevalence and incidence. Gut microbial derivatives are necessary for the regulation of energy metabolism and host immunity, as well as for maintaining homeostasis of the intestinal environment. Gut flora metabolites may be a link between gut microbes and diseases, such as obesity, and help understand why alterations in the microbiota can influence the pathophysiology of human disease. This is supported by emerging evidence that microbial-derived metabolites, such as short-chain fatty acids, bile acids, tryptophan, trimethylamine-N-oxide, and lipopolysaccharides, can be beneficial or detrimental to the host by affecting organs outside the gut, including adipose tissue. Adipose tissue is the largest lipid storage organ in the body and an essential endocrine organ that plays an indispensable role in the regulation of lipid storage, metabolism, and energy balance. Adipose tissue metabolism includes adipocyte metabolism (lipogenesis and lipolysis), thermogenesis, and adipose tissue metabolic maladaptation. Adipose tissue dysfunction causes the development of metabolic diseases, such as obesity. Here, we review the current understanding of how these microbial metabolites are produced and discuss both established mechanisms and the most recent effects of microbial products on host adipose tissue metabolism. We aimed to identify novel therapeutic targets or strategies for the prevention and treatment of obesity and its complications.

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Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

Cited by 155 publications

References 177 publications

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

Microbiota Modulation in Patients with Metabolic Syndrome

Modulation of adipose tissue metabolism by microbial-derived metabolites

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