scholarly journals TRYPTOPHAN: A KEY METABOLITE OF HOMEOSTASIS AND A REGULATOR OF BODY FUNCTIONS

2021 ◽  
Vol 5 (2) ◽  
pp. 143-149
Author(s):  
V. M. Sheibak ◽  
◽  
A. Yu. Pauliukavets ◽  
Keyword(s):  
Intestinal Microbiota ◽  
English Language ◽  
Tryptophan Metabolism ◽  
Biologically Active ◽  
Receptor Ligands ◽  
Aryl Hydrocarbon ◽  
Pathological Conditions ◽  
Tryptophan Metabolites ◽  
Important Therapeutic Target

Background. Tryptophan is an essential amino acid found mainly in protein foods and its availability is highly dependent on a diet. A significant part of tryptophan is metabolized in the gastrointestinal tract by the intestinal microbiota, producing a number of biologically active molecules, including aryl hydrocarbon receptor ligands, kynurenines, and serotonin (5-hydroxytryptamine). Objective. To analyze scientific studies confirming the key role of tryptophan microbial catabolites on the function of a macroorganism. Material and methods. The analysis of 47 English-language literature sources containing information on the effects of tryptophan metabolites on the mammalian organism was carried out. Results. It has been established that tryptophan metabolism plays a central role both in a normal macroorganism and in pathological conditions, it being directly or indirectly controlled by the intestinal microbiota. Conclusions. Thus, tryptophan metabolism is an important therapeutic target, underutilized in the treatment of a number of chronic neurological pathologies and immunocompetent conditions. An important factor is the use of nutraceuticals and probiotics by microorganisms that modulate the metabolism of tryptophan in the intestine and stimulate the synthesis of specific metabolites.

scholarly journals Biological role of zonulin: a biomarker of increased intestinal permeability syndrome

2021 ◽  
Vol 66 (1) ◽  
pp. 31-38
Author(s):  
A. I. Khavkin ◽  
N. M. Bogdanova ◽  
V. P. Novikova
Keyword(s):  
Digestive Tract ◽  
Intestinal Microbiota ◽  
Intestinal Mucosa ◽  
Inflammatory Process ◽  
Biological Rhythms ◽  
Infectious Agent ◽  
Biological Role ◽  
Pathological Conditions ◽  
Intercellular Connections

.Both changes in diet and pathological conditions caused by an infectious agent, allergic or autoimmune inflammatory process, affect the biological rhythms of the digestive tract, which negatively affects the intestinal microbiota and increases the permeability of the intestinal mucosa. The altered microbiota potentiates inflammation and causes a “vicious circle”. The zonulin protein is the agent that modulates the density of intercellular connections. The review presents data on the biological role of zonulin, correction of its synthesis violation with the help of functional products for baby food.

scholarly journals How Ah Receptor Ligand Specificity Became Important in Understanding Its Physiological Function

2020 ◽  
Vol 21 (24) ◽  
pp. 9614
Author(s):  
Iain A. Murray ◽  
Gary H. Perdew
Keyword(s):  
Physiological Function ◽  
Innate Immune ◽  
Ah Receptor ◽  
Ligand Specificity ◽  
Aryl Hydrocarbon ◽  
Innate Immune Signaling ◽  
Tryptophan Metabolites ◽  
Barrier Tissues ◽  
Endogenous Metabolites

Increasingly, the aryl hydrocarbon receptor (AHR) is being recognized as a sensor for endogenous and pseudo-endogenous metabolites, and in particular microbiota and host generated tryptophan metabolites. One proposed explanation for this is the role of the AHR in innate immune signaling within barrier tissues in response to the presence of microorganisms. A number of cytokine/chemokine genes exhibit a combinatorial increase in transcription upon toll-like receptors and AHR activation, supporting this concept. The AHR also plays a role in the enhanced differentiation of intestinal and dermal epithelium leading to improved barrier function. Importantly, from an evolutionary perspective many of these tryptophan metabolites exhibit greater activation potential for the human AHR when compared to the rodent AHR. These observations underscore the importance of the AHR in barrier tissues and may lead to pharmacologic therapeutic intervention.

scholarly journals Microbiota tryptophan metabolism induces aryl hydrocarbon receptor activation and improves alcohol-induced liver injury

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321565 ◽  
Author(s):  
Laura Wrzosek ◽  
Dragos Ciocan ◽  
Cindy Hugot ◽  
Madeleine Spatz ◽  
Margot Dupeux ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Aryl Hydrocarbon Receptor ◽  
Intestinal Microbiota ◽  
Alcoholic Liver Disease ◽  
Receptor Activation ◽  
Liver Lesions ◽  
Knock Out ◽  
Aryl Hydrocarbon ◽  
Tryptophan Metabolites

ObjectiveChronic alcohol consumption is an important cause of liver-related deaths. Specific intestinal microbiota profiles are associated with susceptibility or resistance to alcoholic liver disease in both mice and humans. We aimed to identify the mechanisms by which targeting intestinal microbiota can improve alcohol-induced liver lesions.DesignWe used human associated mice, a mouse model of alcoholic liver disease transplanted with the intestinal microbiota of alcoholic patients and used the prebiotic, pectin, to modulate the intestinal microbiota. Based on metabolomic analyses, we focused on microbiota tryptophan metabolites, which are ligands of the aryl hydrocarbon receptor (AhR). Involvement of the AhR pathway was assessed using both a pharmacological approach and AhR-deficient mice.ResultsPectin treatment modified the microbiome and metabolome in human microbiota-associated alcohol-fed mice, leading to a specific faecal signature. High production of bacterial tryptophan metabolites was associated with an improvement of liver injury. The AhR agonist Ficz (6-formylindolo (3,2-b) carbazole) reduced liver lesions, similarly to prebiotic treatment. Conversely, inactivation of the ahr gene in alcohol-fed AhR knock-out mice abrogated the beneficial effects of the prebiotic. Importantly, patients with severe alcoholic hepatitis have low levels of bacterial tryptophan derivatives that are AhR agonists.ConclusionsImprovement of alcoholic liver disease by targeting the intestinal microbiota involves the AhR pathway, which should be considered as a new therapeutic target.

scholarly journals Role of Tryptophan-Metabolizing Microbiota On Diarrhea Mice Caused by Folium sennae Extracts

2020 ◽  
Author(s):  
Chenyang Zhang ◽  
Haoqing Shao ◽  
Dandan Li ◽  
Nenqun Xiao ◽  
Zhoujin Tan
Keyword(s):  
Cytochrome P450 ◽  
Intestinal Microbiota ◽  
Bacterial Flora ◽  
Shannon Index ◽  
Tryptophan Metabolism ◽  
Control Group ◽  
Cytochrome P450 Enzymes ◽  
Significant Difference ◽  
Tryptophan Derivatives

Abstract Background: Although reports have provided evidence that diarrhea caused by Folium sennae can result in intestinal microbiota diversity disorder, the intestinal bacterial characteristic and specific mechanism are still unknown. The objective of our study was to investigate the mechanism of diarrhea caused by Folium sennae, which was associated with intestinal bacterial characteristic reshaping and metabolic abnormality. Results: For the intervention of Folium sennae extracts, Chao1 index and Shannon index were statistical decreased. The Beta diversity clusters of mice interfered by Folium sennae extracts were distinctly separated from control group. Combining PPI network analysis, cytochrome P450 enzymes metabolism was the main signaling pathway of diarrhea caused by Folium sennae. Moreover, 10 bacterial flora communities had statistical significant difference with Folium sennae intervention: the abundance of Paraprevotella, Streptococcus, Epulopiscium, Sutterella and Mycoplasma increased significantly; and the abundance of Adlercreutzia, Lactobacillus, Dehalobacterium, Dorea and Oscillospira reduced significantly. 7 of the 10 intestinal microbiota communities were related to the synthesis of tryptophan derivatives, which affected the transformation of aminotryptophan into L-tryptophan, leading to abnormal tryptophan metabolism in the host. Conclusions: Folium sennae targeted cytochrome P450 3A4 to alter intestinal bacterial characteristic and intervene the tryptophan metabolism of intestinal microbiota, such as Streptococcus, Sutterella and Dorea, which could be the intestinal microecological mechanism of diarrhea caused by Folium sennae extracts.

COLONIC MICROBIOTA AND CHRONIC KIDNEY DISEASES INTESTINAL MICROBIOTA AND CHRONIC KIDNEY DISEASE. PART II

2019 ◽  
Vol 23 (1) ◽  
pp. 18-31 ◽  
Author(s):  
B. G. Lukichev ◽  
A. Sh. Rumyantsev ◽  
I. Yu. Panina ◽  
V. Akimenko
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Intestinal Microbiota ◽  
Kidney Diseases ◽  
Biologically Active ◽  
Chronic Kidney Diseases ◽  
Mechanical Removal ◽  
Starting Point ◽  
Active Substances

Interest in studying the role of the gastrointestinal tract in maintaining homeostasis in chronic kidney disease is a traditional one. It served, in particular, as a starting point for the creation of enterosorbents. However, if earlier the main attention was paid to the mechanical removal of a number of potentially dangerous biologically active substances, recently an intestinal microbiota has become an object of interest. The first part of the review of the literature on this topic is devoted to questions of terminology, the normal physiology of the colon microbiota. A detailed description of dysbiosis is given. The features of the main groups of microorganisms are reflected. The hypothetical and confirmed interrelations of the intestine-kidney axis are presented. The pathogenetic mechanisms of the influence of colon dysbiosis on the processes of local and systemic inflammation are discussed. The influence of dysbiosis on the state of the kidney parenchyma and its participation in the progression of CKD are debated.

scholarly journals The role of eicosanoids in renal diseases – potential therapeutic possibilities

2018 ◽  
Author(s):  
Maciej Fijałkowski ◽  
Joanna Stępniewska ◽  
Maciej Domański ◽  
Kazimierz Ciechanowski ◽  
Edyta Golembiewska
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Biologically Active ◽  
Renal Diseases ◽  
Membrane Phospholipids ◽  
Future Studies ◽  
Renal Replacement Therapies ◽  
Pathological Conditions ◽  
Inflammatory Processes

Eicosanoids are biologically active molecules that are created in the process of oxidation of arachidonic acid (AA) which is a constituent of the cell membrane phospholipids. Throughout the years it was evidenced by experiments that the lipid and lipid-derived metabolites play an important role in physiological and pathological processes in the kidneys. They are being considered as biomarkers in detecting acute kidney injury, nephrotoxicity, glomerulonephritis and early stages of diabetic nephropathy because of their participation in inflammatory processes and in oxidative stress. They might be also considered as potential novel targets of therapy. However, the role of eicosanoids is still not fully clear and needs to be explored in future studies. In this brief review, studies on the role of eicosanoids in physiological and pathological conditions, e.g. acute kidney injury (AKI) and chronic kidney disease (CKD), and in different renal replacement therapies, including kidney transplantation, are being discussed.

scholarly journals Comorbidity of chronic pancreatitis and metabolic syndrome: mechanisms of development

2019 ◽  
Vol 43 (2) ◽  
pp. 15-19
Author(s):  
T. N. Hristich ◽  
D. O. Hontsariuk
Keyword(s):  
Metabolic Syndrome ◽  
Chronic Pancreatitis ◽  
Intestinal Microbiota ◽  
Metabolic Disorders ◽  
Subsequent Development ◽  
Healthy Person ◽  
Biologically Active ◽  
Endocrine Function ◽  
Intestinal Microbiome

In this article, the authors analyze a number of known and probable mechanisms involved in the formation of metabolic disorders upon chronic pancreatitis in comorbidity with metabolic syndrome. The issue of involvement of pancreatic endocrine apparatus in development of insulin resistance upon chronic pancreatitis, namely, the role of such a hormone as insulin, is highlighted. The role of this hormone in development of disorders of fat metabolism, obesity and arterial hypertension is presented. The authors emphasize the role of adrenal hormones, estrogen in the pathogenesis of both diseases. The issue of effect of endocrine function disorders on the state of external pancreatic secretion with subsequent development of disorders in the microbiota composition is considered (which also contributes to the progression of both diseases). The data on presence of a possible relationship between the composition, functional activity of the intestinal microbiota and development of metabolic syndrome, chronic pancreatitis are given. The significance of intestinal microbiota in the maintenance of various vital processes of a healthy person, food digestion, as well as synthesis, metabolism, recycling, utilization of various biologically active substances (vitamins, hormones, steroids, immunoglobulins) and elimination of toxins is revealed. The role of microorganisms in the formation of feeding behavior via axis “intestinal microbiome — intestine — brain” is analyzed. Modern ideas on the ability of microorganisms to provoke formation of metabolic disorders upon chronic pancreatitis are presented. The data confirming connection of certain dysbiotic changes (increased ratio of Firmicutes/Bacteroidetes, reduced number of Bacteroidetes and increased number of Firmicutes) with development of obesity, overweight, type 2 diabetes mellitus (known risk factors of metabolic syndrome) is given. It is suggested to prevent formation of metabolic syndrome in chronic pancreatitis by increasing the number of specimens of Bifidobacterium genus and Faecalibacteriumprausnitzii strains in the intestine.

scholarly journals Role of intestinal microbiome in the pathogenesis of age-related macular degeneration

2020 ◽  
Vol 1 (1) ◽  
pp. 29-36
Author(s):  
Dimitrios Kalogeropoulos ◽  
Konstantinos Katsikatsos ◽  
Konstantinos Dallas ◽  
Soon Wai Ch’ng ◽  
Ioannis Asproudis ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Intestinal Microbiota ◽  
English Language ◽  
Inflammatory Diseases ◽  
Active Role ◽  
Age Related Macular Degeneration ◽  
Intestinal Microbiome ◽  
Therapeutic Modalities ◽  
Age Related

Background: The microbiome is strongly linked to many extra-intestinal disorders. Gut commensal microbiota, in particular, plays an active role in human immune and intestinal homeostasis. Complex interactions of the microbiota with host genetics and other underlying factors lead to intestinal dysbiosis, which is thought to be linked to ocular inflammatory diseases. Thus, the aim of this review is to analyze the role of intestinal microbiome in age-related macular degeneration (AMD). Methods: A thorough literature search was performed using PubMed/MEDLINE, limited to English language publications, from January 2004 to March 2020. An additional search was made employing Google Scholar to complete the collected data as per the above-mentioned time-line and language limitations. The main keywords used included age-related macular degeneration, microbiome, dysbiosis, autoimmunity, gut microbiota, epigenetics, immune-mediated inflammatory diseases, and gut-retina axis. Results: Recent studies have proposed the role of intestinal microbiota in the pathogenesis of AMD. Changes in the microbiome have been shown to trigger several ocular inflammatory processes. There is increasing evidence demonstrating that intestinal microbial imbalance may play an important role in the pathogenesis of AMD. Conclusions: This review summarizes how alterations in the intestinal microbiota can be associated with the pathogenesis of AMD and how new therapeutic modalities can be designed to target this microbiome to limit the severe nature of this disease. Future advances in microbiome research may unveil a new era in understanding and managing AMD.

scholarly journals Aryl hydrocarbon receptor activation by Lactobacillus reuteri tryptophan metabolism alleviates Escherichia coli-induced mastitis in mice

2021 ◽  
Vol 17 (7) ◽  
pp. e1009774
Author(s):  
Caijun Zhao ◽  
Xiaoyu Hu ◽  
Lijuan Bao ◽  
Keyi Wu ◽  
Lianjun Feng ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Aryl Hydrocarbon Receptor ◽  
Intestinal Microbiota ◽  
Lactobacillus Reuteri ◽  
Underlying Mechanism ◽  
Receptor Activation ◽  
Tryptophan Metabolism ◽  
Dependent Manner ◽  
Aryl Hydrocarbon ◽  
Novel Therapeutic Strategies

The intestinal microbiota has been associated with the occurrence and development of mastitis, which is one of the most serious diseases of lactating women and female animals, but the underlying mechanism has not yet been elucidated. Aryl hydrocarbon receptor (AhR) activation by microbiota tryptophan metabolism-derived ligands is involved in maintaining host homeostasis and resisting diseases. We investigated whether AhR activation by microbiota-metabolic ligands could influence mastitis development in mice. In this study, we found that AhR activation using Ficz ameliorated mastitis symptoms, which were related to limiting NF-κB activation and enhancing barrier function. Impaired AhR activation by disturbing the intestinal microbiota initiated mastitis, and processed Escherichia coli (E. coli)-induced mastitis in mice. Supplementation with dietary tryptophan attenuated the mastitis, but attenuation was inhibited by the intestinal microbiota abrogation, while administering tryptophan metabolites including IAld and indole but not IPA, rescued the tryptophan effects in dysbiotic mice. Supplementation with a Lactobacillus reuteri (L. reuteri) strain with the capacity to produce AhR ligands also improved E. coli-induced mastitis in an AhR-dependent manner. These findings provide evidence for novel therapeutic strategies for treating mastitis, and support the role of metabolites derived from the intestinal microbiota in improving distal disease.

scholarly journals Developmental Programming and Reprogramming of Hypertension and Kidney Disease: Impact of Tryptophan Metabolism

2020 ◽  
Vol 21 (22) ◽  
pp. 8705
Author(s):  
Chien-Ning Hsu ◽  
You-Lin Tain
Keyword(s):  
Kidney Disease ◽  
Metabolic Pathways ◽  
Developmental Programming ◽  
Tryptophan Metabolism ◽  
Induced Hypertension ◽  
Tryptophan Metabolites ◽  
Disease Impact ◽  
The Impact ◽  
In Pregnancy

The concept that hypertension and chronic kidney disease (CKD) originate in early life has emerged recently. During pregnancy, tryptophan is crucial for maternal protein synthesis and fetal development. On one hand, impaired tryptophan metabolic pathway in pregnancy impacts fetal programming, resulting in the developmental programming of hypertension and kidney disease in adult offspring. On the other hand, tryptophan-related interventions might serve as reprogramming strategies to prevent a disease from occurring. In the present review, we aim to summarize (1) the three major tryptophan metabolic pathways, (2) the impact of tryptophan metabolism in pregnancy, (3) the interplay occurring between tryptophan metabolites and gut microbiota on the production of uremic toxins, (4) the role of tryptophan-derived metabolites-induced hypertension and CKD of developmental origin, (5) the therapeutic options in pregnancy that could aid in reprogramming adverse effects to protect offspring against hypertension and CKD, and (6) possible mechanisms linking tryptophan metabolism to developmental programming of hypertension and kidney disease.

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