Plasma microbiome-modulated indole- and phenyl-derived metabolites associate with advanced atherosclerosis and postoperative outcomes

Cason, Cori A.; Dolan, Kyle; Sharma, Gaurav; Tao, Ming; Kulkarni, Rohan; Helenowski, Irene; Doane, Brendan M.; Avram, Michael J.; McDermott, Mary M.; Chang, Eugene B.; Ozaki, C. Keith; Ho, Karen J.

doi:10.1016/j.jvs.2017.09.029

Cited by 127 publications

(104 citation statements)

References 71 publications

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“…In clinical investigations, IDO activity has been reported to be positively correlated with a range of atherosclerosis risk factors in the female population, including LDL-C (Pertovaara et al, 2007). Concerning the indole pathway, tryptophan, indole-3-propionic acid, and indole-3-aldehyde were shown to be decreased in atherosclerotic patients, while kynurenine/tryptophan ratios were increased (Cason et al, 2018); still, no independent correlation with cholesterol has yet been reported. In conclusion, the scarcity of studies does not allow the indole pathway to be implicated in regulation of cholesterolemia ( Figure 2).…”

Section: Diet-associated Tryptophan (Trp) Derivativesmentioning

confidence: 97%

Unraveling Host-Gut Microbiota Dialogue and Its Impact on Cholesterol Levels

Villette

Béliard

et al. 2020

Front. Pharmacol.

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Disruption in cholesterol metabolism, particularly hypercholesterolemia, is a significant cause of atherosclerotic cardiovascular disease. Large interindividual variations in plasma cholesterol levels are traditionally related to genetic factors, and the remaining portion of their variance is accredited to environmental factors. In recent years, the essential role played by intestinal microbiota in human health and diseases has emerged. The gut microbiota is currently viewed as a fundamental regulator of host metabolism and of innate and adaptive immunity. Its bacterial composition but also the synthesis of multiple molecules resulting from bacterial metabolism vary according to diet, antibiotics, drugs used, and exposure to pollutants and infectious agents. Microbiota modifications induced by recent changes in the human environment thus seem to be a major factor in the current epidemic of metabolic/inflammatory diseases (diabetes mellitus, liver diseases, inflammatory bowel disease, obesity, and dyslipidemia). Epidemiological and preclinical studies report associations between bacterial communities and cholesterolemia. However, such an association remains poorly investigated and characterized. The objectives of this review are to present the current knowledge on and potential mechanisms underlying the host-microbiota dialogue for a better understanding of the contribution of microbial communities to the regulation of cholesterol homeostasis.

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Section: Diet-associated Tryptophan (Trp) Derivativesmentioning

confidence: 97%

Unraveling Host-Gut Microbiota Dialogue and Its Impact on Cholesterol Levels

Villette

Béliard

et al. 2020

Front. Pharmacol.

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“…Была найдена обратная корреляция с прогрессирующим атеросклерозом для индола, индол-3-пропионовой кислоты и концентрации индол-3-альдегида, в то время как для соотношения кинуренина к триптофану -положительная корреляция. При многофакторном анализе соотношение кинуренин−триптофан достоверно ассоциировалось с послеоперационными кардиальными осложнениями (отношение шансов 44,1; 95% доверительный интервал 3,3−587,1; р=0,004) [26].…”

Section: сердечно-сосудистые заболеванияunclassified

The role of human and microbial metabolites of triptophane in severe diseases and critical ill (review)

Getsina

Львовна²,

Chernevskaya

et al. 2020

Journal of Clinical Practice

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The growing interest in metabolite circulating in the blood is associated with the accumulation of factual material on the involvement of low-molecular compounds in the development of a number of serious diseases. This review reveals the effect of a whole class of chemical compounds― tryptophan metabolites― on various pathological processes. The following keywords were used to find papers published in the PubMed database for the last 10 years: names of natural indole compounds, methods for their detection, nosology of diseases and critical ill patients. The data is presented in sections, which provide data on the study of tryptophan metabolites in a variety of groups of diseases, such as cancer, cardiovascular disease, kidney disease, bowel, mental disorders, atherosclerosis, etc. Particular attention is paid to the role of indole compounds that enter the systemic circulation as a result of microbial biotransformation of tryptophan, serotonin and other indole metabolites, which can be attributed to the "common metabolites" of humans and microbiota. The most interesting clinical studies are summarized in summary tables and figures. A number of indole metabolites are considered as potential biomarkers. The authors of the review substantiate the metabolomic approach to the study of a number of oncological, septic, mental and other intractable diseases, which opens up new possibilities of influence on the pathological process by targeted regulation in the metabolome/microbiome system.

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“…Since medical researchers have focused on the metabolic products of human multisliced colonizing microbiota film, a new interesting scenario has been proposed. The role of metabolites in host inflammatory process modulation and, consequentially, in atherosclerotic clinical manifestations as PAD has been defined to be much more essential and incisive than the producing microbe itself [145, 146].…”

Section: The Metabolome: From Waste To Biomarkermentioning

confidence: 99%

“…An increasing number of studies enrich the knowledge about the gut metabolome by studying tryptophan (trp), kynurenine/tryptophan (kyn/trp) ratio, indole sulfonate, p-cresyl sulfonate (PCS), hippuric acid (HA), indole-3-carboxaldehyde (i3a), indole 3-proprionic (i3p), H 2 S, and phenylacetylglutamine and their influence on atherosclerotic phenomenon [147], like PAD in patients affected by a high grade of severe atherosclerosis, an end-stage disease characterized by an hemodynamic stenosis of carotid arteries aimed at an endarterectomy, disabling claudication, or critical limb ischemia undergoing an endovascular revascularization procedure or “demolitive” surgery with amputation in nonsolvable PAD [145]. Specifically, the tryptophan depletion determines an overactivation of the transduction signal of a stress pathway [145, 148] and an elevated value of the kyn/trp ratio is found in inflammatory statements, including infections with a proven positive relation to MACE. In addition, a low value of the kyn/trp ratio has been observed in germ-free mice with an interesting opposite tendency of this relation in case used for the first colonization of the same mice [145, 149, 150].…”

Section: The Metabolome: From Waste To Biomarkermentioning

confidence: 99%

“…Specifically, the tryptophan depletion determines an overactivation of the transduction signal of a stress pathway [145, 148] and an elevated value of the kyn/trp ratio is found in inflammatory statements, including infections with a proven positive relation to MACE. In addition, a low value of the kyn/trp ratio has been observed in germ-free mice with an interesting opposite tendency of this relation in case used for the first colonization of the same mice [145, 149, 150]. Data about the gut microbes' metabolic products are continuously developing with several examples of their effect on host homeostasis; for example, indole sulfonate has been observed to have an active role in VSMC dysfunction, vessel calcification, and thickening of arteries [145, 151].…”

Section: The Metabolome: From Waste To Biomarkermentioning

confidence: 99%

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The Role of the Microbiota in the Diabetic Peripheral Artery Disease

Biscetti

Nardella

Cecchini

et al. 2019

Mediators of Inflammation

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Vascular complications of diabetes mellitus represent a major public health problem. Although many steps forward have been made to define the causes and to find the best possible therapies, the problem remains crucial. In recent years, more and more evidences have defined a link between microbiota and the initiation, promotion, and evolution of atherosclerotic disease, even in the diabetic scenario. There is an urgency to develop the knowledge of modern medicine about the link between gut microbiota and its host’s metabolic pathways, and it would be useful to understand and justify the interindividual diversity of clinical disease presentation of diabetic vascular complication even if an optimization of pharmacological treatment has been made or in the case of young patients where hypertension, dyslipidemia, and diabetes are not able to justify a very quick progress of atherosclerotic process. The aim of the present review is to gather all the best available evidence in this regard and to define a new role of the microbiota in this field, from biomarker to possible therapeutic target.

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Plasma microbiome-modulated indole- and phenyl-derived metabolites associate with advanced atherosclerosis and postoperative outcomes

Cited by 127 publications

References 71 publications

Unraveling Host-Gut Microbiota Dialogue and Its Impact on Cholesterol Levels

Unraveling Host-Gut Microbiota Dialogue and Its Impact on Cholesterol Levels

The role of human and microbial metabolites of triptophane in severe diseases and critical ill (review)

The Role of the Microbiota in the Diabetic Peripheral Artery Disease

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