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12 Publications visible to you, out of a total of 12

Abstract (Expand)

Gut microbiota-produced short chain fatty acids (SCFAs) play an important role in the normal human metabolism and physiology. Although the gradients of SCFAs from the large intestine, where they are largely produced, to the peripheral blood as well as the main routes of SCFA metabolism by different organs are known well for the healthy state, there is a paucity of information regarding how these are affected in disease. In particular, how the inflammation caused by infection or autoinflammatory disease affect the concentration of SCFAs in the peripheral venous blood. In this work, we revealed that diseases caused either by infectious agents (two Salmonella enterica serovars, S. Enteritidis, and S. Typhimurium) or by the exacerbation of an autoinflammatory disease, familial Mediterranean fever (FMF), both result in a significantly elevated systemic concentration of SCFAs. In the case of salmonellosis the concentration of SCFAs in peripheral blood was significantly and consistently higher, from 5- to 20-fold, compared to control. In the case of FMF, however, a significant increase of SCFAs in the peripheral venous blood was detected only in the acute phase of the disease, with a lesser impact in remission. It seems counterintuitive that the dysbiotic conditions, with a reduced number of gut microorganisms, produce such an effect. This phenomenon, however, must be appraised within the context of how the inflammatory diseases affect the normal physiology. We discuss a number of factors that may contribute to the "leak" and persistence of gut-produced SCFAs into the systemic circulation in infectious and autoinflammatory diseases.

Authors: Zhanna A Ktsoyan, Mkhitar S Mkrtchyan, Magdalina K Zakharyan, Armine A Mnatsakanyan, Karine A Arakelova, Zaruhi U Gevorgyan, Anahit M Sedrakyan, Alvard I Hovhannisyan, Arsen A Arakelyan, Rustam I Aminov

Date Published: 24th May 2016

Publication Type: Journal

Abstract (Expand)

The main goal of this study was to establish how the inflammation caused by infection with two different Salmonella enterica serotypes, S. Typhimurium and S. Enteritidis, may lead to the predisposition to allergy as measured by total IgE level in the blood. Infection by S. Typhimurium did not affect the systemic IgE concentration while in S. Enteritidis-infected patients there was a significant 3.5-fold increase. This effect was especially profound in patients >4 years old, with up to the 8-fold increase above the norm. The degree of dysbiosis in these two infections measured with the comparative counts of cultivated bacteria showed an inverse relationship with the IgE concentration. Earlier we reported the elevated level of IL-17 in patients infected by S. Enteritidis. In the current study a significant correlation was found between the concentrations of IL-17 and IgE suggesting a possible role played by this cytokine in triggering the production of IgE in response to S. Enteritidis infection.

Authors: Zhanna A Ktsoyan, Mkhitar S Mkrtchyan, Magdalina K Zakharyan, Armine A Mnatsakanyan, Karine A Arakelova, Zaruhi U Gevorgyan, Lusntag A Ktsoyan, Anahit Ì Sedrakyan, Alvard I Hovhannisyan, Karine A Ghazaryan, Anna S Boyajyan, Rustam I Aminov

Date Published: 26th May 2015

Publication Type: Journal

Abstract (Expand)

The main purpose of this study was to investigate the profile of inflammatory response in patients with acute salmonellosis caused by two serotypes of Salmonella enterica, S. Enteritidis and S. Typhimurium, as well as in convalescent patients with previous acute disease caused by S. Enteritidis. Patients with acute disease showed significantly elevated levels of IL-1β, IL-17, IL-10, and calprotectin compared to healthy control subjects. In convalescent patients, these markers were also significantly elevated, with the exception of IL-1β. Multivariate statistical analyses with the use of these variables produced models with a good predictive accuracy resulting in excellent separation of the diseased and healthy cohorts studied. Overall, the results suggest that the profile of inflammatory response in this disease is determined, to a significant degree, by the serotype of Salmonella, and the profile of certain cytokines and calprotectin remains abnormal for a number of months following the acute disease stage.

Authors: Zhanna Ktsoyan, Karine Ghazaryan, Gayane Manukyan, Anush Martirosyan, Armine Mnatsakanyan, Karine Arakelova, Zaruhi Gevorgyan, Anahit Sedrakyan, Ara Asoyan, Anna Boyajyan, Rustam Aminov

Date Published: 16th Sep 2013

Publication Type: Journal

Abstract (Expand)

In our previous works we established that in an autoinflammatory condition, familial Mediterranean fever (FMF), the gut microbial diversity is specifically restructured, which also results in the altered profiles of microbial long chain fatty acids (LCFAs) present in the systemic metabolome. The mainstream management of the disease is based on oral administration of colchicine to suppress clinical signs and extend remission periods and our aim was to determine whether this therapy normalizes the microbial LCFA profiles in the metabolome as well. Unexpectedly, the treatment does not normalize these profiles. Moreover, it results in the formation of new distinct microbial LCFA clusters, which are well separated from the corresponding values in healthy controls and FMF patients without the therapy. We hypothesize that the therapy alters the proinflammatory network specific for the disease, with the concomitant changes in gut microbiota and the corresponding microbial LCFAs in the metabolome.

Authors: Zhanna A Ktsoyan, Natalia V Beloborodova, Anahit M Sedrakyan, George A Osipov, Zaruhi A Khachatryan, Gayane P Manukyan, Karine A Arakelova, Alvard I Hovhannisyan, Arsen A Arakelyan, Karine A Ghazaryan, Magdalina K Zakaryan, Rustam I Aminov

Date Published: 28th Jan 2013

Publication Type: Journal

Abstract (Expand)

The human gastrointestinal tract is inhabited by a diverse and dense symbiotic microbiota, the composition of which is the result of host-microbe co-evolution and co-adaptation. This tight integration creates intense cross-talk and signaling between the host and microbiota at the cellular and metabolic levels. In many genetic or infectious diseases the balance between host and microbiota may be compromised resulting in erroneous communication. Consequently, the composition of the human metabolome, which includes the gut metabolome, may be different in health and disease states in terms of microbial products and metabolites entering systemic circulation. To test this hypothesis, we measured the level of hydroxy, branched, cyclopropyl and unsaturated fatty acids, aldehydes, and phenyl derivatives in blood of patients with a hereditary autoinflammatory disorder, familial Mediterranean fever (FMF), and in patients with peptic ulceration (PU) resulting from Helicobacter pylori infection. Discriminant function analysis of a data matrix consisting of 94 cases as statistical units (37 FMF patients, 14 PU patients, and 43 healthy controls) and the concentration of 35 microbial products in the blood as statistical variables revealed a high accuracy of the proposed model (all cases were correctly classified). This suggests that the profile of microbial products and metabolites in the human metabolome is specific for a given disease and may potentially serve as a biomarker for disease.

Authors: Zhanna A Ktsoyan, Natalia V Beloborodova, Anahit M Sedrakyan, George A Osipov, Zaruhi A Khachatryan, Denise Kelly, Gayane P Manukyan, Karine A Arakelova, Alvard I Hovhannisyan, Andrey Y Olenin, Arsen A Arakelyan, Karine A Ghazaryan, Rustam I Aminov

Date Published: 20th Jan 2011

Publication Type: Journal

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