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3 Publications visible to you, out of a total of 3
Systemic Concentrations of Short Chain Fatty Acids Are Elevated in Salmonellosis and Exacerbation of Familial Mediterranean Fever.

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

Management of familial Mediterranean fever by colchicine does not normalize the altered profile of microbial long chain fatty acids in the human metabolome.

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

Profiles of Microbial Fatty Acids in the Human Metabolome are Disease-Specific.

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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