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

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

doi:10.3389/fmicb.2010.00148

Abstract

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.

Highlights

IntroductIon The human gastrointestinal tract (GIT) represents the main site where intensive cross-talk takes place between the host and the immense, diverse commensal microbiota
Many disorders in humans are due to a restructured microbiota, which fails to “communicate” properly with its host leading to aberrant host responses and contributing to the disease state (Farthing, 2004; Stecher and Hardt, 2008)
We demonstrated recently that in an autoinflammatory disorder, familial Mediterranean fever (FMF, MIM249100), the commensal gut microbiota composition is restructured and that the observed structural changes are determined by the host genotype (Khachatryan et al, 2008)

Summary

MaterIalS and MetHodS

SubjectS A total of 37 FMF patients (13 in remission and 24 in attack periods), 14 PU patients in exacerbation period, and 43 healthy controls participated in the study. Fatty acids and aldehydes were extracted from complex lipids of microorganisms in the form of methyl esters and aldehyde dimethyl acetals. The fraction of methyl esters of fatty acids with other lipid components was extracted twice from the reaction mixture with 200 μl of hexane. ReSultS The GC/MS approach was used in this study to detect and evaluate the concentration of products of microbial origin in blood of FMF (remission and attack) and PU patients compared to healthy control subjects (Table 1). Defrosted blood samples were air dried at 80°C and subjected to Hydroxy fatty acIdS Significantly higher levels of hydroxy acids were detected in blood of PU patients and FMF patients in remission compared with healthy controls, whereas in an FMF attack it was found to be Frontiers in Microbiology | Cellular and Infection Microbiology

CyCloProPyl Fa

Phenylacetic acid

Findings

Test of