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

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.

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

“…Correspondingly, the profile of microbial LCFAs circulating in the blood is also specific for the diseased and healthy states (Ktsoyan et al, 2010). In this work, we addressed the question whether the colchicine therapy that is used to suppress the clinical manifestations of FMF and to extend the remission periods could also have an effect on the level and profile of microbial LCFAs in systemic circulation.…”

“…Previously, we showed that this autoinflammatory condition results in cardinal restructuring of gut microbiota (Khachatryan et al, 2008), accompanied by changes in microbial products circulating in the systemic metabolome (Ktsoyan et al, 2010). We also demonstrated the increased systemic reactivity against the commensal gut microbiota in FMF, thus suggesting a possible mechanism for restructuring the gut microbiota composition in an autoinflammatory condition (Manukyan et al, 2008b).…”

“…In our previous works we focused on host-microbiota interaction in an autoinflammatory disease, familial Mediterranean fever (FMF, MIM249100) (Khachatryan et al, 2008; Manukyan et al, 2008b; Ktsoyan et al, 2010). This disease is the most common member of hereditary autoinflammatory diseases and it is characterized by recurrent self-resolving acute attacks of fever and polyserositis.…”

Integrated omics analyses reveal the details of metabolic adaptation of Clostridium thermocellum to lignocellulose-derived growth inhibitors released during the deconstruction of switchgrass

“…Other odd-carbon fatty acids, such as hentriancontanoic acid (C 31 H 62 O 2 ), nonacosanoic acid (C 29 H 58 O 2 ), heptacosanoic acid (C 27 H 54 O), and the methyl-branched iso-heptadecanoic acid (iso-C 17 H 34 O 2 ), exhibited similar accumulation patterns, the latter of which increased by almost 21-fold. Since these are higher order and have odd numbers of carbon atoms, they are likely of microbial origin [30]. The accumulation of these long-chain, saturated fatty acids, and unique branched fatty acids, indicates cell membrane restructuring to better tolerate increased concentrations of lignocellulose-derived inhibitors that affect membrane fluidity [31–33].…”

Mass spectrometric analysis of medical samples and aspects of clinical diagnostics

“…Both approaches were implemented; however, it is unlikely that they can be considered universal. Minor acids (see [47,52]) are most often considered to be biomarkers; their identification against the background of intense analytical signals of nonspecific compounds in the presence of a great number of isomers (formally appearing in the shift of double bonds in the aliphatic chain and its branching) can, in our opinion, be unre liable. The biomarker approach is, probably, most promising for the recognition of certain genus and species of bacteria [48,49].…”