Serum lipidomics of bovine paratuberculosis: Disruption of choline-containing glycerophospholipids and sphingolipids

Objectives: Bovine paratuberculosis is a devastating infection with Mycobacterium avium subspecies paratuberculosis that ultimately results in death from malnutrition. While the infection is characterized by a long (2–4 years) subclinical phase with immune activation, ultimately host defense mechanisms fail and the bacteria spread from the small intestine to other organs. Since both the gastrointestinal tract and liver are essential for the biosynthesis of structural glycerophospholipids, we investigated the circulating levels of these lipids in field infections and experimentally infected cattle. Methods: Serum lipidomics of control and M. avium subspecies paratuberculosis–infected cattle were performed utilizing high-resolution mass spectrometry. Results: In M. avium subspecies paratuberculosis–positive cattle, demonstrating clinical signs, we monitored large decreases in the levels of circulating phosphocholine-containing lipids. These included phosphatidylcholines, choline plasmalogens, and sphingomyelins. Next, we monitored the time course of these lipid alterations in experimentally infected calves and found that altered lipid levels were only detected in cattle with clinical signs of infection. Conclusions: Our data indicate that altered availability of choline-containing lipids occurs late in the disease process and is most likely a result of malnutrition and altered biosynthetic capacities of the liver and gastrointestinal tract. Alterations in the bioavailability of these critical structural lipids presumably contributes to the demise of M. avium subspecies paratuberculosis–infected cattle. In light of increasing concern that M. avium subspecies paratuberculosis may be a zoonotic bacterium that contributes to the development of Crohn’s disease and multiple sclerosis, our data also have human clinical relevance.