Plasma metabolomics of Mycoplasma synoviae infection in SPF White Leghorn hens by liquid chromatography-tandem mass spectrometry

Mycoplasma synoviae (M. synoviae) is a major bacterial pathogen that causes serious economic losses in the global poultry industry. Systemic changes in specific pathogen free White Leghorn egg-laying hens after M. synoviae infection were investigated using intra-tracheally inoculated animals. Samples were collected 10 days post-infection (dpi) (204-day-old) and 52 dpi (246-day-old). Infection caused air sac lesion, footpad swelling and oviduct atrophy. The qPCR and in situ hybridization showed that bacteria colonized the trachea and oviduct, and that bacterial loads in the magnum and uterus were significantly higher than in the infundibulum and isthmus. Histopathological examination revealed increased tracheal mucosal thickening accompanied by inflammatory cell infiltration, and that tubular glands of the uterus were edematous or dissolved. Infection also induced decreased egg production and eggshell strength, and eggshell apex abnormalities appeared at 14 dpi. Plasma metabolomics of hens analyzed by liquid chromatography-tandem mass spectrometry showed 168 and 128 differentially-expressed metabolites (DEM) at 10 and 52 dpi, respectively. Pathway analysis revealed that DEM at 10 dpi were enriched in five distinctive pathways: regulation of the actin cytoskeleton, neuroactive ligand-receptor interaction, sphingolipid metabolism, gap junctions, and necroptosis. In contrast, DEM at 52 dpi were enriched in fifteen pathways involved in steroid hormone biosynthesis, ferroptosis, the calcium signaling pathway, apelin signaling pathway, progesterone-mediated oocyte maturation, and oocyte meiosis. Combined metabolic analysis demonstrated that changes in ethylsalicylate, nicotinamide, (3-Methoxy-4-hydroxyphenyl) ethylene glycol sulfate, sphingosine-1-phosphate (d18:1), carnitine C24:6, and 15(R)-prostaglandin E1 correlated the best with M. synoviae infection. This study provides new insights into understanding pathogen mechanisms and signposts novel treatments for M. synoviae infection in poultry.