Metabolomic signatures of colonic infection by Brachyspira hyodysenteriae

Abstract Despite swine dysentery’s relevance in the pork industry, there are still gaps in our understanding of its pathogenesis and the impact of the infection in the gut. This study aimed to characterize the in vivo colonic metabolome of pigs experimentally infected with Brachyspira hyodysenteriae at the onset of fecal shedding (Early_inf group, n = 6) and during acute clinical disease characterized by mucohemorrhagic diarrhea (Acute_inf group, n = 8) compared with non-infected controls ( n = 16). The metabolic profile of the colonic contents changed progressively with disease severity, showing an intermediate pattern in the Early_inf group between the control and the Acute_inf groups ( p < 0.05). In acute disease, the metabolome was defined by increased concentrations of amino acids, carnitine derivatives, arachidic acid, 1,2-butanediol, and lactic acid, along with decreased levels of anti-inflammatory compounds. In the Early_inf group, increases were observed in amino acids, organic acids, amines, myo-inositol, quinoline, and 1,2-butanediol, whereas linolenic acid and oxalic acid decreased. Integrated analysis of the colonic metabolome and metagenome revealed a strong correlation between metabolic and microbial profiles, particularly in the Acute_inf group, where differential metabolites were associated with B. hyodysenteriae , Campylobacter hyointestinalis , and Velocimicrobium ethanolgignens . Metabolites showed high predictive potential for the disease stage, with lactic acid and arachidic acid being key markers of acute infection and dihydroxyacetone and leucine distinguishing early infection. Overall, this study reveals significant alterations in the colonic metabolome and its association with the microbiota during swine dysentery, providing new insights into the pathophysiology of the disease and contributing to the development of improved prevention and treatment strategies.