In vivo transcriptomic profiling of colonic mucosa during Brachyspira hyodysenteriae infection in pigs

The little known pathophysiology of swine dysentery (SD) encourages novel studies to decipher the host response to this disease. The present study investigates the in vivo transcriptome of colonic mucosa, using RNA sequencing in 16 pigs experimentally infected with Brachyspira hyodysenteriae (B. hyodysenteriae), at the onset of faecal shedding (Earlyᵢnf group, n = 8), and during the acute clinical disease, with mucohaemorrhagic diarrhoea (Acuteᵢnf group, n = 8). No significant differences in gene expression were observed in Earlyᵢnf group, except for an overexpression of matrix metalloproteinases genes (MMPs), which may be associated with early ulceration of the colonic epithelium. The Acuteᵢnf group showed a significant upregulation of the S100A8, S100A9 and S100A12 genes. However, most of the host biological processes were downregulated, particularly those related to the immune response, such as chemokines and cytokines signalling or immune cells chemotaxis and migration. Accordingly, the prediction of cell types associated with the detected transcripts revealed a depletion of immune cells, except neutrophils, and an enrichment of stromal cells in the Acuteᵢnf group. Marked alterations in mucin gene expression were observed in this group, including overexpression of MUC5AC, MUC20, and GCNT3, a tendency in MUC2, and downregulation of MUC1 and MUC3. Although no significant changes were detected in the Earlyᵢnf group, a similar trend was observed. This study proposes several mechanisms associated with the pathophysiology of SD, revealing key aspects of host–pathogen interactions, particularly the host response to B. hyodysenteriae infection. • This firs in vivo study reveals that colon mucosa changes elicited by Brachyspira hyodysenteriae infection are evident in acute disease but not in early stages of the infection. • Brachyspira hyodysenteriae acute infection prompts large changes in the host immune response, mostly by downregulating early response routes mediated by cytokines and other immune markers. • Immune response is overcome by a depletion of immune cells, except neutrophils, transcripts. • The study offers a relevant number of biomarkers of colitis, some of them identified previously in human colitis and other enteric infections, offering an array of molecules to evaluate the impact of the infection in the gut