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Am J Physiol Gastrointest Liver Physiol. 2019 Jan 10. doi: 10.1152/ajpgi.00348.2018. [Epub ahead of print]

Decreased Electrogenic Anionic Secretory Response in the Porcine Colon Following in vivo Challenge with Brachyspira spp. Supports an Altered Mucin Environment.

Author information

1
Veterinary Biomedical Sciences, University of Saskatchewan.
2
Large Animal Clinical Sciences, University of Saskatchewan.
3
Veterinary Biomedical Sciences, University of Saskatchewan, Canada.

Abstract

Brachyspiraspp. causediarrheal disease in multiple animal species by colonization of the colon, resulting in colitis, mucus induction and disrupted ion transport. Unique to spirochete pathogenesisis the immense production of mucus resulting in a niche mucin environment likely favoring spirochete colonization. Mucin rheological properties are heavily influencedby anionic secretion and loss of secretory function has been implicated in diseases such as cystic fibrosis. Here, the effects on the agonist-inducedelectrogenicanionic secretory response by infectious colonic spirochete bacteria Brachyspirahyodysenteriaeand Brachyspira hampsoniiwere assessedin the proximal, apex and distal sections of colonin Ussing chambers. Activation of secretion via isoproterenol, carbachol, andforskolin / IBMX demonstrated a significantly decreased change in short-circuit current ( Isc) in Brachyspira-infected pigs in all sections. Tissue resistances did not account for this difference, rather, it was attributed to a decrease in anionic secretion as indicated by a decrease in bumetanideinhibitable Isc. RT-qPCR analyses and western blot determined the major anionic channels of the epithelium were down-regulated in diarrheic pigs paired with altered mucin gene expression. The investigated cytokines were not responsible for the down-regulation of anion channel gene transcripts. Although IL-1α was upregulatedin all segments,it did not alter CFTR mRNA expression in Caco-2 monolayers. However, a whole cell Brachyspirahampsoniilysate significantly reduced CFTR mRNA expression in Caco-2 monolayers. Together, these findings indicate that these two Brachyspira spp. may directlycause a decreased anionic secretory response in the porcine colon supporting an altered mucin environment likely favoring spirochete colonization.

KEYWORDS:

Brachyspira; CFTR; TMEM16A; colon; mucin

PMID:
30629469
DOI:
10.1152/ajpgi.00348.2018

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