Short Chain Fatty Acids Modulate the Growth and Virulence of Pathosymbiont Escherichia coli and Host Response

Shiying Zhang; Belgin Dogan; Cindy Guo; Deepali Herlekar; Katrina Stewart; Ellen J Scherl; Kenneth W Simpson

doi:10.3390/antibiotics9080462

Short Chain Fatty Acids Modulate the Growth and Virulence of Pathosymbiont Escherichia coli and Host Response

Antibiotics (Basel). 2020 Jul 30;9(8):462. doi: 10.3390/antibiotics9080462.

Authors

Shiying Zhang¹, Belgin Dogan¹, Cindy Guo¹, Deepali Herlekar^{1

2}, Katrina Stewart^{1

3}, Ellen J Scherl⁴, Kenneth W Simpson¹

Affiliations

¹ Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
² Plainfield Animal Hospital, 2215 Park Ave., South Plainfield, NJ 07080, USA.
³ Sage Veterinary Centers, 1410 Monument Blvd, Concord, CA 94520, USA.
⁴ The Roberts IBD Center, Weill-Cornell Medical College, 71st and York, New York, NY 10065, USA.

Abstract

Short chain fatty acids (SCFA), principally acetate, propionate, and butyrate, are produced by fermentation of dietary fibers by the gut microbiota. SCFA regulate the growth and virulence of enteric pathogens, such as enterohemorrhagic E. coli (EHEC), Klebsiella and Salmonella. We sought to investigate the impact of SCFA on growth and virulence of pathosymbiont E. coli associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC), and their role in regulating host responses to bacterial infection in vitro. We found that under ileal conditions (pH = 7.4; 12 mM total SCFA), SCFA significantly (p < 0.05) potentiate the growth and motility of pathosymbiont E. coli. However, under colonic conditions (pH = 6.5; 65 to 123 mM total SCFA), SCFA significantly (p < 0.05) inhibit growth in a pH dependent fashion (up to 60%), and down-regulate virulence gene expression (e.g., fliC, fimH, htrA, chuA, pks). Functional analysis reveals that colonic SCFA significantly (p < 0.05) inhibit E. coli motility (up to 95%), infectivity (up to 60%), and type 1 fimbria-mediated agglutination (up to 50%). In addition, SCFA significantly (p < 0.05) inhibit the activation of NF-κB, and IL-8 production by epithelial cells. Our findings provide novel insights on the role of the regional chemical microenvironment in regulating the growth and virulence of pathosymbiont E. coli and opportunities for therapeutic intervention.

Keywords: adherent invasive E. coli (AIEC), colorectal cancer (CRC), pathosymbiont; gene expression; host; inflammatory bowel disease (IBD), Crohn’s disease (CD); invasion; motility; short chain fatty acids (SCFA).