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

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-kB, 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.

Opportunities and Challenges for Gut Microbiota in Acute Leukemia

“…The gut microbiota is closely related to the normal immunity of the organism (42). Among the infections present in patients with AL, the gut microbiota has been associated with diarrhea, neutropenic fever, and sepsis, and its diversity and composition are predictive of infection in patients (45)(46)(47)(48)(49)(50)(51)(52)59).…”

“…The use of carbapenem antibiotics in the empirical treatment of fever due to neutropenia in patients with AL reduces gut microbiota diversity and increases colonization by vancomycin-resistant enterococci ( 44 ). SCFAs, a metabolite of gut microbiota, promote the differentiation of T lymphocytes into effector T cells and regulatory T cells by inhibiting histone deacetylase ( 45 ). SCFAs also significantly inhibited the activity and infectivity of E. coli and protected intestinal epithelial cells from damage caused by C. difficile toxins ( 45 , 46 ).…”

“…SCFAs, a metabolite of gut microbiota, promote the differentiation of T lymphocytes into effector T cells and regulatory T cells by inhibiting histone deacetylase ( 45 ). SCFAs also significantly inhibited the activity and infectivity of E. coli and protected intestinal epithelial cells from damage caused by C. difficile toxins ( 45 , 46 ). Treatment of mice with broad-spectrum antibiotics resulted in a decrease in the number of hematopoietic stem cells and pluripotent progenitor cells in their bone marrow, as well as a decrease in granulocytes and B cells in the bone marrow and an increase in CD8+ T cells ( 47 ).…”

“…The presence of disruption of the gut microbiota early in bone marrow transplantation is also a potential risk factor for GVHD ( 86 ). We already know that SCFAs can reduce DNA damage in blood and gastrointestinal tissues during radiation damage ( 31 ), and SCFAs inhibit histone deacetylation ( 45 ). SCFAs mainly include formate, acetate, propionate and butyrate ( 87 ).…”

Special Issue: Pathogenic Escherichia coli: Infections and Therapies

“…Apart from this review, other original articles propose novel approaches to treat and/or prevent E. coli infections. For instance, Zhang et al suggest that colonic butyrate administration could be a novel treatment approach to decrease the growth and virulence gene expression of dysbiotic pathosimbiont E. coli in the context of inflammatory bowel disease [ 9 ]. Bumunang et al propose bacteriophage therapy and phlorotannin as antimicrobials against biofilm-forming Shiga toxin-producing E. coli [ 10 ], and Alves et al propose poly(MeOEGMA) as a polymer brush that prevents bacterial adhesion in urinary tract devices, such as ureteral stents and catheters, which has the potential to eradicate biofilms developed in these biomedical devices [ 11 ].…”