Age-Dependent Effects of Short Chain Fatty Acids on Bacterial Burden In Vivo After Oral Infections with Listeria monocytogenes strains 10403s and 07PF0776

Listeria monocytogenes (LM) is a foodborne pathogen that establishes its intracellular life cycle inside mammalian host cells. In elderly individuals, LM infections can spread to peripheral organs, causing meningitis with high mortality rate. We have previously shown that short chain fatty acids (SCFAs), fermentation acids found in large quantities in the intestinal lumen, exhibit strong regulatory effects on LM virulence gene regulation. In this study, we investigated the effects of SCFAs on LM virulence using an oral feeding model of LM infection with two different LM strains in young (2 months) as well as old (16-18 months) female BALB/c mice. LM strains used in this study include the serotype 1/2a strain 10403s and the cardiotropic serotype 4b strain 07PF0776. Mice were given SCFAs, individually as well as in two different combinations, in drinking water for four weeks, starved for 24 hours, and orally infected with LM-ladened Nutella. At five days post infection, organs (spleens, liver, heart, gallbladder, ileum, and colon) were harvested and homogenized to enumerate LM colony forming units. We found that for both LM strains, SCFA supplements render the young mice more susceptible to infections but prevent old mice from succumbing to infections. Furthermore, low levels of SCFA mixtures led to a decrease in bacterial burden in the heart of old, but not young, animals infected with the cardiotropic strain 07PF0776. To better understand the different infection outcomes by strains 10403s and 07PF0776, we characterized their LLO production in response to SCFAs in vitro under aerobic or anaerobic conditions. We noted that the presence of low levels of SCFA mixture under anaerobic conditions significantly enhanced LLO production in 10403s but not in 07PF0776. These results indicate that there is a strain-dependent difference in LM response to SCFAs. Moreover, there is an age-dependent effect of exogenous SCFAs on the outcome of animal infections