Lactic acid production by Streptococcus thermophilus alters Clostridium difficile infection and in vitro Toxin A production

Abstract

Antibiotic treatment to treat specific infections has the potential to effectively target the offending microbe as well as other microbes that colonize sites within a host. Antibiotic-associated diarrhea (AAD) is a classic example resulting from disruption of host microbial communities; 20% of patients with AAD are likely to become colonized with Clostridium difficile. Restoration of a “normal” microbial community within the host using probiotic bacteria is one approach to circumvent AAD and C. difficile infection. The goals of this study were to assess the interactions between Streptococcus thermophilus, a potential probiotic organism and C. difficile using both in vitro and in vivo systems. Exposure of C. difficile to filtered supernatants from S. thermophilus showed a dose-dependent, bactericidal effect due to lactic acid. Additional studies show that levels of lactic acid (10 mM) that did not inhibit bacterial growth had the potential to decrease tcdA expression and TcdA release into the extracellular milieu. In vivo, treatment with viable S. thermophilus significantly increased luminal levels of lactate in the cecum compared with UV-irradiated S. thermophilus. In the context of infection with C. difficile, mice treated with viable S. thermophilus exhibited 46% less weight loss compared with untreated controls; moreover, less pathology, diarrhea, and lower detectable toxin levels in cecal contents were evident more often in S. thermophillus treated mice. A significant, inverse correlation (Spearman r = -0.942, p = 0.017) between the levels of luminal lactate and abundance of C. difficile were noted suggesting that lactate produced by S. thermophilus is a factor impacting the progression of C. difficile infection in the murine system.

Keywords: :

• Clostridium difficile
• Streptococcus thermophilus
• probiotic
• mouse model

View correction statement:

Correction to Glynis L. Kolling et al., Gut Microbes Volume 3, Issue 6; pp. 523–9

Disclosure of Potential Conflicts of Interest

The authors declare no conflicts of interest.

Acknowledgments

This research was supported by a Young Investigator Grant in Probiotics Research (to G.L.K.) from the Global Probiotics Council and by the National Institutes of Health Grant U01AI075526 (to R.L.G.) and the North Carolina Agricultural Foundation (to E.D. and T.R.K.). The authors thank Pascal Hols for kindly providing the bacteriocin negative mutant of S. thermophilus for use as a control in this study. The authors wish to thank Dr Relana Pinkerton for assistance with a portion of the statistical analysis.