Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon

Abstract

Vancomycin, metronidazole, and the bacteriocin lacticin 3147 are active against a wide range of bacterial species, including Clostridium difficile. We demonstrate that, in a human distal colon model, the addition of each of the three antimicrobials resulted in a significant decrease in numbers of C. difficile. However, their therapeutic use in the gastrointestinal tract may be compromised by their broad spectrum of activity, which would be expected to significantly impact on other members of the human gut microbiota. We used highthroughput pyrosequencing to compare the effect of each antimicrobial on the composition of the microbiota. All three treatments resulted in a decrease in the proportion of sequences assigned to the phyla Firmicutes and Bacteroidetes, with a corresponding increase in those assigned to members of the Proteobacteria. One possible means of avoiding such "collateral damage" would involve the application of a narrow-spectrum antimicrobial with specific anti-C. difficile activity. We tested this hypothesis using thuricin CD, a narrowspectrum bacteriocin produced by Bacillus thuringiensis, which is active against C. difficile. The results demonstrated that this bacteriocin was equally effective at killing C. difficile in the distal colon model but had no significant impact on the composition of the microbiota. This offers the possibility of developing a targeted approach to eliminating C. difficile in the colon, without collateral damage.gut microbiota | pyrosequencing | bacteriocin | antibiotic | thuricin

Streptozotocin-induced type-1-diabetes disease onset in Sprague–Dawley rats is associated with an altered intestinal microbiota composition and decreased diversity

“…A locally installed version of SILVA 16S rRNA database (version 106) (Pruesse et al, 2007) was used to BLAST (Altschul et al, 1997) the trimmed sequence using default parameters. Resulting BLAST output files were parsed through MEGAN (Huson et al, 2007); similar to previous studies a bitscore cut-off of 86 was selected (Rea et al, 2011;Urich et al, 2008). Clustering of sequence reads into operational taxonomical units (OTUs) at 97 % identity and subsequent alignments were achieved using QIIME suite software tools (Caporaso et al, 2010).…”

Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection

“…Since then, FMT has been used to treat over 500 cases of CDI and other disorders with a disturbed intestinal microbiota (Borody et al, 2003;Landy et al, 2011;Vrieze et al, 2012;Kassam et al, 2013). Although it is generally believed that the efficacy of FMT can be explained by restoration of healthy gut microbiota, there are still few studies addressing the microbial composition and dynamics triggered by FMT (Khoruts et al, 2010;Manichanh et al, 2010;Rea et al, 2011;Petrof et al, 2013).…”

Clostridium difficile heterogeneously impacts intestinal community architecture but drives stable metabolome responses

“…This investigation moves beyond descriptive studies of community composition (for example, Rea et al, 2011;Peterfreund et al, 2012;Knecht et al, 2014;Pérez-Cobas et al, 2014) and presents the metabolic profiles of the gut microbiota in patients colonised with C. difficile that were positive or negative for the production of toxins and in noncolonised control patients. The study aimed to determine whether C. difficile has a role in shaping gastrointestinal microbial metabolism and, if so, whether the production of toxins has an influence.…”