The role of Gr-1(+) cells and tumour necrosis factor-α signalling during Clostridium difficile colitis in mice.

The host response to Clostridium difficile infection in antibiotic-treated mice is characterized by robust recruitment of Gr-1(+) cells, increased expression of inflammatory cytokines including tumour necrosis factor-α (TNF-α), and the development of severe epithelial damage. To investigate the role of Gr-1(+) cells and TNF-α during C. difficile colitis, we treated infected mice with monoclonal antibodies against Gr-1 or TNF-α. Mice were challenged with vegetative cells of C. difficile strain VPI 10463 following treatment with the third-generation cephalosporin ceftriaxone. Ceftriaxone treatment alone was associated with significant changes in cytokine expression within the colonic mucosa but not overt inflammatory histopathological changes. In comparison, C. difficile infection following ceftriaxone treatment was associated with increased expression of inflammatory cytokines and chemokines including Cxcl1, Cxcl2, Il1b, Il17f and Tnfa, as well as robust recruitment of Ly6C(Mid)  Gr-1(High) neutrophils and Ly6C(High) Gr-1(Mid) monocytes and the development of severe colonic histopathology. Anti-Gr-1 antibody treatment resulted in effective depletion of both Ly6C(Mid) Gr-1(High) neutrophils and Ly6C(High) Gr-1(Mid) monocytes: however, we observed no protection from the development of severe pathology or reduction in expression of the pro-inflammatory cytokines Il1b, Il6, Il33 and Tnfa following anti-Gr-1 treatment. By contrast, anti-TNF-α treatment did not affect Gr-1(+) cell recruitment, but was associated with increased expression of Il6 and Il1b. Additionally, Ffar2, Ffar3, Tslp, Tff and Ang4 expression was significantly reduced in anti-TNF-α-treated animals, in association with marked intestinal histopathology. These studies raise the possibility that TNF-α may play a role in restraining inflammation and protecting the epithelium during C. difficile infection.

Modulation of post-antibiotic bacterial community reassembly and host response by Candida albicans.

The introduction of Candida albicans into cefoperazone-treated mice results in changes in bacterial community reassembly. Our objective was to use high-throughput sequencing to characterize at much greater depth the specific changes in the bacterial microbiome. The colonization of C. albicans significantly altered bacterial community reassembly that was evident at multiple taxonomic levels of resolution. There were marked changes in the levels of Bacteriodetes and Lactobacillaceae. Lachnospiraceae and Ruminococcaceae, the two most abundant bacterial families, did not change in relative proportions after antibiotics, but there were marked genera-level shifts within these two bacterial families. The microbiome shifts occurred in the absence of overt intestinal inflammation. Overall, these experiments demonstrate that the introduction of a single new microbe in numerically inferior numbers into the bacterial microbiome during a broad community disturbance has the potential to significantly alter the subsequent reassembly of the bacterial community as it recovers from that disturbance.

Prevalence of recurrent vulvovaginal candidiasis in 5 European countries and the United States: results from an internet panel survey.

OBJECTIVE: This study aimed to estimate prevalence of vulvovaginal candidiasis (VVC) and recurring VVC (RVVC). MATERIALS AND METHODS: An online omnibus survey was administered to 6,010 women aged 16 and older in 6 countries. RESULTS: We analyzed surveys from 6,000 women. Depending on the country, between 29% and 49% of participating women reported having a health care provider-diagnosed vaginal yeast infection during their lifetime. More than one fifth of women reporting one vaginal yeast infection also reported a 12-month period with 4 or more infections (RVVC) (overall 9%). The cumulative probability of RVVC after an initial vaginal yeast infection was very high. By age 25 years, the probability was 10% for women having had 1 initial yeast infection. By age 50 years, it was 25%. CONCLUSIONS: The overall rates of VVC and RVVC were high and consistent with previous findings. Results were consistent across countries with the exception of France, which had a lower rate of VVC. This may reflect differences in risk behavior, response to infection, or sampling biases. Recurring VVC is a significant health problem in western countries, and the probability that VVC will progress to RVVC is high.