Reductions in intestinal Clostridiales precede the development of nosocomial Clostridium difficile infection

Abstract

BackgroundAntimicrobial use is thought to suppress the intestinal microbiota, thereby impairing colonization resistance and allowing Clostridium difficile to infect the gut. Additional risk factors such as proton-pump inhibitors may also alter the intestinal microbiota and predispose patients to Clostridium difficile infection (CDI). This comparative metagenomic study investigates the relationship between epidemiologic exposures, intestinal bacterial populations and subsequent development of CDI in hospitalized patients. We performed a nested case–control study including 25 CDI cases and 25 matched controls. Fecal specimens collected prior to disease onset were evaluated by 16S rRNA gene amplification and pyrosequencing to determine the composition of the intestinal microbiota during the at-risk period.ResultsThe diversity of the intestinal microbiota was significantly reduced prior to an episode of CDI. Sequences corresponding to the phylum Bacteroidetes and to the families Bacteroidaceae and Clostridiales Incertae Sedis XI were depleted in CDI patients compared to controls, whereas sequences corresponding to the family Enterococcaceae were enriched. In multivariable analyses, cephalosporin and fluoroquinolone use, as well as a decrease in the abundance of Clostridiales Incertae Sedis XI were significantly and independently associated with CDI development.ConclusionsThis study shows that a reduction in the abundance of a specific bacterial family - Clostridiales Incertae Sedis XI - is associated with risk of nosocomial CDI and may represent a target for novel strategies to prevent this life-threatening infection.

Defining the gut microbiota in individuals with periodontal diseases: an exploratory study

“…Other investigations have shown that reduced alpha diversity is a reliable indicator of disease-associated dysbiosis [1,54–56], corroborating our results. In relation to beta diversity, it was not possible to clearly distinguish individuals with distinct clinical status based on the composition of the gut microbiota.…”

“…Koren et al [56] brought up also the possibility of a link between oral and intestinal microbiota with inflammatory diseases by investigating whether the oral or gut microbiota could contribute to atherosclerosis. They reported that several OTUs from oral and gut sources were also detected in atherosclerotic plaque within the same patients.…”

Effect of Surotomycin, a Novel Cyclic Lipopeptide Antibiotic, on Intestinal Colonization with Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice

“…For mice, we previously demonstrated that the recovery of bacteria from the families Lachnospiraceae and Ruminococcaceae (phylum Firmicutes, order Clostridiales) corresponded directly with the timing of the recovery of in vivo resistance to colonization with VRE and C. difficile (23). For hospitalized patients, a reduction in the abundance of members of the order Clostridiales was independently associated with an increased risk of nosocomial CDI (24).…”

Recurrent Clostridium difficile infection and the microbiome

“…Numerous studies have demonstrated decreased intestinal microbial diversity among patients with rCDI compared to those with only one episode of CDI that does not recur [33], and diversity is reduced in patients with primary or rCDI compared to those with asymptomatic colonization [33,37,38]. Other studies have shown lower proportions of the family Clostridiales Incertae Sedis XI in patients who developed CDI compared to those who did not [39][40][41]. This deviation in the gut microbiota is thought to contribute to the loss of colonization resistance to C. difficile, as seen in animal and in vitro studies [42].…”