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Bloom and bust: intestinal microbiota dynamics in response to hospital exposures and Clostridium difficile colonization or infection.

ABSTRACT: Clostridium difficile infection (CDI) is the leading infectious cause of nosocomial diarrhea. Hospitalized patients are at increased risk of developing CDI because they are exposed to C. difficile spores through contact with the hospital environment and often receive antibiotics and other medications that can disrupt the integrity of the indigenous intestinal microbiota and impair colonization resistance. Using whole metagenome shotgun sequencing, we examined the diversity and composition of the fecal microbiota in a prospective cohort study of 98 hospitalized patients.Four patients had asymptomatic C. difficile colonization, and four patients developed CDI. We observed dramatic shifts in the structure of the gut microbiota during hospitalization. In contrast to CDI cases, asymptomatic patients exhibited elevated relative abundance of potentially protective bacterial taxa in their gut at the onset of C. difficile colonization. Use of laxatives was associated with significant reductions in the relative abundance of Clostridium and Eubacterium; species within these genera have previously been shown to enhance resistance to CDI via the production of secondary bile acids. Cephalosporin and fluoroquinolone exposure decreased the frequency of Clostridiales Family XI Incertae Sedis, a bacterial family that has been previously associated with decreased CDI risk.This study underscores the detrimental impact of antibiotics as well as other medications, particularly laxatives, on the intestinal microbiota and suggests that co-colonization with key bacterial taxa may prevent C. difficile overgrowth or the transition from asymptomatic C. difficile colonization to CDI.

SUBMITTER: Vincent C

PROVIDER: S-EPMC4791782 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Bloom and bust: intestinal microbiota dynamics in response to hospital exposures and Clostridium difficile colonization or infection.

Vincent Caroline C Miller Mark A MA Edens Thaddeus J TJ Mehrotra Sudeep S Dewar Ken K Manges Amee R AR

Microbiome 20160314

<h4>Background</h4>Clostridium difficile infection (CDI) is the leading infectious cause of nosocomial diarrhea. Hospitalized patients are at increased risk of developing CDI because they are exposed to C. difficile spores through contact with the hospital environment and often receive antibiotics and other medications that can disrupt the integrity of the indigenous intestinal microbiota and impair colonization resistance. Using whole metagenome shotgun sequencing, we examined the diversity and ...[more]

PMID: 26975510

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Project description:BACKGROUND:Intestinal colonization by pathogenic bacteria is a risk factor for infection, and contributes to environmental contamination and disease dissemination. Alteration of gut microbiota also plays a pivotal role in the development of disease. Although Clostridium difficile and Staphylococcus aureus are well-recognized pathogens causing nosocomial and community infections, the intestinal colonization was not fully investigated. Herein, we explored their overall carriage rates in healthy adults from the community, and characterized the gut microbiomes of C. difficile and S. aureus carriers. METHODS:Fecal samples were collected from 1709 healthy volunteers from communities in Shanghai, China, and tested for the presence of C. difficile, methicillin-sensitive S. aureus (MSSA), and methicillin-resistant S. aureus (MRSA) using culture-based techniques. To explore differences in the gut microbiome, 16S rRNA gene sequencing was conducted using samples from non-carriers (CH), C. difficile carriers (CCD), MRSA carriers (CM), and MSSA carriers (CS). RESULTS:Overall, we detected 12 C. difficile and 60 S. aureus isolates, accounting for 0.70% and 3.51% of total isolates, respectively. Eight isolates were determined to be MRSA, accounting for 13.3% of the S. aureus population. Sequencing data revealed that the microbial diversity and richness were similar among the four groups. However, at the phylum level, carriage of C. difficile or MRSA was associated with a paucity of Bacteroidetes and an overabundance of Proteobacteria compared with non-carriers. At the genus level, the prevalence of the genera Bacteroides, Prevotella, Faecalibacterium, and Roseburia was decreased in C. difficile-positive samples compared with the controls, while the proportion of Clostridium cluster XIVa species was increased. MRSA carriers exhibited a higher proportion of the genera Parasutterella and Klebsiella, but a decreased prevalence of Bacteroides. Compared with MSSA carriers, Klebsiella was the only genus found to be significantly enriched in MRSA carriers. CONCLUSIONS:In healthy adults, colonization by C. difficile or S. aureus did not significantly affect gut microbiota diversity. However, the alteration of the gut microbiota composition in C. difficile carriers could indicate a predisposition to further infection. Our study provides essential data on the prevalence and effects of C. difficile and S. aureus colonization on gut microbiota composition in healthy adults.

Project description:Clostridium difficile causes antibiotic-associated diarrhea and pseudomembraneous colitis and is responsible for a large and increasing fraction of hospital-acquired infections. Fecal microbiota transplantation (FMT) is an alternate treatment option for recurrent C. difficile infection (RCDI) refractory to antibiotic therapy. It has recently been discussed favorably in the clinical and scientific communities and is receiving increasing public attention. However, short- and long-term health consequences of FMT remain a concern, as the effects of the transplanted microbiota on the patient remain unknown. To shed light on microbial events associated with RCDI and treatment by FMT, we performed fecal microbiota analysis by 16S rRNA gene amplicon pyrosequencing of 14 pairs of healthy donors and RCDI patients treated successfully by FMT. Post-FMT patient and healthy donor samples collected up to one year after FMT were studied longitudinally, including one post-FMT patient with antibiotic-associated relapse three months after FMT. This analysis allowed us not only to confirm prior reports that RCDI is associated with reduced diversity and compositional changes in the fecal microbiota, but also to characterize previously undocumented post-FMT microbiota dynamics. Members of the Streptococcaceae, Enterococcaceae, or Enterobacteriaceae were significantly increased and putative butyrate producers, such as Lachnospiraceae and Ruminococcaceae were significantly reduced in samples from RCDI patients before FMT as compared to post-FMT patient and healthy donor samples. RCDI patient samples showed more case-specific variations than post-FMT patient and healthy donor samples. However, none of the bacterial groups were invariably associated with RCDI or successful treatment by FMT. Overall microbiota compositions in post-FMT patients, specifically abundances of the above-mentioned Firmicutes, continued to change for at least 16 weeks after FMT, suggesting that full microbiota recovery from RCDI may take much longer than expected based on the disappearance of diarrheal symptoms immediately after FMT.

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Bloom and bust: intestinal microbiota dynamics in response to hospital exposures and Clostridium difficile colonization or infection.

Publications

Bloom and bust: intestinal microbiota dynamics in response to hospital exposures and Clostridium difficile colonization or infection.

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