Dataset Information

The Bacterial Gut Microbiota of Adult Patients Infected, Colonized or Noncolonized by Clostridioides difficile.

ABSTRACT: : Gut microbiota composition in patients with Clostridioides difficile colonization is not well investigated. We aimed to identify bacterial signatures associated with resistance and susceptibility to C. difficile colonization (CDC) and infection (CDI). Therefore, gut microbiota composition from patients with CDC (n = 41), with CDI (n = 41), and without CDC (controls, n = 43) was determined through 16S rRNA gene amplicon sequencing. Bacterial diversity was decreased in CDC and CDI patients (p<0.01). Overall microbiota composition was significantly different between control, CDC, and CDI patients (p = 0.001). Relative abundance of Clostridioides (most likely C. difficile) increased stepwise from controls to CDC and CDI patients. In addition, differential abundance analysis revealed that CDI patients' gut microbiota was characterized by significantly higher relative abundance of Bacteroides and Veillonella than CDC patients and controls. Control patients had significantly higher Eubacterium hallii and Fusicatenibacter abundance than colonized patients. Network analysis indicated that Fusicatenibacter was negatively associated with Clostridioides in CDI patients, while Veillonella was positively associated with Clostridioides in CDC patients. Bacterial microbiota diversity decreased in both CDC and CDI patients, but harbored a distinct microbiota. Eubacterium hallii and Fusicatenibacter may indicate resistance against C. difficile colonization and subsequent infection, while Veillonella may indicate susceptibility to colonization and infection by C. difficile.

SUBMITTER: Crobach MJT

PROVIDER: S-EPMC7284656 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Bacterial Gut Microbiota of Adult Patients Infected, Colonized or Noncolonized by Clostridioides difficile.

Crobach Monique J T MJT Ducarmon Quinten R QR Terveer Elisabeth M EM Harmanus Celine C Sanders Ingrid M J G IMJG Verduin Kees M KM Kuijper Ed J EJ Zwittink Romy D RD

Microorganisms 20200506 5

: Gut microbiota composition in patients with Clostridioides difficile colonization is not well investigated. We aimed to identify bacterial signatures associated with resistance and susceptibility to C. difficile colonization (CDC) and infection (CDI). Therefore, gut microbiota composition from patients with CDC (n = 41), with CDI (n = 41), and without CDC (controls, n = 43) was determined through 16S rRNA gene amplicon sequencing. Bacterial diversity w ...[more]

PMID: 32384826

Similar Datasets

Project description:Clostridioides difficile infection (CDI) is most commonly diagnosed using nucleic acid amplification tests (NAAT); the low positive predictive value of these assays results in patients colonized with C. difficile unnecessarily receiving CDI treatment antibiotics. The risks and benefits of antibiotic treatment in individuals with such cases are unknown. Fecal samples of NAAT-positive, toxin enzyme immunoassay (EIA)-negative patients were collected before, during, and after randomization to vancomycin (n = 8) or placebo (n = 7). C. difficile and antibiotic-resistant organisms (AROs) were selectively cultured from fecal and environmental samples. Shotgun metagenomics and comparative isolate genomics were used to understand the impact of oral vancomycin on the microbiome and environmental contamination. Overall, 80% of placebo patients and 71% of vancomycin patients were colonized with C. difficile posttreatment. One person randomized to placebo subsequently received treatment for CDI. In the vancomycin-treated group, beta-diversity (P = 0.0059) and macrolide-lincosamide-streptogramin (MLS) resistance genes (P = 0.037) increased after treatment; C. difficile and vancomycin-resistant enterococci (VRE) environmental contamination was found in 53% of patients and 26% of patients, respectively. We found that vancomycin alters the gut microbiota, does not permanently clear C. difficile, and is associated with VRE colonization/environmental contamination. (This study has been registered at ClinicalTrials.gov under registration no. NCT03388268.)IMPORTANCE A gold standard diagnostic for Clostridioides difficile infection (CDI) does not exist. An area of controversy is how to manage patients whose stool tests positive by nucleic acid amplification tests but negative by toxin enzyme immunoassay. Existing data suggest most of these patients do not have CDI, but most are treated with oral vancomycin. Potential benefits to treatment include a decreased risk for adverse outcomes if the patient does have CDI and the potential to decrease C. difficile shedding/transmission. However, oral vancomycin perturbs the intestinal microbiota and promotes antibiotic-resistant organism colonization/transmission. We conducted a double-blinded randomized controlled trial to assess the risk-benefit of oral vancomycin treatment in this population. Oral vancomycin did not result in long-term clearance of C. difficile, perturbed the microbiota, and was associated with colonization/shedding of vancomycin-resistant enterococci. This work underscores the need to better understand this population of patients in the context of C. difficile/ARO-related outcomes and transmission.

Project description:The severity of Clostridioides difficile infections (CDI) has increased over the last few decades. Patient age, white blood cell count, and creatinine levels as well as C. difficile ribotype and toxin genes have been associated with disease severity. However, it is unclear whether specific members of the gut microbiota are associated with variations in disease severity. The gut microbiota is known to interact with C. difficile during infection. Perturbations to the gut microbiota are necessary for C. difficile to colonize the gut. The gut microbiota can inhibit C. difficile colonization through bile acid metabolism, nutrient consumption, and bacteriocin production. Here, we sought to demonstrate that members of the gut bacterial communities can also contribute to disease severity. We derived diverse gut communities by colonizing germfree mice with different human fecal communities. The mice were then infected with a single C. difficile ribotype 027 clinical isolate, which resulted in moribundity and histopathologic differences. The variation in severity was associated with the human fecal community that the mice received. Generally, bacterial populations with pathogenic potential, such as Enterococcus, Helicobacter, and Klebsiella, were associated with more-severe outcomes. Bacterial groups associated with fiber degradation and bile acid metabolism, such as Anaerotignum, Blautia, Lactonifactor, and Monoglobus, were associated with less-severe outcomes. These data indicate that, in addition to the host and C. difficile subtype, populations of gut bacteria can influence CDI disease severity. IMPORTANCE Clostridioides difficile colonization can be asymptomatic or develop into an infection ranging in severity from mild diarrhea to toxic megacolon, sepsis, and death. Models that predict severity and guide treatment decisions are based on clinical factors and C. difficile characteristics. Although the gut microbiome plays a role in protecting against CDI, its effect on CDI disease severity is unclear and has not been incorporated into disease severity models. We demonstrated that variation in the microbiome of mice colonized with human feces yielded a range of disease outcomes. These results revealed groups of bacteria associated with both severe and mild C. difficile infection outcomes. Gut bacterial community data from patients with CDI could improve our ability to identify patients at risk of developing more severe disease and improve interventions that target C. difficile and the gut bacteria to reduce host damage.

Project description:Clostridioides difficile infection (CDI) imposes a substantial burden on the health care system in the United States. Understanding the biological basis for the spectrum of C. difficile-related disease manifestations is imperative to improving treatment and prevention of CDI. Here, we investigate the correlates of asymptomatic C. difficile colonization using a multi-omics approach. We compared the fecal microbiome and metabolome profiles of patients with CDI versus asymptomatically colonized patients, integrating clinical and pathogen factors into our analysis. We found that CDI patients were more likely to be colonized by strains with the binary toxin (CDT) locus or strains of ribotype 027, which are often hypervirulent. We find that microbiomes of asymptomatically colonized patients are significantly enriched for species in the class Clostridia relative to those of symptomatic patients. Relative to CDI microbiomes, asymptomatically colonized patient microbiomes were enriched with sucrose degradation pathways encoded by commensal Clostridia, in addition to glycoside hydrolases putatively involved in starch and sucrose degradation. Fecal metabolomics corroborates the carbohydrate degradation signature: we identify carbohydrate compounds enriched in asymptomatically colonized patients relative to CDI patients. Further, we reveal that across C. difficile isolates, the carbohydrates sucrose, rhamnose, and lactulose do not serve as robust growth substrates in vitro, consistent with their enriched detection in our metagenomic and metabolite profiling of asymptomatically colonized individuals. We conclude that pathogen genetic variation may be strongly related to disease outcome. More interestingly, we hypothesize that in asymptomatically colonized individuals, carbohydrate metabolism by other commensal Clostridia may prevent CDI by inhibiting C. difficile proliferation. These insights into C. difficile colonization and putative commensal competition suggest novel avenues to develop probiotic or prebiotic therapeutics against CDI.

Project description:Diarrheal disease, a major cause of morbidity and mortality in dairy calves, is strongly associated with the health and composition of the gut microbiota. Clostridioides difficile is an opportunistic pathogen that proliferates and can produce enterotoxins when the host experiences gut dysbiosis. However, even asymptomatic colonization with C. difficile can be associated with differing degrees of microbiota disruption in a range of species, including people, swine, and dogs. Little is known about the interaction between C. difficile and the gut microbiota in dairy calves. In this study, we sought to define microbial features associated with C. difficile colonization in pre-weaned dairy calves less than 2 weeks of age. We characterized the fecal microbiota of 80 calves from 23 different farms using 16S rRNA sequencing and compared the microbiota of C. difficile-positive (n = 24) and C. difficile-negative calves (n = 56). Farm appeared to be the greatest source of variability in the gut microbiota. When controlling for calf age, diet, and farm location, there was no significant difference in Shannon alpha diversity (P = 0.50) or in weighted UniFrac beta diversity (P = 0.19) between C. difficile-positive and-negative calves. However, there was a significant difference in beta diversity as assessed using Bray-Curtiss diversity (P = 0.0077), and C. difficile-positive calves had significantly increased levels of Ruminococcus (gnavus group) (Adj. P = 0.052), Lachnoclostridium (Adj. P = 0.060), Butyricicoccus (Adj. P = 0.060), and Clostridium sensu stricto 2 compared to C. difficile-negative calves. Additionally, C. difficile-positive calves had fewer microbial co-occurrences than C. difficile-negative calves, indicating reduced bacterial synergies. Thus, while C. difficile colonization alone is not associated with dysbiosis and is therefore unlikely to result in an increased likelihood of diarrhea in dairy calves, it may be associated with a more disrupted microbiota.

Dataset Information

The Bacterial Gut Microbiota of Adult Patients Infected, Colonized or Noncolonized by Clostridioides difficile.

Publications

The Bacterial Gut Microbiota of Adult Patients Infected, Colonized or Noncolonized by <i>Clostridioides difficile</i>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets