Manipulating Gut Microbiome Could Reduce Elderly C Difficile Risk

John Haran, MD

New research suggests gut microbiome manipulation could help reduce the risk of Clostridium difficile infections (CDI).

A team, led by John P. Haran, MD, Department of Emergency Medicine, University of Massachusetts Medical School, examined the prevalence of C difficile infections in elderly nursing home residents over time and determined whether the microbiome or other clinical factors are linked to C difficile colonization.

Background

C difficile infections disproportionally affect geriatric patients, particularly those living in nursing homes. The rate of CDI is several fold higher in individuals 65 years of age and older with an increased risk of 2% for each additional year after 65 years. Elderly patients also have higher rates of recurrence, complications, and death.

An average of 40-50% of new CDI cases are attributed to nursing home settings.

“Most NHs in the US have structured infection control and prevention programs, however environmental measures to control CDI, such as enforcing hand hygiene, contact precautions, and decontamination procedures are employed only after CDI is identified,” the authors wrote. “These measures have not been able to stem CDI concerns in NHs.”

Data Collection

In the study, the investigators collected 506 serial stool samples from 167 nursing home residents over a 3 year period and determined C difficile prevalence by quantitative polymerase-chain reaction (PCR) detection of Toxin genes tcdA and tcdB. Microbiome composition was determine using shotgun metagenomic sequencing.

The average age of the participants was 85.2 years old and 18.1% of the patient population was male. Also, 23.9% (n = 40) of the patients were hospitalized in the past year and 18.7% (n = 31) had an antimicrobial exposure in the 6 months preceding enrollment.

The researchers used a mixed-effect random forest modeling machine in order to determine bacterial taxa whose abundance is association with C difficile prevalence while controlling for clinical covariates, including demographics, medications, and past medical history.

Of the 123 participants who provided multiple stool samples, 24.4% (n = 30) elders yielded multiple samples where C difficile was detected. In addition, 46.7% (n = 78) had at least 1 positive C difficile sample.

The Analysis

Further analysis of the positive samples were characterized by increased abundances of pathogenic or inflammatory-associated bacterial taxa and by lower abundances of taxa with anti-inflammatory or symbiotic properties.

There was also trends founds based on medication use.

Residents treated with proton pump inhibitors had a lower prevalence of C difficile (OR, 0.46; 95% CI, 0.22-0.99), while the abundance of bacterial species with known beneficial effects were higher in PPI users and lower in individuals with high C difficile prevalence.

“C. difficile is prevalent among NH elders and a dysbiotic gut microbiome associates with C. difficile colonization status,” the authors wrote. “Manipulating the gut microbiome may prove to be a key strategy in the reduction of C. difficile in the NH.”

The study, “The high prevalence of Clostridioides difficile among nursing home elders associates with a dysbiotic microbiome,” was published online in Gut Microbes.