Microbiome Composition Offers Insight into Clostridium difficile Risk Among Dementia Patients

Erika M. DAgata, MD, MPH, of Lifespan Care, an affiliation of Warren Alpert Medical School of Brown University

Erika M. D'Agata, MD, MPH

Patients with advanced dementia who reside in a long-term care facility are at high risk for dysbiosis of their gut microbiome, and the identification of Akkermansia spp., Dermabacter spp., Romboutsia spp., Meiothermus spp., Peptoclostridium spp. and Ruminococcaceae UGC 009 in these patients may help stratify risk for Clostridium difficile (C. difficile) colonization, according to findings from a retrospective analysis published in Digestive Diseases and Sciences.¹

“The main findings [of this study] were that among this patient population, the overall microbiome diversity was substantially reduced and specific compositional characteristics of the microbiome were associated with C. difficile colonization,” according to leading study investigator Erika M. D'Agata, MD, MPH, of Lifespan Care, an affiliation of Warren Alpert Medical School of Brown University in Providence, RI. “Differences in diversity were not detected between subjects who were colonized with C. difficile compared to those who were not colonized. The absence of significant differences likely reflects the presence of a severely dysbiotic microbiome in the population of advanced dementia patients who have substantial antimicrobial exposure.”

In this retrospective study, investigators assessed rectal samples of 87 patients with advanced dementia who resided in 35 long-term care facilities in Boston, MA. All rectal samples were taken during a prospective, observational study. The investigators identified operational taxonomic units using 16S rRNA sequencing. Using a 1:3 ratio, investigators compared rectal samples that tested positive for C. difficile with matched negative controls, comparing these samples for differences in differentially abundant features as well as alpha and beta diversity.

Approximately 8% of residents in this sample featured sequence variants for C. difficile. There were no differences between cases and controls in regard to antimicrobial exposure and demographic characteristics.

As demonstrated by a median Shannon index of 3.2 (interquartile range 2.7—3.9), there was an observed reduction in overall biodiversity among both cases and controls. Long-term care residents with advanced dementia who had C. difficile colonization had a bacterial community structure predominantly consisting of Akkermansia spp., Dermabacter spp., Romboutsia spp., Meiothermus spp., Peptoclostridium spp. and Ruminococcaceae UGC 009.

The fact that all subjects were exposed to antimicrobials further explained “the reduced diversity in the commensal community structure of the microbiome.”

Additionally, investigators found no differences in diversity between dementia patients who demonstrated C. difficile colonization, suggesting that this homogeneity “likely reflects the presence of a severely dysbiotic microbiome in the population of advanced dementia patients who have substantial antimicrobial exposure.”

Although the findings have the potential for being applicable in clinical practice, the small sample size may limit the generalizability of the findings. Also, the investigators in this study used 16S sequencing for determining C. difficile colonization rather than standard testing, possibly presenting misclassification bias.

“Reconstituting the fecal bacterial community structure to one which represents a healthy microbiome can reduce the risk of recurrence in patients with C. difficile,” the investigators concluded. “The findings of this study suggest that specific microbiome disruption indices may be able to identify subjects at high risk of C. difficile colonization and may assist in the formulation of targeted preventive and therapeutic strategies in the LTCF setting.”

REFERENCE

1. Araos R, Andreatos N, Ugalde J, et al. Fecal Microbiome Among Nursing Home Residents with Advanced Dementia and Clostridium difficile [published online March 28, 2018]. Dig Dis Sci. doi: 10.1007/s10620-018-5030-5037.