Examining Vitamin D’s Role in Preventing C diff

Clostridioides difficile(C diff) remains a scourge in healthcare settings. While actions such as diligent handwashing and careful use of antibiotics can prevent infection, researchers have been interested in how a healthy gut microbiome—and specifically vitamin D’s role in it—acts as a deterrent to the proliferation of C diff bacteria. The vitamin already is known to play a protective role against other infections such as COVID-19.

A team of scientists at Rutgers University Medical School in Newark, New Jersey examined data collected as part of the National Inpatient Sample, a government database containing details of millions of hospital stays nationwide. (The hospitals are not identified.) The Rutgers team narrowed their focus to hospitalizations for C diff infection that occurred between 2016 and 2019, finding 73,745 people in that time span. Out of that subgroup, 1,756 people were diagnosed with vitamin D deficiency.

The vitamin D-deficient and D-sufficient cohorts had similar average ages, 66.12 years vs 66.26 years, respectively. Both groups were comprised mostly of women, with the deficient group 63% female and the sufficient group 57.3% female. The racial composition of both cohorts was similar as well.

The hospital patients who had vitamin D deficiency experienced higher rates of recurrence of C diff infection (17.4% vs. 14.7% recurrence in patients without vitamin D deficiency) and longer hospital stays (10.38 days vs. 9.83 days). However, those without vitamin D deficiency had higher rates of inpatient mortality (6.1% vs. 3.1%) and ileus (3.6% vs. 2.6%) and more expensive hospital stays ($102,527 vs. $93,935). Other outcomes such as toxic megacolon, colonic perforation, and colectomy had relatively equal rates of incidence.

What are the mechanisms by which vitamin D affects C diff risk? According to the study, vitamin D facilitates the expression of certain peptides that fight microbes and preserve the gut microbiome, especially a peptide called cathelicidin that possesses broad antimicrobial properties. Vitamin D also fortifies the intestinal lining, reducing permeability. “Thus, patients with VDD [vitamin D deficiency] may experience impaired immune function through decreased expression of antimicrobial peptides and compromised epithelial barrier integrity, contributing to their increased odds of developing recurrent CDI,” the authors wrote.

The scientists cited previous studies claiming that because vitamin D is so protective of the gut microbiome, supplementing patients with vitamin D is a good way to improve microbiome diversity and boost levels of bacteria that are particularly adept at preventing C diff growth and consequential infection. They posited that patients who have vitamin D deficiency may not have sufficient species diversity in their gut microbiome, leaving them at heightened risk of recurrent C diff infection.

Addressing the Rutgers study’s finding that people without vitamin D deficiency had a higher risk of mortality, which contradicts the results of most prior studies, the authors mentioned that several studies noted raised mortality levels in patients with both very high and very low vitamin D levels. “This could be due to sicker patients being advised to take vitamin D supplementation in an attempt to improve their overall mortality, providing a fictitious inverse correlation between VDD and mortality,” they wrote. “We hypothesize that this discrepancy may be attributed to this phenomenon.”

Given the ability of vitamin D to fortify the gut microbiome and ward off C diff infection, clinicians treating patients hospitalized with thisinfection may want to consider supplementing those lacking in this vitamin in order to minimize their chance of experiencing recurrent C diff infection. The authors noted that future studies hopefully will parse the chances of developing recurrent C diff infection based on the severity of vitamin D deficiency as well as assess how vitamin D supplementation affects patients who are not vitamin D deficient at baseline.

One limitation of the study is its reliance on the accuracy of billing codes, which may be entered incorrectly. The authors warned that some cases of vitamin D deficiency, particularly serious ones, may not be recorded at all. Also, the study did not separate subjects by vitamin D deficiency severity, something that would have allowed for a deeper analysis of the results.