Disturbed Microbiome Clinically Detrimental in ICU

Patients in the intensive care unit with an imbalanced microbiome are at increased risk for complications and longer ICU stays, according to findings presented at Clinical Nutrition Week 2017.

Paul Wischmeyer, MD, professor of anesthesiology and surgery and director of perioperative research at Duke Clinical Research Institute, in Durham, N.C., who also is part of the ICU Microbiome Project, told meeting attendees that ICU patients experience significant microbiome perturbations and added complications, including acute respiratory distress syndrome (ARDS).

“ICU patients have massive loss of health-promoting bacteria and higher levels of pathogenic species, compared with healthy patients,” Dr. Wischmeyer said. “It is astonishing how rapidly pathogenic bacteria flourish and how this shift to dysbiosis appears to affect a variety of outcomes.”

Dr. Wischmeyer and his colleagues have been examining fecal and oral microbiome samples from 115 ICU patients treated at four hospitals and comparing them with samples from healthy people participating in the American Gut project. In previous research, they found decreases in populations of Bacteroides and Firmicutes, as well as the healthy bacterium, Faecalibacterium prausnitzii, which produces short-chain fatty acids that help preserve normal gut barrier function (mSphere 2016;1[4]. pii:e00199-16). Meanwhile, they discovered increases in the relative abundance of Proteobacteria, a phylum of gram-negative bacteria linked to infections in ICU and hospitalized patients.

ICU patients also tended to lose overall fecal microbiota diversity, with some patients having only one organism compose 95% of their fecal bacteria after a short time in the ICU, he explained.

“We even see the microbiome of some ICU patients begin to resemble that of decomposing bodies,” Dr. Wischmeyer said, noting that his group found similar microbiome changes across all ICU study sites. In a new analysis he presented at Clinical Nutrition Week of the same ICU patients’ intestinal metabolome—the collection of microbial metabolites—he and his colleagues again found significant differences between ICU and healthy samples taken from the American Gut project.

The new findings reveal links between several outcomes and metabolomic and microbial changes, Dr. Wischmeyer said. “For example, our initial analysis of these data show increased APACHE [Acute Physiology and Chronic Health Evaluation] and NUTRIC [Nutrition Risk in the Critically Ill] scores correlated with shifts in the fecal metabolome of ICU patients,” he said.

A Loss of Diversity

ICU patients who experienced ARDS also tended to have larger populations of Enterobacteriaceae and Comamonas in their oral samples and greater populations of Coprococcus in their fecal samples. “Loss of microbial diversity was found to correlate with prolonged ICU stay as well,” Dr. Wischmeyer reported.

He said his team is analyzing the data, but they also are finding that the greater the changes in the microbiome between admission and discharge, the more they correlate with adverse outcomes.

Why the microbiome of ICU patients is so imbalanced is yet to be fully understood, but a number of variables likely play a role, Dr. Wischmeyer said. “Dysbiosis of the oral microbiome in our study was significantly affected by total antibiotic pressure in the ICU, but the fecal microbiome was not,” he said. “It is likely that use of other medications, like sedatives and painkillers, as well as a lack of nutrition also have an impact.

“The original illness leading to need for the ICU is an issue, but our treatments are also damaging to normal bacteria, and potentially to a patient’s long-term outcome,” he added.

Other Factors to Consider

Rob MacLaren, PharmD, associate professor at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, in Aurora, agreed that antibiotics are likely only one of the causes of microbial imbalances in ICU patients. “Many other factors, such as acid suppression, feeding and various procedures, will also affect the microbiome,” Dr. MacLaren said.

He called for more research to shed light on what he called “a bit of a chicken-and-egg situation” when it comes to the interplay between a disordered microbiome and ICU stays. Greater changes to the microbiome are associated with longer stays in the ICU, but longer stays increase the likelihood that a patient will be exposed to multiple antibiotics and other treatments, adding to the risk for more illness. “All of these are probable risk factors for altered microbiomes,” Dr. MacLaren said.

To the extent that Dr. Wischmeyer’s data do show antibiotics detrimentally affect the microbiome, clinicians now have another reason to be judicious about their use of antibiotics, Dr. MacLaren noted. “We are taught to start antimicrobials empirically with broad coverage and to switch to a narrow-spectrum agent once we know the organism, but in many cases an offending organism is never identified and we continue administering broad-spectrum agents,” he said. “I suspect that we can do a better job stepping down and limiting the duration of antimicrobial therapies in the ICU.”

Dr. Wischmeyer echoed this, saying that even short periods of broad-spectrum antibiotic use appear to devastate the microbiome. “We hope our data compels providers to realize the extent of the impact they have on patients when they use these agents,” he said.