Select Page
A lethal link between diet, antibiotics, and post-operative infection

A lethal link between diet, antibiotics, and post-operative infection

Oct 9, 2019 | Microbiome, Surgery

by Jordan Greer

Post-operative infections affect an estimated 300,000 patients each year and comprise as many as 11 percent of deaths among patients who end up in an intensive care unit. They are also the most common hospital acquired infection, and treatment costs range between $3.5 to $10 billion annually. Not surprisingly, efforts to reduce post-op infection and understand contributing factors are a major concern—for doctors and patients alike.

New research out of the University of Chicago Medicine’s Department of Surgery shows how the interplay between diet, antibiotics, and the microbiome may lead to fatal post-operative infection.

John Alverdy, MD, and Sanjiv Hyoju, MD, leaders of the study, used mice to explore this relationship. They fed one group of mice standard chow and gave a second group a “western,” high-fat, low-fiber diet which resulted in a near 35 percent increase in weight. Mice then underwent a partial liver resection, an otherwise fully recoverable surgical procedure. Prior to surgery, both groups received prophylactic antibiotics to prevent infection, mimicking common practice in patients.

However, survival outcomes diverged significantly between the two groups. Mice eating a high-fat, low-fiber western type diet suffered major infection-related complications following surgery. Seventy percent of the obese mice on the western diet died from bacteria-related infections—in stark contrast to mice fed standard chow, where only 10 percent suffered similar complications.

The results indicate that changes in the gut microbiome may in part be responsible. After 40 days on the “western” diet, mice showed a massive shift in the bacteria found within their guts. One kind of bacteria, called Bacteroides, were reduced to less than two percent of their former population in the mice’s guts. When the mice got both antibiotics and the western diet, the Bacteroides population was completely lost. Prior research had shown that Bacteroides can suppress harmful bacteria, and their elimination from the mouse gut could represent the loss of an important line of defense against infection.

In theory, antibiotics should be able to prevent infection even when Bacteroides aren’t present. Their job is to fight infectious bacteria, after all. But strangely, to add insult to injury, the antibiotics made some bacteria, especially one type of Serratia, more resistant to the antibiotics in the overweight mice. Though Serratia was found in both mice groups, only in the mice fed a Western diet did this strain develop antibiotic resistance and spread to internal organs, resulting in lethal sepsis. Most disturbingly, this deadly Serratia strain seemed to originate from the mouse’s own gut microbiome. And Serratia strains weren’t the only ones: other antibiotic-resistant bacteria were found in these mice as well.

This research illustrates a potentially troubling finding. As Dr. Alverdy noted, “We may have uncovered a lethal combination developing in some of our most at-risk surgical patients. The combination of a western diet and exposure to certain antibiotics appears to exert a direct—and negative—influence on the microbiome and may predispose certain patients to life-threatening postoperative infections.” Research like this provides greater understanding of the mechanisms of how diet and antibiotics shift the normal microbiome to resistance and suggests a more targeted approach, in which high-risk patients preoperatively rehabilitate their diets and are prescribed a more tailored regimen of antibiotics prior to surgery.

Results from Alverdy’s lab shed important light on other current findings: that organisms resistant to the antibiotics used for prophylaxis cause half of postoperative infections. These studies provide important clues to address this disturbing trend; they suggest we need to invest more attention to the role diet and the microbiome play in immune function and safer surgeries.

Better understanding of this relationship—through research efforts like those in the Duchossois Family Institute—will help medical professionals devise the best standards of surgical care for their patients and save more lives.

Jordan Greer is an Evolutionary Biology graduate student and science communication intern from the University of Chicago

 

Leveraging the microbiome to reduce surgical infections

Leveraging the microbiome to reduce surgical infections

Jul 26, 2018 | Microbiome, Research, Surgery

by Claire Stevenson
Graduate student in the Committee on Development, Regeneration and Stem Cell Biology

John Alverdy, MD, is a gastrointestinal surgeon and researcher studying the mechanisms by which patients develop infections after surgery and figuring out how best to treat—and prevent—them.

“Research suggests that applying microbiome medicine … to surgical patients will change everything.” Alverdy offered that assessment recently on receiving the Flance-Karl Award for seminal contributions to the field of surgical science. The award was presented at the 103rd Clinical Congress of the American Surgical Association, the most prestigious society in the world aimed at keeping physicians up to date in the field.

Surgical site infections can be debilitating and life-threatening, increasing the risk of death after surgery up to 11-fold, even with advances in medical techniques. Alverdy has committed a large portion of his career to understanding how these infections develop following routine surgery.

He questions the assumption that all infections are caused by bacteria that enter the body during the surgical procedure. “Killing as many threatening microbes as possible prior to surgery, although a common practice, remains questionable from a scientific standpoint,” Alverdy says. His research suggests that the patient’s own microbiome, especially the microorganisms that live in each of our guts, could play a key role in these infections. Perhaps simply keeping our own resident bugs healthy and happy may actually make more sense than broadly eliminating all bacteria.

Microbes can exist in two states, a stable low-growth state and a virulent one, and they transition between these states based on cues from their environment. Alverdy reasoned that our bodies could harbor microbes that are normally innocuous, but which can switch to the harmful state when threatened, as when they have inadequate resources to support growth and reproduction.

In intestinal operations, wounds are normally colonized by gut bacteria. Alverdy and his team demonstrated that alarm signals from the patient’s own tissues and diminishing resources can shift normal bacteria to a more harmful state, significantly impairing healing. Sometimes, these normally helpful bacteria can express enzymes and toxins that cause a leak in the gut repair or other major complications.

Alverdy and his team reasoned it might be more effective to provide local resources to resident bacteria, shielding them from the patient’s alarm signals, in lieu of the traditional broad kill approach with antibiotics. By supporting the health of our normal bacteria, it might be possible to preserve them and thus keep the potentially harmful ones at bay. Alverdy’s lab is thus working to identify the “local public goods” the “good” microbes are missing in their environment and provide these directly to tissues at risk for infection.

Every individual’s microbiome is different, influenced by factors that include diet, travel, medications, and home environment. This could explain why, among patients who have been treated with the same high level of care, some develop infections while others do not. According to Alverdy, “It is time we recognize that any given individual’s disease is biologically unique,” and that, “a one-size-fits all approach to preventing infectious-related complications in surgery … will always be insufficient.”

Work like Alverdy’s, on the microbiome’s role in surgical infections, has the potential to revolutionize patient care. According to him, this could change, “the way we diagnose our patients, our approach to preparing them for surgery, the way we operate, and the way we feed and rehabilitate them postoperatively.” This could even lead to individualized medicine, where each patient’s microbiome is tested prior to surgery and their care is adjusted appropriately. The Duchossois Family Institute’s investment in microbiome research will be a part of turning this vision into a reality.