The gut is home to a plethora of bacteria. Some of that bacteria is good, meaning protective, and some is bad. “We are focused on the bad bacteria,” explains Dr. Michael J. Satlin, who serves as Principal Investigator (PI) of a 5-year NIH-funded K23 study that is examining resistant bacteria in the gut of patients with leukemia and bone marrow transplant recipients. Dr. Satlin, an Assistant Professor of Medicine in the Division of Infectious Diseases, has been making critical advances towards understanding how to analyze stool samples to predict which bacterial infections may occur when a patient’s immune system is weakened after chemotherapy.
“By understanding the infections each patient is at risk for, individualized prevention and treatment strategies could be designed, which could be life-saving for these vulnerable patients,” says Dr. Satlin. “We are not using our research data to alter treatment at this point, but we are in the third year of observation, and by the end of our study we will come up with strategies for prevention and treatment based on exactly which bacteria is found within the patient’s intestinal tract.”
As a physician, Dr. Satlin provides infectious disease consultations working with patients at NewYork-Presbyterian/Weill Cornell Medical Center who are receiving chemotherapy and/or have received bone marrow transplants for the treatment of blood cancers, such as leukemia and lymphoma. He has developed a productive partnership with the leukemia and transplant teams – oncologists, nurses, physician assistants, and staff - which has allowed him to recruit patients for his study. “Our study, which involves the collection and examination of stool samples, is not a clinical trial. There is no risk for the patient to participate in the study, but perhaps some inconvenience. Nevertheless, I am always surprised at how many patients willingly want to help by participating.”
In what Dr. Satlin describes as “the perfect storm,” patients with blood cancers who receive chemotherapy are at very high risk of infection. The first sign of trouble ahead for these patients is a fever. “When someone has a fever, and their immune system is compromised from receiving chemotherapy, we can’t know immediately if that person is actually infected with bad bacteria. The fever could be due to something else. But, if there is a fever, we must carry out blood tests to find out whether they have a blood stream infection and what bacteria are causing the infection. Infections must be treated within one hour of discovery or there can be dire consequences – in fact, there is an estimated 70% mortality rate without treatment for certain types of bacterial infections in these immunocompromised patients. It is critical that these patients are treated immediately with the right antibiotic, which quickly kills any infecting bacteria.”
Driving this perfect storm, according to Dr. Satlin, are three main components. One, the chemotherapy used to fight cancer also kills white blood cells (WBC) that are needed to fight infection in the body. Two, chemotherapy also kills cells that line the gastrointestinal tract (causing mucositis), thus impairing the usual protective barrier that prevents bacteria from entering the blood stream. And three, along with low WBC and the disruption of the intestinal tract lining, patients are treated with antibiotics that further disrupt the balance of bacteria. When this happens, good bacteria can be killed off and the pathogenic bacteria can take over.
“By looking at patient stool samples,” explains Dr. Satlin, “we can predict what the patient is at risk for in terms of infection. We use petri dishes and only select out for certain resistant bad bacteria, while asking the question: Do the bacteria that we see colonizing the gut match the bacteria that cause bloodstream infection? We can do this using a technique called genotyping.” With genotyping, Dr. Satlin’s group is able to examine the DNA in the bacteria to provide a genetic fingerprint and to determine whether the gut and bloodstream bacteria are the same.
One of the mechanisms by which resistant bacteria arise is that gut bacteria can transfer genes that confer antibiotic resistance to each other. “Normally, people do not become sick from this gene-swapping process,” explains Dr. Satlin, “but it is much worse for patients with cancer if they acquire a bad bacteria.”
To better understand how bacteria share antibiotic resistance genes, Dr. Satlin has been collaborating with Dr. Ilana Brito, who joined the Biomedical Engineering faculty of Cornell University-Ithaca in July 2016. Dr. Brito uses systems biology approaches to study the transmission of bacterial and genetic components of the human microbiome. “By utilizing Dr. Brito’s state-of-the-art-tools, we are able to directly examine the genes within the gut. We can actually see how the gene-swapping evolves,” explains Dr. Satlin. “This is an example of how a collaboration between technology on the Cornell University campus and medicine here at Weill Cornell can lead to a much more personalized treatment plan for the patient. It is a win-win all around.”