How should doctors measure how messed up someoneâ€™s intestinal microbiome is?
This is the topic of a recent paper in American Journal of Infection Control from Colleen Kraft and colleagues from Emory and the Centers for Disease Control and Prevention. The corresponding author is epidemiologist Alison Laufer Halpin at the CDC.
A â€œmicrobiome disruption indexâ€ could inform decisions on antibiotic stewardship, where a patient should be treated or interventions such as fecal microbial transplant (link to 2014 Emory Medicine article) or oral probiotic capsules.
What the authors are moving towards is similar to Shannonâ€™s index, which ecologists use to measure diversity of species. Another way to think about it is like the Gini coefficient, a measure of economic inequality in a country. If there are many kinds of bacteria living in someoneâ€™s body, the disruption index should be low. If there is just one dominant type of bacteria, the disruption index should be high.
In the paper, the authors examined samples from eight patients in a long-term acute care hospital (Wesley Woods) who had recently developed diarrhea. Using DNA sequencing, they determined what types of bacteria were present in patients’ stool. The patientsâ€™ samples were compared with those from two fecal microbial transplant donors. Read more
Just a quick comment on the potential of research being conducted by Eric Sorscher, who came to Emory from University of Alabama, Birmingham in 2015 and is now a Georgia Research Alliance Eminent Scholar.Â While Sorscherâ€™s lab is working on advancing new treatments for cystic fibrosis patients who currently do not benefit from available drugs, it wasÂ intriguing to learn of potential side benefits beyond cystic fibrosis.
Cystic fibrosis is caused by mutations in the CFTR gene, which encodes a protein with important functions in cells that produce mucus, sweat, saliva, tears and digestive enzymes. But other things can impair the functioning of the CFTR protein besides genetic mutations. Namely, smoking. Read more
Don’t call them alternative careers — since most graduate students in the biomedical sciences won’t end up as professors. Since I found a career outside the laboratory myself, I like to keep an eye out for examples of Emory people who have made a similar jump. [Several more in this Emory Magazine feature, which mentions the BEST program, aimed at facilitating that leap.]
Debra Cooper, PhD
After a postdoc in Texas, former Emory neuroscience graduate student Debra Cooper was awarded a California Council on Science and Technology fellowship to work with the California State Senate staff, and is now a policy consultant there. More about her work can also be found at the CCST blog.
Describe your position as policy consultant now. What types of things do you work on? How does your experience in neuroscience/drug abuse research fit in?
As a policy consultant at the California State Senate Office of Research, I function as a bridge between policy and the technical information that informs public policy. A large component of my time is spent translating research and linking it with relevant policies and regulations. I then synthesize this information and disseminate it to the appropriate audiences through memoranda, reports, or presentations. Sometimes this information is used to advise and make recommendations for legislative ideas.
My main assignments deal with human services (i.e., public services provided by governmental organizations) and veterans affairs. As such, not every project that I work on is directly related to neuroscience, but I often find overlap between my assignments and my academic background. For instance, the intersection of mental health and veterans affairs services is an important topic that bridges my backgrounds. Even when Iâ€™m working on issues that donâ€™t directly link to mental health, the years that I spent analyzing research and statistics comes in handy when evaluating relevant documents.
Describe your graduate research at Emory.
I had co-advisors while working on my PhD at Emory â€“ Drs. David Weinshenker and Leonard Howell. My dissertation research focused on one question answered with two different model animals: rats (Weinshenker lab) and squirrel monkeys (Howell lab). I was studying the effectiveness of a drug, nepicastat, in reducing rates of relapse to cocaine abuse. Nepicastat blocks an enzyme (dopamine beta-hydoxylase) which is crucial for converting the neurochemical dopamine into the neurochemical norepinephrine. Both of these neurochemicals are involved in responses to cocaine, and we hypothesized that nepicastat could help in regulating these neurochemicals to prevent relapse. Read more
Bacterial spores in capsules taken by mouth can prevent recurrent C. difficile infection, results from a preliminary study suggest.
Clostridium difficile is the most common hospital-acquired infection in the United States and can cause persistent, sometimes life-threatening diarrhea. Fecal microbiota transplant has shown promise in many clinical studies as a treatment for C. difficile, but uncertainty has surrounded how such transplants should be regulated and standardized. Also, the still-investigational procedure is oftenÂ performed byÂ colonoscopy, which may be difficult forÂ some patients to tolerate.
The capsule study, published Monday in Journal of Infectious Diseases, represents an important step in moving away from fecal microbiota transplant as a treatment for C. difficile, says Colleen Kraft, MD, assistant professor of pathology and laboratory medicine and medicine (infectious diseases) at Emory University School of Medicine.
Kraft and Tanvi Dhere, MD, assistant professor of medicine (digestive diseases) have led development of the fecal microbiota transplant program at Emory. They are authors on the capsule study, along with investigators from Mayo Clinic, Massachusetts General Hospital, Miriam Hospital (Rhode Island), and Seres Therapeutics, the study sponsor.
While this study involving 30 patients did not include a control group, the reported effectiveness of 96.7 percent compares favorably to published results on antibiotic treatment of C. difficile infection or fecal microbial transplant. Read more
In injured mouse intestines, specific types of bacteria step forward to promote healing, Emory scientists have found.Â One oxygen-shy type of bacteria that grows in the wound-healing environment,Â Akkermansia muciniphila, has already attracted attention for its relative scarcity in both animal andÂ human obesity.
An intestinal wound brings bacteria (red) into contact with epithelial cells (green). The bacteria can provide signals that promote healing, if they are the right kind.
The findings emphasize how the intestinal microbiome changes locally in response to injury and even helps repair breaches. The researchers suggest that some of these microbes could be exploited as treatments for conditions such as inflammatory bowel disease.
The results were published on January 27 inÂ Nature Microbiology.Â Researchers took samples of DNA from the colon tissue of mice after they underwent colon biopsies. They used DNA sequencing to determine what types of bacteria were present.
â€œThis is a situation resembling recovery after a forest fire,â€ says Andrew Neish, MD, professor of pathology and laboratory medicine at Emory University School of Medicine. â€œOnce the trees are gone, there is an orderly succession of grasses and shrubs, before the reconstitution of the mature forest. Similarly, in the damaged gut, we see that certain kinds of bacteria bloom, contribute to wound healing, and then later dissipate as the wound repairs.â€ Read more
One of the speakers at Thursday’s Antibiotic Resistance Center symposium, Gerald Wright from McMaster University, made the case for fighting antibiotic resistance by combining known antibiotics withÂ non-antibiotic drugs that are used to treat other conditions, which he called adjuvants.
As an example, he cited this paper, in which his lab showed that loperamide, known commercially as the anti-diarrhealÂ Immodium, can make bacteria sensitive toÂ tetracycline-type antibiotics.
Wright said that other commercial drugs and compounds in pharmaceutical companies’ libraries could have similar synergistic effects when combined with existing antibiotics. Most drug-like compounds aimed at human physiology follow “Lipinski’s rule of five“, but the same rules don’t apply to bacteria, he said. What might be a more rewarding place to look for more anti-bacterial compounds? Natural products from fungi and plants, Wright proposed.
“I made a little fist-pump when he said that,” says Emory ethnobotanist Cassandra Quave, whose laboratory specializing in looking for anti-bacterial activities in medicinal plants.
Medical ethnobotanist Cassandra Quave collecting plant specimens in Italy
Indeed, many of the points he made on strategies to overcome antibiotic resistance could apply to Quave’s approach. SheÂ and her colleagues have been investigatingÂ compounds that can disruptÂ biofilms, thusÂ enhancingÂ antibiotic activity. More at eScienceCommonsÂ and at her lab’s site.
Part of the problem of antibiotic resistanceÂ involves physiciansâ€™ habits. Doctors are used to prescribing antibiotics in certain situations, even when they may be inappropriate or when alternatives may be best. However, they may be susceptible to â€œnudgesâ€, even if health care organization policies donâ€™t formally restrict their choices. Former White House regulatory policy guru Cass Sunstein has written several books on this concept.
In March 2015, MD/PhD student Kira Newman and colleagues published a studyÂ in Journal of General Internal Medicine that has some bearing on this idea, althoughÂ it doesnâ€™t address antibiotic resistance directly:
Yelp for Prescribers: a Quasi-Experimental Study of Providing Antibiotic Cost Data and Prescription of High-Cost Antibiotics in an Academic and Tertiary Care Hospital.
The authors describe a shift involving the Emory University hospital electronic health record and order entry system. When a patient has systemic or urinary tract bacterial infection, the system shows a table of antibiotic sensitivity data alongside blood or urine culture results.
Beginning in May 2010, cost category data for antibiotics were added. Explicit numbers were not included â€“ too complicated. Instead, the information was coded in terms of $ to $$$$. For the year after the change, the authors report a 31 percent reduction in average cost per unit of antibiotics prescribed. Read more