22 May Prolonged Antibiotic Therapy May Impact Brain Function

MedicalResearch.com Interview with:

Dr. Susanne Asu Wolf

Susanne Asu Wolf PhD
Max-Delbrueck-Center for Molecular Medicine
Berlin, Germany

MedicalResearch.com: What inspired you to research this link between Ly6Chi monocytes, antibiotics and neurogenesis?

Dr. Wolf: As a neuroimmunologist I research the communication between the immune system and the brain. Amongst other research groups we found almost 10 years ago that T cells are needed to maintain brain homeostasis and plasticity, namely neurogenesis. Since only activated T cells enter the brain, we were looking for a mouse model, where immune cells are not activated. My former supervisor Polly Matzinger (NIH), a well-known immunologist, suggested to use germ free mice, born and raised in an isolator without any contact to a pathogen or any bacteria. I did a pilot experiment with the germ free mice, but wanted to get closer to possible applications in humans. Since humans are rarely born and raised in a sterile environment, I was looking for another model. By chance I met with the group of Bereswill and Heimesaat (Berlin, Charite) who provided me with a model, where due to prolonged treatment with an antibiotic cocktail, the microbiota are below detection level and the mice are also virtually germ free. They got me into contact with the second senior author of the paper Ildiko Dunay (University of Magdeburg). Her expertise is the function of Ly6Chi monocytes during infection with malaria or toxoplasmosis.

Now we were ready to investigate the gut-immune-brain axis with the focus on neurogenesis and cognition. Meanwhile the impact of the microbiome on behavior was reported by several research groups using “sterile” germ free mice and I was also curious if we could see similar differences in our antibiotic treated mice.

MedicalResearch.com: Do you think there are more connections between Ly6Chi and side effects of antibiotics elsewhere in the body apart from the brain?

Dr. Wolf: Since we see a dynamic in the Ly6Chi population also in bone marrow and blood and spleen in the antibiotic treated mice, I would speculate that these cell population might contribute to side effects of antibiotics also elsewhere in the body.

MedicalResearch.com: What main point or “take away” would you hope people learn from this paper?

Dr. Wolf: Prolonged antibiotic treatment might impact brain function. Probiotics can balance brain plasticity and should be considered as a real treatment option.

MedicalResearch.com: Did any of your findings surprise, impress or disappoint you? If so, how?

Dr. Wolf: The magnitude of the action of probiotics on Ly6Chi cells, neurogenesis and cognition impressed me. Probiotics had the same effect like running. May be we have something here that we could give to patients who are not able to run 5k per day. It was surprising that the “normal” fecal transplant recovered the broad gut flora, but did not recover neurogenesis. This might be a hint towards direct effects of antibiotics on neurogenesis without using the detour through the gut. To decipher this we might treat “sterile” germ free mice (without gut flora) with antibiotics and see what is different here. That would be a future experiment.

MedicalResearch.com: What do you think are the broader implications of your findings in terms of antibiotic use and future research?

Dr. Wolf: Antibiotics should be used when needed. I am not the one to judge when to prescribe them or not. Sure one could imagine that there would be an easy way to minimize the massive antibiotic treatment of farm animals. Antibiotic resistant bacteria are another story. I hope that the evidences on cellular and molecular level from our study and other research teams highlight the very real effects of antibiotics, diet and lifestyle on brain function and convince clinicians to look outside the (pill)box for treatment options.

MedicalResearch.com: What are the next steps? Where would you like to see this research go next?

Dr. Wolf: I would like to inspire clinical trials in patient cohorts of neurodegenerative and psychiatric disorders using probiotic treatment. We could measure the outcome in mood, psychiatric symptoms, microbiome composition and immune cell function before and after treatment. Moreover it would be interesting to decipher why in our animal model the fecal transplant did not recover neurogenesis. Also investigating the mechanism how the Ly6Chi cells communicate with neuronal stem cells would be of great interest.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Möhle, Mattei, and Heimesaat et al. Ly6Chi Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis.
Cell Reports, 2016 DOI: 10.1016/j.celrep.2016.04.074

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Last Updated on May 22, 2016 by Marie Benz MD FAAD