Mouse study links prolonged antibiotic treatment with impaired neurogenesis and cognitive function

Mouse study links prolonged antibiotic treatment

A new study, led by Dr. Susanne Wolf from the Department of Cellular Neuroscience at Max-Delbrueck-Centre for Molecular Medicine in Berlin (Germany), has found that prolonged antibiotic treatment, which kills gut bacteria, can also stop growth of new brain cells in mice.

Although it has been previously reported that antibiotic-induced gut dysbiosis may lead to impaired cognition in mice, little is known about the link between the brain, the local and systemic immune system, and the gut microbiota. Researchers in this study depleted the gut microbiota in mice by administering broad-spectrum antibiotics for 7 weeks. Compared with untreated mice, adult mice treated with antibiotics showed significantly fewer newly formed brain cells (i.e. reduced neurogenesis) in the hippocampus region of the brain, and subsequently their memory also deteriorated.

In addition to impaired neurogenesis and memory function, levels of a specific immune cell—the Ly6Chi monocytes—decreased significantly in the brain, blood, and bone marrow when the microbiota was depleted.

In order to study whether Ly6Chi monocytes are responsible for the changes in memory and neurogenesis, the researchers removed only these cells from adult mice through genetic and antibody depletion, and found that neurogenesis declined. Furthermore, when they transferred Ly6Chi monocytes to the original antibiotic-treated mice, neurogenesis was restored. Lack of Ly6Chi monocytes decreased neurogenesis and their administration to antibiotic-treated mice rescued neurogenesis, which highlights the intermediary role of these immune cells between gut bacteria and the brain. According to Wolf, the previously unknown intermediary role of these immune cells is of particular scientific interest: “With the Ly6Chi monocytes, we may have discovered a new general communication path from the periphery to the brain”.

Immune function and hippocampal neurogenesis were not restored by faecal transplant using the microbiota of specific pathogen-free (SPF) mice. These results indicate that the antibiotics have a long-lasting effect on brain homeostasis through affecting neurogenesis directly, and not act only via the gut bacteria. However, behavioural (memory task) deficits induced by antibiotics were restored when the mice were given a multispecies probiotic mixture and had access to voluntary training in the running wheel. The increase of Ly6Chi monocytes in the brain by running or probiotic treatment increased neurogenesis, indicating a possible role of probiotic treatment and voluntary exercise in neuronal stem cells and neuronal precursors.

According to Wolf, the new study may lead to new avenues for treating people with mental disorders such as schizophrenia or depression, who also have impaired neurogenesis: “In addition to medication and physical exercise, these patients could potentially also benefit from probiotic preparations”.

In conclusion, antibiotics can decrease neurogenesis and cognitive function, beyond their impact on gut bacteria. However, these adverse effects could be reversed by first restoring a normal microbiota, and then exposing mice to exercise or probiotic treatment. A type of white blood cell—the Ly6Chi monocyte—seems to be involved as the connection between gut bacteria and the brain.

 

 

Reference:

Möhle L, Mattei D, Heimesaat MM, et al. Ly6Chi monocytes provide a link between antibiotic-induced changes in gut microbiota and adult hippocampal neurogenesis. Cell Rep. 2016. doi: http://dx.doi.org/10.1016/j.celrep.2016.04.074.

Andreu Prados
Andreu Prados
Andreu Prados holds a Bachelor of Science Degree in Pharmacy & Human Nutrition and Dietetics. Science writer specialised in gut microbiota and probiotics, working also as lecturer and consultant in nutrition and healthcare. Follow Andreu on Twitter @andreuprados