Çalışkan G, French T, Enrile Lacalle S, Del Angel M, Steffen J, Heimesaat MM, Rita Dunay I, Stork O. Antibiotic-induced gut dysbiosis leads to activation of microglia and impairment of cholinergic gamma oscillations in the hippocampus. Brain Behav Immun. 2022 Jan;99:203-217.
doi: 10.1016/j.bbi.2021.10.007.
Antibiotics are being prescribed to treat bacterial infections for decades and have saved countless lives since their discovery almost 100 years ago. However, experimental findings from preclinical rodent models have provided convincing evidence for the potentially negative impact of antibiotics on cognitive and emotional behaviour. Such behavioural abnormalities have been linked to aberrant gut microbiota-to-brain signalling (gut-brain axis) triggered by depletion of microbiota (dysbiosis) in the gastrointestinal tract. Thus, understanding the impact of gut dysbiosis induced by prolonged antibiotic treatment on immune function and brain physiology are of high clinical relevance to establish alternative strategies such as probiotics / prebiotics to restore gut microbiota composition and associated behavioural and physiological changes. In this work, we provide evidence for an altered expression pattern for several cytokines and neurotrophins that can potentially alter hippocampal physiology. We further show that prolonged antibiotic treatment induces an activated phenotype of microglia, a non-neuronal cell type that is gaining interest in the context of sustainment of hippocampal synaptic transmission and gamma oscillations in pathological conditions. We substantiate these findings via elucidating a strong reduction in baseline synaptic transmission and cholinergic gamma oscillations in the hippocampus. To the best of our knowledge, our work is the first to show the impact of prolonged antibiotic use on behaviorally-relevant network oscillations and synaptic physiology in the hippocampus, a brain region that plays a fundamental role in innate and cognitive behavior. Together, our study provides new insights into the interaction of gut microbiota, immune system and hippocampal function and lay the foundation for future intervention strategies for treatment of gut dysbiosis associated pathologies.
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