id_1030. PRENATAL ANTIBIOTICS INDUCED DYSBIOSIS INDUCES PERSISTENT HIPPOCAMPAL MICROGLIOSIS AND ANXIETY-LIKE BEHAVIOR IN OFFSPRING
Rishikesh1, Dayamrita K K1, Krishnapriya1, Ayswaria Deepti1, Aneesa P A1, Baby Chakrapani P S1,6, Shubham Upadhyay2, Keshava Prasad T S2, Unnikrishnan Sivan3, Isabell Haack4,5, Shirin Hosseini4,5, Martin Korte4,5
1 Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology (CUSAT), Kochi, Kerala, India
2 Centre for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India
3 Department of FSQA, FFE, Kerala University of Fisheries and Ocean Studies (KUFOS), Panangad, Kochi, Kerala, India
4 Department of Cellular Neurobiology, Zoological Institute, Technical University Braunschweig, Germany
5 Helmholtz Centre for Infection Research, Neuroinflammation and Neurodegeneration Group, Braunschweig, Germany
6 Centre of Excellence in Neurodegeneration and Brain Health, Cochin University of Science and Technology (CUSAT), Kochi, Kerala, India
INTRODUCTION: Maternal gut dysbiosis during pregnancy influences offspring neurodevelopment via immune, metabolic, and microglial pathways. While severe disruptions are known to affect brain maturation, the impact of short-term antibiotic exposure remains unclear. Even subtle microbiota perturbations may alter neuroimmune programming, potentially increasing long-term behavioral vulnerability.
AIM(S): This study aimed to determine whether transient maternal antibiotic exposure during pregnancy alters maternal and offspring gut microbiota and programs persistent neurobehavioral and neuroimmune alterations in adolescent offspring.
METHOD(S): Pregnant dams received an oral antibiotic cocktail for 7 days to induce gut microbiota perturbation. Maternal and offspring phenotypes were assessed using 16S rRNA sequencing, behavioral testing (Elevated Plus Maze, Y-maze, Forced Swim Test, sociability and recognition paradigms), peripheral immune profiling, cytokine analysis, metabolomics, and hippocampal immunohistochemistry at postnatal day 49.
RESULTS: Maternal antibiotic exposure did not alter microbial diversity, maternal care, intestinal integrity, HPA-axis function, or developmental milestones, though offspring ASV distribution differed. Adolescent offspring displayed anxiety-like behavior and cognitive deficits despite intact recognition memory and sociability.
Peripheral immune cells (WBCs, neutrophils) were elevated without changes in cytokines or BDNF. Hippocampal analysis revealed marked microgliosis, enhanced synaptic engulfment, and astrocytic reactivity.
CONCLUSIONS: Transient maternal antibiotic exposure, even without major microbiome shifts, triggers lasting neuroimmune remodeling in offspring—characterized by microglial activation, synaptic pruning, peripheral immune changes, and anxiety-like behaviors. The findings underscore the developing brain's sensitivity to subtle maternal gut perturbations and the need for judicious antibiotic use during pregnancy.
FINANCIAL SUPPORT: Funding from project