PREBIOTIC SUPPLEMENTATION MODULATES MICROGLIAL MORPHOLOGY ALTERATIONS IN OBESE AGED MICE

Consumption of a chronic high-fat diet (HFD) and ageing are both associated with metabolic dysfunction and increased neuroinflammation. It contributes to the loss of gut microbiota diversity and the development of neurodegenerative diseases. Microglia are highly sensitive to inflammatory signals, and their morphology is closely linked to their functional state. These molecular signals can derive from gut microbiota and influence microglia activation and disease progression. Gut microbiota-focused interventions have the potential to reduce chronic inflammation and have a protective effect on microglia. This study investigated how prebiotic supplementation with galactooligosaccharides and fructooligosaccharides (GOS+FOS) modulates microglial morphology in aged mice exposed to long-term HFD. C57BL/6J mice were assigned to four dietary conditions for 18 months: control diet (CD), CD - GOS+FOS, HFD, and HFD - GOS+FOS. We utilised immunohistochemical staining to quantify three-dimensional branching architecture and two-dimensional shape descriptors. Compared with CD, microglia in HFD-fed conditions exhibited measurable morphological changes consistent with a metabolically primed microglia phenotype. HFD supplementation with GOS+FOS reduced those HFD-induced structural alterations: average branch length decreased towards CD levels, projected soma area was significantly smaller than in HFD, indicating partial structural recovery. In the CD - GOS+FOS group, microglial morphology was similar to the CD group, indicating that the effects of GOS+FOS are specific to reducing HFD-associated microglial alterations rather than modifying baseline microglial structure. These findings suggest that prebiotic supplementation with GOS+FOS can modulate microglial structural remodelling in the aged brain under metabolic challenge, highlighting a protective role of gut microbiota-targeted interventions in diet-induced neuroinflammatory conditions.