Gut microbes shape microglia and cognitive function during malnutrition.
Kylynda C BauerElisa M YorkMihai S CirsteaNina RadisavljevicCharisse PetersenKelsey E HuusEric M BrownTahereh BozorgmehrRebeca BerdúnLouis-Philippe BernierAmy H Y LeeSarah E WoodwardZakhar KrekhnoJun HanRobert E W HancockVictoria AyalaBrian A MacVicarBarton Brett FinlayPublished in: Glia (2022)
Fecal-oral contamination promotes malnutrition pathology. Lasting consequences of early life malnutrition include cognitive impairment, but the underlying pathology and influence of gut microbes remain largely unknown. Here, we utilize an established murine model combining malnutrition and iterative exposure to fecal commensals (MAL-BG). The MAL-BG model was analyzed in comparison to malnourished (MAL mice) and healthy (CON mice) controls. Malnourished mice display poor spatial memory and learning plasticity, as well as altered microglia, non-neuronal CNS cells that regulate neuroimmune responses and brain plasticity. Chronic fecal-oral exposures shaped microglial morphology and transcriptional profile, promoting phagocytic features in MAL-BG mice. Unexpectedly, these changes occurred independently from significant cytokine-induced inflammation or blood-brain barrier (BBB) disruption, key gut-brain pathways. Metabolomic profiling of the MAL-BG cortex revealed altered polyunsaturated fatty acid (PUFA) profiles and systemic lipoxidative stress. In contrast, supplementation with an ω3 PUFA/antioxidant-associated diet (PAO) mitigated cognitive deficits within the MAL-BG model. These findings provide valued insight into the malnourished gut microbiota-brain axis, highlighting PUFA metabolism as a potential therapeutic target.
Keyphrases
- blood brain barrier
- cerebral ischemia
- fatty acid
- high fat diet induced
- early life
- cognitive impairment
- resting state
- inflammatory response
- oxidative stress
- white matter
- neuropathic pain
- single cell
- magnetic resonance
- functional connectivity
- physical activity
- risk assessment
- high glucose
- wild type
- gene expression
- weight loss
- transcription factor
- drug induced
- insulin resistance
- multiple sclerosis
- lipopolysaccharide induced
- human health
- heat stress
- spinal cord
- computed tomography
- diabetic rats
- brain injury
- signaling pathway
- stress induced
- heavy metals