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Gut microbes shape microglia and cognitive function during malnutrition.

Kylynda C Bauer1,2, Elisa M York3, Mihai S Cirstea1,2

  • 1Michael Smith Laboratories, University of British Columbia, Vancouver, Canada.

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Early life malnutrition and gut microbe exposure impair cognitive function. Supplementing with omega-3 polyunsaturated fatty acids (PUFAs) and antioxidants can improve brain health and cognitive deficits.

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Area of Science:

  • Neuroscience
  • Microbiology
  • Nutritional Science

Background:

  • Early life malnutrition has lasting cognitive consequences, but the mechanisms involving gut microbes are unclear.
  • Gut-brain axis disruptions are implicated in malnutrition-associated neurodevelopmental issues.
  • Microglia play key roles in neuroimmune responses and brain plasticity.

Purpose of the Study:

  • To investigate the impact of malnutrition combined with fecal-oral contamination on cognitive function and brain pathology in a murine model.
  • To explore the role of gut microbiota and associated changes in microglia.
  • To identify potential therapeutic targets for cognitive impairment in malnutrition.

Main Methods:

  • Utilized a murine model (MAL-BG) with malnutrition and iterative fecal commensal exposure, compared to malnourished (MAL) and healthy (CON) controls.
  • Assessed spatial memory, learning plasticity, microglial morphology, and transcriptional profiles.
  • Performed metabolomic profiling of the cortex and analyzed cytokine and blood-brain barrier (BBB) integrity.
  • Investigated the effects of omega-3 polyunsaturated fatty acid (PUFA)/antioxidant (PAO) diet supplementation.

Main Results:

  • Malnourished mice (MAL-BG) exhibited impaired spatial memory and learning plasticity.
  • Chronic fecal-oral exposures altered microglial morphology and transcriptional profiles, promoting phagocytic features.
  • These microglial changes occurred independently of significant inflammation or BBB disruption.
  • Cortical metabolomics revealed altered PUFA profiles and systemic lipoxidative stress in MAL-BG mice.
  • PAO diet supplementation mitigated cognitive deficits in the MAL-BG model.

Conclusions:

  • Early life malnutrition combined with gut microbial exposure negatively impacts cognitive function via altered microglial responses and PUFA metabolism.
  • Gut microbiota-brain axis dysregulation in malnutrition involves lipoxidative stress and altered PUFA profiles.
  • Targeting PUFA metabolism, potentially through dietary interventions like PAO supplementation, offers a promising therapeutic strategy for malnutrition-induced cognitive impairment.