Refined diet consumption increases neuroinflammatory signalling through bile acid dysmetabolism

Emily Connell, Britt Blokker, Lee Kellingray, Gwénaëlle Le Gall, Mark Philo, Matthew G. Pontifex, Arjan Narbad, Michael Müller, David Vauzour

Research output: Contribution to journalArticlepeer-review

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Abstract

Over recent decades, dietary patterns have changed significantly due to the increasing availability of convenient, ultra-processed refined foods. Refined foods are commonly depleted of key bioactive compounds, which have been associated with several deleterious health conditions. As the gut microbiome can influence the brain through a bidirectional communication system known as the ‘microbiota-gut-brain axis’, the consumption of refined foods has the potential to affect cognitive health. In this study, multi-omics approaches were employed to assess the effect of a refined diet on the microbiota-gut-brain axis, with a particular focus on bile acid metabolism. Mice maintained on a refined low-fat diet (rLFD), consisting of high sucrose, processed carbohydrates and low fibre content, for eight weeks displayed significant gut microbial dysbiosis, as indicated by diminished alpha diversity metrics (p < 0.05) and altered beta diversity (p < 0.05) when compared to mice receiving a chow diet. Changes in gut microbiota composition paralleled modulation of the metabolome, including a significant reduction in short-chain fatty acids (acetate, propionate and n-butyrate; p < 0.001) and alterations in bile acid concentrations. Interestingly, the rLFD led to dysregulated bile acid concentrations across both the colon (p < 0.05) and the brain (p < 0.05) which coincided with altered neuroinflammatory gene expression. In particular, the concentration of TCA, TDCA and T-α-MCA was inversely correlated with the expression of NF-κB1, a key transcription factor in neuroinflammation. Overall, our results suggest a novel link between a refined low-fat diet and detrimental neuronal processes, likely in part through modulation of the microbiota-gut-brain axis and bile acid dysmetabolism.
Original languageEnglish
JournalNutritional Neuroscience
Early online date3 Jan 2024
DOIs
Publication statusE-pub ahead of print - 3 Jan 2024

Keywords

  • Refined diet
  • Microbiota-gut-brain axis
  • Microbiome
  • Metabolome
  • Bile acid dysmetabolism
  • Neuroinflammation
  • Fibres
  • Refined carbohydrates
  • fibres
  • microbiome
  • refined carbohydrates
  • neuroinflammation
  • bile acid dysmetabolism
  • microbiota-gut-brain axis
  • metabolome

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