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

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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
Publication statusE-pub ahead of print - 3 Jan 2024


  • 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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