TY - JOUR
T1 - Refined diet consumption increases neuroinflammatory signalling through bile acid dysmetabolism
AU - Connell, Emily
AU - Blokker, Britt
AU - Kellingray, Lee
AU - Le Gall, Gwénaëlle
AU - Philo, Mark
AU - Pontifex, Matthew G.
AU - Narbad, Arjan
AU - Müller, Michael
AU - Vauzour, David
N1 - Data availability statement: The data that support the findings of this study are available on request from the corresponding author.
Funding information: The author(s) reported there is no funding associated with the work featured in this article.
PY - 2024/10
Y1 - 2024/10
N2 - 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.
AB - 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.
KW - Refined diet
KW - Microbiota-gut-brain axis
KW - Microbiome
KW - Metabolome
KW - Bile acid dysmetabolism
KW - Neuroinflammation
KW - Fibres
KW - Refined carbohydrates
KW - fibres
KW - microbiome
KW - refined carbohydrates
KW - neuroinflammation
KW - bile acid dysmetabolism
KW - microbiota-gut-brain axis
KW - metabolome
UR - http://www.scopus.com/inward/record.url?scp=85181233303&partnerID=8YFLogxK
U2 - 10.1080/1028415X.2023.2301165
DO - 10.1080/1028415X.2023.2301165
M3 - Article
SN - 1028-415X
VL - 27
SP - 1088
EP - 1101
JO - Nutritional Neuroscience
JF - Nutritional Neuroscience
IS - 10
ER -