A diet-induced gut microbiota component and related plasma metabolites are associated with depressive-like behaviour in rats
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A diet-induced gut microbiota component and related plasma metabolites are associated with depressive-like behaviour in rats. / Abildgaard, Anders; Kern, Timo; Pedersen, Oluf; Hansen, Torben; Lund, Sten; Wegener, Gregers.
In: European Neuropsychopharmacology, Vol. 43, 2021, p. 10-21.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - A diet-induced gut microbiota component and related plasma metabolites are associated with depressive-like behaviour in rats
AU - Abildgaard, Anders
AU - Kern, Timo
AU - Pedersen, Oluf
AU - Hansen, Torben
AU - Lund, Sten
AU - Wegener, Gregers
PY - 2021
Y1 - 2021
N2 - It is well-established in preclinical studies that various probiotics may improve behaviours related to psychiatric disease. We have previously shown that probiotics protected against high-fat diet (HFD)-induced depressive-like behaviour in Flinders Sensitive Line (FSL) rats, whereas FSL rats on control (CON) diet were unaffected. Therefore, we hypothesised that a dysmetabolic component of depression may exist that involves the gut microbiota and that such component may be reflected in the plasma metabolome. The aims of the present study post hoc analyses were 1) to study the effect of probiotics on gut microbiota composition and its association with depressive-like behaviour in FSL rats, and 2) to identify plasma metabolites associated with gut microbiota and depressive-like behaviour. Forty-six FSL rats were fed CON or HFD and treated with multi-species probiotics (nine Bifidobacterium, Lactococcus and Lactobacillus species) for 12 weeks. Faecal samples were collected for 16S rRNA (VR4) gene amplicon sequencing (Illumina MiSeq), and an untargeted plasma metabolomics was performed. We found that probiotics increased the relative faecal abundance of the Bifidobacterium, Lactococcus and Lactobacillus genera in HFD-fed rats only. Also, a HFD-induced microbiota component associated with depressive-like behaviour was identified, and probiotics improved the component score. Finally, the plasma levels of 44 metabolites correlated with the depression-related microbiota component, and three such metabolites had good predictive ability for depressive-like behaviour. Potentially, our findings imply that a subtype of depression characterised by a diet-induced, pro-depressant gut microbiota may exist and that analysis of related plasma metabolites may reveal aberrant microbiota functioning related to depression.
AB - It is well-established in preclinical studies that various probiotics may improve behaviours related to psychiatric disease. We have previously shown that probiotics protected against high-fat diet (HFD)-induced depressive-like behaviour in Flinders Sensitive Line (FSL) rats, whereas FSL rats on control (CON) diet were unaffected. Therefore, we hypothesised that a dysmetabolic component of depression may exist that involves the gut microbiota and that such component may be reflected in the plasma metabolome. The aims of the present study post hoc analyses were 1) to study the effect of probiotics on gut microbiota composition and its association with depressive-like behaviour in FSL rats, and 2) to identify plasma metabolites associated with gut microbiota and depressive-like behaviour. Forty-six FSL rats were fed CON or HFD and treated with multi-species probiotics (nine Bifidobacterium, Lactococcus and Lactobacillus species) for 12 weeks. Faecal samples were collected for 16S rRNA (VR4) gene amplicon sequencing (Illumina MiSeq), and an untargeted plasma metabolomics was performed. We found that probiotics increased the relative faecal abundance of the Bifidobacterium, Lactococcus and Lactobacillus genera in HFD-fed rats only. Also, a HFD-induced microbiota component associated with depressive-like behaviour was identified, and probiotics improved the component score. Finally, the plasma levels of 44 metabolites correlated with the depression-related microbiota component, and three such metabolites had good predictive ability for depressive-like behaviour. Potentially, our findings imply that a subtype of depression characterised by a diet-induced, pro-depressant gut microbiota may exist and that analysis of related plasma metabolites may reveal aberrant microbiota functioning related to depression.
KW - Animal model
KW - Diet, high-fat
KW - Major depressive disorder
KW - Metabolome
KW - Microbiota
KW - Probiotics
U2 - 10.1016/j.euroneuro.2020.09.001
DO - 10.1016/j.euroneuro.2020.09.001
M3 - Journal article
C2 - 32933808
AN - SCOPUS:85090728172
VL - 43
SP - 10
EP - 21
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
SN - 0924-977X
ER -
ID: 251690737