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Mice lacking Casp1, Ifngr and Nos2 genes exhibit altered depressive- and anxiety-like behaviour, and gut microbiome composition.

ABSTRACT: Converging evidence supports the involvement of pro-inflammatory pathways and the gut microbiome in major depressive disorder (MDD). Pre-clinical and clinical studies suggest that decreasing pro-inflammatory signaling may provide clinical benefit in MDD. In this study, we used the chronic unpredictable stress (CUS) paradigm to assess whether mice lacking the pro-inflammatory caspase 1, interferon gamma-receptor, and nitric oxide synthase (Casp1, Ifngr, Nos2)^-/- present altered depressive- and anxiety-like behaviour at baseline and in response to CUS. In comparison to wild-type (wt) mice, (Casp1, Ifngr, Nos2)^-/- mice displayed decreased depressive- and anxiety-like behaviour, and increased hedonic-like behaviour and locomotor activity at baseline, and resistance to developing anhedonic-like behaviour and a heightened emotional state following stress. Plasma levels of ACTH and CORT did not differ between the triple knockout and wt mice following stress. The faecal microbiome of (Casp1, Ifngr, Nos2)^-/- mice differed from that of wt mice at baseline and displayed reduced changes in response to chronic stress. Our results demonstrate that simultaneous deficit in multiple pro-inflammatory pathways has antidepressant-like effects at baseline, and confers resilience to stress-induced anhedonic-like behaviour. Moreover, accompanying changes in the gut microbiome composition suggest that CASP1, IFNGR and NOS2 play a role in maintaining microbiome homeostasis.

SUBMITTER: Inserra A

PROVIDER: S-EPMC6478737 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Mice lacking Casp1, Ifngr and Nos2 genes exhibit altered depressive- and anxiety-like behaviour, and gut microbiome composition.

Inserra Antonio A Choo Jocelyn M JM Lewis Martin D MD Rogers Geraint B GB Wong Ma-Li ML Licinio Julio J

Scientific reports 20190423 1

Converging evidence supports the involvement of pro-inflammatory pathways and the gut microbiome in major depressive disorder (MDD). Pre-clinical and clinical studies suggest that decreasing pro-inflammatory signaling may provide clinical benefit in MDD. In this study, we used the chronic unpredictable stress (CUS) paradigm to assess whether mice lacking the pro-inflammatory caspase 1, interferon gamma-receptor, and nitric oxide synthase (Casp1, Ifngr, Nos2)<sup>-/-</sup> present altered depress ...[more]

PMID: 31015500

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Project description:Rumen microbiome composition and functionality is linked to animal feed efficiency, particularly for bovine ruminants. To investigate this in sheep, we compared rumen bacterial and archaeal populations (and predicted metabolic processes) of sheep divergent for the feed efficiency trait feed conversion ratio (FCR). In our study 50 Texel cross Scottish Blackface (TXSB) ram lambs were selected from an original cohort of 200 lambs. From these, 26 were further selected for experimentation based on their extreme FCR (High Feed Efficiency, HFE = 13; Low Feed Efficiency, LFE = 13). Animals were fed a 95% concentrate diet ad libitum over 36 days. 16S rRNA amplicon sequencing was used to investigate the rumen bacterial and archaeal communities in the liquid and solid rumen fractions of sheep divergent for FCR. Weighted UniFrac distances separated HFE and LFE archaea communities from the liquid rumen fraction (Permanova, P < 0.05), with greater variation observed for the LFE cohort (Permdisp, P < 0.05). LFE animals exhibited greater Shannon and Simpson diversity indices, which was significant for the liquid rumen fraction (P < 0.05). Methanobrevibacter olleyae (in liquid and solid fractions) and Methanobrevibacter millerae (liquid fraction) were differentially abundant, and increased in the LFE cohort (P.adj < 0.05), while Methanobrevibacter wolinii (liquid fraction) was increased in the HFE cohort (P.adj < 0.05). This suggests that methanogenic archaea may be responsible for a potential loss of energy for the LFE cohort. Bacterial community composition (Permanova, P > 0.1) and diversity (P > 0.1) was not affected by the FCR phenotype. Only the genus Prevotella 1 was differentially abundant between HFE and LFE cohorts. Although no major compositional shifts of bacterial populations were identified amongst the feed efficient cohorts (FDR > 0.05), correlation analysis identified putative drivers of feed efficiency with Ruminococcaceae UCG-014 (liquid, rho = -0.53; solid, rho = -0.56) and Olsenella (solid, rho = -0.40) exhibiting significant negative association with FCR (P < 0.05). Bifidobacterium and Megasphaera showed significant positive correlations with ADG. Major cellulolytic bacteria Fibrobacter (liquid, rho = 0.43) and Ruminococcus 1 (liquid, rho = 0.41; solid, rho = 41) correlated positively with FCR (P < 0.05). Our study provides evidence that feed efficiency in sheep is likely influenced by compositional changes to the archaeal community, and abundance changes of specific bacteria, rather than major overall shifts within the rumen microbiome.

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Dataset Information

Mice lacking Casp1, Ifngr and Nos2 genes exhibit altered depressive- and anxiety-like behaviour, and gut microbiome composition.

Publications

Mice lacking Casp1, Ifngr and Nos2 genes exhibit altered depressive- and anxiety-like behaviour, and gut microbiome composition.

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