Serum cortisol mediates the relationship between fecal Ruminococcus and brain N-acetylaspartate in the young pig

Abstract

A dynamic relationship between the gut microbiota and brain is pivotal in neonatal development. Dysbiosis of the microbiome may result in altered neurodevelopment; however, it is unclear which specific members of microbiota are most influential and what factors might mediate the relationship between the gut and the brain. Twenty-four vaginally-derived male piglets were subjected to magnetic resonance spectroscopy at 30 d of age. Ascending colon contents, feces, and blood were collected and analyzed for volatile fatty acids, microbiota relative abundance by 16s rRNA, and serum metabolites, respectively. A mediation analysis was performed to assess the mediatory effect of serum biomarkers on the relationship between microbiota and neurometabolites. Results indicated fecal Ruminococcus and Butyricimonas predicted brain N-acetylaspartate (NAA). Analysis of serum biomarkers indicated Ruminococcus independently predicted serum serotonin and cortisol. A 3-step mediation indicated: i) Ruminococcus negatively predicted NAA, ii) Ruminococcus negatively predicted cortisol, and iii) a significant indirect effect (i.e., the effect of fecal Ruminococcus through cortisol on NAA) was observed and the direct effect became insignificant. Thus, serum cortisol fully mediated the relationship between fecal Ruminococcus and brain NAA. Using magnetic resonance spectroscopy, this study used a statistical mediation analysis and provides a novel perspective into the potential underlying mechanisms through which the microbiota may shape brain development. This is the first study to link Ruminococcus, cortisol, and NAA in vivo, and these findings are substantiated by previous literature indicating these factors may be influential in the etiology of neurodevelopmental disorders.

Crosstalk of multi-omics reveals specific characteristics in active ulcerative colitis patients with depression and anxiety

“…The increase of Bacteroidaceae in the patients with depression and anxiety is consistent with a previous study that mice monocolonized with Bacteroides fragilis, which could also produce GABA [20], display de cits in serum serotonin [19]. Ruminococcus could predict serum serotonin and cortisol levels [30], and is signi cantly associated with a depression indicator [31] and IBD [32] and gut in ammation [33]. Lachnospiraceae and Ruminococcaceae, which accounted for 42.62% of the identi ed gut microbiota, could produce butyric acid, a subtype of short-chain fatty acids (SCFAs).…”

Characteristic of polysaccharides from Flammulina velutipes in vitro digestion under salivary, simulated gastric and small intestinal conditions and fermentation by human gut microbiota

“…At the genus level, FVP treatment increased the Bifidobacterium, Bacteroides and Butyricimonas level but decreased the Ruminococcus levels. Bifidobacterium, Bacteroides and Butyricimonas can positively predicte brain N‐acetylaspartate, a marker of neuronal health (Mudd et al ., ). Ruminococcus is negatively correlated with brain N‐acetylaspartate.…”

Early life stress causes persistent impacts on the microbiome of Atlantic salmon

“…Cortisol-mediated stress response in salmonids is established at two weeks post hatching (Barry et al 1995), and in mammals cortisol is known to directly affect microbiome diversity and composition. Specifically, elevated glucocorticoid concentrations have been shown to promote Gammaproteobacteria and inhibit probiotic taxa including Lactobacilliales (Mudd et al 2017; Stothart et al 2016; Zijlmans et al 2015). This is highly consistent with the changes we observed in the gut microbiome.…”