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Serum cortisol mediates the relationship between fecal Ruminococcus and brain N-acetylaspartate in the young pig
Open accessAbstract
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.
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In the citing paper
“Microorganisms can influence CNS processes bidirectionally via the vagus nerve (12) and through modulation of the immune system (6), the hypothalamic-pituitary-adrenal (HPA) axis (13, 14), and tryptophan metabolism (15), along with their ability to synthetize a number of neurotransmitters (16–18) and produce metabolites, such as short-chain fatty acids (SCFAs), that possess neuroactive properties”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [14]
Experimental — accuracy not yet measuredIn the citing paper
“Microbes influence CNS processes via modulation of the nervous system (52), endocrine system (51, 126), and immune system (120), together with their ability to synthesize neurotransmitters (127–129) and produce metabolites (127, 130–132) ( Figure 1 ).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [126]
In the citing paper
“A study by Mudd et al. reported a predictive relationship between levels of fecal Ruminococcus, serum cortisol, and brain N-acetylaspartate in young pigs (126).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [126]
In the citing paper
“Bifidobacteria are major producers of lactic acid, which suppress the growth of pathogens such as E. coli across the epithelium, reduce inflammation in the gut, and cooperate with the immune system (67, 68).”
From Association Between Gut Microbiota and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis (2019) · cites this paper as [68]
In the citing paper
“Bifidobacteria are major producers of lactic acid, which suppress the growth of pathogens such as E. coli across the epithelium, reduce inflammation in the gut, and cooperate with the immune system (67, 68).”
From Association Between Gut Microbiota and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis (2019) · cites this paper as [68]
In the citing paper
“Bifidobacteria are major producers of lactic acid, which suppress the growth of pathogens such as E. coli across the epithelium, reduce inflammation in the gut, and cooperate with the immune system (67, 68).”
From Association Between Gut Microbiota and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis (2019) · cites this paper as [68]
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Metadata
- Authors
- Mudd, A. T., Berding, K., Wang, M., Donovan, S. M., & Dilger, R. N.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Dilger, Ryan N.
- Venue
- Gut Microbes
- Publisher
- Informa UK Limited
- Published
- 2017-08-18
- Volume
- 8
- Issue
- 6
- Pages
- 589-600
- ISSN
- 1949-0976 (ISSN-L)
- 1949-0984
- PMC
- PMC5730385
- OpenAlex
- W2735229722
- Cited by
- 134
- References
- 44
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 15 · 2023: 19 · 2022: 18 · 2021: 18 · 2020: 17 · 2019: 9 · 2018: 12 · 2017: 4
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Gut Microbes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- University of Illinois at Urbana-Champaign
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- Ruminococcus, serum cortisol, N-acetylaspartate, gut-brain axis, newborn piglets, gut microbiota, brain development, serotonin, Butyricimonas, mediation analysis, neurodevelopmental disorders, fecal microbiota, neurometabolites
- MeSH terms
- Gastrointestinal Microbiome, Animals, Animals, Newborn, Aspartic Acid, Brain, Fatty Acids, Volatile, Feces, Hydrocortisone, Male, Magnetic Resonance Spectroscopy, Swine, Colon, Ascending, Ruminococcus, Dysbiosis
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