Cited by 134Gut microbiota and healthAnimal Nutrition and PhysiologyMetabolomics and Mass Spectrometry Studies

The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.

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

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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.

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Crossref · 10.1080/19490976.2017.1353849

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Figure 1. Serum cortisol fully mediates the relationship between fecal Ruminococcus and MRS-derived brain N-acetylaspartate. First, fecal Ruminococcus negatively predicted MRS-derived brain NAA concentrations (path A). Second, fecal Ruminococcus negatively predicted serum cortisol concentrations (path B). Third, mediation effects were assessed for serum cortisol concentrations. The indirect effect (i.e., the effect of fecal Ruminococcus through serum cortisol on MRS-derived brain NAA; path B × C) was significant, and the direct effect (path A’) was not significant. Thus, serum cortisol fully mediates the relationship between fecal Ruminococcus and MRS-derived brain NAA. Abbreviation: N-acetylaspartate (NAA).
Figure 1. Serum cortisol fully mediates the relationship between fecal Ruminococcus and MRS-derived brain N-acetylaspartate. First, fecal Ruminococcus negatively predicted MRS-derived brain NAA concentrations (path A). Second, fecal Ruminococcus negatively predicted serum cortisol concentrations (path B). Third, mediation effects were assessed for serum cortisol concentrations. The indirect effect (i.e., the effect of fecal Ruminococcus through serum cortisol on MRS-derived brain NAA; path B × C) was significant, and the direct effect (path A’) was not significant. Thus, serum cortisol fully mediates the relationship between fecal Ruminococcus and MRS-derived brain NAA. Abbreviation: N-acetylaspartate (NAA).CC BY-NC-ND · PubMed Central
Figure 2. Cited literature for mediation results. Previous studies which support the findings of our mediation analysis are presented in the figure with appropriate literature citations. Abbreviations: autism spectrum disorder (ASD), N-acetylaspartate (NAA).
Figure 2. Cited literature for mediation results. Previous studies which support the findings of our mediation analysis are presented in the figure with appropriate literature citations. Abbreviations: autism spectrum disorder (ASD), N-acetylaspartate (NAA).CC BY-NC-ND · PubMed Central

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  1. Naseribafrouei A. Correlation between gut microbiota and depression (Masters Thesis). Hedmark University College. 2013. Retrieved from BRAGE Hihm.

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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
Published
2017-08-18
Volume
8
Issue
6
Pages
589-600
ISSN
  • 1949-0976 (ISSN-L)
  • 1949-0984
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
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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