Glutamate interactions with obesity, insulin resistance, cognition and gut microbiota composition

Acta Diabetol. 2019 May;56(5):569-579. doi: 10.1007/s00592-019-01313-w. Epub 2019 Mar 19.

Abstract

Aims: To investigate the interactions among fecal and plasma glutamate levels, insulin resistance cognition and gut microbiota composition in obese and non-obese subjects.

Methods: Gut microbiota composition (shotgun) and plasma and fecal glutamate, glutamine and acetate (NMR) were analyzed in a pilot study of obese and non-obese subjects (n = 35). Neuropsychological tests [Trail making test A (TMT-A) and Trail making test B (TMT-B)] scores measured cognitive information about processing speed, mental flexibility and executive function.

Results: Trail-making test score was significantly altered in obese compared with non-obese subjects. Fecal glutamate and glutamate/glutamine ratio tended to be lower among obese subjects while fecal glutamate/acetate ratio was negatively associated with BMI and TMT-A scores. Plasma glutamate/acetate ratio was negatively associated with TMT-B. The relative abundance (RA) of some bacterial families influenced glutamate levels, given the positive association of fecal glutamate/glutamine ratio with Corynebacteriaceae, Coriobacteriaceae and Burkholderiaceae RA. In contrast, Streptococaceae RA, that was significantly higher in obese subjects, negatively correlated with fecal glutamate/glutamine ratio. To close the circle, Coriobacteriaceae/Streptococaceae ratio and Corynebacteriaceae/Streptococaceae ratio were associated both with TMT-A scores and fecal glutamate/glutamine ratio.

Conclusions: Gut microbiota composition is associated with processing speed and mental flexibility in part through changes in fecal and plasma glutamate metabolism.

Keywords: Cognition; Glutamate; Metabolomics; Microbiota; Trail making test.

MeSH terms

  • Acetic Acid / analysis
  • Acetic Acid / blood
  • Bacteria / isolation & purification
  • Cognition / physiology*
  • Feces / chemistry*
  • Female
  • Gastrointestinal Microbiome / physiology*
  • Glutamic Acid / analysis*
  • Glutamic Acid / blood
  • Glutamine / analysis
  • Glutamine / blood
  • Humans
  • Insulin Resistance*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Obesity / complications
  • Obesity / microbiology
  • Obesity / physiopathology*
  • Pilot Projects
  • Trail Making Test

Substances

  • Glutamine
  • Glutamic Acid
  • Acetic Acid