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

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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.

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References

  1. Dinan TG, Cryan JF (2015) The impact of gut microbiota on brain and behaviour: implications for psychiatry. Curr Opin Clin Nutr Metab Care 18:552–558. https://doi.org/10.1097/MCO.0000000000000221

    Article  PubMed  Google Scholar 

  2. Clarke G, Stilling RM, Kennedy PJ, Stanton C, Cryan JF, Dinan TG (2014) Minireview: Gut microbiota: the neglected endocrine organ. Mol Endocrinol 28:1221–1238. https://doi.org/10.1210/me.2014-1108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mazzoli R, Pessione E (2016) The neuro-endocrinological role of microbial glutamate and GABA signaling. Front Microbiol 7:1934. https://doi.org/10.3389/fmicb.2016.01934

    Article  PubMed  PubMed Central  Google Scholar 

  4. Hedberg TG, Stanton PK (1996) Long-term plasticity in cingulate cortex requires both NMDA and metabotropic glutamate receptor activation. Eur J Pharmacol 310:19–27. https://doi.org/10.1016/0014-2999(96)00371-8

    Article  CAS  PubMed  Google Scholar 

  5. Ernst T, Jiang CS, Nakama H, Buchthal S, Chang L (2010) Lower brain glutamate is associated with cognitive deficits in HIV patients: a new mechanism for HIV-associated neurocognitive disorder. J Magn Reson Imaging 32:1045–1053. https://doi.org/10.1002/jmri.22366

    Article  PubMed  PubMed Central  Google Scholar 

  6. Corrigan JD, Hinkeldey NS (1987) Relationships between Parts A and B of the trail making test. J Clin Psychol 43:402–409

    Article  CAS  PubMed  Google Scholar 

  7. Lezak MD, Howieson DB, Loring DW, Hannay HJ, Fischer JS (2004) Neuropsychological assessment, 4th edn. Oxford University, New York

    Google Scholar 

  8. Okumoto S, Funck D, Trovato M, Forlani G (2016) Editorial: amino acids of the glutamate family: functions beyond primary metabolism. Fornt Plant Sci 7:318. https://doi.org/10.3389/fpls.2016.00318

    Article  Google Scholar 

  9. Yan D (2007) Protection of the glutamate pool concentration in enteric bacteria. Proc Natl Acad Sci USA 104:9475–9480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Buckel W, Barker HA (1974) Two pathways of glutamate fermentation by anaerobic bacteria. J Bacteriol 117:1248–1260. https://doi.org/10.1073/pnas.0703360104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Org E, Blum Y, Kasela S, et al (2017) Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort. Genome Biol 18:70. https://doi.org/10.1186/s13059-017-1194-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Moszak M, Klupczyńska A, Kanikowska A, et al (2018) The influence of a 3-week body mass reduction program on the metabolic parameters and free amino acid profiles in adult Polish people with obesity. Adv Clin Exp Med 27:749–757. https://doi.org/10.17219/acem/70796

    Article  PubMed  Google Scholar 

  13. Wahl S, Yu Z, Kleber M, et al (2012) Childhood obesity is associated with changes in the serum metabolite profile. Obes Facts 5:660–670. https://doi.org/10.1159/000343204

    Article  CAS  PubMed  Google Scholar 

  14. Reinehr T, Wolters B, Knop C, et al (2014) Changes in the serum metabolite profile in obese children with weight loss. Eur J Nutr 54:173–181. https://doi.org/10.1007/s00394-014-0698-8

    Article  CAS  PubMed  Google Scholar 

  15. Cheng S, Rhee EP, Larson MG, et al (2012) Metabolite profiling identifies pathways associated with metabolic risk in humans. Circulation 125:2222–2231. https://doi.org/10.1161/CIRCULATIONAHA.111.067827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI (2001) Molecular analysis of commensal host-microbial relationships in the intestine. Science 291:881–884

    Article  CAS  PubMed  Google Scholar 

  17. Liu R, Hong J, Xu X, et al (2017) Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention. Nat Med 23:859–868. https://doi.org/10.1038/nm.4358

    Article  CAS  PubMed  Google Scholar 

  18. Serrano M, Moreno-Navarrete JM, Puig J, et al (2013) Serum lipopolysaccharide-binding protein as a marker of atherosclerosis. Atherosclerosis 230:223–227. https://doi.org/10.1016/j.atherosclerosis.2013.07.004

    Article  CAS  PubMed  Google Scholar 

  19. Wishart DS, Jewison T, Guo AC, et al (2013) HMDB 3. 0—the human metabolome. Database 41:D801–D807. https://doi.org/10.1093/nar/gks1065

    Article  CAS  Google Scholar 

  20. Ulrich EL, Akutsu H, Doreleijers JF, et al (2008) BioMagResBank. Nucl Acids Res 36:402–408. https://doi.org/10.1093/nar/gkm957

    Article  CAS  Google Scholar 

  21. Langmead B, Salzberg SL (2012) Fast gapped-read alignment with Bowtie 2. Nat Methods 9:357–359. https://doi.org/10.1038/nmeth.1923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lezak MD (1984) Neuropsychological assessment in behavioral toxicology—developing techniques and interpretative issues. Scand J Work Environ Heal 10:25–29

    Article  Google Scholar 

  23. Newgard CB, An J, Bain JR, et al (2009) A branched-Chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab 9:311–326. https://doi.org/10.1016/j.cmet.2009.02.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ottosson F, Brunkwall L, Ericson U, et al (2018) Connection between BMI-related plasma metabolite profile and gut microbiota. J Clin Endocrinol Metab 103:1491–1501. https://doi.org/10.1210/jc.2017-02114

    Article  PubMed  Google Scholar 

  25. Fernandez-Real JM, Serino M, Blasco G, et al (2015) Gut microbiota interacts with brain microstructure and function. J Clin Endocrinol Metab 100:4505–4513. https://doi.org/10.1210/jc.2015-3076

    Article  CAS  PubMed  Google Scholar 

  26. Leibowitz A, Boyko M, Shapira Y, Zlotnik A (2012) Blood glutamate scavenging: insight into neuroprotection. Int J Mol Sci 13:10041–10066. https://doi.org/10.3390/ijms130810041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zhang K, Fan Z, Wang Y, Faraone SV, Yang L, Chang S (2017) Genetic analysis for cognitive flexibility in the trail-making test in attention deficit hyperactivity disorder patients from single nucleotide polymorphism, gene to pathway level. World J Biol Psychiatry. https://doi.org/10.1080/15622975.2017.1386324

    Article  PubMed  Google Scholar 

  28. Ibrahim-Verbaas CA, Bressler J, Debette S et al (2016) GWAS for executive function and processing speed suggests involvement of the CADM2 gene. Mol Psychiatry 21:189–197. https://doi.org/10.1038/mp.2015.37

    Article  CAS  PubMed  Google Scholar 

  29. Sano C (2009) History of glutamate production. Am J Clin Nutr 90:728–732. https://doi.org/10.3945/ajcn.2009.27462F

    Article  CAS  Google Scholar 

  30. Kinoshita S, Udaka S, Shimono M (2004) Studies on amino acid fermentation production of L-glutamic acid by various microorganisms. J Gen Appl Microbiol 50:331–343

    PubMed  Google Scholar 

  31. Lee JY, Na YA, Kim E, Lee HS, Kim P (2016) The Actinobacterium corynebacterium glutamicum, an industrial workhorse. J Microbiol Biotechnol 26:807–822. https://doi.org/10.4014/jmb.1601.01053

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors acknowledge the technical assistance of Emilio Loshuertos (Girona Biomedical Research Institute, IdIBGi) and Oscar Rovira.

Funding

This work was supported by FIS Grant (PI15/01934), FIS Grant (PI16/02064) from the National Institute of Health Carlos III and by ERDF (European Regional Development Fund).

Author information

Author notes

  1. María Encarnación Palomo‑Buitrago and Mònica Sabater‑Masdeu contributed equally to this work.

Authors and Affiliations

  1. Department of Diabetes, Endocrinology and Nutrition, Hospital of Girona “Dr Josep Trueta”, Institut d’Investigació Biomèdica de Girona (IDIBGI), Avinguda de França s/n, 17007, Girona, Spain

    María Encarnación Palomo-Buitrago, Mònica Sabater-Masdeu, Jose Maria Moreno-Navarrete, Estefanía Caballano-Infantes, María Arnoriaga-Rodríguez, Wifredo Ricart & José Manuel Fernández-Real

  2. CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERobn, CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain

    Mònica Sabater-Masdeu, Jose Maria Moreno-Navarrete, Estefanía Caballano-Infantes, María Arnoriaga-Rodríguez, Wifredo Ricart & José Manuel Fernández-Real

  3. Department of Neurology, Institut d’Investigació Biomèdica de Girona (IDIBGI), Hospital of Girona “Dr Josep Trueta”, Girona, Spain

    Clàudia Coll & Lluís Ramió

  4. Medical Molecular Imaging Research Group, Vall d’Hebron Research Institute, Instituto de Salud Carlos III (ISCIII), CIBBIM-Nanomedicine, CIBER-bbn, Barcelona, Spain

    Patricia Gutiérrez-Carcedo & José Raúl Herance

  5. Genomics and Health Area, Foundation for the Promotion of Sanitary and Biomedical Research (FISABIO), València, Spain

    Vicente Pérez-Brocal & Andrés Moya

  6. CIBER de Epidemiology y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain

    Vicente Pérez-Brocal & Andrés Moya

  7. Diabetes and Metabolism Research Unit, Vall d’Hebron Research Institute, Barcelona, Spain

    Rafael Simó

  8. Department of Endocrinology, Vall d’Hebron Research Institute, Instituto de Salud Carlos III (ISCIII), CIBERDEM, Barcelona, Spain

    Rafael Simó

  9. NMR Facility, Centro de Investigación Principe Felipe, Valencia, Spain

    Martina Palomino-Schätzlein

Authors
  1. María Encarnación Palomo-Buitrago
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  2. Mònica Sabater-Masdeu
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  3. Jose Maria Moreno-Navarrete
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  6. Clàudia Coll
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Contributions

MEPB, MSM and MAR researched the data, performed the statistical analysis and wrote and edited the manuscript. CC and LR researched the data and performed neuropsychological assessment TMT-A and TMT-B MP-S, PG-C and JRH researched the data, performed the 1H-NMR for plasma and feces metabolomic analysis and contributed to the writing and editing of the manuscript. VP-B, AM performed the gut microbiota composition analysis and contributed to the writing of the manuscript. JMM-N, EC-I, RS, JRH, WR contributed to the discussion and reviewed the manuscript. JMF-R Carried out the conception and coordination of the study, contributed to statistical analysis and writing the manuscript and directly participated in the execution of the study. JMF-R is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding authors

Correspondence to José Raúl Herance or José Manuel Fernández-Real.

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The authors declare no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Palomo-Buitrago, M.E., Sabater-Masdeu, M., Moreno-Navarrete, J.M. et al. Glutamate interactions with obesity, insulin resistance, cognition and gut microbiota composition. Acta Diabetol 56, 569–579 (2019). https://doi.org/10.1007/s00592-019-01313-w

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  • DOI: https://doi.org/10.1007/s00592-019-01313-w

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