Gut microbiome and brain functional connectivity in infants-a preliminary study focusing on the amygdala

  • Wei GaoEmail author
  • Andrew P. Salzwedel
  • Alexander L. Carlson
  • Kai Xia
  • M. Andrea Azcarate-Peril
  • Martin A. Styner
  • Amanda L. Thompson
  • Xiujuan Geng
  • Barbara D. Goldman
  • John H. Gilmore
  • Rebecca C. KnickmeyerEmail author
Original Investigation


Recently, there has been a surge of interest in the possibility that microbial communities inhabiting the human gut could affect cognitive development and increase risk for mental illness via the “microbiome-gut-brain axis.” Infancy likely represents a critical period for the establishment of these relationships, as it is the most dynamic stage of postnatal brain development and a key period in the maturation of the microbiome. Indeed, recent reports indicate that characteristics of the infant gut microbiome are associated with both temperament and cognitive performance. The neural circuits underlying these relationships have not yet been delineated. To address this gap, resting-state fMRI scans were acquired from 39 1-year-old human infants who had provided fecal samples for identification and relative quantification of bacterial taxa. Measures of alpha diversity were generated and tested for associations with measures of functional connectivity. Primary analyses focused on the amygdala as manipulation of the gut microbiota in animal models alters the structure and neurochemistry of this brain region. Secondary analyses explored functional connectivity of nine canonical resting-state functional networks. Alpha diversity was significantly associated with functional connectivity between the amygdala and thalamus and between the anterior cingulate cortex and anterior insula. These regions play an important role in processing/responding to threat. Alpha diversity was also associated with functional connectivity between the supplementary motor area (SMA, representing the sensorimotor network) and the inferior parietal lobule (IPL). Importantly, SMA-IPL connectivity also related to cognitive outcomes at 2 years of age, suggesting a potential pathway linking gut microbiome diversity and cognitive outcomes during infancy. These results provide exciting new insights into the gut-brain axis during early human development and should stimulate further studies into whether microbiome-associated changes in brain circuitry influence later risk for psychopathology.


Amygdala Functional connectivity Gut microbiome Infant brain development 



Jennifer Prater was the lead study coordinator with assistance from Dianne Evans and Wendy Neuheimer. We are grateful to the research assistants collecting 2-year cognitive data: Margaret Hamilton Fox, Mallory Turner, Margo Williams, Haley Parrish Black, and Emma Brink. Joe Blocher and Rachel Steiner at the Neuro Image Research and Analysis Laboratories provided image processing support.

Funding information

This work was supported by National Institutes of Health (R01DA042988, R01DA043678, R21NS088975, R21DA043171, R03DA036645 to WG; R01MH070890 and R01HD053000 to JHG; R01 MH092335 and R33MH104330 to RKS; T32 NS007432 to ALC) and Cedars-Sinai Precision Medicine Initiative Award and institutional support to WG.

Compliance with ethical standards

Conflict of interest

RCK is a co-investigator and WG is a consultant on a grant sponsored by Nestle/Wyeth (RDNN201704/4520562240); RCK has also received travel support to present at the 7th Annual Wyeth Nutrition Science Center Global Summit. The other authors declare no competing financial interests.

Supplementary material

213_2018_5161_MOESM1_ESM.docx (26 kb)
ESM 1 (DOCX 25 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Wei Gao
    • 1
    • 2
    Email author
  • Andrew P. Salzwedel
    • 1
  • Alexander L. Carlson
    • 3
  • Kai Xia
    • 4
  • M. Andrea Azcarate-Peril
    • 5
    • 6
  • Martin A. Styner
    • 4
    • 7
  • Amanda L. Thompson
    • 8
    • 9
  • Xiujuan Geng
    • 10
  • Barbara D. Goldman
    • 11
    • 12
  • John H. Gilmore
    • 4
  • Rebecca C. Knickmeyer
    • 4
    • 13
    • 14
    Email author
  1. 1.Department of Biomedical Sciences and Imaging, Biomedical Imaging Research InstituteCedars-Sinai Medical CenterLos AngelesUSA
  2. 2.Department of MedicineUniversity of CaliforniaLos AngelesUSA
  3. 3.Neuroscience CurriculumUniversity of North Carolina at Chapel HillChapel HillUSA
  4. 4.Department of PsychiatryUniversity of North Carolina at Chapel HillChapel HillUSA
  5. 5.Department of MedicineUniversity of North Carolina at Chapel HillChapel HillUSA
  6. 6.Microbiome Core FacilityUniversity of North Carolina at Chapel HillChapel HillUSA
  7. 7.Department of Computer ScienceUniversity of North Carolina at Chapel HillChapel HillUSA
  8. 8.Department of AnthropologyUniversity of North Carolina at Chapel HillChapel HillUSA
  9. 9.Department of NutritionUniversity of North Carolina at Chapel HillChapel HillUSA
  10. 10.Brain and Mind InstituteChinese University of Hong KongHong KongChina
  11. 11.Department of Psychology and NeuroscienceUniversity of North Carolina Chapel HillChapel HillUSA
  12. 12.Frank Porter Graham Child Development InstituteUniversity of North Carolina Chapel HillChapel HillUSA
  13. 13.Department of Pediatrics and Human DevelopmentMichigan State UniversityEast LansingUSA
  14. 14.Institute for Quantitative Health Sciences and EngineeringMichigan State UniversityEast LansingUSA

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