Gut microbiome is associated with insula structure in neonates

Michelle Graf; Nicolas Murgueitio; Margaret A Sheridan; Robert A Quinn; Alexander L Carlson; Sarah C Vogel; Martin A Styner; Ann M Alex; Rebecca L Stephens; Jeff Roach; Nicole Sagarnaga; W Roger Mills-Koonce; M Andrea Azcarate-Peril; Sarah J Short; Rebecca C Knickmeyer; Cathi B Propper

doi:10.1016/j.physbeh.2025.115001

Gut microbiome is associated with insula structure in neonates

Physiol Behav. 2025 Jun 16:299:115001. doi: 10.1016/j.physbeh.2025.115001. Online ahead of print.

Authors

Michelle Graf¹, Nicolas Murgueitio², Margaret A Sheridan³, Robert A Quinn⁴, Alexander L Carlson⁵, Sarah C Vogel⁶, Martin A Styner⁷, Ann M Alex⁸, Rebecca L Stephens⁷, Jeff Roach⁹, Nicole Sagarnaga¹⁰, W Roger Mills-Koonce¹¹, M Andrea Azcarate-Peril⁹, Sarah J Short¹², Rebecca C Knickmeyer¹³, Cathi B Propper¹⁴

Affiliations

¹ School of Nursing, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Virginia Commonwealth University, School of Nursing, Richmond, VA, USA. Electronic address: michgraf@unc.edu.
² Department of Psychology and Neuroscience, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: jnicolas@email.unc.edu.
³ Department of Psychology and Neuroscience, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴ Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
⁵ Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, USA.
⁶ Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
⁷ Department of Psychiatry, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁸ Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.
⁹ The Division of Gastroenterology and Hepatology, Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; UNC Microbiome Core, Center for Gastrointestinal Biology and Diseases, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹⁰ Frank Porter Graham Child Development Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹¹ School of Education, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹² Department of Educational Psychology, University of Wisconsin-Madison, Madison, WI, USA; Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA.
¹³ Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI, USA.
¹⁴ School of Nursing, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Frank Porter Graham Child Development Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

PMID: 40532867
DOI: 10.1016/j.physbeh.2025.115001

Abstract

The infant brain and gut microbiome both develop rapidly in early infancy. Growing evidence indicates that the gut microbiome plays a critical role in shaping neurodevelopment early in life, possibly through effects on brain regions involved in affective, interoceptive, and sensory processing. This study used magnetic resonance imaging (MRI) and whole genome sequencing of fecal samples to examine associations between the gut microbiome and brain structures in infants at 2 weeks of age. We identified significant relationships between specific gut microbiome characteristics and brain volumes in key regions involved in affective, sensory, and interoceptive processing. Our most consistent findings were associations between gut microbiome and insula volume, suggesting that the insula may be particularly sensitive to gut microbiome influences during the neonatal period. Specifically, a significant negative association between insula volume and the abundance of Veillonella was observed. Alpha diversity (Shannon) and functional pathways were also related to insula structure. Enterobacter was negatively associated with thalamus volume. These findings contribute to the growing evidence of a developing gut-brain axis, highlighting links between the gut and brain as early as 2 weeks of age. Future research should investigate the mechanisms by which specific microbial features impact neurodevelopment by way of the insula, as well as explore the potential long-term implications of these early relationships on sensory, interoceptive, and affective processing, and behavioral outcomes.

Keywords: Amygdala; Insula; Microbiome; Neonate; Thalamus.