A recent review, published by postdoctoral researcher Dr. Eldin Jasarevic from the Department of Animal Biology in the University of Pennsylvania, argues that sex differences influence the development, maturation, and maintenance of the gut microbiome-brain axis throughout the lifespan.


The gut-brain axis (GBA) involves bidirectional communication between the central and enteric nervous systems, which facilitates the integration of peripheral and central immune, metabolic, and endocrine signals. Recent advances have described the importance of gut microbiota in influencing these interactions. The formation of the gut-brain axis begins immediately following colonization by microbial communities that reside within the birth canal. Sex-specific maturation of the gut, hormones, and brain occur in parallel across the lifespan. Shifts in structure and function of the gastrointestinal tract and brain provide windows of opportunity for intervention during distinct life stages.


Existing evidence from studies both in animals and humans supports that during the prenatal period, the metabolic demand of male and female foetuses on the mother differs, and the maternal gut microbiome orchestrates nutritional status during development. For instance, during the first trimester there is a rise in short chain fatty acid (SCFA)-producing microbiota, which suggests a role for maternal-derived microbial substrates in foetal neurodevelopment. However, there is a vast expansion of bacterial diversity during late gestation when oestrogens are at maximal peak and SCFA exposure decreases in order to meet the offspring’s increased nutritional and metabolic demands. During the postnatal period, microbial colonization may influence sex differences in immunocompetent cells’ maturation and function in the brain. Environmental perturbations such as stress during critical windows of development influence gut-brain signalling and are linked to metabolic reprogramming of the offspring gut and brain. Sex differences in the gut microbiome emerge during puberty and continue into adulthood. Puberty is a period of increased sex-specific risk for stress, which could affect later-life behaviour and anxiety. Likewise, the researchers suggest that gut microbial communities may alter host hormones and affect neurotransmitters that are critical for normal communication between the gut and brain. In adulthood, gut microbiota are more stable and appear better adapted to environmental challenges. Interestingly, sex may determine risk for negative symptoms related to gut health. Indeed, gender bias in autoimmunity is influenced by microbiota. For instance, sex-specific changes on gut physiology and gut microbiota composition can explain, at least in part, the increased female risk for autoimmune disorders and allergies.


In conclusion, microbial communities contribute to several physiological processes throughout the lifespan. Sexually dimorphic communication between the gut microbiome and the brain occurs in parallel to immune, metabolic and neural changes, which suggests that sex-specific transitions could be considered in health and disease states.



Jasarevic E, Morrison KE, & Bale TL. Sex differences in the gut microbiome-brain axis across the lifespan. Philos Trans R Soc Lond B Biol Sci. 2016; 371(1688):20150122. doi:10.1098/rstb.2015.0122.