The Role of the Microbiome-Gut Brain Axis in Women’s Health and Pain

While chronic pain affects approximately 20% of adults, women and girls are disproportionally affected. Despite this, traditionally most of the pain research in the pre-clinical setting has been conducted solely in male animals. More recently, with the inclusion of females in animal research it has been revealed that sex differences exist in many of the fundamental mechanisms underlying pain. Human studies have also identified differences in the neural circuitry involved in pain processing between the sexes using neuroimaging (Osborne and Davis, 2022). The gut microbiome is defined as the ecosystem of commensal, symbiotic, and pathogenic microorganisms (Armet et al., 2022) and is different between the sexes (Caputi et al., 2022). This community of microorganisms has been associated with both health and disease states and through a series of pathways, referred to as the microbiome-gut-brain axis, can impact the central nervous system including pain processing.

The microbiome-gut-brain axis is composed of neuronal, immune, and endocrine signalling pathways allowing bi-directional interactions between the gastrointestinal tract and the central nervous system (Cryan et al., 2019). The microbiome is capable of producing neurotransmitters as well as microbial-derived neuroactive products such as short-chain fatty acids, which allow microbes to directly impact the nervous systems. The gut microbiome is also directly involved in the production and metabolism of female hormones such as oestrogen, progesterone and luteinizing hormone (Diviccaro et al., 2021). The physiological levels of these hormones vary across the menstrual cycle and menstruation itself has various biological, social and psychological aspects associated with it (Jain et al., 2023) with the period preceding menstruation being linked to several nervous system and peripheral symptoms including anxiety, fatigue, decreased concentration, and abdominal bloating (Jain et al., 2023). The gut microbiome has been noted to be altered in certain female-specific conditions linked with hormonal imbalance such as polycystic ovaries, endometriosis and menopause (Siddiqui et al., 2022) with a specific community of gut bacteria, referred to as the estrobolome, being capable of metabolising oestrogens and preventing their excretion.