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.
The association between the gut microbiome and visceral pain as noted in irritable bowel syndrome has been extensively studied and verified in many cases (Moloney et al., 2016). In more recent times the gut microbiome has been proposed as being used to predict somatic pain conditions such as post-operative pain (Masaud et al., 2024). Furthermore, certain microbes are associated with female-specific pain conditions and those that present more frequently in women such as post-operative pain, fibromyalgia and endometriosis. The interaction of the gut microbiome and female hormones as well as the potential links to pain syndromes in women provides potential therapeutic opportunities such as microbiome-modulating interventions such as diet changes particularly increasing fibre and prebiotic foods that enhance microbes associated with anti-inflammatory properties and anti-nociceptive properties. Other potential interventions include synbiotics where both prebiotics and probiotics (health-promoting bacteria) are administered together to optimise colonisation and efficacy. While fecal microbiota transplantation has been used to define the role of the microbiome in pain (Lucarini et al., 2022) there is still a long road to develop it as a therapeutic for pain.
Given the potential of the microbiome in healthcare for women, there is a real need to conduct further research into sex-specific therapeutic interventions that alleviate painful conditions in women. This research will hopefully shape the future of women’s health and improve outcomes for women’s health and pain management.
Written by Dr Siobhain O’Mahony and Dr Mariarosaria Cuozzo, Department of Anatomy and Neuroscience, APC Microbiome Ireland, University College Cork, Ireland
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