The gut microbiota and chronic pain
Gut microbes and their products are thought to contribute to chronic pain by sensitising pain-sensing neurons in the periphery and by driving neuroinflammation through the gut–brain axis. Many chronic pain conditions show dysbiosis of the gut microbiota. Probiotics and faecal microbiota transplantation had reduced pain in individual studies by 2025, while whether dysbiosis or chronic pain comes first remained unresolved.
The gut as a factor in chronic pain
Recent studies point to the gut microbiota as a potential new factor in chronic pain. Emerging evidence highlights the role of the gut–brain axis in chronic pain, particularly through the activation of immune cells and neuroinflammation. In the years before 2025 the interaction between the microbiota and the immune system had been investigated in chronic pain.
Dysbiosis and the leaky gut
In balance, or homeostasis, the gut microbiota helps digestion, immune regulation and overall health. When the balance is disrupted, the composition of the microbiota changes, and the result is dysbiosis. Dysbiosis can disturb the immune system and lead to chronic inflammation.
Many chronic pain conditions show an imbalance in the gut microbiota. It is often marked by an increase in obligately or facultatively anaerobic and aerobic bacteria, such as Clostridiaceae, Enterobacteriaceae and Proteobacteria. At the same time, the commensal bacteria, which live in harmony with the body, are reduced, disrupting the microbial ecosystem. Pain itself may also affect the microbiota profile across different painful conditions.
Microbial metabolism in the gut produces products such as lipopolysaccharides and short-chain fatty acids. These products can act as pro-inflammatory substances by activating immune cells that release cytokines and chemokines. Over time this exacerbates inflammation and can damage the intestinal barrier, a condition often called "leaky gut". Once the barrier is compromised, microbial products normally confined to the gut can cross into the bloodstream and reach distant organs, including the nervous system.
Peripheral and central sensitisation
Gut microbes may contribute to pain sensitisation by a peripheral and a central mechanism. In the periphery, gut microbes and their products may activate nociceptive neurons in the peripheral nerve fibres, such as nerves in the skin, muscles and joints, directly. They may also act indirectly, by activating immune cells and the release of pro-inflammatory substances such as IL-1β and TNF-β.
In the central mechanism, along the gut–brain axis, lipopolysaccharides and short-chain fatty acids cross the blood–brain barrier and interact with and activate glial cells (microglia and astrocytes). These cells release further inflammatory mediators and interact with neurons, which causes neuroinflammation and worsens pain sensitisation. Recent clinical studies suggest that communication between the gut microbiota and microglia plays a key role in the development of chronic pain. Restoring the homeostasis of the microbiota can therefore reduce microglial activation, and with it neuroinflammation and chronic pain.
Microbiota-based therapies
Some alternatives have been proposed to restore the balance of the gut microbiota.
In one study, eight weeks of the probiotics Lactobacilli, Bifidobacterium and Saccharomyces reduced pain and improved sleep quality, meaning uninterrupted and refreshing sleep, as well as depression and anxiety in patients with fibromyalgia. In another, four weeks of Lactobacillus reduced pain in children. Ten weeks of Lactobacilli, Bifidobacteria and Streptococcus also had a positive effect in migraine.
In fibromyalgia, faecal microbiota transplantation reduced widespread pain, anxiety and depression and improved sleep quality at 3, 6 and 12 months after the procedure. In another study, it reduced abdominal pain, discomfort and severity 12 weeks after the procedure, but these effects were reduced over one year.
Open questions
Whether neuroinflammation and chronic pain or dysbiosis comes first was still unresolved in 2025. The relationship between the gut microbiome and chronic pain is undeniable, but more needs to be understood about the microbiota profiles of different types of chronic pain and their clinical implications. There is no simple solution, but the gut microbiota may offer new hope for the treatment of chronic pain.