Gut Microbiota and Pain Modulation

The human gastrointestinal tract harbours a vast microbial ecosystem that communicates bidirectionally with the nervous system through neural, immune and endocrine pathways, collectively known as the gut–brain axis. Emerging evidence reveals that metabolites produced by gut microbes, notably short‐chain fatty acids, neurotransmitter precursors and bile acids, can influence nociceptive signalling at peripheral sites and within the central nervous system. Alterations in microbial composition—termed dysbiosis—have been linked to enhanced neuronal sensitisation, activation of glial cells and aberrant immune responses, all of which contribute to acute and chronic pain states. These insights have spurred interest in microbiota‐targeted therapies, including dietary modulation, probiotics, prebiotics and faecal microbiota transplantation, as novel strategies to complement conventional analgesic regimens. The global burden of pain, spanning postoperative, neuropathic, inflammatory and functional visceral disorders, underscores the clinical potential of microbiome‐based interventions to improve patient outcomes and reduce reliance on opioids.

Research from Nature Portfolio

Recent clinical investigations have demonstrated a clear association between gut microbial diversity and the risk of persistent postoperative pain. In patients undergoing breast cancer surgery, those who developed prolonged pain exhibited reduced alpha diversity and characteristic shifts in key taxa, including lower levels of Bifidobacterium longum and Faecalibacterium prausnitzii. Conversely, enriched populations of Megamonas, Bacteroides and Ruminococcus correlated with ongoing pain, suggesting potential microbial biomarkers and targets for perioperative modulation. In parallel, experimental work in chemotherapy‐induced neuropathy models has shown that transfer of microbiota from pain‐sensitive mice exacerbates nociception and microglial activation, whereas microbiota from pain‐resistant strains confers protection. Loss of Akkermansia muciniphila and disruption of intestinal barrier function were implicated in systemic exposure to proalgesic metabolites, highlighting a microbe–immune–brain axis in chemotherapy‐related pain.

Gut Microbiota and Pain Modulation publication trend

The graph below shows the total number of articles in gut microbiota and pain modulation across all publications each year (not limited to Nature Index journals).

Technical terms

Gut–brain axis: The complex network of neural, hormonal and immune pathways linking the gastrointestinal tract with the central nervous system.

Dysbiosis: A state of microbial imbalance in the gut associated with disease processes.

Short‐chain fatty acids (SCFAs): Microbial metabolites, chiefly acetate, propionate and butyrate, that influence host immunity and neural signalling.

Microglia: Resident immune cells of the central nervous system that modulate inflammation and neuronal function.

Central sensitisation: Enhanced responsiveness of nociceptive neurons in the spinal cord and brain leading to persistent pain amplification.

References

1. Modulation of Glial Cell Functions by the Gut–Brain Axis: A Role in Neurodegenerative Disorders and Pain Transmission. Cells (2023).
2. Global Trends in Research of Pain–Gut-Microbiota Relationship and How Nutrition Can Modulate This Link. Nutrients (2023).
3. The gut microbiota in persistent post-operative pain following breast cancer surgery. Scientific Reports (2024).
4. Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain. Scientific Reports (2019).
5. The Role of the Human Microbiome in the Pathogenesis of Pain. International Journal of Molecular Sciences (2022).
6. Alterations of the gut microbiota in patients with postherpetic neuralgia. AMB Express (2023).