Chemotherapy-Induced Gastrointestinal Toxicity and Microbiota Dynamics

Cancer chemotherapy frequently provokes gastrointestinal toxicity, manifesting as mucositis, nausea, diarrhoea and altered motility. These adverse effects arise from damage to rapidly dividing epithelial cells, inflammation and disrupted barrier integrity. Concurrently, chemotherapeutic agents perturb the ecological balance of gut microbiota, leading to reduced diversity and loss of beneficial commensals. This bidirectional interplay influences both treatment efficacy and patient tolerance: dysbiosis can exacerbate inflammatory signalling and epithelial injury, whereas the native microbiota can mediate drug metabolism, modulate immune responses and foster mucosal repair. Recent advances illustrate how targeted modulation of microbial communities—via prebiotic nanoparticles, probiotics or controlled low-dose regimens—can attenuate toxicity without compromising anti-tumour activity. Growing evidence also reveals that chemotherapy-induced changes in gut ecology can have systemic consequences, including effects on neuroinflammation and response to immunotherapy. A deeper understanding of microbiota dynamics under chemotherapeutic stress promises novel adjuvant strategies to enhance clinical outcomes and quality of life.

Research from Nature Portfolio

Innovative delivery systems have been developed to synchronise chemotherapeutic dosing with microbiota modulation. One approach encapsulates capecitabine within a prebiotic nanoparticle, delaying systemic clearance, boosting intratumoral drug levels and selectively promoting short-chain fatty acid production by beneficial bacteria. The combined effect is enhanced anti-tumour immunity, markedly improved tumour inhibition and prolonged survival in animal models. Separately, studies of paclitaxel treatment in female mice have demonstrated concurrent alterations in colonic bacterial composition, increased crypt depth and transient cytokine elevations. These gut changes correlate with microglial activation in the brain and behavioural fatigue, uncovering a novel gut–brain axis linking chemotherapy-induced mucosal disruption to neuroinflammatory sequelae.

Chemotherapy-Induced Gastrointestinal Toxicity and Microbiota Dynamics publication trend

The graph below shows the total number of articles in chemotherapy-induced gastrointestinal toxicity and microbiota dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Mucositis: Inflammation and ulceration of the gastrointestinal mucosal lining induced by chemotherapy or radiotherapy.

Microbiota: The community of microorganisms residing in a specific environment, such as the gut.

Prebiotic: A substrate selectively utilised by host microorganisms, promoting the growth of beneficial bacteria.

Short-chain fatty acids (SCFAs): Metabolic by-products of microbial fermentation of dietary fibres, important for epithelial health.

Inflammasome: A multiprotein complex that detects cellular stress and activates inflammatory cytokines.

Interleukin-10 (IL-10): An anti-inflammatory cytokine produced by immune cells that limits tissue damage.

References

1. Combining gut microbiota modulation and chemotherapy by capecitabine-loaded prebiotic nanoparticle improves colorectal cancer therapy. Nature Communications (2023).
2. Chemotherapy-induced neuroinflammation is associated with disrupted colonic and bacterial homeostasis in female mice. Scientific Reports (2019).
3. Low‐Dose Chemotherapy Preferentially Shapes the Ileal Microbiome and Augments the Response to Immune Checkpoint Blockade by Activating AIM2 Inflammasome in Ileal Epithelial Cells. Advanced Science (2024).
4. Chemotherapy-induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin-10 from macrophages. Gut Microbes (2024).