# Chemotherapy-induced gut microbiota dysbiosis exacerbates cancer-related fatigue in breast cancer patients via neuroimmune-endocrine indicators

## TL;DR

This study shows that changes in gut bacteria before chemotherapy can predict severe cancer-related fatigue in breast cancer patients.

## Contribution

The study identifies gut microbiota signatures that predict chemotherapy-induced fatigue severity via neuroimmune-endocrine pathways.

## Key findings

- Baseline Bacteroidetes/Firmicutes ratios and Proteobacteria levels predict moderate-to-severe fatigue.
- Reduced short-chain fatty acid-producing bacteria correlate with increased fatigue severity.
- Lower Firmicutes/Blautia and serum BDNF levels are associated with higher fatigue.

## Abstract

Breast cancer patients frequently experience debilitating cancer-related fatigue (CRF) during chemotherapy. Emerging evidence implicates the gut microbiota (GM) and the gut-brain axis in CRF pathogenesis, yet whether pre-chemotherapy GM profiles can predict CRF remains unclear.

This prospective cohort study enrolled 100 breast cancer patients initiating chemotherapy. GM profiling and fatigue assessment (Visual Analogue Fatigue Scale, Cancer Fatigue Scale) were performed at baseline and the third chemotherapy cycle. Serum levels of neuroimmune-endocrine markers were also measured. Multivariate logistic regression was used to build a predictive model for moderate-to-severe CRF.

Patients experiencing moderate-to-severe CRF at the third chemotherapy cycle demonstrated higher baseline Bacteroidetes/Firmicutes ratios, increased Proteobacteria/Enterobacteriales levels, and reduced abundance of short-chain fatty acid-producing bacteria. The predictive model incorporating baseline GM signatures and clinical covariates achieved an AUC of 0.82, demonstrating good predictive accuracy for moderate-to-severe CRF. Decreased levels of Firmicutes/Blautia in the gut mucosal microenvironment, along with reduced serum brain-derived neurotrophic factor (BDNF), were associated with increased CRF.

Baseline GM characteristics predict the risk and severity of chemotherapy-induced CRF, potentially through modulation of neuroimmune-endocrine pathways via gut-brain axis. These findings underscore the potential role of GM as a predictive biomarker and a therapeutic target for chemotherapy-induced CRF.