Baseline gut microbiome alpha diversity predicts chemotherapy-induced gastrointestinal symptoms in patients with breast cancer

Abstract

Chemotherapy frequently causes debilitating gastrointestinal symptoms, which are inadequately managed by current treatments. Recent research indicates the gut microbiome plays a role in the pathogenesis of these symptoms. The current study aimed to identify pre-chemotherapy microbiome markers that predict gastrointestinal symptom severity after breast cancer chemotherapy. Fecal samples, blood, and gastrointestinal symptom scores were collected from 59 breast cancer patients before, during, and after chemotherapy. Lower pre-chemotherapy microbiome alpha diversity and abundance of specific microbes (e.g., Faecalibacterium) predicted greater chemotherapy-induced gastrointestinal symptoms. Notably, tumor and diet characteristics were associated with lower pre-chemotherapy alpha diversity. Lower baseline alpha diversity also predicted higher chemotherapy-induced microbiome disruption, which was positively associated with diarrhea symptoms. The results indicate certain cancer patients have lower microbiome diversity before chemotherapy, which is predictive of greater chemotherapy-induced gastrointestinal symptoms and a less resilient microbiome. These patients may be strong candidates for pre-chemotherapy microbiome-directed preventative interventions (e.g., diet change).

Fig. 1. Gastrointestinal symptoms over chemotherapy treatment.

Trajectories of A diarrhea and B nausea/vomiting over chemotherapy treatment. Results shown are mean ± standard error from linear mixed-effects models. *p < 0.05.

Fig. 2. Participant factors influencing baseline microbiome alpha diversity.

A Baseline alpha diversity composite of HER2- and HER2+ participants. Trajectories of (B) diarrhea symptoms and (C) nausea/vomiting symptoms of HER2 negative and positive participants. D Baseline alpha diversity composite of adjuvant and neoadjuvant participants. Trajectories of (E) diarrhea symptoms and (F) nausea/vomiting symptoms of adjuvant and neoadjuvant participants. Baseline alpha diversity composite compared via independent sample t-tests. Trajectory results shown are mean ± standard error from linear mixed-effects models. *p < 0.05.

Fig. 3. Participant baseline diet factors influencing baseline microbiome alpha diversity.

A Correlation of baseline dietary carbohydrates (as a percent of overall daily calories) and baseline alpha diversity. Trajectories of (B) diarrhea symptoms and (C) nausea/vomiting symptoms of those with low, medium, and high dietary carbohydrates. D Correlation of baseline daily calories from sugary beverages and baseline alpha diversity. Trajectories of (E) diarrhea symptoms and (F) nausea/vomiting symptoms of those with low and high daily calories from sugary beverages. Correlations determined via Pearson correlations. Trajectory results shown are mean ± standard error from linear mixed-effects models. *p < 0.05.

Fig. 4. Baseline microbiome alpha diversity predicts beta diversity change over chemotherapy treatment.

Relationship of baseline alpha diversity composite to Bray Curtis beta diversity distance from (A) pre- to during chemotherapy treatment and (B) pre- to post-chemotherapy treatment determined via Pearson correlation.