Effect of Chemotherapy on the Gut Microbiome of Breast Cancer Patients During the First Year of Treatment

Abstract

Introduction There is accumulating information of the effects of chemotherapy and weight changes on the gut microbiome of breast cancer patients. Methods In this 1-year follow-up study, we investigated gut microbiome of 33 breast cancer patients who donated fecal samples at baseline and after completion of treatment. We compared alpha diversity and mean taxa abundance at baseline and absolute taxa abundance changes (final-baseline) by treatment (16 neoadjuvant [neoADJ], 13 adjuvant [ADJ], 4 no chemotherapy [noC]) and specific chemotherapy agent using Wilcoxon rank sum and negative binomial mixed model (NBMM) analysis. Results All four gut alpha diversity measures changed in association with chemotherapy treatment; they increased in the neoADJ (+16.4% OTU p = 0.03; +51.6% Chao1 p = 0.03; +7.0% Shannon index p = 0.02; +11.0% PD whole tree p = 0.09) but not in the ADJ and noC group (ADJ+noC). The difference in Chao1 index change between groups was statistically significant (p neoADJ vs. ADJ+noC =0.04). Wilcoxon p values of 0.03–0.003 were observed for five taxa. In NBMM analysis, changes in taxa abundance differed (Bonferroni-adjusted p ≤ 0.0007) for two Bacteroidetes taxa ( g_Alistipes , f _S24-7 ) and two Firmicutes taxa (g_Catenibacterium, g_Eubacterium ). NBMM analysis results remained unchanged with adjustment for weight changes. Alpha diversity changes were also found by receipt of chemotherapy agents. Consistent increases in alpha diversity were observed among those treated with TCHP (OTU p = 0.009; Chao1 p = 0.02; Shannon p = 0.02; PD whole tree p = 0.05) but not AC, Taxol or Herceptin. Those treated with TCHP or Herceptin showed increases in Verrucomicrobia (g_Akkermansia) but decreases of Bacteroidetes(g _ Alistipes ); the differences in changes in taxa abundance were statistically significant. Conclusion Results from this pilot longitudinal study support an effect of chemotherapy, particularly neoADJ on the gut microbiome of breast cancer patients even after adjustment for weight changes. Further investigations are needed to confirm these findings in larger studies and with longer follow-up and to assess the impact of these microbiome changes on patient outcome.

Sex differences in cachexia and branched‐chain amino acid metabolism following chemotherapy in mice

“…The increase in plasma BCAA in males can be related to the release of these AAs from skeletal muscle, a tissue that may rely on the oxidation of AAs during substrate deficits (Lamont et al., 2001 ). Also, a previous review has outlined that dysregulation of BCAA metabolism in the gut microbiome can result in elevated plasma BCAA (Li et al., 2023 ), an interesting finding as chemotherapy may cause changes in gut microbiome (Wu et al., 2022 ). However, we did not measure gut microbiome in this study.…”

Preliminary Analysis of Gut Microbiome and Gastrointestinal Symptom Burden in Breast Cancer Patients Receiving Chemotherapy Compared to Healthy Controls

“…Data from clinical studies involving cancer patients receiving chemotherapy revealed that pediatric patients receiving chemotherapy for acute myelogenous leukemia had a depletion in Clostridium cluster XIVa , Faecalibacterium prausnitzii and Bifidobacterium compared to healthy controls, adult patients with non-Hodgkin’s lymphoma showed an enrichment in Bacteroides and Escherichia and depletion in Blautia , Faecalibacterium , Roseburia , and Bifidobacterium after chemotherapy relative to before, adult cancer patients receiving one of many chemotherapy regimens showed an enrichment in Bacteroides and Clostridium cluster IV and a depletion in Bifidobacteria and Clostridium cluster XIVa after chemotherapy relative to before, and adult cancer patients receiving one of many chemotherapy regimens and reporting diarrhea showed an enrichment in Escherichia coli and Staphylococcus spp and depletion in Lactobacillus spp ., Bacteroides spp ., Bifidobacterium sp p., and Enterococcus spp compared to healthy controls. In a recent study, Wu and her team (2022) collected stool samples and symptom data from breast cancer patients before they started chemotherapy and at the end of treatment. Of the chemotherapy regiments included in their study, TCHP (Taxotere, Carboplatin, Herceptin, and Perjeta) and Taxol alone most closely resembled regimens received by the breast cancer participants in our study.…”

“…Chemotherapy-associated gastrointestinal (GI) symptoms are known to be influenced by inflammation and damage to GI epithelial cells (Akbarali et al, 2022; Chen, et al, 2022). Chemotherapy is a frequently used treatment for breast cancer, but research on the effects of chemotherapy on the GI microbiome of breast cancer patients showed a reduction in the overall diversity of the GI microbiome (Aarnoutse et al, 2022) and changes in the richness of individual bacteria (Walker et al, 2023; Wu et al, 2022). These microbial changes can in turn influence the presence and severity of GI symptoms.…”

Exploring the human microbiome – A step forward for precision medicine in breast cancer

“…In the context of therapeutic advancements, the microbiota may play a crucial role in predicting individual breast cancer risk and prognosis, as well as the pharmacokinetics, pharmacodynamics, and clinical efficacy of treatments 41,131 . Recent research has revealed that certain gut commensals, which are present in excess in breast cancer patients compared to healthy individuals, have a negative impact on breast cancer prognosis, are influenced by chemotherapy, and may also affect weight gain and neurological side effects of breast cancer therapies 132,133 . Clinical researchers are therefore interested in the potential of the gut microbiota as a biomarker for predicting the efficacy of cancer treatment.…”