Breast Cancer: Targets and Therapy (Dec 2022)
Effect of Chemotherapy on the Gut Microbiome of Breast Cancer Patients During the First Year of Treatment
Abstract
Anna H Wu,1 Cheryl Vigen,2 Chiuchen Tseng,1 Agustin A Garcia,3 Darcy Spicer4 1Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 2Mrs. TH Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, CA, USA; 3Department of Medicine, Louisiana State University School of Medicine, New Orleans, LA, USA; 4Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USACorrespondence: Anna H Wu, Department of Population and Public Health Sciences, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Rm 4443, Los Angeles, CA, 90089, USA, Tel +1 323 865-0484, Email [email protected]: 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 (pneoADJ 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.Keywords: neoadjuvant, adjuvant chemotherapy, gut microbiome, alpha diversity, breast cancer
