TY - JOUR
T1 - Chemotherapy-induced gut microbiome disruption, inflammation, and cognitive decline in female patients with breast cancer
AU - Otto-Dobos, L. D.
AU - Grant, C. V.
AU - Lahoud, A. A.
AU - Wilcox, O. R.
AU - Strehle, L. D.
AU - Loman, B. R.
AU - Adarkwah Yiadom, S.
AU - Seng, M. M.
AU - Halloy, N. R.
AU - Russart, K. L.G.
AU - Carpenter, K. M.
AU - Dawson, E.
AU - Sardesai, S. D.
AU - Williams, N. O.
AU - Gatti-Mays, M. E.
AU - Stover, D. G.
AU - Sudheendra, P. K.
AU - Wesolowski, R.
AU - Kiecolt-Glaser, J. K.
AU - Bailey, M. T.
AU - Andridge, R. R.
AU - Pyter, L. M.
N1 - Publisher Copyright:
© 2024 Elsevier Inc.
PY - 2024/8
Y1 - 2024/8
N2 - Chemotherapy is notorious for causing behavioral side effects (e.g., cognitive decline). Notably, the gut microbiome has recently been reported to communicate with the brain to affect behavior, including cognition. Thus, the aim of this clinical longitudinal observational study was to determine whether chemotherapy-induced disruption of the gut microbial community structure relates to cognitive decline and circulating inflammatory signals. Fecal samples, blood, and cognitive measures were collected from 77 patients with breast cancer before, during, and after chemotherapy. Chemotherapy altered the gut microbiome community structure and increased circulating TNF-α. Both the chemotherapy-induced changes in microbial relative abundance and decreased microbial diversity were related to elevated circulating pro-inflammatory cytokines TNF-α and IL-6. Participants reported subjective cognitive decline during chemotherapy, which was not related to changes in the gut microbiome or inflammatory markers. In contrast, a decrease in overall objective cognition was related to a decrease in microbial diversity, independent of circulating cytokines. Stratification of subjects, via a reliable change index based on 4 objective cognitive tests, identified objective cognitive decline in 35% of the subjects. Based on a differential microbial abundance analysis, those characterized by cognitive decline had unique taxonomic shifts (Faecalibacterium, Bacteroides, Fusicatenibacter, Erysipelotrichaceae UCG-003, and Subdoligranulum) over chemotherapy treatment compared to those without cognitive decline. Taken together, gut microbiome change was associated with cognitive decline during chemotherapy, independent of chemotherapy-induced inflammation. These results suggest that microbiome-related strategies may be useful for predicting and preventing behavioral side effects of chemotherapy.
AB - Chemotherapy is notorious for causing behavioral side effects (e.g., cognitive decline). Notably, the gut microbiome has recently been reported to communicate with the brain to affect behavior, including cognition. Thus, the aim of this clinical longitudinal observational study was to determine whether chemotherapy-induced disruption of the gut microbial community structure relates to cognitive decline and circulating inflammatory signals. Fecal samples, blood, and cognitive measures were collected from 77 patients with breast cancer before, during, and after chemotherapy. Chemotherapy altered the gut microbiome community structure and increased circulating TNF-α. Both the chemotherapy-induced changes in microbial relative abundance and decreased microbial diversity were related to elevated circulating pro-inflammatory cytokines TNF-α and IL-6. Participants reported subjective cognitive decline during chemotherapy, which was not related to changes in the gut microbiome or inflammatory markers. In contrast, a decrease in overall objective cognition was related to a decrease in microbial diversity, independent of circulating cytokines. Stratification of subjects, via a reliable change index based on 4 objective cognitive tests, identified objective cognitive decline in 35% of the subjects. Based on a differential microbial abundance analysis, those characterized by cognitive decline had unique taxonomic shifts (Faecalibacterium, Bacteroides, Fusicatenibacter, Erysipelotrichaceae UCG-003, and Subdoligranulum) over chemotherapy treatment compared to those without cognitive decline. Taken together, gut microbiome change was associated with cognitive decline during chemotherapy, independent of chemotherapy-induced inflammation. These results suggest that microbiome-related strategies may be useful for predicting and preventing behavioral side effects of chemotherapy.
KW - Cognitive impairment
KW - Cytokines
KW - Differential abundance analysis
KW - Microbial diversity
KW - Objective cognition
KW - Subjective cognition
UR - http://www.scopus.com/inward/record.url?scp=85195166633&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2024.05.039
DO - 10.1016/j.bbi.2024.05.039
M3 - Article
C2 - 38823430
AN - SCOPUS:85195166633
SN - 0889-1591
VL - 120
SP - 208
EP - 220
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -