Chemotherapy-induced gut microbiome disruption, inflammation, and cognitive decline in female patients with breast cancer

认知功能衰退 微生物群 认知 化疗 乳腺癌 医学 内科学 免疫学 肠道菌群 炎症 癌症 肿瘤科 生物 生物信息学 痴呆 疾病 精神科
作者
Lauren Otto,Corena V. Grant,Ashley A. Lahoud,Olivia Wilcox,Lindsay Strehle,Brett R. Loman,Seth Adarkwah Yiadom,Melina Seng,Nicklaus Halloy,Kathryn L.G. Russart,Kristen M. Carpenter,Erica Dawson,S.D. Sardesai,Nicole Williams,Margaret E. Gatti‐Mays,Daniel G. Stover,P.K. Sudheendra,Robert Wesolowski,Janice K. Kiecolt‐Glaser,Michael T. Bailey
出处
期刊:Brain Behavior and Immunity [Elsevier BV]
卷期号:120: 208-220 被引量:7
标识
DOI:10.1016/j.bbi.2024.05.039
摘要

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 all 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.
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