Abstract # 3083 The role of gut-brain axis in chemotherapy-induced behavioral comorbidities

Abstract

Recent evidence indicates that the gut microbiome can influence brain and behavior, including cognition. Approximately one-third of cancer survivors report cognitive impairments after receiving chemotherapy. Many of these cancer patients also experience adverse effects on their gut, including diarrhea and vomiting, along with a shift in community structure of their natural gut microbiota. However, very little is known about the potential role of the gut microbiome in the enduring and prevalent consequences of chemotherapy on the brain and cognitive function. The present hypothesis is that chemotherapy shifts composition in the gut microbiota, leading to neuroinflammation and cognitive impairments. Here, half of the adult Balb/c female mice received 6 doses of paclitaxel chemotherapy (30 mg/kg; i.p.; every other day); the others received vehicle (n = 5–10/group). Immediately or 2 weeks after chemotherapy, cognition was assessed by fear conditioning and tissues were collected to assess neuroinflammation and 16S fecal microbial profiles. These preliminary data suggest that chemotherapy treatment impaired cued conditioning and decreased diversity of fecal microbial taxa (marked by increased abundance of Turicibacter species), which was correlated with brain inflammatory markers. Paclitaxel also increased gut and spleen masses, while altering transcript expression of genes necessary for paclitaxel excretion in both the brain and the colon. These results suggest that the gut microbiota may exert indirect effects of chemotherapy on the brain, thereby potentiating behavioral comorbidities.