Chemotherapy-induced neuroinflammation is associated with disrupted colonic and bacterial homeostasis in female mice

Abstract

Chemotherapy treatment negatively affects the nervous and immune systems and alters gastrointestinal function and microbial composition. Outside of the cancer field, alterations in commensal bacteria and immune function have been implicated in behavioral deficits; however, the extent to which intestinal changes are related to chemotherapy-associated behavioral comorbidities is not yet known. Thus, this study identified concurrent changes in behavior, central and peripheral immune activation, colon histology, and bacterial community structure in mice treated with paclitaxel chemotherapy. In paclitaxel-treated mice, increased fatigue and decreased cognitive performance occurred in parallel with reduced microglia immunoreactivity, increased circulating chemokine expression (CXCL1), as well as transient increases in pro-inflammatory cytokine/chemokine (Il-1β, Tnfα, Il-6, and Cxcl1) gene expression in the brain. Furthermore, mice treated with paclitaxel had altered colonic bacterial community composition and increased crypt depth. Relative abundances of multiple bacterial taxa were associated with paclitaxel-induced increases in colon mass, spleen mass, and microglia activation. Although microbial community composition was not directly related to available brain or behavioral measures, structural differences in colonic tissue were strongly related to microglia activation in the dentate gyrus and the prefrontal cortex. These data indicate that the chemotherapeutic paclitaxel concurrently affects the gut microbiome, colonic tissue integrity, microglia activation, and fatigue in female mice, thus identifying a novel relationship between colonic tissue integrity and behavioral responses that is not often assessed in studies of the brain-gut-microbiota axis.

Bidirectional interaction between intestinal microbiome and cancer: opportunities for therapeutic interventions

“…Increases gut permeability, as indicated by 5-fold elevation in circulating LPS-binding protein and systemic inflammation [ 69 ]…”

CaCO3-Assisted Preparation of pH-Responsive Immune-Modulating Nanoparticles for Augmented Chemo-Immunotherapy

“…Emerging evidences have shown that the tumor microenvironment (TME) would foist a series of biological barriers to retard effective cancer treatment [1][2][3][4][5]. As a mainstream cancer treatment modality in the clinic, chemotherapy is far from satisfactory due to its limited therapeutic efficacy and severe side effects [6][7][8][9]. To achieve effective cancer chemotherapy with high safety, various nanoscale drug delivery systems enabling tumor-targeted delivery of chemotherapeutics have been intensively explored in the past decades [10][11][12][13].…”

Efficient extraction of cucurbitacins from Diplocyclos palmatus (L.) C. Jeffrey: Optimization using response surface methodology, extraction methods and study of some important bioactivities

“…Hence, a high demand of the drugs for new therapies to treat or prevent this life threatening disease is the need of the time 11 . Natural drugs are more preferred in the cancer treatment as chemoand radiation therapy have several ill effects on human beings 12 . Plant based metabolites have been studied extensively for their anticancer properties 13 .…”