Gut microbiota‐immune‐brain interactions in chemotherapy‐associated behavioral comorbidities

Abstract

Increasing scientific attention is focused on the gut-brain axis, including the ability of the gastrointestinal (GI) tract to modulate central nervous system function. Changes in the intestinal microbiome can influence affective-like behavior, cognitive performance, fatigue, and sleep in rodents and humans. Patients with cancer who are receiving chemotherapy experience similar negative behavioral changes and concurrent GI symptoms. These chemotherapy comorbidities can be long-lasting and may reduce patients' quality of life and motivation to comply with treatment. This review summarizes the clinical and preclinical evidence supporting a role for the intestinal microbiome in mediating behavioral comorbidities through peripheral immune activation in patients with cancer who are receiving chemotherapy. In addition, evidence suggesting that targeted modification of the intestinal microbiome during cancer treatment could ameliorate associated behavioral comorbidities is reviewed.

The Role of Gut Microbiome Perturbation in Fatigue Induced by Repeated Stress from Chemoradiotherapy: A Proof of Concept Study

“…e etiology and associated mechanism of the cancer-related fatigue during CRT treatment remain elusive [3]. ere is some evidence, however, that suggests that cancer treatment-induced gut microbial perturbation/dysbiosis (an imbalance in the intestinal microbiota or microorganism that live in the gut) contributes to inflammation-enabling translocation of bacteria and microbially-mediated metabolites into systemic circulation and inducing aberrant activation of the immune system such as cytokine-induced (i.e., interleukin-6) inflammatory reaction, which can affect brain function and induce behavioral symptoms such as fatigue [4][5][6][7][8]. However, not enough microbiomic studies exist to identify associations between changes of the gut microbiota and fatigue severity during CRT for RC.…”

“…and an increase in Escherichia spp., as well as a decrease of goblet cell numbers or mucus secretion in the jejunum of rats [13]. e aforementioned evidence suggests that patients undergoing chemotherapy or RT may exhibit marked changes in their intestinal microbiota [4,5,9]. However, these studies focused on chemotherapy or RT, not both, had heterogeneous groups and small sample sizes suggesting that more research is needed regarding the disruption of the intestinal microbiata during CRT.…”

“…One small cohort study found that fatigue symptoms were positively correlated with the systemic markers of inflammation (haptoglobin), and the microbial diversity, richness, and the Firmicutes/Bacteroidetes ratio was significantly altered prior to pelvic RT in patients who later developed diarrhea with significant worsening in fatigue [14]. ere is an emerging interest in how CRT can play a part in decreased microbial diversity and increased bloom of pathobionts to influence systemic inflammatory responses with consequential behavioral effects [4,5,8,14]. is pilot study is aligned with that interest.…”

Gut microbiota perturbation is associated with acute sleep disturbance among rectal cancer patients

“…A larger sample size would have permitted examining other variables of interest that could account for variance in the diversity of gastrointestinal bacterial populations and/or the SD experience (e.g. stress, pain, age, circadian rhythms, diet, exercise, gastrointestinal disturbances [abdominal pain, mucositis], tumour characteristics [location, stage]; Jordan et al., ; Krueger & Opp, ; Paulsen et al., ) that were not included in the analysis; however, collection of data on some variables is currently ongoing; on other variables, data will be collected in future studies. Although our initial results should be interpreted with caution because of the study limitations mentioned, they do have potential clinical implications.…”

“…Acute CRT‐related SD remains inadequately managed in part because the aetiology remains poorly understood. Some studies have suggested that perturbation of the gut microbiota, known as dysbiosis, potentially leads to co‐morbidities including SD among cancer survivors, presumably involving the “gut–brain axis” (Jordan, Loman, Bailey, & Pyter, ). However, it is unclear whether there is a relationship between gut microbiome perturbation and SD despite that work demonstrating a link between gut microbiome perturbation and SD has promising clinical implications.…”