Fig. 1.

Chemotherapy Driven Dysbiosis of the Microbiota-Gut-Brain Axis. The Chemotherapy Driven Dysbiosis of the Microbiota-Gut-Brain Axis model posits that chemotherapy given to young cancer patients induces long-term gut dysbiosis, increasing intestinal permeability (i.e. “leaky gut”), which allows bacterial toxins, such as lipopolysaccharide (LPS), to enter the blood stream. This subsequently leads to systemic inflammation via increases in pro-inflammatory cytokines, especially IL-6, IL-1b, and TNF-a, and C-reactive protein, as well as dysregulation of the HPA-axis. This creates a feedback loop in which inflammatory mechanisms trigger the stress response to increase systemic cortisol, feeding back into the immune system to exacerbate levels of inflammation. Gut microbiota dysbiosis and dysregulation of the immune system and HPA-axis attenuate levels of serotonin (5-HT) and brain derived neurotrophic factor (BDNF), which then work in tandem to induce changes in psychological and cognitive function, including increased symptoms of anxiety and depression (i.e. “sickness behaviours”), pain, fatigue, and social and cognitive deficits. Finally, gut dysbiosis, immune, and HPA-axis dysregulation may also augment patients’ vulnerability to increased adipose tissue, and subsequent overweight and obesity, further compromising their health