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.

Keywords: chemotherapy; cognition; gut microbiome; inflammation; mood.

Figure 1. Gut-Immune-Brain Axis After Chemotherapy

Chemotherapy alters the composition of the intestinal microbial structure, reducing alpha diversity and species associated with anti-inflammatory activities, while increasing intestinal inflammation and permeability. Simultaneously, chemotherapy results in increased peripheral inflammation, neuroinflammation, and impaired CNS function. Alteration of the intestinal microbial community may result in and exacerbate neuroinflammation and behavioral comorbidities after chemotherapy. While the brain and the gut can communicate bi-directionally through multiple pathways, including through neuroendocrine pathways and the autonomic nervous system, we hypothesize that in the context of chemotherapy, the peripheral immune system is the most relevant mediator between the gut and the brain.