The microbiota-gut-brain axis: An emerging therapeutic target in chemotherapy-induced cognitive impairment

Chemotherapy-induced cognitive impairment (CICI) is an ill-defined complication of chemotherapy treatment that places a significant psychosocial burden on survivors of cancer and has a considerable impact on the activities of daily living. CICI pathophysiology has not been clearly defined, with candidate mechanisms relating to both the direct cytotoxicity of chemotherapy drugs on the central nervous system (CNS) and more global, indirect mechanisms such as neuroinflammation and blood brain barrier (BBB) damage. A growing body of research demonstrates that changes to the composition of the gastrointestinal microbiota is an initiating factor in numerous neurocognitive conditions, profoundly influencing both CNS immunity and BBB integrity. Importantly, chemotherapy causes significant disruption to the gastrointestinal microbiota. While microbial disruption is a well-established factor in the development of chemotherapy-induced gastrointestinal toxicities (largely diarrhoea), its role in CICI remains unknown, limiting microbial-based therapeutics or risk prediction strategies. Therefore, this review aims to synthesise and critically evaluate the evidence addressing the microbiota-gut-brain axis as a critical factor influencing the development of CICI.