Pre-treatment gut microbiome and salivary metabolome signatures associate with chemotherapy-induced cognitive decline in women with breast cancer: A prospective pilot study

Chemotherapy remains the primary treatment for advanced cancers and while efficacious, it causes widespread cytotoxicity and a battery of side effects. Of these, chemotherapy-induced cognitive impairment (CICI) has been consistently identified as an unmet need. Experienced by up to 75 % of people in the acute treatment setting and 40 % following treatment cessation, CICI impacts almost all facets of a person's cognitive capacity. This impairs adherence to long-term therapies, academic and vocational performance and is thus a major cause of un(der)-employment as well as financial and psychosocial distress.

CICI presentation is highly heterogenous. Despite intensive research efforts, risk factors remain poorly defined. Proposed factors such as lower cognitive reserve, baseline psychological distress (e.g. depression, fatigue, sleep disturbances) and single nucleotide polymorphisms (SNPs) of the apolipoprotein ɛ4 (APOE4) gene, fail to adequately account for the prevalence of CICI. Thus, CICI is unpredictable, with management largely reactive in nature – a significant downfall when management options (e.g. cognitive rehabilitation, neuropsychological training) have greater depth of response when delivered proactively.

Advances in molecular profiling have made multi-omics more accessible and cost-effective for clinical research. By integrating data from multiple biological sources, multi-omics provides a complete picture of biological systems, uncovering complex interactions shaping human health and disease. Notably, emerging evidence links omic measures (e.g. microbiome, metabolome) with CICI through gut-brain communication and their influence over immune and neuroinflammatory processes. However, the utility of multi-omics in predicting CICI remains unknown. Here, we conducted a prospective, hypothesis-generating pilot study exploring whether pre-treatment omic profiles associate with, and may help predict, the development of CICI.