Cognitive Function, Diet, and Gender are Associated with Unique Microbiome Signatures in Cancer Survivors
Authors: Miller Brandi C. , Haggler Jayden A. , Chaudhari Diptaraj S. , Yadav Hariom , Jain Shalini , Consortium MiaGB 
Published: May 2024

Despite the development of new and highly effective cancer therapies, emerging evidence suggests that these treatments are associated with long-term side effects, which may contribute to cognitive impairment (CI) or dementia in cancer survivors. Many of these side effects are linked to gut health and a perturbed gut microbiome. However, the role of the gut microbiota in cancer treatment-related side effects, especially in older adults, remains largely unknown. Furthermore, it remains elusive how other factors, such as diet and gender, may impact gut microbiota. We hypothesize that cancer survivors have a distinct microbiome signature compared to non-cancer controls and that CI, diet, and gender are associated with unique microbiomes in survivors. Here, we analyzed the gut microbiome (using whole genome sequencing) and cognitive function (using the Montreal Cognitive Assessment [MoCA]) of 150 older adults (≥ 60 years) from the MiaGB (Microbiome in aging Gut and Brain) consortium. We first assessed microbiome signatures of cancer survivors in our cohort compared to non-cancer controls. We show that the gut of cancer survivors is significantly enriched with Escherichia, Eggerthella lenta, and Lachnospiraceae bacterium OF09 33XD. Next, participants were further stratified based on MoCA score, diet (yogurt/probiotic consumption), and gender and we assessed their microbiota. E. lenta and L. bacterium OF09 33XD remained enriched in cancer survivors when separating based on all three of these factors. We also found that cognitive function, yogurt/probiotic use, and gender were linked with unique microbiome signatures in cancer survivors. Interestingly, the abundances of two well-studied probiotics, Streptococcus thermophilus and Lactobacillus rhamnosus, were significantly low in cancer survivors with CI. Additionally, increased S. thermophilus abundance was positively correlated with MoCA score (Spearman p = 0.054, r = 0.159). Our results indicate that older adult cancer survivors harbor a unique gut microbiome, which could also be impacted by cognitive function, yogurt/probiotic consumption, and gender. Elucidating how these factors modulate the microbiome, independently and together, will aid in the development of novel and precision microbiome-based therapies to combat cancer treatment-related side effects in survivors. We would like to thank the Ed and Ethel Moore Alzheimer’s Disease Research Program of the Florida Department of Health (22A17), the National Institutes of Health, National Institute of Aging (R56AG069676, R56AG064075, RF1AG071762, R21AG072379, U01AG076928), and the Department of Defense (W81XWH-18-PRARP AZ180098) for funding support. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.