Abstract 121: Gut microbiome association with dietary habits and abemaciclib-induced diarrhea:A multicenter, prospective study

Abstract Background: Abemaciclib, a leading treatment used for HR-positive, HER2-negative metastatic and primary breast cancer patients, often causes diarrhea. Understanding the reasons machinery behind this adverse event leads to reduce the toxicity and improve the quality of life. This study explores a hypothesis that specific gut microbiota profiles are engaged in gastrointestinal toxicities caused by abemaciclib and may be influenced by patients' dietary habits. We assessed it using the Brief Diet History Questionnaire (BDHQ). Materials and Methods: Our research involved collecting blood and stool samples, as well as dietary data through the BDHQ from 39 patients diagnosed with HR-positive, HER2-negative metastatic breast cancer. These were obtained prior to the start of abemaciclib treatment, at the first imaging evaluation, and at either disease progression or treatment discontinuation due to adverse effects. Incidence and severity of diarrhea were evaluated by the Bristol stool scale at baseline, from day 1 to day 14, and at day 90 of treatment. Stool samples were collected at baseline and at day 90 after the start of abemaciclib treatment. We conducted 16S metagenomic sequencing for gut microbiome analysis and used mass cytometry along with RNA-sequencing to profile immune cells. Results: Our findings indicate a significant association between the gut microbiota composition and abemaciclib-induced diarrhea, which also appears to be modulated by dietary patterns. An increase in Dorea was observed with higher Bristol Stool Scale scores, while Bifidobacterium and Sellimonas abundances were inversely related to changes in stool characteristics. The presence of Dorea was also positively associated with the consumption of specific food items such as tea, root vegetables, and dietary minerals. In contrast, Collinsella abundance decreased as the frequency of diarrhea increased and it was associated with the consumption of fried foods and certain fats. Conclusion: The prevalence of diarrhea as a side effect of abemaciclib treatment highlights the need for better management strategies. Our study indicates that gut microbiota, altered by dietary habits, is linked to this adverse effect. The data suggest a possibility of using specific gut bacteria as probiotics to alleviate this condition, pointing towards personalized dietary interventions as a potential avenue for improving treatment tolerance. Citation Format: Yuri Fujimoto, Kosuke Kawaguchi, Yurina Maeshima, Hiroshi Ishiguro, Kazuhiko Yamagami, Sachiko Takahara, Hirofumi Suwa, Masae Torii, Shigenori Nagai, Yasuaki Sagara, Wakako Tsuji, Hiroyasu Yamashiro, Takeshi Kotake, Shinji Fukuda, Kuniaki Saito, Yasuko Yamamoto, Masako Kataoka, Yuki Himoto, Atsushi Yonezawa, Yukiko Fukui, Yuki Nakamura, Wei Li, Sunao Tanaka, Masahiro Takada, Satoshi Morita, Masakazu Toi. Gut microbiome association with dietary habits and abemaciclib-induced diarrhea: A multicenter, prospective study abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 121.