Long-term intermittent caloric restriction remodels gut microbiota in genetic predisposition to breast cancer

Abstract

ObjectiveGut microbiota dysbiosis is among the risk factors for breast cancer development, together with genetic background and dietary habits. Caloric restriction remodels gut microbiota and slows tumor growth. Here, we investigated whether gut microbiota mediates the preventive effects of long-term chronic or intermittent caloric restriction in breast cancer predisposition. Research Methods & Procedures10-week-old transgenic breast cancer-prone mice were randomly assigned to dietary groups (Ad libitum group, chronic caloric restriction group, intermittent caloric restriction group) and fed up to week 81. Stool samples were collected at weeks 10 (baseline), 17 (young), 49 (adult), and 81 (old). 16S rRNA gene sequencing was performed to identify the gut microbiota profile of the different groups. On the other hand, to investigate the gut microbiota profile in breast cancer within genetically predisposed individuals regardless of the diet, mammary tumor-bearing mice and mammary tumor-free but genetically prone mice were selected from the AL group (n=6). ResultsIntermittent caloric restriction increased the microbial diversity of adult mice and modified age-related compositional changes. A total of 13 genera were differentially abundant over time. A pathogenic genus Mycoplasma was enriched in the re-feeding period of the old intermittent caloric restriction group compared to the baseline. Furthermore, mammary tumor-free mice showed shared gut microbiota characteristics with mammary tumor-bearing mice, suggesting an early link between genetic predisposition, gut microbiota, and breast cancer development. ConclusionOur study revealed the role of gut microbes in the preventive effects of CR against breast cancer development, implying the significance of diet and microbiome interplay.