High-fat diet during early life reshapes the gut microbiome and is associated with the disrupted mammary microenvironment in later life in mice

Ying Tang; Ting-Chun Lin; Hong Yang; Yanjiao Zhou; Lindiwe Sibeko; Zhenhua Liu

doi:10.1016/j.nutres.2024.04.006

High-fat diet during early life reshapes the gut microbiome and is associated with the disrupted mammary microenvironment in later life in mice

Nutr Res. 2024 Apr 30:127:1-12. doi: 10.1016/j.nutres.2024.04.006. Online ahead of print.

Authors

Ying Tang¹, Ting-Chun Lin², Hong Yang³, Yanjiao Zhou⁴, Lindiwe Sibeko², Zhenhua Liu⁵

Affiliations

¹ School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA; Center for Regenerative Medicine and Skeletal Development, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT, USA.
² School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA.
³ Department of Oncology and Pathology, Hunan Provincial People's Hospital, Changsha, China.
⁴ Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA; Hunan, China.
⁵ School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA; UMass Cancer Center, University of Massachusetts Chan Medical Chan Medical School, Worcester, MA, USA. Electronic address: zliu@nutrition.umass.edu.

PMID: 38763113
DOI: 10.1016/j.nutres.2024.04.006

Abstract

The influence of gut microbiota on gut health is well-documented, but it remains obscure for extraintestinal diseases such as breast cancer. Moreover, it is entirely unknown how gut dysbiosis during early life contributes to breast tumorigenesis later in life. In this study, we hypothesized that a high-fat diet during early life leads to alterations in the gut microbiome and is associated with disruptions in the mammary microenvironment. Female C57BL/6 mice were fed a low-fat diet (10% kcal fat) or a high-fat diet (HF, 60% kcal fat) for 8 weeks from the age of 4 to 12 weeks, which is equivalent to human childhood and adolescence. Twelve mice were sacrificed immediately after the 8-week feeding, the remainder were euthanized after switching to a normal lifecycle-supporting diet for an additional 12 weeks; the gut microbiome was then sequenced. The 8-week HF diet feeding altered the beta-diversity (Bray & Jaccard P < .01), and the difference remained significant after switching the diet (Bray & Jaccard P < .05). Immediately after HF feeding, a greater number of microbial taxa (>50) were altered, and about half of the taxa (25) remained significantly changed after switching the diet. The abundance of Alistipes, Bilophila, and Rikenellaceae stood out as significantly associated with multiple metabolic and inflammatory biomarkers in mammary tissue, including aromatase, Ccl2, and Cox2. In conclusion, an 8-week early-life HF feeding reshaped the gut microbiome, which connected with disrupted mammary microenvironments.

Keywords: Early life; Gut microbiome; High-fat diet; Mammary microenvironment; Obesity.