Low-Fat Cheddar Cheese Influences Gut Microbiota Composition and Diversity in Human Microbiota–Associated Mice

Cheese is a complex fermented dairy food containing bioactive nutrients and microorganisms that can influence host physiology. However, most existing evidence of its health effects derives from observational studies or investigations of isolated components rather than the whole food matrix. The present study examined the impact of low-fat Cheddar cheese as a whole food on the gut microbiota using a human microbiota-associated (HMA) mouse model. Germ-free C57BL/6 mice were colonized with human fecal microbiota and randomly assigned to either a control diet or a diet supplemented with low-fat Cheddar cheese (7.5% <i>w</i>/<i>w</i>) for six weeks. Fecal samples were collected longitudinally and analyzed by 16S rRNA gene (V3-V4 region) amplicon sequencing. Human microbiota transplantation successfully established a stable, human-like gut microbial community in the mice. Cheese supplementation significantly increased alpha diversity (Shannon and Chao1 indices) and altered microbial composition, characterized by a higher relative abundance of <i>Firmicutes</i> and a reduction in <i>Bacteroidetes</i> (<i>p</i> < 0.001). At the genus level, <i>Lactococcus</i> and <i>Streptococcus</i> were enriched in cheese-fed mice, reflecting potential viable transfer of cheese-derived lactic acid bacteria. These findings provide experimental evidence that low-fat Cheddar cheese can beneficially influence the human-derived gut microbiota in an animal model and highlight the need for further clinical research to validate these effects in humans.