肠道微生物群对肠道健康的影响是有据可查的,但对于乳癌等肠外疾病仍不清楚。此外,生命早期的肠道菌群失调如何导致生命后期的乳腺肿瘤发生是完全未知的。在这项研究中,我们假设生命早期的高脂肪饮食会导致肠道微生物组的改变,并与乳腺微环境的破坏有关.雌性C57BL/6小鼠饲喂低脂肪饮食(10%千卡脂肪)或高脂肪饮食(HF,60%千卡脂肪)从4到12周龄的8周,相当于人类的童年和青春期。12只小鼠在8周喂养后立即处死,在转换为正常的生命周期支持饮食再持续12周后,其余的人实施安乐死;然后对肠道微生物组进行测序.8周的HF饮食喂养改变了β-多样性(Bray和JaccardP<0.01),改变饮食后,差异仍然显着(Bray&JaccardP<0.05)。在HF进料后立即,更多的微生物类群(>50)被改变,改变饮食后,大约一半的分类单元(25)仍然发生了显着变化。丰富的Alistipes,双亲,Rikenellaceae与乳腺组织中的多种代谢和炎症生物标志物显着相关,包括芳香化酶,Ccl2和Cox2。总之,一个为期8周的生命早期HF喂养重塑了肠道微生物组,这与乳房微环境的破坏有关。
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.