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Epigenetic Reprogramming Mediated by Maternal Diet Rich in Omega-3 Fatty Acids Protects From Breast Cancer Development in F1 Offspring.

ABSTRACT: Diets rich in omega-3 fatty acids (FA) have been associated with lowered risks of developing certain types of cancers. We earlier reported that in transgenic mice prone to develop breast cancer (BCa), a diet supplemented with canola oil, rich in omega-3-rich FA (as opposed to an omega-6-rich diet containing corn oil), reduced the risk of developing BCa, and also significantly reduced the incidence of BCa in F1 offspring. To investigate the underlying mechanisms of the cancer protective effect of canola oil in the F1 generation, we designed and performed the present study with the same diets using BALB/c mice to remove any possible effect of the transgene. First, we observed epigenetic changes at the genome-wide scale in F1 offspring of mothers fed diets containing omega-3 FAs, including a significant increase in acetylation of H3K18 histone mark and a decrease in H3K4me2 mark on nucleosomes around transcription start sites. These epigenetic modifications contribute to differential gene expressions associated with various pathways and molecular mechanisms involved in preventing cancer development, including p53 pathway, G2M checkpoint, DNA repair, inflammatory response, and apoptosis. When offspring mice were exposed to 7,12-Dimethylbenz(a)anthracene (DMBA), the group of mice exposed to a canola oil (with omega 3 FAs)-rich maternal diet showed delayed mortality, increased survival, reduced lateral tumor growth, and smaller tumor size. Remarkably, various genes, including BRCA genes, appear to be epigenetically re-programmed to poise genes to be ready for a rapid transcriptional activation due to the canola oil-rich maternal diet. This ability to respond rapidly due to epigenetic potentiation appeared to contribute to and promote protection against breast cancer after carcinogen exposure.

SUBMITTER: Abbas A

PROVIDER: S-EPMC8222782 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The neonatal intestinal tract is immature and can be easily infected by pathogens causing inflammation. Maternal diet manipulation is a promising nutritional strategy to enhance the gut health of offspring. A fermented diet is a gut microbiota targeting diet containing live probiotics and their metabolites, which benefit the gut and overall health host. However, it remains unclear how a maternal fermented diet (MFD) affects neonatal intestinal inflammation. Here, in vivo and in vitro models together with multi-omics analysis were applied to investigate the impacts and the underlying mechanism through which an MFD prevents from gut inflammation in neonates. An MFD remarkably improved the performance of both sows and piglets and significantly altered the gut microbiome and milk metabolome of sows. In addition, the MFD significantly accelerated the maturation of the gut microbiota of neonates and increased the abundance of gut Lactobacillus and the microbial functions of amino acid-related enzymes and glucose metabolism on the weaning day. Notably, the MFD reduced susceptibility to colonic inflammation in offspring. The fecal microbiota of sows was then transplanted into mouse dams and it was found that the mouse dams and pups in the MFD group alleviated the LPS-induced decrease in gut Lactobacillus abundance and barrier injury. Milk L-glutamine (GLN) and gut Lactobacillus reuteri (LR) were found as two of the main MFD-induced sow effectors that contributed to the gut health of piglets. The properties of LR and GLN in modulating gut microbiota and alleviating colonic inflammation by inhibiting the phosphorylation of p38 and JNK and activation of Caspase 3 were further verified. These findings provide the first data revealing that an MFD drives neonate gut microbiota development and ameliorates the colonic inflammation by regulating the gut microbiota. This fundamental evidence might provide references for modulating maternal nutrition to enhance early-life gut health and prevent gut inflammation.

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Epigenetic Reprogramming Mediated by Maternal Diet Rich in Omega-3 Fatty Acids Protects From Breast Cancer Development in F1 Offspring.

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