The disparate effects of omega-3 PUFAs on intestinal microbial homeostasis in experimental rodents under physiological condition

The health benefits of omega-3 polyunsaturated fatty acids (omega-3 PUFAs), primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are linked to their regulatory effects on the composition of the gut microbiota. However, there is a lack of direct evidence on whether omega-3 PUFAs regulate the gut microbial homeostasis under physiological conditions. This study investigated the impact of equivalent doses of EPA, DHA, and fish oil (FO) with a DHA to EPA ratio of approximately 1:1 on the bacterial and fungal composition of normal young mice. This study also analyzed changes in key components of the gut microenvironment, including the colonic mucus barrier and short-chain fatty acids, to address the prebiotic potential of omega-3 PUFAs. The results showed that all three omega-3 PUFAs interventions induced significant fluctuations in the gut bacteria and fungi, leading to an increase in the abundance of some probiotics. Notably, DHA, EPA, and FO interventions significantly increased the abundance of the probiotic Lactobacillus, Bifidobacterium, and Akkermansia, respectively. Both DHA and fish oil interventions also significantly reduced the abundance of potentially pathogenic fungi, such as Aspergillus and Penicillium. Association analysis of the top 19 differential fungal and bacterial genera in abundance revealed a much more bacteria-bacteria and bacteria-fungi connections, but fewer fungi-fungi connections. This highlights the importance of bacteria in the gut microecological network. Furthermore, the levels of butyric acid and valeric acid in the colonic contents of DHA intervention group were significantly increased, and the colonic mucus layer thickness was increased in three treatment groups. In summary, DHA, EPA and FO interventions showed targeted enhancement of different probiotics and enhanced colon defense barrier (mucus barrier), showing potential prebiotic effects.