Microbial polyunsaturated fatty acids (PUFAs) for human health: A comprehensive review of evidence from in vivo preclinical models

Polyunsaturated fatty acids (PUFAs), including C18 PUFAs (linoleic [LA] and alpha-linolenic [ALA] acids) and their longer-chain derivatives (LC-PUFAs such as arachidonic [AA], eicosapentaenoic [EPA], and docosahexaenoic [DHA] acids), are essential nutrients for human health. As a dietary source, microbially derived PUFAs offer a vegan, scalable, and sustainable alternative to traditional fish, meat and other sources due to their higher purity, easier industrial production, and lower environmental impact. This review comprehensively analyzes preclinical safety and efficacy research findings on microbially derived PUFAs using various animal models. Studies have evaluated the toxicity and effects of single PUFA oils, their combinations, and even whole PUFA-rich microbial biomass on the health of various organs. While many studies suggest potential benefits, there are conflicting findings regarding gut health, brain function, reproductive organs, and inflammation regulation. These findings highlight the need for further research to understand the effects of microbial PUFAs on human health. Additionally, we propose Caenorhabditis elegans as a potential in vivo preclinical model for future PUFA studies. To facilitate the exploitation and commercial production of microbial PUFAs, we also highlight the importance of addressing the demand-supply landscape and current regulatory environment. In summary, this review provides a comprehensive overview of the research landscape, identifies knowledge gaps, and proposes areas for further investigation involving microbial PUFAs. We emphasize the need for a roadmap to foster self-sufficiency in PUFA production for import-dependent nations like India through indigenous research and commercial capabilities. Preclinical studies are essential for assessing the safety of microbially derived PUFAs in animal models before commercialization.The microbially derived PUFAs market is driving the US$6019 million nutraceutical industry with a CAGR of 5.4%.Caenorhabditis elegans and zebrafish models can be effectively used as alternatives to mammalian models in preclinical studies involving PUFAs.