Several fatty acid (FA) families with established, debated, or emerging health relevance-including long-chain n-3 (EPA, DHA), n-6 (GLA, ARA), branched-chain FA (BCFA), and odd-chain FA (OCFA)-remain scarce in conventional diets, largely absent from plant-based diets, or face supply vulnerabilities driven by climate change and declining marine resources. Bridging the gap between nutritional demand and sustainable supply requires both a clearer understanding of these FA physiological roles and the development of alternative production systems. This narrative review integrates three interconnected dimensions of this challenge. First, current evidence on the physiological functions and health outcomes of these key FA families is critically evaluated, noting that while robust consensus supports the benefits of n-3 and, to a lesser extent, ARA, evidence for most other FA discussed herein remains either limited or controversial. Second, traditional dietary sources of these FA are described alongside advances in non-photosynthetic microbial platforms (yeasts, filamentous fungi, bacteria, and thraustochytrids) as scalable, climate-resilient production alternatives, evaluating both naturally occurring and genetically engineered strains. Third, the key challenges to commercial translation are assessed, including economic feasibility, regulatory frameworks, and consumer acceptance. This review argues that microbial fermentation represents a resource-efficient pathway to secure global access to health-relevant FA under mounting environmental constraints. However, translating this potential into commercial reality demands coordinated progress in strain engineering, bioprocess intensification, regulatory harmonization across jurisdictions, and clinical validation of microbially derived FA.
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