Omega-3 fatty acids, gut microbiota and associated inflammatory outcomes

Abstract

The overall aim of this thesis was to investigate the potential of omega-3 polyunsaturated fatty acids (n-3 PUFA), particularly from algal sources, as regulators of gut microbiota development, behaviour and associated inflammatory and metabolic outcomes. In chapter 2, omega-3 supplemented (O3+), omega-3 deficient (O3-) and control diets were compared for their effect on behaviour and gut microbiota development in both adolescence and adulthood. O3- impaired communication, social and depressionrelated behaviours, whereas O3+ enhanced cognition. These behavioural changes were associated with alterations to gut microbiota composition and inflammatory outcomes such that O3- mice displayed an elevated Firmicutes:Bacteroidetes ratio and blunted systemic LPS responsiveness. Contrastingly, O3+ mice displayed greater fecal Bifidobacterium and Lactobacillus abundance and dampened hypothalamic-pituitaryadrenal axis activity. These results suggest that the beneficial effects of n-3 PUFA on neurobehavioural development are closely associated with comprehensive alterations in gut microbiota composition, HPA-axis activity and inflammation. Chapter 3 further assessed the role of n-3 PUFA on the cecal microbiota and metabolome. n-3 PUFA status induced subtle changes to the cecal microbiota in mothers and their offspring and, in addition, O3+ induced increased production of energy metabolites. O3- reduced production of short chain fatty acids. These results indicate that n-3 PUFA modulate cecal microbiota composition and function, which may have implications for chronic disease risk. In chapter 4, the transgenic fat-1 mouse model was utilised to examine the effects of maternal n-3 PUFA on offspring obesity risk. Offspring of mothers with a lower n-6/n-3 tissue ratio gained significantly less weight on a high fat diet. This reduced weight gain was associated with reduced gut permeability and changes to the gut microbiota and inflammatory outcomes. These results indicate that maternal n-3 PUFA status can significantly influence offspring adiposity through changes associated with gut microbiota. Algae are potent sources of n-3 PUFA and pose potential as alternative sustainable sources of such fatty acids than fish. However, little research has examined the effect of algae-derived n-3 PUFA on health. The aim of Chapter 5 was to screen the anti-inflammatory bioactivity of n-3 PUFA-rich algae lipid extracts. Exposure of the algae lipid extracts to lipopolysaccharide-stimulated THP-1 macrophages significantly reduced production of the pro-inflammatory cytokines IL-6 and IL-8 and the expression of a number of pro-inflammatory genes associated with toll-like receptor and chemokine activity. These data reveal that such n-3 PUFA-rich algae lipid extracts pose potential as anti-inflammatory functional ingredients. The aim of chapter 6 was to investigate the suitability of yoghurt as a food matrix in which to supplement an n-3 PUFA-rich lipid extract of Pavlova lutheri. Addition of the extract had little negative effect on the techno-functional properties of yoghurt. Furthermore, addition of the extract dose-dependently increased concentrations of n−3 PUFA. However, sensory analysis revealed that supplemented yoghurts were not well accepted. These results suggest that addition of this extract to yoghurt is a suitable method to increase n-3 PUFA concentration. Finally, Chapter 7 discusses the major findings and general conclusions arising from the work presented in this thesis.