Abstract
Fish is highly nutritious and an important source of dietary n-3 polyunsaturated fatty acids (PUFA) which have potent anti-inflammatory effects and immune regulatory functions. In recent years, research has shown that n-3 PUFAs also possess the capacity to exert prebiotic effects on the gut microbiota, which may be beneficial towards immune regulation. Nevertheless, all fish contain methylmercury (MeHg), a known neurotoxicant which has also been implicated as a potential environmental factor involved in disease including autoimmunity. Globally, one in five people rely on fish consumption as their main source of protein therefore understanding the benefits and risk of fish consumption is of public health concern. This thesis examined the relationship between fish consumption and the n-3 polyunsaturated fatty acids on immune function, taking into consideration mercury and the gut microbiota.During pregnancy, the long chain n-3 PUFAs, specifically eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6), are required for optimal foetal development. To date, the role of maternal fish consumption with the asthma development is not fully understood as previous work has yielding inconsistent findings and no research conducted in high fish-eating populations. Utilising data from the Seychelles Child Development Study Nutrition Cohort 2 (n=923), where mothers consumed on average 8 fish meals per week, no significant association was observed between maternal fish consumption or maternal n-3 PUFA status and prevalence of childhood asthma (n = 97; 10.5%). Higher concentrations of DHA in cord blood were observed to be predictive of childhood asthma (OR 2.21; CI 1.15-4.27). It is known that DHA is preferentially transferred from the placenta to foetus during pregnancy, and this may be upregulated to mitigate asthma-related inflammation in these children. MeHg exposure has been shown to increase inflammatory cytokine production in cells derived from systemic lupus erythematosus (SLE) patients. No research has considered the exposure of inorganic mercury (iHg), present in dental amalgams and arising from the demethylation of MeHg by the gut microbiota and lymphoid tissues. Therefore, an ex-vivo study aimed to explore the anti-inflammatory effects of n-3 PUFA on iHg induced Th17-associated inflammation in systemic lupus erythematosus (SLE) patients (n=15) compared to healthy matched controls (n=15). While no significant changes were noted in IL-17A, iHg exposure increased IL-27 in peripheral blood mononuclear cells from both groups which was mitigated by pre-incubation with EPA in SLE patients compared to controls. IL-27’s role in SLE pathology is unclear owing to its pleiotropic nature; nevertheless, these results reveal distinct differences in IL-27 production exist between SLE and controls when exposed to EPA suggesting the immune response in SLE cells is hampered. These results also provide some indication that n-3 PUFAs in fish may mitigate the inflammatory risk linked to mercury.
A comprehensive review summarised recent advances on the prebiotic potential of n-3 PUFAs on the gut microbiota, highlighting that most of the research has been conducted in animals along with the need for more human research which links changes in gut microbiota to health outcomes. Few studies have investigated fish consumption and gut microbiota therefore, the effect of consuming fish (1-2 portions of either tuna or sardines) for 8 weeks on gut microbiota composition and inflammatory cytokine status was investigated in women of childbearing age (n=41). This study reported fish consumption had no significant impact on gut microbiota alpha diversity. Those consuming sardines which are high in n-3 PUFA experienced a 17% reduction in the Bacteroidetes phylum compared to those receiving the control diet. Changes in gut microbiota were associated with Th17 cytokines, suggesting links with autoimmune responses nevertheless the clinical implications are uncertain.
Overall, this thesis offers evidence supporting the beneficial role of fish consumption in immune-mediated disease and highlights the protective nature of n-3 PUFAs against mercury-induced inflammation. The gut microbiota’s role in immune function is constantly evolving and while it is clear that fish consumption influences the gut microbiota, its impact on immune function and health requires further investigation.
Date of Award | Feb 2024 |
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Original language | English |
Sponsors | Department for the Economy & National Institutes of Health |
Supervisor | Philip Allsopp (Supervisor) & Emeir Mc Sorley (Supervisor) |
Keywords
- Autoimmunity
- Docosahexaenoic acid
- Eicosapentaenoic acid
- Fish consumption
- Gut microbiota
- Inflammation
- Polyunsaturated fatty acids