Health promoting fatty acids and the gut microbiota

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Coakley, Mairead
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University College Cork
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Consensus on the role of fatty acids in human health is difficult to achieve, with some fatty acids being mooted as detrimental to health and others having proposed benefits. The human intestinal microbiota impacts health and well-being, with disruption to the microbiota composition being chronicled as a potential cause of short-term and chronic health issues. The human gut microbiota assembles from birth and co-evolves with its host throughout life. One of the mechanisms by which the gut microbiota contributes to health is through the production of bioactive compounds such as peptides and fatty acids, including conjugated linoleic acid (CLA). This thesis aimed to confirm the presence of CLA-producing bacteria among the human gut microbiota, and to exploit bacteria with the ability to produce bioactive fatty acids, including CLA, for human health promotion. In addition, the thesis investigated means of increasing dietary CLA and determined links between human health, health-promoting fatty acids, antibiotic therapy and the human gut microbiota. The ability of selected bacteria of human origin to produce CLA from the essential fatty acid linoleic acid was investigated in Chapter 2. Nine strains of the Bifidobacterium sp. produced cis-9, trans-11 CLA (c9, t11 CLA). The trans-9, trans-11 CLA (t9, t11 CLA) isomer was also produced by some strains, but at much lower concentrations. There was considerable interspecies variation in relation to CLA production by bifidobacteria, with B. breve and B. dentium being the more efficient CLA producers. The ability of Bifidobacterium species to isomerise a range of C18:2 polyunsaturated fatty acids was then examined and the anti-proliferative activities of the two main microbially-produced CLA isomers (c9, t11 CLA and t9, t11 CLA) were screened against colon cancer cell lines (Chapter 3.1); whereupon it was observed that t9, t11 CLA had a more potent anti-proliferative effect than c9, t11 CLA. Chapter 3.2 investigated the production of bioactive fatty acids from alpha (α)-linolenic acid by Bifidobacterium species and determined the inhibitory effect of this microbially produced c9, t11, c15 conjugated α-linolenic acid (CNLA) on colon cancer cells. Having demonstrated the health-promoting properties of conjugated fatty acids (CFA), CLA-enriched cheese was manufactured from milk produced as a result of dietary supplementation of cows on pasture with plant oils (Chapter 4). Supplementation included (a) sunflower oil (rich in linoleic acid; Chapter 4.1) and (b) sunflower and linseed oils (rich in linoleic and linolenic acid, respectively; Chapter 4.2). The CLA enrichment translated from the milk to the cheese following manufacture and was stable during cheese ripening. The CLA-enriched cheese was subsequently evaluated in a human feeding study to assess its contribution to human fatty acid and CLA status. The link between health, diet and the gut microbiota was extensively explored in the ELDERMET cohort (, with blood samples available from this study enabling screening of the serum long chain fatty acids of these elderly subjects (Chapter 5). Associations were determined between these serum fatty acids and residence, health status, diet and gut microbiota composition of the subjects. These elderly Irish people have a diverse range of serum fatty acids, with community-dwellers having an overall healthier profile; rich in essential fatty acids and omega (n)-3 fatty acids. Increased circulating C22:5 docosapentaenoic acid (DPA) correlated with lower indicators of depression and increased serum linoleic acid, C20:5 eicosapentaenoic acid (EPA), C22:5 DPA, C22:6 docosahexaenoic acid (DHA) correlated with improved cognitive function. In addition, increased serum concentrations of the n-3 fatty acids C20:5 EPA and C22:6 DHA correlated with increased gut microbiota diversity in these elderly subjects. A number of factors influence the human gut microbiota and in Chapter 6 the impact of antibiotic therapy on the intestinal microbiota of the ELDERMET subjects was determined. Culture-dependent methods indicated that faecal Bifidobacterium spp. numbers were significantly reduced following antibiotic treatment, while levels of Lactobacillus spp. and Enterobacteriaceae were unaffected. Culture-independent microbiota profiling revealed a significant change across nine bacterial genera following antibiotic therapy, in addition to a decrease in the number of genera identified in the antibiotic-treated subjects, when compared with untreated subjects. The impact of antibiotic class was also assessed, with the largest decrease in Bifidobacterium spp. being linked to the administration of the nucleic acid synthesis inhibitors. This work confirmed that the production of bioactive fatty acids (CLA and CNLA) by selected gut bacteria of human origin had the potential to positively impact human health. CLA occurs naturally in ruminant milk fat, and dietary supplementation of cows on pasture with linoleic and linolenic acids generated CLA-enriched milk from which CLA-enriched cheese was produced. The link between human health, health-promoting fatty acids, antibiotic therapy and the human gut microbiota was determined in a large cohort of elderly Irish subjects.
CLA , Conjugated linoleic acid , Bifidobacteria , Fatty acids , Human gut microbiota
Coakley, M. 2018. Health promoting fatty acids and the gut microbiota. PhD Thesis, University College Cork.