Modulation of gut-immune-brain axis by non-digestible oligosaccharides and omega-3 fatty acids in health and allergic disease: Synergy or rivalry?

Abstract

In early life, the intestinal microbiota undergoes a tremendous maturation and if disturbed this has been associated with negative effects on immune and brain development. Healthy microbiome maturation is supported by components like prebiotics like short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS) and omega-3 polyunsaturated fatty acids (n-3 PUFAs), which are present in infant formula milk to mimic human breast milk. The aim of this thesis was to evaluate the additional effects of a dietary combination of scGOS:lcFOS and n-3 PUFAs to improve health as well as to prevent cow’s milk allergy (CMA) development. In healthy mice, the combination of scGOS:lcFOS and n-3 PUFAs altered the intestinal bacterial composition in a distinct manner compared to the effects of the compounds individually. Additionally, scGOS:lcFOS improved social behaviour and reduced anxiety-like and repetitive behaviour, however, the n-3 PUFA and the combined interventions had limited to no effect on the evaluated behaviours and immune system parameters. CMA development was partly prevented by scGOS:lcFOS or n-3 PUFAs in mice but no additional effect was observed by the combination. Splenic cytokine responses were reduced and caecal butyrate level was induced by scGOS:lcFOS which tended to be impaired when combined with n-3 PUFAs, indicating the individual effects seemed to be negatively impacted when combined. It could also suggest a possible interaction between the dietary components, which was evaluated by studying modulation of intestinal Pparɣ expression, physical and chemical interaction and modulation of intestinal bacterial fermentation. It is no option to leave scGOS:lcFOS or n-3 PUFAs out of formula milk but it is essential to evaluate individual components and combinations as they might act differently than expected.