High-resolution investigation of personalised post-prandial inflammation biomarkers

The impact of our diet on our immune system is poorly understood. As the importance of controlling inflammation becomes evermore apparent in the context of both acute and chronic diseases, there is increasing interest in the role of nutrition on these processes. As DayTwo have demonstrated using plasma glucose tracking, continuous monitoring and multi-omic technologies provide a fresh opportunity to tackle the problem of host response to dietary ingredients. Combined with a quantitative understanding of the contribution of the gut microbiome to host inflammatory processes, we can gain clinically actionable insights that can be directly applied to clinical trials targeting conditions ranging from Inflammatory Bowel Disease to cancer immunotherapy.

Using an innovative study design and scalable implementation, we propose to measure the postprandial inflammatory response of different individuals to different extreme diets, and contrast these with the response to a personalised dietary fibre supplement chosen to minimise inflammation through maximizing microbial butyrate production. To do this, we will employ an experimental framework that allows us to measure a patient’s Microbial Metabolic Phenotype’ (MMP), which we define as the microbiome’s capability of roducing the Short Chain Fatty Acids (SCFAs) acetate, propionate and butyrate from specific dietary fibres. SCFAs are the end products of bacterial fermentation of dietary fibre in the colon, and are of increasing clinical interest as imbalances in their production have been associated with a growing list of clinical indications. Moreover, it is now known that SCFAs can alter gene expression in the host, and it is therefore an open question whether these effects transcend the gut. Most importantly, SCFAs are known to have significant impact on the production of pro- and anti-inflammatory cytokines, with resulting impact on inflammatory status of the host.

Unfortunately, it is not currently possible to measure real-time SCFA production in vivo. SCFAs can be quantified in stool samples, but it remains unclear to what extent they are representative of the amounts produced and absorbed during intestinal transit. We herefore lack a good in vivo read-out that could be used to rigorously investigate whether our personalised fibre interventions do indeed lead to increased production of specific SCFAs in vivo, as expected. Such a biomarker would constitute an important step in graduating from highly general notions such as the fact that ‘high fibre intake’ is conducive to health, and moving towards a quantitative and mechanistic understanding of the role of different fibres in different individuals.