The carbohydrate dimension of nutrition in gut microbiome modulation

Abstract

Dietary carbohydrates that escape host digestion and are microbiota-accessible (MAC) are increasingly recognised as essential for individual and public health. Inadequate consumption of MAC is associated with the global crisis of chronic diseases. Dietary MAC supplementation has previously been used to modulate the gut microbiota to benefit host health. However, a key challenge in the application of MAC is high individual variability in response, with poor predictability of which individuals will benefit. In this thesis, my goal was to identify the factors that contributed to this variability and to identify approaches to improve the manipulation of dietary carbohydrates to modulate the gut microbiome for health. This thesis incorporated a human observational study and four animal experimental studies. I classified four categories of carbohydrates: accessible mainly by the host, accessible by both the host and the microbiota, accessible by the microbiota only, or inaccessible to both the host and the microbiota. I tested the hypotheses that microbial and host responses to diet were dependent on the category of carbohydrate and dietary protein content. My studies showed that despite individual variability, there were predictable elements of diet-microbiome interactions. Introducing new sources of MAC resulted in the greatest changes in the microbiome composition and metabolism, while the microbiota accessibility of diet determined the extent of change. Using ecological theory, I identified individual and dietary contributors to variability in response. Furthermore, I showed that in the context of intestinal damage, stimulating microbial activity with MAC was detrimental to health. Overall, the outcome of MAC supplementation may beneficial, inconsequential, or harmful, and cannot be predicted without consideration of other microbiome and host factors. In conclusion, my thesis supports the paradigm shift from one-size-fits-all to the personalisation of diet.