The gut microbiota is intimately linked with the host in healthy and disease states, and there is great interest in diet supplementation with microbial-accessible carbohydrates (MAC) to promote microbial activity that confers host health benefits. However, MAC-supplemented diets do not consistently produce desired microbial and host responses. We propose that this variability is because the outcome of microbial competition for MACs is dependent on the availability of other required nutrients.
We categorised carbohydrates into four functional types based on host- and microbiota-accessibility: host-accessible simple (HAS), host-accessible complex (HAC), host-inaccessible microbiota-accessible (HI-MAC), and inaccessible carbohydrates (IC). To test the microbial and host response, we designed 40 defined diets that varied in the relative abundance of these carbohydrates, protein and caloric density. These diets were investigated sequentially in a mouse model, with a subset of diets tested in a host disease state using a DSS-induced colitis model.
Notably, we found that specific carbohydrates had distinct effects on the microbiota and host depending on the protein and energy intake. Gut environment: Using blood in stool as an indicator of intestinal epithelial health, consumption of HAC improved gut health at high carb:prot diets, but was detrimental high prot:carb diets. Microbial composition: Bifidobacterium and Lactobacillus are common targets of prebiotics and both taxa increased in abundance with HI-MAC intake, but Bifidobacterium dominated at low protein intake and Lactobacillus at high protein intake. Host health: MAC intake increased the severity of DSS-induced colitis, and symptoms were exacerbated at a high prot:carb dietary context.
We show that the outcome of MAC-supplemented diets cannot be predicted as beneficial or detrimental without knowledge of the diet context, microbial composition and gut health. We conclude that identifying specific conditions to accompany diet manipulation will increase the success in engineering desirable microbial and health outcomes.