Diet-microbiome-disease: Investigating diet's influence on infectious disease resistance through alteration of the gut microbiome

Abstract

Abiotic and biotic factors can affect host resistance to parasites. Host diet and host gut microbiomes are two increasingly recognized factors influencing disease resistance. In particular, recent studies demonstrate that (1) particular diets can reduce parasitism; (2) diets can alter the gut microbiome; and (3) the gut microbiome can decrease parasitism. These three separate relationships suggest the existence of indirect links through which diets reduce parasitism through an alteration of the gut microbiome. However, such links are rarely considered and even more rarely experimentally validated. This is surprising because there is increasing discussion of the therapeutic potential of diets and gut microbiomes to control infectious disease. To elucidate these potential indirect links, we review and examine studies on a wide range of animal systems commonly used in diet, microbiome, and disease research. We also examine the relative benefits and disadvantages of particular systems for the study of these indirect links and conclude that mice and insects are currently the best animal systems to test for the effect of diet-altered protective gut microbiomes on infectious disease. Focusing on these systems, we provide experimental guidelines and highlight challenges that must be overcome. Although previous studies have recommended these systems for microbiome research, here we specifically recommend these systems because of their proven relationships between diet and parasitism, between diet and the microbiome, and between the microbiome and parasite resistance. Thus, they provide a sound foundation to explore the three-way interaction between diet, the microbiome, and infectious disease.

Fig 1. Direct and indirect relationships between host diet, host gut microbiome, and parasites.

In bees, studies have independently shown that diets modulate resistance to parasites [9,21], diets alter gut microbiomes [75], and gut microbiomes modulate parasitism [90,107]. However, it is not known whether there is an indirect link between the three based on these direct relationships. Alternatively, the host immune system can indirectly alter this potential three-way interaction by modulating antimicrobial peptides or pattern recognition receptors via diet or the gut microbiome to fight parasites [11,110].

Fig 2. Animal systems showing three separate, direct relationships between diet, parasites, and the gut microbiome.

Mice and insects are ideal systems to study the potential indirect, three-way link due to the systems’ controlled host diets, tractable and relatively simple microbiota, and tractability of parasites.

Fig 3. Properties of the gut microbiome that could reduce parasitism.

The protective effects of the gut microbiome may derive from colonization resistance, the abundance and evenness of one or more species at various taxonomic levels, the presence or absence of particular species, or the presence or abundance of certain genes. These scenarios are not exhaustive nor mutually exclusive [107].