Human nutrition, the gut microbiome and the immune system

Abstract

Marked changes in socio-economic status, cultural traditions, population growth and agriculture are affecting diets worldwide. Understanding how our diet and nutritional status influence the composition and dynamic operations of our gut microbial communities, and the innate and adaptive arms of our immune system, represents an area of scientific need, opportunity and challenge. The insights gleaned should help to address several pressing global health problems.

Fig. 1. A schematic of envisioned interrelationships between the gut microbiota, the immune system and diet that underlies the development of malnutrition

Under-nutrition is associated with a variety of defects in the innate and adaptive immune system that, in turn, are associated with increased predisposition to diarrheal illnesses. Recurrent (enteric) infections predispose to macro- and micronutrient deficiencies, as well as impaired intestinal mucosal barrier function . These factors lead to a cycle of further susceptibility to infection and worsening nutritional status. A confounding problem is that vaccines designed to protect children from certain pathogens (including enteropathogens) exhibit poor efficacy in areas of the world where poor nutrition is rampant . A testable hypothesis is that the gut microbiota may contribute to disease risk and pathogenesis through effects on nutrient processing and absorption, and on immune function. These interrelationships are illustrated in the Figure. Diet shapes gut microbial community structure and function while the microbiota adapts in ways that promote nutrient processing; the ability of the microbiota to process a given diet affects the nutrient and energetic value of that diet. The microbiota and immune systems co-evolve: malnutrition affects the innate and adaptive immune system as well as the microbiota. The microbiota serves as a barrier to enteropathogen infection; this barrier function may be disrupted by malnutrition as well as by perturbations in immune system function. The microbiota affects nutrient processing and nutrient distribution to the host, including the expression of host genes involved in nutrient transport and metabolism.

Fig. 2. Metabolic sensors that help co-ordinate immune responses

(1) Dietary intake of macro- and micro- nutrients shape (2) microbial community structure which, in turn, changes the nutritional value of the consumed food. (3) Unmodified dietary components are directly absorbed in the intestine where they can interact with a variety of immune cells (e.g., omega 3-fatty acids). (4) Microbial signals in the form of Microbe Associated Molecular Patterns (MAMPs) modify local mucosal immune responses through innate signaling pathways such as the inflammasome or TLRs. (5) Microbe-modified dietary components (e.g. acetate produced from fermentation of polysaccharides) provide signals by which the immune system can monitor the metabolic activities of the microbiota. (6) An example of micronutrients directly modifying intestinal microbial ecology: vitamin A can modify the representation of segmented filamentous bacterium (SFB) in the mouse gut microbiota; SFB induce differentiation of Th17 cells.