Nutrition, Immunosenescence, and Infectious Disease: An Overview of the Scientific Evidence on Micronutrients and on Modulation of the Gut Microbiota

Abstract

The immune system is key to host defense against pathogenic organisms. Aging is associated with changes in the immune system, with a decline in protective components (immunosenescence), increasing susceptibility to infectious disease, and a chronic elevation in low-grade inflammation (inflammaging), increasing the risk of multiple noncommunicable diseases. Nutrition is a determinant of immune cell function and of the gut microbiota. In turn, the gut microbiota shapes and controls the immune and inflammatory responses. Many older people show changes in the gut microbiota. Age-related changes in immune competence, low-grade inflammation, and gut dysbiosis may be interlinked and may relate, at least in part, to age-related changes in nutrition. A number of micronutrients (vitamins C, D, and E and zinc and selenium) play roles in supporting the function of many immune cell types. Some trials report that providing these micronutrients as individual supplements can reverse immune deficits in older people and/or in those with insufficient intakes. There is inconsistent evidence that this will reduce the risk or severity of infections including respiratory infections. Probiotic, prebiotic, or synbiotic strategies that modulate the gut microbiota, especially by promoting the colonization of lactobacilli and bifidobacteria, have been demonstrated to modulate some immune and inflammatory biomarkers in older people and, in some cases, to reduce the risk and severity of gastrointestinal and respiratory infections, although, again, the evidence is inconsistent. Further research with well-designed and well-powered trials in at-risk older populations is required to be more certain about the role of micronutrients and of strategies that modify the gut microbiota-host relationship in protecting against infection, especially respiratory infection.

Keywords: aging; gut microbiota; immunity; infection; inflammation; selenium; vitamin C; vitamin D; vitamin E; zinc.

FIGURE 1

The components of the immune system and their division into innate and acquired immunity. ILC, innate lymphoid cell; MAIT, mucosal associated invariant T; TGF, transforming growth factor; Th, T helper. Reproduced from reference .

FIGURE 2

The central role of inflammaging in chronic conditions of aging. Adapted (color changes) from reference .

FIGURE 3

How the gut microbiota shapes host immunity. Multiple immune effectors function together to minimize bacterial-epithelial invasion. These include the mucus layer, epithelial antibacterial proteins, and IgA secreted by lamina propria plasma cells. Compartmentalization is accomplished by unique anatomic adaptations that limit commensal bacterial exposure to the immune system. Some microbes are sampled by intestinal dendritic cells. The loaded dendritic cells traffic to the mesenteric lymph nodes through the intestinal lymphatic but do not migrate to distal tissues. This compartmentalizes live bacteria and induction of immune responses to the mucosal immune system. Induced B cells and T-cell subsets recirculate through the lymphatic and the bloodstream back to mucosal sites, where B cells differentiate into IgA-secreting plasma cells. Thus, the intestinal microbiota shapes host mucosal as well as systemic immunity. ILF, isolated lymphoid follicle; iNKT, invariant natural killer T; PSA, polysaccharide A; SFB, segmented filamentous bacteria; Th, T helper. Treg, regulatory T cell. Reproduced from reference with permission.

FIGURE 4

Changes to the gut microbiota with age and with duration of residential care. Redundancy analysis plot of microbiota composition (log-transformed OTU dataset) of (A) community-dwelling individuals by age (years) (n = 176; P < 0.002). (B) Full dataset of community and long-term residential care individuals by duration in care (months) (n = 282; P < 0.001). OTU, operational taxonomic unit. Reproduced from reference with permission from American Association for the Advancement of Science (AAAS). PC, principal component; RDA, redundancy analysis.