Aging, Frailty, and the Microbiome-How Dysbiosis Influences Human Aging and Disease

Abstract

The human gut microbiome is a collection of bacteria, protozoa, fungi, and viruses that coexist in our bodies and are essential in protective, metabolic, and physiologic functions of human health. Gut dysbiosis has traditionally been linked to increased risk of infection, but imbalances within the intestinal microbial community structure that correlate with untoward inflammatory responses are increasingly recognized as being involved in disease processes that affect many organ systems in the body. Furthermore, it is becoming more apparent that the connection between gut dysbiosis and age-related diseases may lie in how the gut microbiome communicates with both the intestinal mucosa and the systemic immune system, given that these networks have a common interconnection to frailty. We therefore discuss recent advances in our understanding of the important role the microbiome plays in aging and how this knowledge opens the door for potential novel therapeutics aimed at shaping a less dysbiotic microbiome to prevent or treat age-related diseases.

Keywords: Age-related Diseases; Elderly; Frailty; Inflammation; Microbiome.

Figure 1.

Human microbiota: onset and shaping through life stages. The graph provides a global overview of the relative abundance of key phyla of the human microbiota composition in different stages of life. Measured by either 16S RNA or metagenomic approaches (DNA). Data arriving from infants breast-and formula-fed (Schwartz et al, 2012), infant solid food (Koenig et al., 2011), toddler antibiotic treatment (Koenig et al., 2011), toddler healthy or malnourished (Monira et al., 2011), adult, elderly, and centenarian healthy (Biagi et al., 2010), and adult obese (Zhang et al., 2009).

Figure 2.

Inflamm-aging and related ARDs. The intestinal microbiome has been linked to disorders of the brain, heart, endocrine, musculoskeletal, and immune systems. This is an overview of the sections along the inflamm-aging to age-related disease pathways.

Figure 3.

The MRP2/HXA₃ (hepoxilin A3) axis forms the proinflammatory arm of a dynamically regulated system in which inflammatory pathways that activate responses to pathogens or aberrant signals are balanced against the anti-inflammatory P-glycoprotein (P-gp)/endocannabinoid (eCB) pathway that suppresses neutrophil responses in the context of normal commensal colonization. The 2 sets of lipid-based signaling molecules (eCB and HXA₃) are released from the apical surface during periods of either tolerance or inflammation, which control the recruitment of neutrophils to the intestinal lumen. Dysregulation of this critical balance may contribute directly to inflammatory disorders of the intestine (108).