Nutritional modulation of gut microbiota - the impact on metabolic disease pathophysiology

Abstract

The obesity epidemic afflicts over one third of the United States population. With few therapies available to combat obesity, a greater understanding of the systemic causes of this and other metabolic disorders is needed to develop new, effective treatments. The mammalian intestinal microbiota contributes to metabolic processes in the host. This review summarizes the research demonstrating the interplay of diet, intestinal microbiota and host metabolism. We detail the effects of diet-induced modifications in microbial activity and resultant impact on (1) sensory perception of macronutrients and total energy intake; (2) nutrient absorption, transport and storage; (3) liver and biliary function; (4) immune-mediated signaling related to adipose inflammation; and (5) circadian rhythm. We also discuss therapeutic strategies aimed to modify host-microbe interactions, including prebiotics, probiotics and postbiotics, as well as fecal microbiota transplantation. Elucidating the role of gut microbes in shaping metabolic homeostasis or dysregulation provides greater insight into disease development and a promising avenue for improved treatment of metabolic dysfunction.

Keywords: Circadian Rhythm; High fat diet; Inflammation; Metabolism; Microbiota; Obesity.

Figure 1. Mechanisms by which microbial alterations, induced by Western diet consumption, cause metabolic dysfunction in peripheral tissues of the host

ABCG, ATP-binding cassette sub-family G; SREBP1C, sterol regulatory element-binding protein 1; CIDEA – Cell death activator; SCFAs, Short-chain fatty acids; Gpr, G-coupled protein receptor; ANGPTL4, angiopoietin-type 4; LPS, lipopolysaccharide; LTA – lipoteichoic acid; NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells; TNFα, tumor necrosis factor alpha; LPL, lipoprotein lipase.

Figure 2. Mechanisms of diet-induced gut microbial regulation of intestinal, central and peripheral circadian clocks and metabolic outcome

(Top) Feeding patterns and other inputs produce day-night cycling of intestinal microbial communities and their associated metabolites, promoting proper circadian timing in the host. (Bottom) High-fat Western diets create dysbiosis and alter oscillations of bacteria. Dysregulation of host and microbial signaling molecules leads to desynchronization of clocks in multiple tissues and promotes metabolic disorder. SCFAs, Short-chain fatty acids; TLRs, Toll-like receptors; Reverb, Nuclear receptor subfamily 1, group D, member 1; PPARa, peroxisome proliferator-activated receptor; H2S – Hydrogen sulfide