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 pre-, pro-, and post-biotics, 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.

The Gut Microbiota

“…Although differences existed in the relative abundance of specific microbes (e.g., increase in Verrucomicrobia in TPN group), diurnal shifts were still evident, indicating that microbial abundance may fluctuate based on host cues, such as the release of mucin or other epithelial proteins and secretions. Altogether these findings suggest that the regulation of host circadian function is dependent on the activity of the gut microbiota and conversely, the circadian behavior of the gut microbiota is dependent on host physiology 13,45 . Identifying the host-microbe interactions that facilitate microbial control of circadian rhythm may lead to therapies targeting the gut microbiota to restore the metabolic consequences of disrupted sleep, common in obesity.…”

“…In addition to composition, major functional differences are observed in metabolic capacity of the microbial community. For instance, decreases in SCFA producers, such as from the phylum Actinobacteria and blooms in pathogenic bacteria from the phylum Proteobacteria, occur in obesity 13 . In addition to bacteria, recent work demonstrates the microbiota metabolic networks include yeast and archaea, which synergistically produce and utilize metabolites collectively with bacteria 14 .…”

“…Several mechanisms to explain microbe-mediated obesity have been proposed, including 1) short chain fatty acid (SCFA) production, 2) regulation of food intake and sensory perception of food, 3) nutrient absorption, 4) circulation of microbe-derived enterotoxins like LPS and reduced production of angiopoietin like 4 (angptl4) resulting in increased fatty acid uptake in liver and adipose tissue 13 , 5) and peripheral control of circadian rhythm which is intimately links metabolic coordination between the brain and peripheral organs 44,45 .…”

“…This has important implications for fighting obesity, as the disruption of the natural cycle of day and night (e.g., jet lag, shift work and sleep apnea) contributes to the increasing prevalence of metabolic disorders 13 . Circadian rhythms are regulated by molecular clocks that coordinate regularly timed events (i.e., states of feeding vs fasting) and the necessary physiological responses to enhance metabolic efficiency.…”

“…It is important to consider the composition of probiotic formulations as each strain may have a different impact on microbial structure/function or on the host immune response, for instance. Wang et al 66 demonstrated in mice that three strains of bacteria including Lactobacillus Paracasei CNCM I-4270, L. rhamnosus I-3690 and Bifidobacterium animalis subsp Lactis I-2494 independently decreased body weight and improved glucose tolerance but through different mechanisms (reviewed in 13 ). Daily gavage of the probiotic yeast Saccharomyces boulardii or Biocodex, elicited changes in gut microbiota, reflecting a less obesogenic state, as well as improved the metabolic profile of genetically obese and diabetic db/db mice 17 .…”