Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health

Abstract

Gut microbes comprise a high density, biologically active community that lies at the interface of an animal with its nutritional environment. Consequently their activity profoundly influences many aspects of the physiology and metabolism of the host animal. A range of microbial structural components and metabolites directly interact with host intestinal cells and tissues to influence nutrient uptake and epithelial health. Endocrine, neuronal and lymphoid cells in the gut also integrate signals from these microbial factors to influence systemic responses. Dysregulation of these host-microbe interactions is now recognised as a major risk factor in the development of metabolic dysfunction. This is a two-way process and understanding the factors that tip host-microbiome homeostasis over to dysbiosis requires greater appreciation of the host feedbacks that contribute to regulation of microbial community composition. To date, numerous studies have employed taxonomic profiling approaches to explore the links between microbial composition and host outcomes (especially obesity and its comorbidities), but inconsistent host-microbe associations have been reported. Available data indicates multiple factors have contributed to discrepancies between studies. These include the high level of functional redundancy in host-microbiome interactions combined with individual variation in microbiome composition; differences in study design, diet composition and host system between studies; and inherent limitations to the resolution of rRNA-based community profiling. Accounting for these factors allows for recognition of the common microbial and host factors driving community composition and development of dysbiosis on high fat diets. New therapeutic intervention options are now emerging.

Keywords: Microbiome; Dysbiosis; High fat diet; Bile; Intestinal mucosa; Microbe-associated molecular patterns; Short chain fatty acids; Immunomodulation; Enteroendocrine cells

Core tip: The development of dysbiosis is driven by multiple factors. These include selective pressures imposed on the microbial community by the diet composition and feedback effects that involve either diet-host interaction or diet-microbiome-host interaction. The role of microbial signals in dysbiosis is well established but the involvement of host feedback mechanisms in aberrant host-microbial interactions is an under-appreciated part of disease progression. New opportunities to intervene in diseases of dysbiosis can result from targeting these distinct processes. These include stimulation of the host ability to self-regulate and blocking of deleterious host responses.