Panorganismal Gut Microbiome−Host Metabolic Crosstalk

Abstract

Coevolution shapes interorganismal crosstalk leading to profound and diverse cellular and metabolic changes as observed in gut dysbiosis in human diseases. Here, we modulated a simplified gut microbiota using pro-, pre-, and synbiotics to assess the depth of systemic metabolic exchanges in mice, using a multicompartmental modeling approach with metabolic signatures from 10 tissue/fluid compartments. The nutritionally induced microbial changes modulated host lipid, carbohydrate, and amino acid metabolism at a panorganismal scale. Galactosyl-oligosaccharides reduced lipogenesis, triacylglycerol incorporation into lipoproteins and triglyceride concentration in the liver and the kidney. Those changes were not correlated with decreased plasma lipoproteins that were specifically induced by L. rhamnosus supplementation. Additional alteration of transmethylation metabolic pathways (homocysteine-betaine) was observed in the liver and the pancreas following pre-and synbiotic microbial modulation, which may be of interest for control of glucose metabolism and insulin sensitivity. Probiotics also reduced hepatic glycogen and glutamine and adrenal ascorbate with inferred effects on energy homeostasis, antioxidation, and steroidogenesis. These studies show the breadth and the depth of gut microbiome modulations of host biochemistry and reveal that major mammalian metabolic processes are under symbiotic homeostatic control.

The Gut Microbiota: Ecology and Function

“…Studies comparing the blood metabolites of germ-free to conventional animals indicate that the metabolites produced by bacteria can have systemic effects (Wikoff et al, 2009). Modifying the composition of the microbiota using nutritional changes can modulate host lipid, carbohydrate, and amino acid metabolism (Martin et al, 2009). These effects may improve health because, for example, some bacteria cause reduced plasma lipoproteins (Martin et al, 2009).…”

“…Modifying the composition of the microbiota using nutritional changes can modulate host lipid, carbohydrate, and amino acid metabolism (Martin et al, 2009). These effects may improve health because, for example, some bacteria cause reduced plasma lipoproteins (Martin et al, 2009). The composition of the microbiota has been shown to correlate with components of the fecal metabolome as well as metabolites found in the urine Jansson et al, 2009).…”

The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases

“…The existence of bacteria in the large intestine and their fundamental functions in nutrition and metabolism (fermentation of nondegradable oligosaccharides, metabolism of xenobiotics and activation or destruction of mutagenic metabolites) make the colonic microbiota a large fermentative organ. 5 Metagenomic approaches have recently been used to demonstrate that the main functions of the small intestine microbiota may differ from the function of the colonic microbiota. The microbiota present in the small intestine is enriched in pathways and functions related to carbohydrate uptake and metabolism.…”

Nutraceuticals as Chemopreventive and Therapeutic agents in Gut Associated Pathogenesis

“…Certain enteric bacteria have potential to synthesize enzymes for the digestion of these polysaccharides. According to the recently revolved functional genomics of "Bacteroides thetaiotaomicron" 400 different enzymes are encoded play crucial role in various cellular activities including digestion of complex sugars [20], and well-understood starch utilization system [37,38]. Gut-associated microbiome regulates fat storage in the host.…”

“…Probiotics are microbial symbionts which colonize in different ecological niche in the gut and exist predominantly since the birth of an individual. Co-evolution of profound and diverse cellular and metabolic processes of the gut microflora modulates physiology and metabolism of the gut [20]. The genetic composition of enteric microbes helps them to synthesize certain enzymatic profile which is entirely different from the host enzymatic profile.…”