Modulation of the gut microbiota by nutrients with prebiotic properties: consequences for host health in the context of obesity and metabolic syndrome

Abstract

The gut microbiota is increasingly considered as a symbiotic partner for the maintenance of health. The homeostasis of the gut microbiota is dependent on host characteristics (age, gender, genetic background...), environmental conditions (stress, drugs, gastrointestinal surgery, infectious and toxic agents...). Moreover, it is dependent on the day-to-day dietary changes. Experimental data in animals, but also observational studies in obese patients, suggest that the composition of the gut microbiota is a factor characterizing obese versus lean individuals, diabetic versus non diabetic patients, or patients presenting hepatic diseases such as non alcoholic steatohepatitis. Interestingly, the changes in the gut microbes can be reversed by dieting and related weight loss. The qualitative and quantitative changes in the intake of specific food components (fatty acids, carbohydrates, micronutrients, prebiotics, probiotics), have not only consequences on the gut microbiota composition, but may modulate the expression of genes in host tissues such as the liver, adipose tissue, intestine, muscle. This in turn may drive or lessen the development of fat mass and metabolic disturbances associated with the gut barrier function and the systemic immunity. The relevance of the prebiotic or probiotic approaches in the management of obesity in humans is supported by few intervention studies in humans up to now, but the experimental data obtained with those compounds help to elucidate novel potential molecular targets relating diet with gut microbes. The metagenomic and integrative metabolomic approaches could help elucidate which bacteria, among the trillions in human gut, or more specifically which activities/genes, could participate to the control of host energy metabolism, and could be relevant for future therapeutic developments.

Figure 1

Obesity and related metabolic diseases: which role for the gut microbiota? In several organs and in the serum, lipid accumulation and pro-inflammatory processes contribute to metabolic alterations leading to an increased risk of cardiovascular disease, diabetes and non alcoholic steato-hepatitis. The production of metabolites and cytokines by the adipose tissue is playing a crucial role. A novel partner to consider would be the gut microbiota which could, depending on its composition and activity, either positively or negatively contribute to metabolic syndrome. NASH, Non-Alcoholic SteatoHepatitis

Figure 2

Occurrence of entotoxemia upon high fat diet feeding and obesity. An increase level of lipopolysaccharides (LPS) characterizes obese and diabetic individuals. This effect is mostly due to processes involving the transport of LPS from the gut to the blood, those processes being an increase in chylomicron-driven transport of LPS, a rupture of the gut barrier integrity leading to abnormal gut permeability, and a decrease in processes involved in intestinal LPS degradation (alkaline phosphatase activity). The increase in LPS (endotoxemia) thereby activates the macrophages in the different tissues leading to a low tone inflammation involved in the metabolic alterations occurring upon obesity.

Figure 3

Improvement of obesity and related metabolic disorders by the prebiotic approach. Nutrients with prebiotic properties allows, by changing the gut microbiota, to promote the endocrine function of the gut (increase in GLP-1, and GLP-2 producing cells), and to modulate the activation of the endocannabinoid system in the intestine and in the adipose tissue. All those effects contribute to lessen gut permeability (improved distribution of the tight junction proteins ZO-1 and Occludin), thereby decreasing endotoxemia, and systemic inflammation. Changes in GLP-1 contribute to decrease food intake, fat mass, glycemia and insulin resistance. eCB, endocannabinoid; GLP-1, glucagon-like peptide 1; GLP-2, glucagon-like peptide 2; LPS, lipopolysaccharides; ZO-1, zonula occludens 1.