Gut Microbes and Health: A Focus on the Mechanisms Linking Microbes, Obesity, and Related Disorders

Abstract

The past decade has been characterized by tremendous progress in the field of the gut microbiota and its impact on host metabolism. Although numerous studies show a strong relationship between the composition of gut microbiota and specific metabolic disorders associated with obesity, the key mechanisms are still being studied. The present review focuses on specific complex pathways as well as key interactions. For instance, the nervous routes are explored by examining the enteric nervous system, the vagus nerve, and the brain, as well as the endocrine routes (i.e., glucagon-like peptide-1, peptide YY, endocannabinoids) by which gut microbes communicate with the host. Moreover, the key metabolites involved in such specific interactions (e.g., short chain fatty acids, bile acids, neurotransmitters) as well as their targets (i.e., receptors, cell types, and organs) are briefly discussed. Finally, the review highlights the role of metabolic endotoxemia in the onset of metabolic disorders and the implications for alterations in gut microbiota-host interactions and ultimately the onset of diseases.

Figure 1

Gut microbiota is involved in a complex interaction with host metabolism. The gut microbiota is involved in complex interaction between food (i.e., dietary ingredients changing the microbiota) and consequently the metabolite produced. Gut bacteria also contribute to the regulation of the production of neurotransmitters, different hormones, and finally host metabolism. Numerous data suggest that the composition and the activity of the gut microbes are responsible for the protection or the onset of diseases associated with obesity, such as insulin resistance, low‐grade inflammation, fatty liver, and diabetes. Thus, the gut and microbes are communicating with all the organs via specific metabolites, hormones, and neurotransmitters, acting through direct or indirect pathways (i.e., the vagus nerve).

Figure 2

Mechanisms of interaction between bacterial products and host organs: the role of the gut lining. Numerous metabolites are produced upon the metabolic activity of the gut microbes. Most of them are chemically similar to those produced by the host cells (i.e., nitric oxide [NO]; gamma‐aminobutyric acid [GABA]; serotonin [5‐hydroxytriptamine, (5‐HT)]; short chain fatty acids [SCFAs], and indoles), whereas others result from the chemical transformations of host molecules by microbes, namely the bile acids (BAs). All these molecules are recognized by the host cells and may act on specific receptors (both nuclear and membrane receptors) or eliciting the secretion of other hormonal signals such as the gut peptides glucagon‐like peptide‐1 (GLP‐1) or peptide YY (PYY) that both act on energy metabolism by acting through nervous routes or blood relay. Translocation of lipopolysaccharides (LPS) through the gut lining is a hallmark of obesity, diabetes, and related disorders. Leakage of LPS into the blood triggers low‐grade inflammation and thereby affects liver, adipose tissue, and muscle metabolism. In addition, those endotoxins can alter the activity of the enteric nervous system (ENS) as well as the gut‐brain axis via the vagus nerve, hence affecting appetite regulation.