From the mouth to the large intestine, a large, rich, diverse and complex prokaryotic community live in straight contact with the host (Fig.
1). Between 2000 and 2010, numerous studies pointed out the importance of the microbiota in the energetic metabolism regulation. It was showed that germ-free (GF) mice are leaner and have a better glucose tolerance than their conventionally-raised counterpart (Conv-R). The colonization of GF mice with an intestinal microbiota coming from a Conv-R resulted in a worse insulin tolerance and a 60%-increase of body fat induced by a higher lipogenic activity within the liver [
75‐
77].
The microbiota can interact with the host through different mechanism (Fig.
1). By digesting fibers and nutrients, the microbiota can produce different molecules as 1) short chain fatty acids (SCFA) with the most well-known byturate, propionate and lactate but also succinate 2) indole and its derivatives, 3) some neuro-hormones or mimetics as GABA [
78], ClpB (αMSH mimetic) [
79], and 4) others molecules affecting the host as imidazole propionate [
80]. The microbiota also modifies and transforms the biliary acids secreted in the intestinal lumen to secondary biliary acids by deconjugation, dehydrogenation, dihydroxylation or epimerization [
81]. One the other hand, the microbiota interacts through its own components as lipopolysaccharides (LPS) or RNA and DNA fragments through the transmembrane and cytosolic receptors TLR and as peptidoglycanes through the receptor NOD. During the last decades, numerous studies contributed to improve the knowledge about the microbiota-host interactions particularly in the metabolism context. It was shown 1) that LPS, through TLR4 and CD14, participates to the low-grade inflammation observed during the metabolic diseases and aggravating the diseases and it was called endotoxemia [
82,
83] and peptidoglycans through NOD2 can modulate colonization and intestinal inflammation influencing the sensitivity to insulin [
84]; 2) the importance of dietary fibers and the SCFA production in the metabolism regulation through a GLP-1-dependant mechanism [
85‐
88] and 3) the role of secondary biliary acid through TGR5 and FXR [
81,
89,
90]. More recently, it was observed that succinate is a critical molecule produced essentially by Prevotella in the regulation of glucose metabolism and the weight in mice [
91]. Also, it was observed that
E. coli produces ClpB, an αMSH mimetic, controlling then the food intake [
79]. Indole and its interaction with the receptor AhR plays also a critical role in the regulation of intestinal immune system activity and glucose metabolism through a GLP-1-dependant mechanism [
92]. Similarly, a study observed that Akkermansia, a mucin-degradating bacteria, and particularly a membrane protein, prevented obesity and associated complications in mice [
93]. Finally, recently, a new bacterially-produced molecule in a context of type 2 diabetes, imidazole propionate, was identified to modulate the liver activity and impair glucose metabolism [
80].