Microbiome involvement in satiety regulation

In satiety regulation, the balance between anorexigenic (PP, CCK, PYY3-36, incretins, leptin, OXM) and orexigenic (ghrelin, insl5, adiponectin) signals is determinant. A special attention should be attributed to incretins (GLP-1, GIP). Incretins are key gut-derived hormones, secreted after a post-prandial increase of blood glucose level, with effects on glycemic control by stimulation of insulin secretion and inhibition of glucagon release [1].

     In the last decades, the link between microbiome and human health has been largely documented. Beside the digestive environment, the gut microbiome is known to modulate the whole human physiology and psychological statement. The ‘crosstalk’ between the microbes and the host-organs are mediated via hormone secretion, signaling mediators such as metabolites or neuromediators that activate or inactivate the cascade of downstream signaling pathways involved in satiety.

       Despite advances in correlating microbiome changes with human physiology, specific mechanisms of host-microbiome signaling in satiety remained largely elusive. Recently, the production of SCFAs produced by bacterial fermentation of non digestive fibers was shown to modulate GLP-1 and PYY secretion (via GPR41, GPR43 receptors) [2]. In addition, the microbiome contributes to bile acids releases that stimulate GLP-1 and PYY secretion [1]. Furthermore, in mice model, Escherichia coli proteins were shown to stimulate GLP-1 and PYY secretion [3]. E. coli produced ClpB, an antigen-mimetic of α-MSH neuropeptide having a role in influencing feeding behavior via activation of brain anorexigenic pathways [3]. Other bacterial compounds might be involved in satiety and they should be explored by metabolomic and functionally characterized. Among them, indole (produced from tryptophan by gut bacteria) is known to affect GLP-1 secretion and may be also considered [1, 4]. All mice observations should be confirmed in clinical studies.

       Microbiome would be also involved in glycemic control through the secretion of mediators such as incretins [3]. A positive correlation between Bacteroidetes to Firmicutes ratio and elevated plasma glucose levels were found in human with type 2 diabetes (T2D) [2]. Moreover, insulin resistance, as well as increased adiposity, were shown to be characterized by lower bacterial richness, higher abundances of Proteobacteria and Bacteroidetes. At the genus level, associations were found between T2D and higher levels of E. coli and Bacteroides, Akkermansia muciniphila and various Clostridia in mice model. Investigations should be provided to validate the functionality of these bacteria and explore the role of other gut bacteria taxa in appetite-modulating properties and possible involvement in host metabolic profiles.  

Microbiome is a new land of investigation for scientist and healthcare companies for promising health challenges. Especially, targeting the incretins may have effective perspective in satiety control with associated benefits on pre-diabetics people through glycemic control.

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PP (pancreatic polypeptide)

CCK (Cholecystokinin)

PYY (Peptide YY)

OXM (Oxyntomodulin)

GLP-1 (Glucagon-like peptide 1)

GIP (Gastric inhibitory polypeptide)

GPR41 (G protein-coupled receptors 41)

GPR43 (G protein-coupled receptors 43)

ClpB (Caseinolytic peptidase B protein homolog)

α-MSH (α-Melanocyte-stimulating hormone)

CRO (Contract Research Organization)

– References – 

1.  Pais R, Gribble FM, Reimann F. Stimulation of incretin secreting cells. Therapeutic advances in endocrinology and metabolism 2016, 7(1):24-42.

2. Suez J, Shapiro H, Elinav E. Role of the microbiome in the normal and aberrant glycemic response. Clinical Nutrition Experimental 2016, 6:59-73.

3. Breton J, Tennoune N, Lucas N, Francois M, Legrand R, Jacquemot J, Goichon A, Guerin C, Peltier J, Pestel-Caron M et al: Gut Commensal E. coli Proteins Activate Host Satiety Pathways following Nutrient-Induced Bacterial Growth. Cell metabolism 2016, 23(2):324-334.

4. Sharon G, Garg N, Debelius J, Knight R, Dorrestein PC, Mazmanian SK: Specialized metabolites from the microbiome in health and disease. Cell metabolism 2014, 20(5):719-730.