Gut microbes and food reward: From the gut to the brain

Abstract

Inappropriate food intake behavior is one of the main drivers for fat mass development leading to obesity. Importantly the gut microbiota-mediated signals have emerged as key actors regulating food intake acting mainly on the hypothalamus, and thereby controlling hunger or satiety/satiation feelings. However, food intake is also controlled by the hedonic and reward systems leading to food intake based on pleasure (i.e., non-homeostatic control of food intake). This review focus on both the homeostatic and the non-homeostatic controls of food intake and the implication of the gut microbiota on the control of these systems. The gut-brain axis is involved in the communications between the gut microbes and the brain to modulate host food intake behaviors through systemic and nervous pathways. Therefore, here we describe several mediators of the gut-brain axis including gastrointestinal hormones, neurotransmitters, bioactive lipids as well as bacterial metabolites and compounds. The modulation of gut-brain axis by gut microbes is deeply addressed in the context of host food intake with a specific focus on hedonic feeding. Finally, we also discuss possible gut microbiota-based therapeutic approaches that could lead to potential clinical applications to restore food reward alterations. Therapeutic applications to tackle these dysregulations is of utmost importance since most of the available solutions to treat obesity present low success rate.

Keywords: food intake; food reward; gut microbes; gut microbiome; gut-brain-axis; obesity.

FIGURE 1

The homeostatic control of food intake upon peripheric signals. Orexigenic hormones or neurotransmitters are in green; anorexigenic hormones or neurotransmitters are in red. PVN: paraventricular nucleus; SIM1, single–minded family BHLH transcription factor 1; LH, lateral hypothalamus; MCH, melanin-concentrating hormone; Arc, arcuate nucleus; AgRP, agouti-related protein; NPY, neuropeptide Y; POMC, pro-opiomelanocortin; CART, cocaine-amphetamine-related transcript; NTS, nucleus tractus solitarus; VAN, vagal afferent nerves; CCK, cholecystokinin; GLP-1, glucagon-like peptide 1; PYY, peptide YY; MC4R, Melanocortin 4 receptor. Created with BioRender.com.

FIGURE 2

The reward system controlling non-homeostatic food intake. Nac, nucleus accumbens; GABA, γ-aminobutyric acid; VTA, ventral tegmental area. Created with BioRender.com.

FIGURE 3

The role of the gut microbiota in homeostatic and non-homeostatic controls of food intake. Potential links are represented in dashed arrows. Demonstrated links are represented in solid arrows. PVN, paraventricular nucleus; SIM1, single–minded family BHLH transcription factor 1; LH, lateral hypothalamus; Str, striatum; Nac, nucleus accumbens; GABA, γ-aminobutyric acid; PFC, prefrontal cortex; Arc, arcuate nucleus; AgRP, agouti-related protein; NPY, neuropeptide Y; POMC, pro-opiomelanocortin; CART, cocaine-amphetamine-related transcript; NTS, nucleus tractus solitarus; VTA, ventral tegmental area; DA, dopamine; VAN, vagal afferent nerves; CCK, cholecystokinin; GLP-1, glucagon-like peptide 1; PYY, peptide YY; SCFAs, short-chain fatty acids; LPS, lipopolysaccharide; MC4R, Melanocortin 4 receptor. Created with BioRender.com.