Roles for the gut microbiota in regulating neuronal feeding circuits

Abstract

The gut microbiota has the capacity to affect host appetite via intestinal satiety pathways, as well as complex feeding behaviors. In this Review, we highlight recent evidence that the gut microbiota can modulate food preference across model organisms. We discuss effects of the gut microbiota on the vagus nerve and brain regions including the hypothalamus, mesolimbic system, and prefrontal cortex, which play key roles in regulating feeding behavior. Crosstalk between commensal bacteria and the central and peripheral nervous systems is associated with alterations in signaling of neurotransmitters and neuropeptides such as dopamine, brain-derived neurotrophic factor (BDNF), and glucagon-like peptide-1 (GLP-1). We further consider areas for future research on mechanisms by which gut microbes may influence feeding behavior involving these neural pathways. Understanding roles for the gut microbiota in feeding regulation will be important for informing therapeutic strategies to treat metabolic and eating disorders.

Figure 1. Gut microbiota–mediated changes in homeostatic and non-homeostatic neural substrates.

See Tables 1 and 2 for more detailed information. AA, amino acid; ABX, antibiotics; AgRP, agouti-related peptide; BDNF, brain-derived neurotrophic factor; CART, cocaine- and amphetamine-regulated transcript; ClpB, caseinolytic protease B; CONV-R, conventionally raised; DRN, dorsal raphe nucleus; FOS, fructo-oligosaccharides; GABA, γ-aminobutyric acid; GF, germ free; GLP-1, glucagon-like peptide-1; GOS, galacto-oligosaccharides; HFD, high-fat diet; HFHS, high-fat, high-sugar; HIPP, hippocampus; 5-HT, serotonin; HYP, hypothalamus; LPS, lipopolysaccharide; NAc, nucleus accumbens; NGFI-A, nerve growth factor–inducible clone A; NMDA, N-methyl-d-aspartate; NTS, nucleus of the solitary tract; PFC, prefrontal cortex; POMC, pro-opiomelanocortin; PSD-95, postsynaptic density protein 95; STR, striatum; VTA, ventral tegmental area.

Figure 2. Proposed sites of action for microbial metabolites to influence vagal activity.

Dotted lines indicate multisynaptic pathways. AhR, aryl hydrocarbon receptor; ARC, arcuate nucleus of the hypothalamus; CCK, cholecystokinin; CCK1R, CCK receptor 1; FFAR2, free fatty acid receptor 2 (formerly GPR43); FFAR3, free fatty acid receptor 3 (formerly GPR41); GLP-1, glucagon-like peptide-1; GLP-1R, GLP-1 receptor; HIPP, hippocampus; LPS, lipopolysaccharide; NTS, nucleus of the solitary tract; NTS1R, neurotensin receptor 1; Olfr558, olfactory receptor 558; S1PR3, sphingosine-1-phosphate receptor 3; STR, striatum; TGR5, Takeda G protein–coupled receptor 5; TLR4, Toll-like receptor 4. Adapted with permission from Molecular Metabolism (155).