How gut microbiota control feelings of fullness after eating

By Tarun Sai LomteReviewed by Benedette Cuffari, M.Sc.Mar 7 2023

A recent study published in the journal Trends in Endocrinology and Metabolism discusses recent findings linking satiety to the gut microbiome.

Study: Influence of the gut microbiota on satiety signaling. Image Credit: FOTOKITA / Shutterstock.com

The microbiome and metabolism

A growing body of evidence suggests a role for the gut microbiota in regulating the metabolic phenotype. In fact, several studies suggest a pivotal role of the gut microbiota in regulating energy intake and satiety signaling.

Microbial metabolites such as short-chain fatty acids (SCFAs) produced by the gut microbiota can influence satiety. In the present study, researchers summarize the current understanding of interactions between microbial metabolites and satiety signaling.

SCFAs involved in satiety regulation

SCFAs are mainly formed from the fermentation of dietary fiber. Acetate, propionate, and butyrate are the most abundant SCFAs and account for about 95% of all SCFAs synthesized in humans. These SCFAs induce the secretion of satiation-related hormones, such as peptide YY (PYY) and glucagon-like peptide 1 (GLP-1).

Colonic infusion of SCFAs has been shown to increase circulatory levels of GLP-1 and PYY. In vivo studies in humans suggest that distal SCFA administration, but not proximal, leads to increased PYY levels. Additionally, SCFAs influence the secretion of GLP-2, cholecystokinin (CCK), and gastric inhibitory peptide (GIP).

Acute increases in serum SCFAs have been linked to declines in systemic concentrations of ghrelin in obese/overweight humans, thus suggesting the potential of SCFAs to influence hunger sensations. Moreover, SCFAs have been implicated in regulating leptin signaling.

A systematic review concluded that SCFAs enhance leptin secretion in white adipose tissue. SCFAs can also affect nerve signaling in the gut, as one study in mice showed the role of the vagus nerve in SCFA-dependent signaling.

SCFAs are also capable of crossing an in vitro model of the blood-brain barrier (BBB). Furthermore, colonic and intravenous administration of radiolabeled acetate in mice revealed the uptake of the SCFA in the hypothalamus. Nonetheless, human studies found no such uptake of the labeled SCFAs in the brain.

Dietary modulation of SCFA production and satiety regulation

Dietary fiber intake has been shown to reduce subjective feelings of appetite and energy intake. Nevertheless, human studies on the associations between dietary fiber intake, gut microbiota, and satiety-related effects are scarce.

The researchers identified 18 short-term and nine long-term studies focusing on the association between fiber-dependent/prebiotic alteration of the gut microbiota, satiety signaling, and energy intake.

Among short-term studies, six revealed that fiber intervention reduced ad libitum energy intake. Nine studies reported on the effects of the intervention on subjective appetite ratings, with eight of these studies reporting elevated breath hydrogen levels, which is indicative of microbial fermentation. Notably, increased breath hydrogen levels were also reported in studies that found no effect of the intervention.

Seven studies reported higher secretion of satiety hormones in response to fiber/prebiotic intervention. Two long-term studies showed reduced ad libitum energy intake following a 12-week fiber and eight-week oligofructose intervention in obese/overweight people.

Only two studies identified elevations in satiety hormones with fiber intervention. Seven studies observed positive intervention effects on satiety ratings.

Bacterial compounds and neuroactive metabolites influence satiety

Recent evidence suggests that gut microbiota synthesizes neurotransmitters regulating food intake. Up to 95% of serotonin is produced by enteroendocrine cells in the human gut, and the remaining 5% is synthesized by the central nervous system (CNS). In fact, in vitro studies have demonstrated serotonin production by specific bacteria, including Escherichia coli, Streptococcus thermophilus, and Lactiplantibacillus plantarum.

The gut microbiota has been shown to produce about 49% of circulatory serotonin and 64% of colonic serotonin in mice. In humans, gut microbiota-derived serotonin is associated with processes contributing to satiety and energy intake regulation.

In humans, serotonin has been shown to regulate satiety in the hypothalamus and extrahypothalamic sites. Different bacteria can synthesize γ-aminobutyric acid (GABA),

Commensals from the Lactobacillus and Bifidobacterium genera can produce GABA in vitro. In one previous mouse study, reduced fecal and systemic levels of GABA were observed in germ-free mice.

GABA receptor interactions in enteroendocrine cells appear to stimulate serotonin release. Additionally, GABA might regulate vagal and spinal afferent sensitivity. Peripherally synthesized GABA has been reported to regulate the secretion of hormones in satiety signaling.

Concluding remarks

Recent evidence, most of which has been preclinical, confirms the association between gut microbiota functionality and the regulation of satiation, satiety, and energy intake.

Notably, most of the work on the gut-brain axis has been performed in animal or in vitro models, whereas human and in vivo mechanistic studies are scarce. Specifically, studies on gut microbiota composition and functionality in the context of energy intake and satiety are lacking.