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Where appetite is born: the role of microbial metabolites in the control of nutrition
Last reviewed: 09.08.2025
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In a review published in Trends in Endocrinology & Metabolism, leading microbiologists and endocrinologists explore a new paradigm: Not only host hormones, but also gut bacterial metabolites—short-chain fatty acids (SCFAs), tryptophan derivatives, secondary bile acids, and other substances—shape food cravings and regulate energy balance.
Main ideas of the review
Microbial Metabolites as Hunger and Satiety Signals
SCFA (acetate, propionate, butyrate) activate FFAR2/3 receptors on intestinal enteroendocrine cells → release of PYY and GLP-1 → appetite suppression and delayed gastric emptying.
Indoles and indoleacetic acid from tryptophan induce the release of serotonin in enterochromaffin cells, which indirectly affects the satiety centers in the brain.
Metabolites' journey to the brain
Some of the microbial products enter the bloodstream, cross the blood-brain barrier and act on hypothalamic neurons (NPY/AgRP and POMC cells), changing the feeling of hunger.
Secondary bile acids influence energy metabolism via TGR5 and FXR modulation in the liver and brain.
The Impact of Diet on the Microbiome and Behavior
A high-fiber diet stimulates SCFA production and increases sensitivity to satiety signals.
High-fat, low-carbohydrate diets create an imbalance in the microbiota, reducing SCFA producers and increasing overeating.
Clinical Perspectives
Probiotics and prebiotics: targeted intake of Bifidobacterium, Akkermansia strains and specific fibers to correct metabolic signals.
Microbial metabolites as drugs: development of inhaled or injected butyrate and propionate for appetite control in patients with obesity and metabolic syndrome.
“Our review highlights that the microbiome is not just a ‘household’ flora, but an active endocrine organ that controls our nutrition through its products,” comments Dr. Li Jing from the University of Colorado.
Why is this important?
- The new target in the fight against obesity and eating disorders is not the brain directly, but its “messengers” from the gut.
- Personalization of therapy: analysis of the microbiota metabolite profile will allow for individual adjustment of diet and probiotics.
- Disease prevention: Normalizing microbial signals can help reduce the risk of type 2 diabetes and cardiovascular complications.
The authors point out several key points:
The Microbiome as an Endocrine Organ
“Microbial metabolites are not just fermentation ‘waste’ but full-fledged signaling molecules that affect enteroendocrine cells and hypothalamic neurons,” emphasizes Dr. Li Jing, the first author of the review.Precise targeting of metabolites
“We’re not talking about a comprehensive microbiota correction, but rather targeted interventions: introducing specific probiotics or prebiotics that stimulate the production of precisely the SCFAs that we need,” notes co-author Professor Sarah Morgan.Personalizing Therapy
“Each person has their own microbial fingerprint, so effective appetite control requires first analyzing the microbiome and metabolites, then tailoring diet and supplements,” recommends Dr. Juan Park.New clinical trials
“Randomized trials are already being planned where butyrate and propionate will be prescribed for obesity and prediabetes, and the endpoints will be assessed not only by body weight, but also by changes in the microbiota profile and levels of appetite hormones,” says Dr. Emily Chen.
This review opens the prospect of microbial-mediated strategies to regulate appetite and energy homeostasis, offering new avenues for the treatment and prevention of nutrition-related diseases.