Your gut bacteria could be the key to controlling hunger

The regulation of appetite is a complex, multi-dimensional process that plays a pivotal role in maintaining energy homeostasis. Satiety, distinct from hunger and satiation, is central to this regulation. 

• Hunger represents the physiological need for food, typically driven by signals from the brain in response to energy depletion.
• Satiation, on the other hand, marks the sensation of fullness experienced during a meal, signalling an end to eating.
• In contrast, satiety refers to the prolonged sense of fullness that suppresses further eating between meals, thus influencing the timing of subsequent food intake.

Understanding the mechanisms behind satiety is critical for healthcare professionals and individuals alike striving to combat obesity, diabetes, and other metabolic disorders. Increasingly, research points to the gut microbiota as a key regulator of satiety signalling, linking the microbial environment of the gut to brain function via what is commonly termed the gut-brain axis. Emerging evidence suggests that gut bacteria and their metabolites, particularly short-chain fatty acids (SCFAs (sidenote: SCFAs Short Chain Fatty Acids are a source of energy (fuel) for the cells of the individual. They interact with the immune system and are involved in the communication between the intestine and the brain. Sources:
Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) ), are integral to satiety regulation, influencing the release of satiety hormones and modulating appetite. ^1,2,3

We invite you in this article to explores the growing body of evidence on the gut microbiota’s role in regulating satiety, focusing on microbial metabolites, their interaction with the gut-brain axis, and the implications for clinical practice. We will analyse how dietary interventions aimed at modifying gut microbiota composition, such as the use of probiotic, prebiotics and fiber-rich diets, can influence satiety and offer novel approaches for managing obesity and related metabolic conditions.

Gut-brain conversations: how the microbiota shapes satiety signals?

The gut-brain axis is an intricate network that communicates satiety signals between the gut and brain. This interaction is largely influenced by the gut microbiota, which regulates appetite through hormones like glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and cholecystokinin (CCK). These hormones are produced by specialized cells in the gut called enteroendocrine cells (EECs) in response to food intake.

Together, these hormones act on the brain to reduce food intake and prolong the feeling of fullness, helping to maintain a healthy balance in food consumption.

One of the microbiota’s key contributions is the production of SCFAs - acetate, propionate, and butyrate - during fiber fermentation. SCFAs stimulate the release of GLP-1 and PYY, reinforcing fullness and helping control appetite. ¹ Additionally, SCFAs interact with the vagus nerve, which directly connects the gut to the brain’s hunger centers, enhancing satiety signals. ²

The microbiota’s role extends beyond signaling; SCFAs also reduce inflammation in the hypothalamus, preserving the integrity of satiety regulation and helping prevent obesity-related metabolic disorders. ² But how do probiotic and specific dietary interventions, such as prebiotics, influence the gut microbiota to enhance satiety?

The role of probiotics in enhancing satiety signals

Recent studies have shown that certain bacteria can produce proteins that send signals to our brain, telling us we’re full. One example is a protein called ClpB, produced by some bacteria like Hafnia alvei. This protein behaves similarly to alpha-MSH, a hormone that helps regulate appetite. This protein stimulates the release of PYY, a hormone that promotes feelings of fullness and reduces appetite. ³

Preclinical studies have shown that Hafnia alvei can help reduce food intake and body weight gain in animal models by amplifying these satiety signals. ³ When used as a probiotic supplement, Hafnia alvei may enhance the feeling of fullness in humans, supporting healthy eating behaviors and contributing to long-term weight management. ⁴ Although more research is needed, early findings suggest that probiotics could offer a complement to dietary interventions aimed at controlling appetite and reducing excess weight. ³

Fueling satiety: how prebiotics and dietary fibers modulate the microbiota?

Dietary interventions, particularly those involving prebiotics and dietary fibers, offer a direct way to influence the gut microbiota and enhance satiety. Prebiotics are non-digestible food components that selectively stimulate the growth and activity of beneficial gut bacteria. A prime example is inulin, a fiber that increases the production of SCFAs, notably propionate and butyrate, which play a key role in satiety signaling. ²

In human studies, inulin-propionate ester (IPE) supplementation has shown promising results. For instance, subjects who consumed IPE experienced a decrease in ad libitum energy intake, meaning they naturally reduced their food consumption without conscious effort. ² The SCFAs produced from fiber fermentation, particularly propionate, directly stimulated the release of GLP-1 and PYY, enhancing feelings of fullness. ¹

Additionally, resistant starch, another fermentable fiber, has demonstrated its ability to reduce postprandial glucose levels and influence satiety hormones. One study showed that resistant starch supplementation over six weeks reduced leptin levels, a hormone involved in long-term energy balance, signaling improved appetite regulation. ¹

These examples highlight how fiber-rich diets can modulate gut microbial activity to positively affect satiety. But what about other microbial metabolites beyond SCFAs? How do they influence the central and peripheral regulation of hunger?

Beyond fiber: the role of neuroactive metabolites in appetite control

In addition to SCFAs, gut bacteria produce several neuroactive metabolites that play crucial roles in regulating appetite and satiety through both central and peripheral pathways. Among these, serotonin, gamma-aminobutyric acid (GABA), and dopamine are key neurotransmitters involved in modulating food intake and energy balance. ²

In the case of GABA, certain strains of Lactobacillus and Bifidobacterium can produce this neurotransmitter. GABA affects the hypothalamus, which is central to hunger regulation, by modulating neural circuits that control feeding behaviour. Studies have shown that germ-free mice exhibit altered GABA signalling, resulting in increased appetite, highlighting the critical role of gut-derived GABA in controlling hunger. ³

Moreover, dopamine, which is involved in food reward mechanisms, is also influenced by the gut microbiota. Imbalances in dopamine pathways can lead to overeating and even binge-eating behaviours, underscoring the microbiota’s potential role in managing not just hunger but food addiction.¹

Dysbiosis: when gut imbalance sabotages satiety

Dysbiosis, the imbalance or maladaptation of the gut microbiota, has emerged as a critical factor in the disruption of normal satiety signals. In individuals with obesity and metabolic disorders, dysbiosis is commonly observed, characterized by a reduction in microbial diversity and an overgrowth of certain pathogenic bacteria. ³ This imbalance can impair the production of key microbial metabolites, particularly SCFAs, which are essential for regulating the hormones responsible for satiety, such as GLP-1 and PYY. ¹

Research shows that individuals with dysbiotic microbiomes often exhibit elevated levels of the appetite-stimulating hormone ghrelin, leading to persistent feelings of hunger and difficulty in maintaining a healthy energy balance. ³ These disruptions highlight the importance of maintaining a healthy, diverse microbiota not only for digestive health but also for proper appetite regulation and long-term metabolic control.

Rewiring satiety: harnessing probiotic, prebiotics and fiber-rich diets for therapeutic gain

The therapeutic potential of probiotics, prebiotics and fiber-rich diets in modulating the gut microbiota offers a powerful tool to enhance satiety and manage metabolic disorders. ⁸ Research consistently shows that dietary fibers, such as inulin, fructooligosaccharides (FOS), and resistant starch, serve as critical agents in stimulating SCFA production - specifically butyrate, propionate, and acetate - which directly influence satiety regulation through the gut-brain axis. ⁹

The evidence points to a future where precision nutrition - tailored dietary interventions based on an individual’s microbiome profile - could be a key therapeutic strategy. ¹⁰ By targeting the microbiota with specific probiotic, prebiotics and fibers, clinicians can restore gut balance, enhance satiety, and help patients manage both appetite and metabolic health more effectively. As the understanding of the microbiota’s role in satiety deepens, it offers a new horizon of personalized therapies that go beyond traditional approaches to treating obesity and metabolic diseases. ¹¹