Do Gut Microbiota Play an Important Role in Regulating Food Intake and Satiety?

• A review published in the Journal of Physiological Sciences discussed how the human body regulates satiety and food intake.
• GLP-1 encourages the development of various advantageous bacteria in the gut, making it easier to produce satiety-related microbial products.
• Gut microorganisms that produce short-chain fatty acids stimulate cells in the colon lining to produce GLP-1 and other hormones.
• Other types of gut microorganisms produce substances that can affect inflammatory processes in the hypothalamus, disrupting or restoring the functionality of the body’s food intake regulation mechanism.

Living beings need to eat to stay alive. Multiple times daily, processes in our body tell our brain that we need to eat. We feel hunger, prompting us to look for food and eat it. After we have eaten, we feel satiated. This cycle continues as long as we live. But how does this function on the neural and biochemical level?

Hunger and satiety

A complex interaction between the digestive system, the brain, and various hormones regulates hunger and satiety. Satiety is the feeling of being full or satisfied after eating. It’s a physiological state where the body senses that it has consumed enough food. This allows it to regulate how much and how often a person eats. Satiety is influenced by various factors, including the type and volume of food consumed, its nutrient content, and hormonal responses during and after a meal. 

When the stomach is empty, the hormone ghrelin is released, which signals the brain to trigger feelings of hunger. After eating, the stomach and intestines produce hormones like glucagon-like peptide-1 (or GLP-1), peptide YY (PYY), and others, signaling the brain to produce feelings of satiety. Leptin, a hormone primarily produced by fat tissue, acts in a similar fashion, signaling the brain to suppress appetite. The more fat tissue there is, the higher the production of leptin (Hedrih, 2023; Stevenson et al., 2023; Swami et al., 2022) (see Figure 1).

 

Figure 1. Complex interaction between the digestive system, brain, and hormones to regulate hunger and satiety

 

These hormones act on the hypothalamus, a region of the brain that plays a key role in regulating hunger and satiety. This structure of the brain contains groups of neurons that increase the feeling of satiety, such as the pro-opiomelanocortin (POMC) and cocaine–amphetamine-regulated transcript-containing (CART) neurons, but also those that trigger appetite and eating behaviors—neuropeptide Y (NPY) and agouti-related peptide (AgRP) (Barakat et al., 2024).

AgRP neurons are also known as “hunger neurons” because studies demonstrate that artificially triggering them (in rodents) initiates feeding behavior (Chen et al., 2016) (see Figure 2).

 

Figure 2. “Hunger and satiety neurons” in the hypothalamus

 

The sensation of hunger

Hunger is not only a physiological process but also a subjective sensation. This sensation makes us more sensitive to stimuli related to food, pay more attention to food items and to things we learned to associate with food (e.g., restaurant or food brand logos), and be willing to eat (Hedrih, 2023; Lazarus et al., 1953; McKiernan et al., 2008).

 

Hunger is not only a physiological process but also a subjective sensation

 

Scientists initially thought that hunger results from decreased levels of nutrients in the body (e.g., lower blood sugar levels, decreased fat contents, empty stomach), but more novel studies indicated that many other conditions can trigger this sensation. These include (but are not limited to) boredom, desire for sensory stimulation, lack of sleep, and chronic stress (Brondel et al., 2010; Hedrih, 2023; Levine & Morley, 1981; McKiernan et al., 2008; Swami et al., 2022). Also, humans and animals can develop eating habits at specific times. These habits make them feel hungry when what they perceive as mealtime arrives (Isherwood et al., 2023) (Nutritional Psychology Research Library, 2024) (see Figure 3).

 

Figure 3. Factors influencing our sense of hunger

 

The role of GLP-1 and gut microbiota in satiety

In their review, Ghinwa M. Barakat and her colleagues note that recent discoveries indicate that gut microbiota, the community of microorganisms living in our gut, play an important role in human metabolism. This became particularly evident with the discovery of the microbiota-gut-brain axis, a bidirectional communication pathway that allows gut microbiota to influence processes in the brain and vice versa (Barakat et al., 2024; Bonaz et al., 2018; Heiss et al., 2021).

Recent findings indicate that GLP-1 hormone might be particularly important for gut microbiota’s role in the feeling of satiety. GLP-1 is produced by specialized endocrine cells located in the lining of the small intestine and the colon called L cells. Receptors for this hormone, i.e., proteins on the surface of cells that react with it, are abundant in the hypothalamus, particularly in the arcuate nucleus region. Studies have demonstrated that injections of GLP-1 and medicines that behave like GLP-1 in the body reduce food intake (Barakat et al., 2024; Heiss et al., 2021) (see Figure 4).

 

Figure 4. GLP-1 hormone stimulates the feelings of satiety

 

Recent studies on mice indicated that Liraglutide, a substance commonly used to treat diabetes and obesity, mimics the effects of GLP-1 and can also affect the gut microbiota composition. High levels of GLP-1 or substances that act like it seems to help enrich microbiota strains more abundant in lean individuals and reduce the abundance of strains of microorganisms more common in obese individuals. For example, these injections increased the amounts of Akkermansia muciniphila, a species known to be more present in the gut when an individual loses weight and in lean individuals. On the other hand, it reduces the amount of Proteobacteria, which is more abundant in obese individuals.

Gut microbiota participate in satiety hormone regulation

Studies also indicate that gut microbiota might participate in regulating the release of satiety hormones. The authors of this review point to several studies indicating that some short-chain fatty acids (SFCAs) produced by gut bacteria increase the production and release of GLP-1 into the bloodstream. If more gut bacteria produce these substances, the digestive system lining will produce more GLP-1, sending a stronger satiety signal to the brain.

This effect is achieved through specific receptors on the intestine’s GLP-1-producing cells, which react to short-chain fatty acids, such as acetate, propionate, and butyrate, produced by gut bacteria (see Figure 5).

 

Figure 5. Role of gut microbiota in regulating satiety hormone secretions

 

Gut microbiota affect inflammatory processes

Another way in which gut microbiota can affect satiety is by affecting the inflammatory processes in the hypothalamus. Specific species of gut microorganisms can produce substances that increase inflammatory processes in the hypothalamus. This reduces its ability to regulate appetite (e.g., through reducing sensitivity to leptin). These types of bacteria tend to be more abundant in the guts of obese individuals. Studies on mice indicated that this could be countered by introducing bacteria into the gut that have the opposite effect, such as Lactobacillus rhamnosus, Lactobacillus acidophilus, and Bifidobacterium bifidum. Research results indicate that these bacteria restore sensitivity to leptin, thus helping reduce excessive weight (see Figure 6).

 

Figure 6. Role of gut microbiota in leptin sensitivity

 

Conclusion

The review discusses the various mechanisms through which the body regulates food intake and satiety. It points to the important role gut microorganisms play in this system and how it can be affected by gut microbiota.

The presented findings potentially open a new avenue of research to look for methods to prevent and treat obesity by influencing the gut microbiome. Future discoveries may lead to a new group of obesity treatments based on probiotics, devise ways to detect developing obesity, and allow effective prevention.

The paper “Satiety: a gut–brain–relationship” was authored by Ghinwa M. Barakat, Wiam Ramadan, Ghaith Assi, and Noura B. El Khoury.

For more information on mechanisms influencing dietary intake and food satiety, enroll in NP 150: Mechanisms in the Diet-Mental Health Relationship (DMHR). Find NP 150 and other courses in the DMHR through The world’s leader in nutritional psychology education here.  

 

References

Barakat, G. M., Ramadan, W., Assi, G., & Khoury, N. B. E. (2024). Satiety: A gut–brain–relationship. The Journal of Physiological Sciences, 74(1), 11. https://doi.org/10.1186/s12576-024-00904-9

Bonaz, B., Bazin, T., & Pellissier, S. (2018). The vagus nerve at the interface of the microbiota-gut-brain axis. Frontiers in Neuroscience, 12(FEB). https://doi.org/10.3389/fnins.2018.00049

Brondel, L., Romer, M. A., Nougues, P. M., Touyarou, P., & Davenne, D. (2010). Acute partial sleep deprivation increases food intake in healthy men. The American Journal of Clinical Nutrition, 91(6), 1550–1559. https://doi.org/10.3945/ajcn.2009.28523

Chen, Y., Lin, Y.-C., Zimmerman, C. A., Essner, R. A., & Knight, Z. A. (2016). Hunger neurons drive feeding through a sustained, positive reinforcement signal. eLife, 5, e18640. https://doi.org/10.7554/eLife.18640.001

Hedrih, V. (2023). Food and Mood: Is the Concept of ‘Hangry’ Real? CNP Articles in Nutritional Psychology. https://www.nutritional-psychology.org/food-and-mood-is-the-concept-of-hangry-real/

Heiss, C. N., Mannerås-Holm, L., Lee, Y. S., Serrano-Lobo, J., Håkansson Gladh, A., Seeley, R. J., Drucker, D. J., Bäckhed, F., & Olofsson, L. E. (2021). The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism. Cell Reports, 35(8). https://doi.org/10.1016/j.celrep.2021.109163

Isherwood, C. M., van der Veen, D. R., Hassanin, H., Skene, D. J., & Johnston, J. D. (2023). Human glucose rhythms and subjective hunger anticipate meal timing. Current Biology, 33(7), 1321-1326.e3. https://doi.org/10.1016/j.cub.2023.02.005

Lazarus, R. S., Yousem, H., & Arenberg, D. (1953). Hunger and Perception. Journal of Personality, 21(3), 312–328. https://doi.org/10.1111/J.1467-6494.1953.TB01774.X

Levine, A. S., & Morley, J. E. (1981). Stress-induced eating in rats. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology, 241(1), R72–R76.

McKiernan, F., Houchins, J. A., & Mattes, R. D. (2008). Relationships between human thirst, hunger, drinking, and feeding. Physiology & Behavior, 94(5), 700. https://doi.org/10.1016/J.PHYSBEH.2008.04.007

Nutritional Psychology Research Library (NPRL). (n.d.). The Center for Nutritional Psychology. Retrieved May 1, 2024, from https://www.nutritional-psychology.org/np-research-library/

Stevenson, R. J., Bartlett, J., Wright, M., Hughes, A., Hill, B. J., Saluja, S., & Francis, H. M. (2023). The development of interoceptive hunger signals. Developmental Psychobiology, 65(2), 1–11. https://doi.org/10.1002/dev.22374

Swami, V., Hochstöger, S., Kargl, E., & Stieger, S. (2022). Hangry in the field: An experience sampling study on the impact of hunger on anger, irritability, and affect. PLOS ONE, 17(7), e0269629. https://doi.org/10.1371/JOURNAL.PONE.0269629