The Gut Microbiota Also Communicates Through Intestinal Hormones

When we eat, the intestine does much more than digest and absorb nutrients. Within minutes, it recognizes what has arrived, assesses both the quantity and composition of the meal, and sends a series of signals to the pancreas, stomach, liver, and brain.

These signals help determine how much insulin should be released, how quickly food should move through the digestive tract, when gastric emptying should slow down, and when we begin to feel full.

Much of this response is coordinated by intestinal hormones. Over the last few years, it has become increasingly clear that the gut microbiota is one of their major regulators. By influencing their production and release, the microbiota helps regulate digestion, metabolism, blood glucose, intestinal motility, and even eating behavior.

 

The Gut Microbiota Regulates Enteroendocrine Cells

Some dietary components, particularly dietary fibers and non-digestible carbohydrates, pass through the small intestine without being absorbed and eventually reach the colon.

There, they become substrates for bacterial fermentation.

The gut microbiota possesses enzymes that the human body simply does not have. These enzymes enable intestinal bacteria to break down otherwise indigestible compounds and convert them into biologically active molecules known as microbial metabolites. Among the best studied are the short-chain fatty acids (SCFAs): acetate, propionate, and butyrate.

Each of these SCFAs has distinct biological functions, yet all three can also act as signaling molecules by activating specific receptors on different types of cells throughout the body.

Within the intestinal lining are specialized cells known as enteroendocrine cells, which are responsible for producing a wide range of intestinal hormones. Although they account for less than 1% of the intestinal epithelium, they are strategically distributed throughout the gastrointestinal tract.

These cells contain receptors capable of detecting both nutritional and microbial signals, including the SCFAs produced by intestinal bacteria.

When stimulated by microbial metabolites such as SCFAs, enteroendocrine cells release different hormones depending on their location within the intestine, the type of stimulus received, and the specific cell population involved.

Among the most important hormones produced by enteroendocrine cells are:

• GLP-1, which stimulates insulin secretion after meals and slows gastric emptying;
• PYY, which reduces intestinal motility and contributes to the feeling of fullness;
• GIP, which plays a key role in the insulin response to nutrients;
• Cholecystokinin (CCK), which promotes fat digestion, pancreatic enzyme secretion, and appetite regulation;
• Ghrelin, primarily associated with hunger signals and energy balance;
• Serotonin, which plays an essential role in intestinal motility, visceral sensitivity, and communication between the gut and the nervous system.

Enteroendocrine cells therefore act as genuine biological "translators." They receive information generated by the gut microbiota and convert it into hormonal signals capable of influencing the entire body.

The endocrine response depends not only on the presence of SCFAs but also on their concentration, the balance between acetate, propionate, and butyrate, the intestinal site where they are produced, and the responsiveness of receptors expressed by enteroendocrine cells.

Consequently, the same metabolite can have different physiological effects depending on the context. Elevated SCFA production may simply reflect healthy fermentation of dietary fiber, whereas under different conditions it may be associated with increased energy extraction from food or with reduced metabolic responsiveness to these signaling molecules.

 

Beyond Fiber: Bile Acids and Protein-Derived Metabolites

Short-chain fatty acids represent only one part of the communication between the gut microbiota and the intestinal endocrine system.

Bile acids also play a central role in this dialogue.

Produced by the liver and released into the intestine to facilitate fat digestion, bile acids are subsequently modified by bacterial enzymes, generating secondary bile acids with biological properties that differ from those of the original molecules.

These modified bile acids are recognized by specific receptors expressed on enteroendocrine cells, contributing to the regulation of hormone secretion and energy metabolism.

By altering the composition of bile acids, the gut microbiota can therefore modify the signals received by enteroendocrine cells.

Another important regulatory pathway involves protein and amino acid metabolism. During bacterial metabolism of tryptophan, for example, compounds such as indole are generated. These molecules can modulate intestinal cell activity and contribute to regulating endocrine function as well as communication between the microbiota and its host.

The endocrine response of the intestine therefore results from the integration of multiple signals derived from carbohydrates, lipids, proteins, dietary fiber, bile acids, and microbial metabolites.

 

When Communication Becomes Unbalanced

Changes in the composition and activity of the gut microbiota may alter microbial metabolite production, bile acid metabolism, receptor activation, and the secretion of enteroendocrine hormones.

These alterations have been associated with obesity, insulin resistance, and type 2 diabetes. However, establishing a direct cause-and-effect relationship remains challenging.

An altered microbiota may contribute to metabolic dysfunction, but diet, obesity, and changes in host metabolism can also reshape the intestinal microbial ecosystem.

As a result, a dynamic feedback loop develops in which diet, the gut microbiota, intestinal hormones, and metabolism continuously influence one another.

 

A New Way of Looking at the Gut Microbiota

Through the metabolites it produces, the gut microbiota helps determine how intestinal cells perceive a meal and which signals they send to the pancreas, the brain, the nervous system, and other metabolically active organs.

To fully understand the role of the gut microbiota, it is not enough to identify which microorganisms are present. It is equally important to understand what they produce, which cells they interact with, and which physiological responses they trigger.

The gut microbiota is far more than a collection of microorganisms living inside the intestine. It is an integral part of a sophisticated biological communication network in which nutrients, bacteria, endocrine cells, the nervous system, and metabolism constantly interact to maintain the body's physiological balance.