We are bacteria as much as we are human. For a given individual, the most recent estimated ratio of bacterial cells to human cells is roughly 1:1. Therefore, it is no wonder that the molecules made by bacteria living in and on us can greatly impact our well-being. Of particular interest are the bacteria that live in our intestines — the gut microbiota. Through their roles in digestion and communication along the gut-brain axis, they can impact our health from nutrient availability to weight gain. While it often seems that imbalances in the gut microbiome can be the root of many problems, it is also apparent that the trillions of bacteria that live there also provide important benefits to our overall health.

One such benefit is the production of short-chain fatty acids (SCFA) in the gut. SCFA are a class of small molecules that are the primary metabolic output of the gut microbiome. These small fatty acids are produced during the digestion of dietary fibers and starchy foods (also known as complex carbohydrates) in the colon, with the most common SCFAs being acetate, propionate, and butyrate. These three molecules constitute more than 95% of the SCFAs produced by gut bacteria. Because these fatty acids are produced in such high quantities in the gut, their presence has become a crucial factor in maintaining both a healthy digestive tract and body. For example, the presence of acetate has been observed to have a positive effect on exercise endurance in laboratory mice. Similarly, a recent study has shown that athlete microbiomes have higher proportions of SCFA-producing bacteria than their inactive counterparts. Furthermore, a chemical derivative of propionate called indole-3-propionic acid was demonstrated to play a key role in nerve repair and regeneration in mice models.

As such, acetate and propionate are good examples of how gut metabolites can impact physical health — but what about mental health? Butyrate is a short-chain fatty acid that has been consistently linked to mental health outcomes with particular connections to depression. 

What is Butyrate?

Butyrate is a short-chain fatty acid (SCFA) produced in the colon through the fermentation of dietary fiber by beneficial gut microbiota. As one of several SCFAs, it plays a critical role in maintaining gut health and overall physiological balance.

One of butyrate’s primary functions is serving as a key energy source for colon cells (colonocytes), meeting approximately 70% of their energy demands. Beyond its metabolic role, butyrate has been recognized for its potential health benefits, including modulation of the immune system, reduction of inflammation, and possible protective effects against conditions such as colorectal cancer.

Forms of Butyrate

Butyrate exists in several forms, each with distinct applications in health and industry. The most common form is butyric acid (also known as butanoic acid), which is naturally occurring and also used in food products and dietary supplements. Additional forms of butyrate include:

• Ethyl butyrate: Commonly used as a flavoring agent to enhance the taste and aroma of various food products.
• Hydrocortisone butyrate: A corticosteroid applied in medical treatments for its anti-inflammatory properties.
• Sodium butyrate: Often found in dietary supplements, supporting gut health and metabolic processes.

The various forms of butyrate contribute to its broad applications in nutrition, medicine, and the food industry, highlighting its importance in maintaining health and well-being.

Butyrate for Gut Health

Samples taken from human gut microbiomes have shown that two known butyrate-producing bacteria, Faecalibacterium and Coprococcus, were associated with positive indicators of quality of life. Moreover, the same study highlighted that patient samples with self-reported depression also had diminished populations of Coprococcus. In a separate study, patient samples indicated decreased levels of another butyrate-producing bacterium —Fusicatenibacter saccharivorans — as associated with feelings of anxiety and depression. More and more, it is becoming very clear that the gut microbiome is an important player in affecting how we feel, with butyrate playing a key molecule in this connection. One working hypothesis might be that butyrate positively influences levels of brain-derived neurotrophic factor — a protein important for brain cell maintenance and growth. The gut microbiota produces the SCFA butyrate (molecule shown) which has beneficial effects on our health.

Although it’s not clear how butyrate mechanistically improves depression, it is evident that it is an approach worth exploring for its treatment. In animal models it has already been shown that supplementation of sodium butyrate can alleviate depression-like behaviours. In one of these studies, depression-induced mice treated with sodium butyrate revealed changes in neural cell DNA packaging leading to the expression of genes in the brain that elicit anti-depressive effects. Human clinical trials are underway to specifically test the role of butyrate supplementation in the treatment of depression.

What Foods Contain Butyrate?

One can still work towards potentially improving personal butyrate levels through dietary means. As noted above, short-chain fatty acid production comes from the digestion of fibers and starches. To enhance butyrate production, consuming a diet rich in fermentable fiber is essential. Foods that support this process include fruits such as apples, bananas, pears, and raspberries, as well as fiber-rich vegetables and legumes like broccoli, carrots, chickpeas, and leafy greens. Whole grains and resistant starches, such as boiled potatoes and rice, also contribute to butyrate synthesis. Additionally, full-fat dairy products, including butter, cheese, and milk, can be included in moderation due to their high saturated fat and cholesterol content. When increasing fiber intake, it is important to do so gradually while ensuring adequate hydration to prevent digestive discomfort such as bloating or constipation. Maintaining proper fluid intake helps optimize digestion and fiber utilization, promoting gut health and overall well-being.

Butyrate is truly a multifunctional short-chain fatty acid. It is noteworthy to mention that in addition to its related effects on depression, butyrate has several other health benefits such as controlling inflammation and maintaining the intestinal barrier (that is, avoiding leakiness). Therefore, keeping your gut bacteria happy with complex carbohydrates can keep you happy too!