Butyrate for Gut Health

Dr Carly Polland ND in autoimmune butyrate leaky gut Metabolites Prebiotics 07 Jul 2023 • 3 min read

Author Bio

Dr Carly Polland ND | Clinical Lead at Biomesight

Dr. Carly Polland is an integrative physician focused on the intersection of endocrinology and immunology with the microbiome. Early in her clinical practice, she focused on hormonal imbalances, but she quickly realized these patients also had digestive issues and autoimmune disease. She dug into the research and realized the microbiome was connecting these symptoms. Standard stool testing was not useful in decoding the microbiome so she upgraded to microbiome testing like Biomesight. She has used this technology for over 6 years to help her patients modulate their microbiomes and improve their symptoms.

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Butyrate is a short chain fatty acid produced by the microbiome and is probably one of the most important features of the microbiome.

How is butyrate produced?

Butyrate is primarily produced when certain bacteria ferment various starches¹  from the diet. Some bacteria can also use metabolites from other bacteria, like acetate and lactate¹ , to make butyrate. And lastly, some bacteria can use amino acids like lysine¹  to make butyrate. 

Which bacteria produce butyrate?

Butyrate is made primarily by bacteria in the Firmicutes phylum^{1 ,2}. The top butyrate producers tend to be Faecalibacterium, Blautia, and Roseburia³. Other important butyrate producers include Ruminoccocus, Eubacterium, Butyrivibrio, and Anaerostipes⁴, but there are a wide variety of bacteria at different abundances in the gut capable of producing butyrate. 

Why is butyrate important for gut health?

Butyrate maintains a healthy large intestine because it is the preferred source of fuel for colon cells². But it doesn’t just keep the colon cells thriving individually. It also maintains gut integrity¹, meaning it keeps those colon cells locked together, preventing leaky gut in the large intestine. Butyrate also regulates the immune response in the large intestine, essentially decreasing inflammation by decreasing IL-6 (inflammatory messenger) and increasing IL-10 (anti-inflammtory messenger)¹. Butyrate also helps to regulate motility in the large intestine, possibly by modulating serotonin¹. So butyrate is very important to basic functionality of the large intestine.

But butyrate also modulates the microbiome and is crucial for maintaining a healthy microbial ecosystem. 

• Prevents pathogenic bacteria from colonizing the large intestine¹
• Creates an anaerobic environment in the large intestine that prevents opportunistic bacteria (like Proteobacteria) from blooming¹
• Regulates the production of anti-microbial peptides by the immune system in the large intestine to keep pathogenic and opportunistic bacteria in check¹
• Protects the beneficial bacteria in the gut from excessive immune response so they can maintain a healthy population¹

So butyrate is not just important for gut health but it is also key to maintaining a healthy microbiome. 

Does butyrate have benefits outside the gut?

The main site of action for butyrate is the large intestine, but butyrate does have benefits outside the large intestine. The large intestine uses up about 70%¹ of butyrate produced by the microbiome. The remaining butyrate will be absorbed into the bloodstream where it will next go to the liver. The liver will use up about 28%¹ of the butyrate produced by the microbiome. In the liver, butyrate will impart benefits on blood sugar and cholesterol⁴. The remaining 2% of butyrate will enter systemic circulation where it can have impacts on the rest of the body. This can have benefits for cardiovascular health, brain health, metabolic health, autoimmune disease and more⁴. The research is ongoing, but it looks like butyrate can have benefits for most cell types, which means butyrate may help with many different health conditions.

If you have low production of butyrate in the large intestine, your large intestine may actually use up most of the butyrate, so you don’t get the extra benefits of butyrate. If you have really robust production of butyrate in your large intestine, then your liver and the rest of your body will get more butyrate.

How is butyrate anti-inflammatory?

A primary health benefit of butyrate is how it modulates inflammation, both in the large intestine and the rest of the body. In the large intestine, butyrate binds to free fatty acid receptors (FFAR) which results in production of anti-inflammatory messengers, such as IL-18¹². This may be important for cases of inflammatory bowel disease (IBD). Research shows patients with IBD may have lower amounts of butyrate and lower amounts of butyrate producers¹². Additional research indicates that IBD patients may need higher amounts of butyrate compare to healthy people to achieve the same anti-inflammatory effects¹². 

Butyrate also deactivates an enzyme involved in the expression of genes, histone deacetylase (HDAC)¹. By blocking this enzyme, butyrate helps keep potentially cancerous pathways turned off in the colon¹. Butyrate also helps to maintain healthy levels of TGF-B, which regulates how cells grow and divide, helping to destroy cells that are behaving irregularly, thereby preventing cancer in the colon¹. 

Butyrate is not just directly anti-inflammatory to cells. It also modulates the immune system. For healthy immune function, we need balance between the different types of T helper cells (Th): Th1, Th2, and Th17. We also need enough regulatory T cells (Tregs) to monitor the T helper cells, which is important for preventing autoimmune disease or achieving remission in autoimmune disease. When butyrate interacts with immune cells, it results in more Tregs, less Th17 cells, less Th1 and more Th2 cells¹. The net result is less inflammation and less autoimmune reactivity, which is largely driven by Th17 cells.¹ More Tregs is also important for preventing food allergies¹².

Butyrate also helps to maintain healthy levels of secretory IgA, which regulates the microbiome¹². It also may help to stabilize mast cells to reduce the release of histamine and other mast cell mediators¹². So butyrate may be important in cases of mast cell activation syndrome (MCAS).

Increasing Butyrate

The best way to increase butyrate is to increase the relative abundance of butyrate producers in the large intestine. You increase butyrate producers by feeding them what they like.

• Faecalibacterium: arabinogalactan⁵, inulin⁶, galactooligosaccharides⁷, green tea⁸
• Blautia: fructooligosaccharides⁹, omega-3⁹, type 4 resistant starch¹⁰
• Roseburia: fructooligosaccharides¹¹, galactooligosaccharides¹¹, xylooligosaccharides¹¹

 This is by no means an exhaustive list—it is just a starting point. Not all species within the same genus will have the same response to prebiotics, but in general most prebiotics are supportive of a decent amount of butyrate producers. 

What about supplementing with butyrate?

Oral butyrate will be absorbed in the small intestine and enter the bloodstream. In the small intestine, butyrate may have some anti-inflammatory effects, but small intestine cells do not utilize butyrate the way colon cells do. So butyrate in the small intestine is not as beneficial to the gut as butyrate in the large intestine. 

Oral butyrate absorbed into the bloodstream can have beneficial, anti-inflammatory effects on different organs. So if you want the systemic benefits of butyrate, then oral butyrate supplements may be beneficial, albeit expensive.

However, if you want the gut benefits of butyrate, supplementation is not going to be that helpful. Scientists are working on a way to formulate butyrate supplements so butyrate is not absorbed in the small intestine and does get to the large intestine, but for now, the best way to get butyrate in the large intestine is to have your microbiome make it. A compounding pharmacy can make butyrate rectal suppositories or enemas to deliver butyrate to either your rectum or sigmoid colon, but these will not deliver butyrate to the majority of your large intestine. 

Before making any changes, be sure to talk to your doctor first. If you have an overgrowth of bacteria in your small intestine, prebiotics are not appropriate for you at this time. 

References

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