Blog Post

Butyrate: Everything You Need To Know

Butyrate

Butyrate is one of the three primary short-chain fatty acids (SCFA), alongside acetate and propionate that is produced in our gut.

This tiny molecule has been shown to have far-reaching effects, from supporting gut health to lowering inflammation.

Dietary Sources

Dietary Fibre

Butyrate actually comes from the Latin word ‘butyrum’, which means butter. Butter contains 3-4% butyric acid, making it the richest dietary source of butyrate.

Despite this, most of this SCFA is produced by gut bacteria when dietary fibre is ingested.

Therefore, to increase butyrate production you should consume a variety of fruits, vegetables, legumes, whole grains, and nuts/seeds.

Aim for at least 25-30g fibre per day.

You can also get butyrate through supplements such as sodium butyrate. This could be considered in some situations such as serious GI disorders, IBD or antibiotic consumption, as these can reduce butyrate synthesis. Supplements often are associated with an unpleasant taste and odour.

Anti-inflammatory Effects

Butyrate has been shown to reduce the activation of a molecule called NF-kB, which is responsible for increasing the production of inflammatory cytokines such IL-1b, & TNF-α.

Higher levels of butyrate have also been shown to increase the production of glutathione, an antioxidant produced in the body that can help neutralize free radicals in the gut.

Gut Barrier Integrity

how does leaky gut work?

The lining of your intestines serves as a crucial barrier between the contents of your gut and the rest of your body.

Usually, small molecules like nutrients are able to pass through. When this barrier becomes compromised, larger molecules, harmful bacteria, and toxins can pass through into your bloodstream, triggering inflammation.

Butyrate plays a vital role in preserving the integrity of this gut barrier. This is because it serves as a primary energy source for the cells lining our gut, known as colonocytes, and provides about 70% of their energy.

Subsequently, this helps to maintain the integrity of the gut lining, decreasing the permeability.

As a result, it has been shown to reduce the production of pathobionts and decrease several markers of inflammation.

Immune Function

Immune cells

Butyrate plays a role in the modulation of immune cells such as macrophages, T cells, and dendritic cells by increasing their functionality and also prevents excessive damage and inflammation caused by other molecules.

Through butyrate’s effect on influencing inflammation and immune function, it has been investigated for its potential role in the prevention and management of various diseases.

Colorectal Cancer

Colorectal cancer

It is well known that dietary fibre, and subsequently an environment encouraging butyrate production, is associated with being a protected risk factor for developing colorectal cancer.

One study highlighted its ability to inhibit glucose metabolism and DNA synthesis of colorectal cancer cells through the suppression of various pathways. The same study showed that it promoted the efficacy of chemotherapy on colorectal cells.

Another study found that sodium butyrate stopped the growth of colorectal cancer cells and caused cancer cell death (known as apoptosis). 

Butyrate has also been demonstrated to increase intestinal motility. This contributes to reducing the exposure of the mucosa to luminal carcinogens and may also partly explain the observational outcomes.

Other mechanisms may be through its ability to suppress the angiogenesis, metastasis, and proliferation of colorectal cells themselves

It’s important to note that most of the studies directly looking at the anticarcinogenic effects of Butyrate on colorectal cancer have been done in vitro or in animal models, therefore more research is needed in humans.

However, the numerous mechanisms and observational data linking dietary fiber overall show positive outcomes.

Effect of butyrate on intestinal health.
(Wu et al., 2018)

Irritable Bowel Syndrome (IBS)

IBS

A randomized control trial found that those who supplemented 300mg per day (150mg twice daily) of sodium butyrate for 4 weeks, reported a reduction in pain during defecation compared with the control group and saw improvements in urgency after 12 weeks.

Additionally, a prospective study including almost 3000 participants with IBS, showed significant improvements in the severity of abdominal pain, flatulence, diarrhea, constipation, urgency of bowel movements, nausea, and vomiting, after 12 weeks of 150mg twice daily supplementation of sodium butyrate.

Another study found that after 6 weeks of supplementation led to improvements in abdominal pain and discomfort, defecation rhythm, and improved quality of life compared with placebo.

As the passive absorption of water in the colon can be influenced by the presence of SCFA, this may partly explain the improvements seen in IBS-D.

Inflammatory Bowel Disease (IBD)

Intestinal dysbiosis has been proposed as being one of the primary mechanisms of the pathogenesis of IBD. Subsequently, butyrate and its role in the correction of gut dysbiosis has been explored as a potential approach to successfully reequilibrate inflammatory responses in IBD.

IBD: Ulcerative Colitis vs Crohn's Disease

Crohn’s Disease (CD)

There are limited studies looking directly at butyrate in Crohn’s disease.

One study had 13 people with CD take 4g butyric acid per day for 8 weeks. 9 patients (69%) reported significant clinical improvements, with 7 of them (53%) achieving remission.

Ulcerative Colitis (UC)

One study looked at 22 patients with quiescent UC who added 60 g oat bran (corresponding to 20 g dietary fiber) to their daily intake for 4 weeks. They saw a 34% increase in fecal butyrate and had significant improvements in abdominal pain and reflux symptoms.

In a double-blind, placebo-controlled trial 51 patients with active distal UC were split into two groups: one taking Mesalamine (IBD medication) + 80mmol/L twice daily of sodium butyrate or Mesalamine alone.

Remission occurred in 6 patients taking the medication + butyrate supplement and 12 saw clinical improvements in symptoms. On the other hand, only 1 had remission in the medication-alone group, but 13 saw improvements.

The number of bowel movements, urgency, and the patients’ self-evaluation were also significantly greater in the medication + butyrate group.

Another study involved 10 patients with distal ulcerative colitis who had been unresponsive to or intolerant of standard therapy for 8 weeks. They were treated for 2 weeks with sodium butyrate (100 mmol/L per day) and 2 weeks with placebo in random order.

After butyrate irrigation, stool frequency (n/day) decreased from 4.7  to 2.1 and discharge of blood ceased in 9 of 10 patients. Endoscopic scores, crypto proliferation, and histological inflammation also significantly improved. In the placebo group, all of these parameters were unchanged.

Other studies that have looked at specific bacterial species that are known to produce substantial amounts of butyrate, show an inverse correlation of these with IBD disease severity.

Insulin Sensitivity

BGL reading

Butyrate has been linked to improved insulin sensitivity, potentially reducing the risk of type 2 diabetes.

This is because it has been shown to induce the production of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), which in turn stimulate insulin secretion and therefore decrease blood sugar levels.

This is highlighted through other studies, where a reduction in butyrate-producing bacteria led to adverse effects on glucose metabolism after an OGTT. Additionally, high amounts of butyrate were associated with improved insulin response from the same test.

Studies where fecal transplant occurs between lean and obese individuals, which then lead to changes in the composition of the gut microbiome, showed improvements in insulin sensitivity.

It has also been well-researched that individuals living with T2DM have a reduction of butyrate-producing bacteria.  

Weight Management

Scale and tape measure

It is proposed that butyrate may enhance feelings of fullness and satiety, which could potentially lead to reduced food intake.

This effect may be mediated by its influence on the release of gut hormones like glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), which are involved in appetite control.

It’s important to note that most of the research showing positive outcomes has only been conducted in animal models.

The limited number of human studies that are available show inconsistencies due to the complicated nature of metabolic and lifestyle-related variables.

Overall, more research is needed to generalize these satietogenic effects of butyrate on humans

Neurodegenerative Disease

Brain health

The gut microbiota is recognized as being a crucial factor for various brain-related physiological functions and has subsequently been explored in relation to various neurodegenerative diseases.

In vivo studies and animal studies also suggest that butyrate can influence the CNS by reducing blood-brain barrier permeability and relieving symptoms of anxiety and depression.

Several molecules such as lipopolysaccharides (LPS), and trimethylamines (TMAs) are associated with the permeability of BBB and have been shown to be causal factors of neuroinflammation or neurodegeneration.

Therefore, the potential mechanism role that butyrate plays in decreasing this permeability may translate to a reduction in this neuroinflammation.

Parkinson’s Disease

There is a strong link between a reduced abundance of SCFA-producing bacteria and Parkinson’s disease (PD) across studies.

Fecal samples from PD patients have been shown to consist of significantly lower concentrations of butyrate when compared to healthy controls, as well as other butyrate-producing bacteria.

Alzheimer’s Disease

Sodium butyrate may be a potential therapeutic agent through improving some of the causes of AD such as amyloid beta accumulation, tau pathology, oxidative stress, and inflammation and glucose metabolism.

It has also been shown to improve memory in mouse models with Alzheimer’s.

Overall, the studies looking at neurodegenerative diseases are either observational in manner or are conducted in cell or animal models. This is important to consider before drawing strong conclusions, however, the mechanisms are viable.

The proposed mechanisms for the neuroprotective effects of butyrate and the diseases which may benefit from butyrate treatment or a high fiber diet.
(Bourassa et al., 2016)

Cardiovascular Disease

Dysbiosis of gut microbiota is now being recognized as a factor involved in the development of CVD.

Additionally, some prominent butyrate-producing bacteria have been shown to be reduced with atherosclerosis, contributing to the progression of the disease.

Similar findings of reduced bacteria are also evident in those with heart failure.

Some researchers suggest that this may be because the amount of butyrate-producing bacteria is negatively associated with blood pressure.

Additionally, butyrate can help mitigate excessive amounts of adhesion molecules.

Summary

Butyrate, like most aspects associated with the gut microbiome, can be very complex.

The lack of human trials directly focusing on butyrate (rather than fibre) and specific outcomes makes it difficult to extrapolate findings. However, the mechanisms shown through non-human studies do highlight a lot of potential.

From what we know though, consuming adequate dietary fibre is associated with an array of health outcomes and will naturally increase butyrate production and should ultimately be something to aim for.

By Josh Wernham

Josh is a Dietitian based in Brisbane who's passion for nutrition stemmed from an interest in optimising sports performance and body composition. He has a lot of experience in bodybuilding style training and also has a background in team sports, strength and endurance events. As he has grown in the field, this enthusiasm has extended beyond just sports and continuously immerses himself in the latest research to support those with general health conditions. He strives to help a range of individuals, from athletes to anyone seeking to improve the quality of their life.