How butyrate modulates inflammation and overall health
Our gut depends on trillions of bacteria to facilitate digestion, immunity, and many other functions. Until recently, however, the mechanisms by which the microbiome regulates so many aspects of human health have remained elusive.
There are at least three nutritional strategies to support the microbiome and overall health.
- Probiotics are live bacteria that confer a health benefit if consumed in adequate amounts.
- Prebiotics are compounds in food that induce the growth of beneficial bacteria. They include fermentable fibers that generate butyrate (and other short-chain fatty acids) in the colon.
- Postbiotics are soluble factors secreted by live bacteria, providing physiological benefits to the host. They include vitamins, peptides, proteins, enzymes, fatty acids (including butyrate, acetate, and propionate) and other bioactive molecules that have beneficial effects within the gut and throughout the body.[1],[2]
Of all the postbiotic substances, butyrate is among the most commonly celebrated for its effects on health. It is produced by indigenous bacteria that ferment dietary fibers in the colon.[1] Healthy microbiomes have abundant populations of butyrate-producing species.[3],[4]
Aging, infections, antibiotic use, and low-fiber diets all cause a decline in butyrate production. This decline can trigger inflammation, damage the colon lining, and increase the risk of various diseases.[5],[6],[7] In fact, low butyrate levels are associated with asthma, colorectal cancer, diabetes, fatty liver, inflammatory bowel disease, kidney disease, and other ailments.[3],[8],[9],[10],[11],[12],[13]
It’s no wonder that scientists are investigating whether supplemental butyrate may reduce the risk of these and other diseases.[14]
Butyrate promotes colon health
Butyrate helps protect the lining of the colon, reduce inflammatory tone, and improve the microbiome.
Butyrate is necessary to support the health of colonocytes, cells that line the surface of the large intestine (colon).[15] Unlike other cells in the body that metabolize glucose, colonocytes rely on butyrate for most of their energy.[16],[17],[18]
Colonocytes begin to die off if they are deprived of butyrate.[16],[19] Their death damages the intestinal lining, promotes inflammation, and facilitates the expansion of pathogenic bacteria that irritate the bowel.[20],[21]
Butyrate helps protect the lining of the colon, reduce inflammatory tone, and improve the microbiome. Specifically, butyrate has been shown to:
- Stimulate the growth and survival of normal colon epithelial cells[22]
- Selectively inhibit the growth of cancer cells[23]
- Reduce excessive inflammation[24]
- Boost innate defenses against bacterial pathogens[25]
- Reduce oxidative stress[26]
- Strengthen the intestinal barrier (more below)
- Support regular bowel movements and alleviate constipation[27],[28]
- Increase sodium and water absorption in the colon, thereby reducing the risk of diarrhea.[29] [In a placebo-controlled trial with 60 adults, supplementation with sodium butyrate (1500 mg/day) and other short-chain fatty acids reduced the incidence of traveler’s diarrhea by more than 80% as compared to a placebo.][30]
Butyrate helps reduce gut inflammation
Butyrate reduces inflammation in part by strengthening the intestinal barrier.
Diverticulitis is the inflammation of pouches that can form in the intestines. In a randomized controlled trial of sodium butyrate (300 mg/day) in 52 people with diverticular disease, less than 7% of those in the butyrate group experienced clinical symptoms of diverticulitis, compared with slightly more than 31% in the placebo group.[31]
Butyrate reduces inflammation in part by strengthening the intestinal barrier. This barrier comprises a layer of cells that block pathogens, toxins, and other waste products in the gut from penetrating the gut wall and entering the circulation.[32]
Butyrate has been shown to work in multiple ways. It stimulates the innate immune response;[33] enhances the production of mucin, which protects the intestinal tract;[34],[35] and has a beneficial effect on “tight junctions,” the connections between gut cells.[36],[37],[38]
In animal models, butyrate supplementation has been shown to ameliorate a variety of disease conditions including diabetes, fatty liver, inflammatory bowel disease, lung inflammation, and kidney disease.[39],[40],[41],[42],[43],[44],[45] All of these conditions are associated with low butyrate levels in humans, so correcting this problem could potentially improve outcomes.
Can butyrate inhibit colon cancer?
In animals, supplemental butyrate has been shown to interfere with the development and progression of colorectal cancer.
Patients with colorectal cancer, or with colorectal adenoma (polyps), have lower levels of butyrate compared to healthy controls.[8],[46],[47],[48] In one study of colorectal cancer patients, butyrate levels were reduced by nearly a half as compared to a control group.[49] Low butyrate production is correlated with a greater potential for malignancy.[50]
High-fiber diets support healthier levels of butyrate-producing bacteria and can lower the risk of cancer by nearly a third as compared to traditional low-fiber “Western” diets.[8],[51],[52]
Interestingly, many of the beneficial effects of fiber are attributable to its ability to increase butyrate production.[53] Direct supplementation with butyrate has thus been considered as a possible preventive strategy. In animals, supplemental butyrate has been shown to interfere with the development and progression of colorectal cancer.[17],[54],[55],[56] These results obviously need to be confirmed in human studies.
Dietary sources of butyrate
The main way to increase butyrate is to consume more dietary fiber from a variety of sources.
Butyrate (as butyric acid) is found in the diet, with butter being the main source. In fact, the name comes from the Greek word for butter, the substance in which butyrate was first found.
One tablespoon of butter provides about 560 mg of butyric acid.[57] It is quite possible for an individual to consume in excess of one gram of butyrate in a day from butter along with other high-fat dairy products. However, butter is high in saturated fat and calories, so thankfully there are other sources of butyrate besides eating butter.
The majority of butyrate in the body is derived from dietary fibers that are fermented in the colon. Healthy individuals can produce up to 10 grams of butyrate per day. While levels can drop to 1 gram per day in extreme cases, the average is about 5 to 7 grams per day.[58] The amount of butyrate that is produced depends on the amount of dietary fiber that is consumed, and on the composition of the gut microbiome, which varies widely among individuals.[59],[60]
The main way to increase butyrate is to consume more dietary fiber from a variety of sources (fruits, vegetables, whole grains and legumes.) Increasing dietary fiber helps protect against colorectal cancer and many other conditions.56,[61] Experts recommend that adults consume at least 21 to 38 grams of fiber daily, depending on age and gender.[62]
It’s worth noting that some individuals experience bloating and abdominal cramps when they ramp up fiber intake, and they may not tolerate certain foods for this reason.[63],[64] It’s important to figure out what works best for your own digestive comfort.
The effects of probiotics and prebiotics on butyrate
Probiotic supplementation can enhance butyrate levels and improve the microbiome.
Probiotic supplementation can help enhance butyrate levels and improve the microbiome overall. Supplemental Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus, and/or Lactobacillus paracasei, were all shown to increase fecal butyrate levels after a month or more of daily supplementation.[65],[66],[67]
In studies of prebiotics, supplemental xylo-oligosaccharides (XOS) and arabinoxylan-oligosaccharides (AXOS) were shown to increase butyrate production as well.[3],[68],[69] The magnitude of the effect, however, depends on the individual’s microbiome: if butyrate-producing species have declined, prebiotics will be less effective at boosting butyrate levels.[70]
Results with supplemental fructo-oligosaccharides (FOS) have been mixed, with some studies showing an increase in butyrate production and other studies showing a decrease.[71],[72] Further studies are needed.
Human trials of butyrate supplementation
Butyrate supplementation may expand the populations of butyrate-producing bacteria.
As mentioned, oral butyrate supplementation is of great interest.[63] In two randomized, double-blind, placebo-controlled trials of diabetic adults, supplementation with sodium butyrate (600 mg/day for 45 days) significantly reduced blood markers of inflammation and oxidative stress as compared with placebo.[73],[74]
In one study of 60 diabetic adults who were overweight or obese, butyrate supplementation significantly decreased blood pressure as compared to a placebo.[74] In the same study, butyrate decreased circulating levels of high-sensitive C-reactive protein (hs-CRP). This protein is a marker for cardiovascular disease, so by reducing hs-CRP, butyrate may reduce this risk. Taken together, the results suggest that orally administered butyrate can have beneficial physiological effects at fairly low doses of 600 mg/day.[73],[74]
Butyrate supplementation may even improve the overall health of the microbiota by expanding the populations of butyrate-producing bacteria.[74],[75],[76] This newly-discovered property of butyrate has been described as a “virtuous circle” – wherein butyrate increases the abundance of butyrate-producing species, which then produce more butyrate, and so on. In one study there was even an increase in A. muciniphila,[74] a valuable bacterial species that assists with blood glucose control.[77],[78]
In sum, butyrate may be one of the most valuable postbiotic substances yet discovered, with significant implications for the microbiome and overall health. If you are contemplating butyrate supplementation, consider formulations comprising calcium butyrate and magnesium butyrate. They are sodium-free, and they provide essential calcium and magnesium along with butyrate.
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