Butyrate and other short-chain fatty acids

What gut bacteria make from fibre and what the body needs these substances for.

How solid is the research? Promising

That gut bacteria make short-chain fatty acids from fibre and that these feed the gut cells is well established. Many effects on the immune system and metabolism, however, come from animal studies, and butyrate as a supplement has barely been studied.

Cause or consequence? Cause and consequence

Butyrate is made from fibre, processed by a species-rich flora. If it is missing, the gut wall is less well supplied and can become more permeable; this has been shown mainly in animal and cell experiments. A consequence that has consequences of its own.

Healthy state

Short-chain fatty acids Acids such as acetate, propionate and butyrate that gut bacteria make from fibre. They nourish the gut wall and act throughout the body. are produced when gut bacteria ferment fibre and resistant starch. The three most important are acetate, propionate and Butyrate A short-chain fatty acid and the main energy source for the cells of the colon wall. It strengthens the barrier and dampens inflammation. , roughly in a ratio of 3 to 1 to 1. Which ones form depends on the food: in one measurement in humans, inulin was fermented mainly to acetate and only in smaller parts to butyrate and propionate. They are formed mostly in the first section of the large intestine, where food arrives fresh. Further along it is mostly used up.

Butyrate is the main fuel of the cells of the large intestine. In isolated cells from the human colon, it covered about three quarters of oxygen consumption. Because the cells use a lot of oxygen in the process, the gut contents stay low in oxygen. This protects the beneficial, oxygen-avoiding bacteria. In addition, according to animal and cell experiments, butyrate promotes mucus production and the cohesion of cells, that is, the tightness of the gut barrier.

Propionate travels via the blood to the liver, where part of it is turned into sugar. Acetate reaches the whole body and serves muscles and fat tissue as energy. All three also act as messengers: via receptors such as GPR43 and by inhibiting certain enzymes (histone deacetylases), butyrate and propionate in particular promote regulatory T cells, which dampen inflammation. Other receptors in the gut wall stimulate hormones such as GLP-1 A hormone from the gut wall that controls insulin release after eating, slows the stomach and makes you feel full. Weight-loss injections mimic it. More in the chapter “GLP-1 from the gut: what bacteria do and what “natural Ozempic” cannot do” and PYY, which influence satiety and blood sugar. For propionate delivered to the colon, a study in humans showed less appetite and less weight gain.

Hardly any bacterium turns fibre into butyrate on its own. Bifidobacteria break down fibre into acetate and lactate, and butyrate producers such as Faecalibacterium prausnitzii, Roseburia or Eubacterium rectale (now often called Agathobacter rectalis) turn these into butyrate. The Mucus layer A gel layer of mucins on the gut wall that keeps bacteria at a distance. In the colon, the inner layer is almost free of microbes. More in the chapter “The mucus layer and additives” of the gut wall is food too: in moderation that is normal and healthy, as long as enough fibre keeps arriving.

Two things are easy to misunderstand. First: a stool test shows only a small remainder. By far the largest part of the fatty acids is already absorbed in the gut wall, so their amount in stool only roughly tells you how much was made. Second: fermentation produces gas. It also yields hydrogen and carbon dioxide, and some archaea turn these into methane. If you suddenly eat much more fibre, you often notice it first as bloating, which in healthy people mostly settles after a few weeks.

Bacteria make fatty acids from fibre. Butyrate fuels the gut cells, which use up oxygen in the process.

Disrupted state: causes and effects

If fibre is missing, butyrate production drops. The gut cells then switch to sugar and use less oxygen. More oxygen reaches the gut contents, which benefits germs such as E. coli or Salmonella. Mouse studies showed exactly this chain when antibiotics displaced the butyrate producers. If food is missing altogether, some bacteria turn to the mucus layer and break it down, which made the barrier thinner in mice.

Without fermentable carbohydrates, bacteria in the far end of the large intestine switch to protein. This produces substances such as ammonia, phenols and hydrogen sulphide, which can strain the gut lining. This also happens with slow gut transit: if contents sit for a long time, the carbohydrate food is used up and protein fermentation increases. Hard, infrequent stool is therefore not just uncomfortable but also shifts the metabolism of the microbiota. As a guide, Bristol stool types 3 and 4 count as ideal, that is, a soft sausage, smooth or with fine cracks.

How much butyrate someone produces depends strongly on their own Microbiome, gut microbiota The community of all microbes in the gut, mainly bacteria, plus viruses, fungi and archaea. Most live in the colon. More in the chapter “Building microbial diversity”. In a study with 174 adults, resistant potato starch raised butyrate the most, but not in everyone: those who had butyrate producers such as Eubacterium rectale (now often called Agathobacter rectalis) benefited much more. Inulin changed the microbiota but did not measurably raise butyrate in the stool.

The place of fermentation matters too. It belongs in the large intestine, but it can slip into the small intestine, for example with an overgrowth or too few cleaning waves. Then gas and acids form where they cause symptoms, and some people tolerate fibre badly at first. That does not mean fibre is wrong, but that dose, type and pace must suit your own situation.

Finally, an honest perspective: many of the effects described on the immune system, barrier and metabolism come from animal and cell experiments. In humans it is established that butyrate feeds the colon cells and that fibre increases its production. Whether adding individual fatty acids or supplements is worthwhile is far less clear than the benefit of a high-fibre diet.

Without fibre there is no butyrate. More oxygen reaches the gut, E. coli and protein fermenters grow.

Where it comes from and where it leads

The same symptoms can have different roots. This map shows what may be involved in this problem and what may follow from it.

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Connections, not certainty: a link means “can”, not “must”. What applies to you is best clarified in a talk with your doctor.

What often helps

Lifestyle

Diet, exercise, sleep, social contact and dealing with stress.

Fibre from many sources Legumes, whole grains, vegetables, nuts and seeds. Different fibres feed different bacteria and together produce more short-chain fatty acids. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [1]
Resistant starch It forms when cooked potatoes, rice or pasta cool down, and is found in green bananas, oats and legumes. Potato starch raised butyrate the most in one study. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [1]
Balance a lot of protein with fibre A lot of meat or protein powder with little fibre shifts fermentation in the large intestine towards unfavourable breakdown products. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.
Increase fibre in small steps Raise the amount over several weeks and drink enough. This gives the microbiota time to adapt, and bloating usually stays bearable. With a sensitive gut, well-cooked foods and small portions suit a start. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [2]
Use stool form as feedback Watch your Bristol stool form: types 3 and 4 count as ideal. Very hard, infrequent stool points to long transit with more protein fermentation. Enough fluid, exercise and fibre often help. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [3]

Natural supplements

Supplements do not replace a medical check-up. Discuss dosage and interactions with your doctor or pharmacist.

Butyrate capsules Sodium or calcium butyrate has been studied in small trials in ulcerative colitis and IBS, with mixed results. A large part is already absorbed in the small intestine; encapsulated forms are meant to prevent this. Fibre is the better-supported route. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [4]
Tributyrin Tributyrin is marketed as a precursor of butyrate. Human studies are still lacking. Experimental How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.
Partially hydrolysed guar gum A mild, well-tolerated soluble fibre that improved symptoms in IBS in a randomised, placebo-controlled trial. It suits a gentle start when other fibres cause a lot of bloating. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [5]

Medical treatments

Information, not a treatment recommendation. Decide together with a doctor. Approval and availability differ from country to country.

Butyrate enemas in ulcerative colitis For inflammation in the rectum, butyrate enemas added to standard treatment improved the outcome in a randomised trial. This is a medical treatment, not a self-experiment. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [6]
Have strong symptoms after fibre checked If even small amounts of fibre trigger severe bloating or pain, small intestinal bacterial overgrowth or another digestive disorder may be behind it. A breath test and a talk with your doctor can clarify this before you give up fibre altogether. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [7]

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How we rate the evidence

Trust score 5 of 5:Established: Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies.
Trust score 4 of 5:Well supported: Several randomised studies in humans with largely consistent results.
Trust score 3 of 5:Promising: Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies.
Trust score 2 of 5:Plausible: Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms.
Trust score 1 of 5:Experimental: Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

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