Butyrate (Butyric Acid)

Fuels the colon

Butyrate is a four-carbon short-chain fatty acid. Bacteria in the colon make it by fermenting fibre and resistant starch that the small intestine couldn't digest. The main producers are Faecalibacterium prausnitzii, Roseburia and Eubacterium rectale. Gut lining cells (colonocytes) take butyrate up and burn it in their mitochondria through fat oxidation.

It's their preferred fuel. In colon cells taken from surgical patients, butyrate accounted for about 70–75% of the cells' oxygen use when it was the only fuel offered, and they still preferred it over glucose when both were present.¹ That's unusual. Most cells in the body run mainly on glucose, but the colon lining runs on food its bacteria make.

What happens when the supply stops. When surgery diverts faeces away from a section of colon, that section gets no fibre and so no butyrate, and it becomes inflamed and bleeds (diversion colitis). In four patients, running a short-chain fatty acid solution into the cut-off section twice daily cleared symptoms and inflammation within 4–6 weeks.² Starve the colon lining of its bacterial fuel and it breaks down. Give the fuel back and it recovers.

Strengthens the gut lining

Burning butyrate does more than feed the colon lining. It also uses up oxygen. When colonocytes oxidise butyrate, they use so much oxygen that the inner surface of the colon stays almost oxygen-free. That has two effects:

• It strengthens the barrier. Low oxygen stabilises HIF-1, a transcription factor that switches on barrier-protecting genes in the gut lining. In mice and cultured cells, depleting butyrate-producing bacteria lowered HIF signalling and made the barrier leakier, and adding butyrate back restored it.³ Butyrate also tightens the junctions that seal gut lining cells together.
• It keeps harmful bacteria in check. Butyrate activates PPAR-γ in colonocytes, which keeps them burning fat (using oxygen) instead of glucose and suppresses nitrate production. When antibiotics wipe out butyrate producers, the gut surface gets more oxygen and nitrate, which favours oxygen-tolerant E. coli and Salmonella (Enterobacteriaceae) over the beneficial strict anaerobes.⁴

In people, patients with ulcerative colitis have markedly fewer of the main butyrate producers, F. prausnitzii and Roseburia hominis.⁵ Whether that's a cause or a result of the disease isn't settled, and trials of butyrate supplements in IBD are small and mixed. This claim is marked "early" because the mechanism is from animals and cells, and the human data are associations.

Calms immune signaling

Butyrate acts on immune cells through two routes:

• As an HDAC inhibitor. Histone deacetylases (HDACs) remove acetyl tags from DNA-packaging proteins, which keeps genes switched off. Butyrate blocks them, so genes it would normally silence stay active. In T cells, one of those is Foxp3, the master switch for regulatory T cells (Tregs), which hold back inflammation. In germ-free mice, butyrate from gut bacteria raised Foxp3 activity, expanded colon Treg numbers and protected the mice from colitis.⁶
• Through receptors. Butyrate binds GPR43, GPR41 and GPR109A on gut lining and immune cells. Through GPR109A, it pushes macrophages and dendritic cells to make IL-10 (calming) rather than IL-6 and IL-17 (inflammatory).

The overall effect, in animals, is a gut immune system that tolerates food and resident bacteria instead of attacking them. Human evidence is indirect: fewer butyrate producers in inflammatory bowel disease, and lower faecal butyrate in some allergic and autoimmune conditions. No trial has shown that raising butyrate prevents these diseases.

How to get it

There's no RDA, because the body makes butyrate from what reaches the colon. Eating butyrate directly mostly doesn't work: butter is about 3–4% butyrate, and most of it is absorbed before reaching the colon. What matters is feeding the bacteria that make it. See Fiber and resistant starch.

Top foods

• Lentils and black beans: rich in resistant starch and fermentable fibre
• Oats and barley: beta-glucan and resistant starch
• Cooked-and-cooled potatoes or rice: cooling turns some starch into resistant starch (retrogradation)
• Onion, garlic, leeks: inulin and fructans, which feed the bacteria that cross-feed butyrate producers
• Butter and ghee: a little direct butyrate, mostly absorbed higher up the gut

Go slowly. Adding a lot of fermentable fibre at once causes gas and bloating while the bacteria adjust. Increase over 2–3 weeks.