Gallstones

How Gut Bacteria Change the Chemistry of Bile

The evidence here is strong for a condition usually explained without mentioning bacteria at all. Most gallstones are made of cholesterol that has come out of solution in bile and hardened. Bile is the fluid the liver makes to help digest fat, and it's stored in the gallbladder between meals. Whether cholesterol stays dissolved depends on the mix of bile acids around it, and gut bacteria are what determine that mix.

The chemistry bacteria control

The liver makes primary bile acids and releases them into the gut with each meal. Most are reabsorbed further down and returned to the liver.

On the way, gut bacteria modify them. Some strip off an attached amino acid. Others perform a reaction called dehydroxylation, converting primary bile acids into secondary ones. Only a small number of bacterial species can do that second reaction.

Secondary bile acids behave differently from the primary ones. They're more water-repelling, which changes how much cholesterol gets absorbed from the intestine and how much cholesterol the liver then pushes into bile.

Push enough cholesterol into bile and it stops staying dissolved. That's the point at which stones start to form.

What was measured in people

Researchers compared stool from 80 people with cholesterol gallstones against 49 people without them.

One bacterial order stood out as enriched in the gallstone group: Desulfovibrionales. These bacteria produce hydrogen sulphide, a gas that acts on the liver to suppress the enzyme controlling how bile acids are made.

Carrying them was linked to more secondary bile acid production, more water-repelling bile, and more cholesterol absorbed from the intestine. That cholesterol accumulated in the liver and was then secreted into bile.

A separate study of 30 patients and 30 healthy volunteers found the gallstone group had lower overall bacterial variety, with Firmicutes particularly reduced. Free bile acids and secondary bile acids were both raised in their circulation.

Source: Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion

Source: Intestinal flora imbalance affects bile acid metabolism and is associated with gallstone formation

Transplanting the tendency

Two groups differing is one thing. The researchers went further.

They took gut bacteria from the gallstone patients and transplanted them into a strain of mice bred to be resistant to forming gallstones.

Those mice formed stones.

The animals hadn't changed their diet and weren't genetically prone to the condition. What changed was which bacteria were living in their intestines, and that was enough to overcome a built-in resistance.

This is the finding that moves gut bacteria from bystander to participant in how gallstones form.

Why fibre variety matters here specifically

The bacteria doing this chemistry are shaped by what reaches them, which gives food a direct route in.

Bile acid conversion happens in the large intestine, where fibre arrives undigested. The species performing the conversions compete with fibre fermenters for the same territory.

There's also a mechanical effect. Fibre binds bile acids and carries a proportion of them out of the body rather than letting them be reabsorbed. That forces the liver to make more from cholesterol, drawing cholesterol down.

Long gaps without eating matter too. The gallbladder only empties when a meal arrives. Bile that sits still for long periods concentrates, which is why skipping meals is associated with stones.

The reaction converting primary bile acids into secondary ones is carried out by only a limited number of species, most of them in the genus Clostridium. A community with little variety leaves that job concentrated in fewer hands.

What this means for you

Severe pain in the upper right abdomen, particularly with fever or yellowing of the skin or eyes, needs urgent medical attention, and gallstones causing symptoms are usually treated by removing the gallbladder. In addition, the research above shows gut bacteria setting the bile chemistry that decides whether cholesterol stays dissolved, and transplanting those bacteria was enough to make stones form in resistant mice. A varied, plant-rich diet supports the same gut bacteria this research ties to bile that holds cholesterol in solution. That's the same idea behind GutLab, everyday gut health starts with regularly feeding the microbiome a broad range of plant-rich ingredients.