Bile Flow Problems

The Conversation Between Bile and Bacteria

The evidence here is strong in animals and consistent in people, and it describes a loop rather than a one-way street. Bile flow problems, known medically as cholestasis, mean bile isn't moving properly from the liver into the intestine. That causes itching, jaundice and pale stools. What's less obvious is that bile and gut bacteria each control the other, so when flow drops, both halves of that relationship come apart.

Bile as an antibacterial

Bile isn't only a digestive fluid. Bile acids are detergents, and they dissolve bacterial membranes.

A steady flow of bile into the small intestine is one of the main reasons that stretch of gut stays sparsely populated. Reduce the flow and that restraint disappears, which is why bacterial overgrowth is common in cholestasis.

Bile acids also act as signals. They switch on a receptor called FXR in the cells lining the intestine, and FXR activation turns on genes that produce the body's own antibacterial molecules.

So bile suppresses bacterial growth twice over. It kills bacteria directly and it instructs the gut to defend itself.

The feedback loop bacteria complete

That signal doesn't stop at the gut wall. It travels back.

When bile acids activate FXR in the small intestine, the cells release a hormone called FGF19 into the portal vein, the vessel running from the intestines to the liver. Arriving at the liver, it tells it to slow down bile acid production.

That's a thermostat. Plenty of bile acids reaching the intestine means the signal to make more gets turned down.

Gut bacteria sit inside this loop, because they modify bile acids before the receptor sees them. They strip off attached amino acids and convert primary bile acids into secondary ones, and the two forms activate the receptor to very different degrees.

Change which bacteria are present and you change how loudly the thermostat is signalling.

Removing the right bacteria, then putting them back

That loop was tested directly, and the experiment is unusually clean.

Researchers gave mice vancomycin, an antibiotic that kills a particular group of gut bacteria. The animals developed worse liver scarring and injury, with bile acids accumulating and the FXR signal to the liver suppressed.

The bacteria wiped out included Clostridia XIVa, and one species in particular, Clostridium scindens. That species performs one of the key conversions in bile acid chemistry.

The researchers then gave Clostridium scindens back by mouth. Bile acid accumulation eased and the liver scarring improved, with the FXR signalling restored.

One species removed, damage. The same species returned, recovery. That's a direct demonstration that bacteria hold part of this system open.

Source: Clostridium Scindens Protects Against Vancomycin-Induced Cholestasis and Liver Fibrosis by Activating Intestinal FXR-FGF15/19 Signaling

What's been measured in people

Human evidence comes largely from primary sclerosing cholangitis, a disease in which bile ducts become inflamed and narrowed.

Researchers sampled the bacteria attached to the gut lining at several points along the intestine. The overall profile was consistent within each person regardless of location, and patients showed enrichment of Blautia and of the family Barnesiellaceae.

Around 86% of the bacterial shifts identified sat within a single order, the Clostridiales, which is the order containing most of the species performing bile acid conversions.

A separate study compared 30 people with extensive colitis, 15 of whom also had the bile duct disease, and found their gut bacteria and their stool bile acids both differed.

The direction remains unresolved. Reduced bile flow changes which bacteria survive, and altered bacteria change the bile acid signal reaching the liver. Both are happening at once.

Source: The features of mucosa-associated microbiota in primary sclerosing cholangitis

Source: The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease

What this means for you

Yellowing of the skin or eyes, persistent itching, pale stools or dark urine need prompt medical assessment, since blocked bile flow has causes that require specific treatment. In addition, the research above shows gut bacteria completing the feedback loop that tells the liver how much bile to make, and restoring one missing species reversed liver scarring in animals. A varied, plant-rich diet supports the same gut bacteria this research ties to a properly working bile acid signal. That's the same idea behind GutLab, everyday gut health starts with regularly feeding the microbiome a broad range of plant-rich ingredients.