What is already known on this topic
The gallbladder stores bile produced by the liver and is connected to the duodenum, so it is exposed to the gut microbiota. Because of this exposure, the dominant epithelial cell type in the gallbladder produces antimicrobial factors such as mucins. However, the role of a smaller population of cells, called tuft cells, in regulating innate defense responses remains unknown.
What this research adds
To investigate the role of tuft cells, researchers stimulated the cells in gallbladders from mice. They found that tuft cells release two molecules that promote innate defense responses. One molecule, acetylcholine, caused the cells lining the bile ducts to secrete mucus, whereas cysteinyl leukotrienes caused the contraction of smooth muscles. The researchers also found that the microbial metabolite propionate triggers tuft cells in the gallbladder to release acetylcholine and cysteinyl leukotrienes.
Conclusions
The findings suggest that tuft cells in the gallbladder act as sensors of the microbial metabolite propionate, which may represent a danger signal of inadvertent ascent of gut microbiota in the biliary system.
Gut bacteria have been implicated in the regulation of countless biological processes — from digestion to metabolism. Now, researchers have found that the gut microbiota can help the gallbladder to regulate innate defense responses.
The findings, published in Science Immunology, suggest that a specialized population of cells in the gallbladder act as sensors of the microbial metabolite propionate, which may represent a danger signal of inadvertent ascent of gut microbiota in the gallbladder, bile ducts and associated structures.
The gallbladder stores bile produced by the liver and is connected to the duodenum, so it is exposed to the gut microbiota. Because of this exposure, the dominant epithelial cell type in the gallbladder produces antimicrobial factors such as mucins. However, the role of a smaller population of cells, called tuft cells, in regulating innate defense responses remains unknown.
To investigate the role of tuft cells, researchers led by Burkhard Schütz at Philipps University and Wolfgang Kummer at Justus Liebig University Giessen used a light-sensitive model to stimulate tuft cells in gallbladders from mice.
Innate defense
Tuft cells in the gallbladder release two types of molecules, the researchers found. One is acetylcholine, the main neurotransmitter of the part of the nervous system responsible for processes including the contraction of smooth muscles, the dilation of blood vessels and the increase in bodily secretions.
Tuft cells also produced cysteinyl leukotrienes, a family of fatty molecules that promote inflammation and are typically produced by immune cells such as macrophages.
The researchers found that acetylcholine caused the cells lining the bile ducts to secrete mucus, whereas cysteinyl leukotrienes caused the contraction of smooth muscles. Both molecules thus help to promote innate defense responses, the researchers say.
Danger signal
Next, the team set out to investigate what caused tuft cells in the gallbladder to release acetylcholine and cysteinyl leukotrienes. Since the gallbladder is exposed to the gut microbiota, the researchers suspected that the trigger could be a microbial metabolite.
Further experiments revealed that the trigger was indeed the microbial metabolite propionate, a short-chain fatty acid that the human gut microbiota produces upon fermentation of dietary non-digestible carbohydrates.
“Propionate surveillance by gallbladder tuft cells reflects local production of propionate by bacteria or reflux from the duodenum, both representing a pathological condition,” the researchers say. This suggests that tuft cells in the gallbladder can sense the ascent of gut microbiota in the biliary system, they say.
