HomeLifestyleHealth & FitnessFat-dissolving bile acids could help regulate gut inflammation and immunity

Fat-dissolving bile acids could help regulate gut inflammation and immunity

Published on

Could bile acids, which dissolve fat in the liver and gallbladder, also help regulate gut inflammation or immunity?

According to two Harvard Medical School research published in Nature, the answer appears to be yes.

Bile acids stimulate the development and activation of numerous types of T lymphocytes involved in controlling inflammation and associated to intestinal inflammatory diseases, according to the findings of two studies conducted in mice. They also show that gut microorganisms play an important role in turning bile acids into immune-signaling chemicals.

The findings point to potential therapeutic avenues for reducing intestinal inflammation, which is linked to the development of autoimmune diseases including inflammatory bowel disease (IBD).

The first study, conducted by immunologist Jun Huh and published in Nature, shows that bile acids modulate immunity through interacting with immune cells in the gut. After completing their fat-dissolving functions in the gallbladder, bile acids travel down the digestive tract, where they are transformed into immune-regulatory chemicals by gut bacteria. The changed bile acids subsequently activate two types of immune cells: regulatory T cells (Tregs) and effector helper T cells (Th17), both of which are important for modifying immune responses by reducing or boosting inflammation.

Under normal circumstances, the proportions of proinflammatory Th17 cells and anti-inflammatory Treg cells balance out, providing some protection against infections without causing tissue damage. In the context of intestinal infection, these cells play a critical function. Th17 cells cause inflammation in order to combat infection, but Tregs reduce inflammation once the threat has passed. Th17 activity that is unchecked can cause abnormal inflammation that promotes autoimmune illness and damages the gut.

As part of the study, the researchers used undifferentiated (or naive) mouse T cells, which they were then exposed to several bile acid metabolites one at a time until they reached the desired response. The investigations revealed that two distinct bile acid molecules had differing impacts on T cells, with one promoting Treg differentiation and the other inhibiting Th17 cell differentiation. When the researchers gave each chemical to mice, they noticed that the animals’ Th17 and Treg cells decreased and increased in response. The researchers also discovered that the two bile acid byproducts are present in human stool, including stools from persons with IBD, implying that the same process is at work in humans.

“Our findings identify an important regulatory mechanism in gut immunity, showing that microbes in our intestines can modify bile acids and turn them into regulators of inflammation,” says Huh.

If the findings are confirmed in more research, small-molecule treatments targeting Treg and Th17 cells could be developed to regulate inflammation and treat autoimmune illnesses of the gut.

The second study, conducted by Dennis Kasper and published in Nature, focused on a subpopulation of inflammation-taming regulatory T cells, or Tregs, that develop in the colon as a result of gut microbial exposure. The thymus, on the other hand, produces the majority of immune cells.

Colonic regulatory T cells (colonic Tregs) are thought to play a role in the development of autoimmune diseases such IBD and Crohn’s disease.

In mice, Kasper’s findings show that gut microorganisms and food work together to change bile acids, which affects the amounts of colonic Tregs. They also discovered that mice with low numbers of Treg cells, which are caused by a shortage of bile acids or a defect in bile acid sensors, are more likely to develop inflammatory colitis, which is similar to human IBD.

In order to test the idea that gut bacteria turn food-derived bile acids into immune signaling molecules, they silenced the genes that make bile acid-converting enzymes in a variety of gut microbes. They then put both the modified and unmodified microbes in mice that had been bred not to have any germs in their bodies. Treg cells were found in reduced numbers in animals whose stomachs were colonized by bacteria lacking bile acid-converting genes. The animals were then fed either nutrient-dense meals or very little food.

Mice eating rich diet had higher levels of colonic Tregs and lower levels of bile acid than mice with normal microbial populations in their stomachs. However, animals with germ-free intestines who were fed a high-fat diet had lower numbers of Treg cells, indicating that both gut microorganisms and food-derived bile acids are needed to adjust immune cell levels.

Animals with low Treg cell levels and low calorie diets were fed water containing various bile acid compounds to see if they had an effect on Treg cell levels. These rats demonstrated an increase in inflammation-controlling Treg cells a few weeks later.

Finally, the researchers gave three groups of mice a colitis-inducing chemical. One group was given a low-calorie diet, another was given nutrient-dense meals, and a third group was given low-calorie food and drank bile acid-fortified water. Only mice fed a low-fat diet without bile acid molecules developed colitis, as expected. The study found that bile acids influence Treg modulation, intestinal inflammation, and colitis risk.

“Our results demonstrate an elegant three-way interaction between gut microbes, bile acids and the immune system,” adds Kasper. “Importantly, our work suggests it is plausible to think of harnessing certain gut bacteria as a way to modulate disease risk.”

Image Credit: Getty

You were reading: Fat-dissolving bile acids could help regulate gut inflammation and immunity

Latest articles

Here’s How and When Mount Everest-sized ‘Devil Comet’ Can Be Seen With Naked Eye

Mount Everest sized Comet 12P/Pons-Brooks, also known as "devil comet" which is making its...

Something Fascinating Happened When a Giant Quantum Vortex was Created in Superfluid Helium

Scientists created a giant swirling vortex within superfluid helium that is chilled to the...

The Science of Middle-aged Brain and the Best Thing You Can Do to Keep it Healthy, Revealed

Middle age: It is an important period in brain aging, characterized by unique biological...

Science Shock: Salmon’s Food Choices Better at Reducing Risk of Heart Disease and Stroke

Salmon: Rich in Health Benefits, Yet May Offer Less Nutritional Value - This is...

More like this

Here’s How and When Mount Everest-sized ‘Devil Comet’ Can Be Seen With Naked Eye

Mount Everest sized Comet 12P/Pons-Brooks, also known as "devil comet" which is making its...

Something Fascinating Happened When a Giant Quantum Vortex was Created in Superfluid Helium

Scientists created a giant swirling vortex within superfluid helium that is chilled to the...

The Science of Middle-aged Brain and the Best Thing You Can Do to Keep it Healthy, Revealed

Middle age: It is an important period in brain aging, characterized by unique biological...