HomeLifestyleHealth & FitnessInflammation and autoimmune diseases affecting gut may be treated with bile acids,...

Inflammation and autoimmune diseases affecting gut may be treated with bile acids, says research

Published on

The research suggests therapeutic pathways for modulating intestinal inflammation, a process that leads to autoimmune diseases like inflammatory bowel disease (IBD).

Two studies, which were conducted in mice, demonstrated that bile acids promote the differentiation and activity of several types of T cells involved in inflammation regulation and associated with intestinal inflammatory conditions. Additionally, they demonstrate that gut microbes are required for the conversion of bile acids to immune signalling molecules.

The first study, led by immunologist Jun Huh and published in Nature, demonstrates that bile acids modulate the immune system by interacting with immune cells in the gut.

After completing their fat-dissolving duties in the gallbladder, bile acids travel down the digestive tract, where they are modified into immune-regulatory molecules by gut bacteria.

The modified bile acids then activate two types of immune cells: regulatory T cells (Tregs) and effector helper T cells (Th17), each of which is responsible for modulating the immune response by either suppressing or promoting inflammation.

Under normal conditions, the ratio of proinflammatory Th17 cells to antiinflammatory Treg cells balances out, ensuring that pathogens are protected without causing excessive tissue-damaging inflammation. These cells play a critical role during intestinal infection. Th17 cells initiate inflammation in order to combat infection, whereas Tregs suppress inflammation after the threat has passed. When left unchecked, Th17 activity can also result in aberrant inflammation, promoting autoimmune disease and causing damage to the intestine.

To do their study, the researchers used undifferentiated, or naive, mouse T cells and exposed them one by one to various bile acid metabolites. Two distinct bile acid molecules were found to have distinct effects on T cells: one molecule promoted Treg differentiation, while the other inhibited Th17 cell differentiation. When the researchers gave each molecule to mice, they observed that the animals’ Th17 and Treg cells decreased and increased in proportion. Additionally, the researchers discovered that the two bile acid byproducts are present in human stool, including that of people with inflammatory bowel disease (IBD) – implying that the same mechanism operates in humans.

The findings were able to establish a critical regulatory mechanism in gut immunity by demonstrating that microbes in our intestines can modify bile acids and transform them into inflammatory regulators.

The second study, led by Dennis Kasper and published in Nature, focused on a subset of anti-inflammatory regulatory T cells, or Tregs, that develop in the colon as a result of exposure to gut microbes. In comparison, the majority of other immune cells are produced in the thymus.

Colonic regulatory T cells (colonic Tregs) deficiency has been linked to the development of autoimmune diseases such as inflammatory bowel disease (IBD) and Crohn’s disease.

Kasper’s experiments show that gut microbes and diet interact to modify bile acids, which in turn affects the colonic Treg levels in mice. Additionally, they demonstrate that low levels of Treg cells caused by a lack of bile acids or a deficiency in bile acid sensors predispose animals to develop inflammatory colitis, a condition that mimics human inflammatory bowel disease.

To test their theory that gut bacteria convert food-derived bile acids produced in response to food into immune signalling molecules, the researchers silenced bile acid-converting genes in a variety of gut microbes and then injected both modified and unmodified microbes into mice with germ-free guts. Animals with gut microbes lacking bile acid-converting genes had significantly fewer Treg cells. The researchers then fed either nutrient-dense meals or very little food to the animals.

Mice fed a low-fat diet had lower levels of colonic Tregs and bile acid than mice fed a high-fat diet. Nevertheless, animals with germ-free guts fed a high-fat diet had low levels of Treg cells, indicating that both gut microbes and food-derived bile acids are required to modulate immune cell levels.

To determine whether bile acids play a direct role in immune cell regulation, the researchers then added various bile acid molecules to the drinking water of animals with low Treg cell counts and restricted diets. Several weeks later, these animals’ levels of inflammation-fighting Treg cells increased.

Finally, the researchers administered a compound that induces colitis to three groups of mice. One group was fed a restricted diet, another was fed nutrient-dense meals, and a third group was fed a restricted diet and given water supplemented with bile acid molecules. As expected, colitis developed only in mice fed a minimal diet devoid of bile acid molecules. The experiment established that bile acids are required for Treg regulation, intestinal inflammation, and the risk of colitis.

The study stressed that the findings reveal a sophisticated three-way interaction between gut microbes, bile acids, and the immune system.

Notably, the research suggests that harnessing specific gut bacteria as a means of reducing disease risk is a possibility, concluded the study author.

Image Credit: Getty

Latest articles

3600 Steps Per Day At A Normal Pace Could Reduce the Risk of Heart Failure By 26%, Says New Study

10,000 steps per day? Scientific evidence strongly supports that physical activity is good for...

New Research Reveals Surprising Unknown Benefits of Female Ginseng – Here’s What You Need to Know

Here's Why Female Ginseng Could Be A New Treatment Option For Millions of Americans...

The Way This New Species Kills Its Host is ‘Absolutely Fascinating’ – ‘It’s Like Something Out Of A James Cameron Movie’

The newly discovered species, named Steinernema adamsi, belongs to the Steinernema family of nematodes....

Plant Eaters Beware: Researchers Reveal Surprise Smell Can Prevent Plants Being Eaten

A new study reveals how it is possible to protect plants from the hungry...

More like this

3600 Steps Per Day At A Normal Pace Could Reduce the Risk of Heart Failure By 26%, Says New Study

10,000 steps per day? Scientific evidence strongly supports that physical activity is good for...

New Research Reveals Surprising Unknown Benefits of Female Ginseng – Here’s What You Need to Know

Here's Why Female Ginseng Could Be A New Treatment Option For Millions of Americans...

The Way This New Species Kills Its Host is ‘Absolutely Fascinating’ – ‘It’s Like Something Out Of A James Cameron Movie’

The newly discovered species, named Steinernema adamsi, belongs to the Steinernema family of nematodes....