CHICAGO—Certain saturated fats that are common in the modern Western diet can initiate a chain of events leading to complex immune disorders such as inflammatory bowel diseases (IBD) in people with a genetic predisposition, according to a study to be published early online in the journal Nature.
The finding helps explain why once-rare immune-mediated diseases have become more common in westernized societies in the last half century. It also provides insights into why many individuals who are genetically prone to these diseases are never affected and how certain environmental factors can produce inflammation in individuals already at risk.
Researchers at the University of Chicago found that concentrated milk fat alter the composition of bacteria in the intestines. The changes can disrupt the delicate truce between the immune system and the complex but largely beneficial mix of bacteria in the intestines. The emergence of harmful bacterial strains in this setting can unleash an unregulated tissue-damaging immune response that can be difficult to switch off.
“This is the first plausible mechanism showing step-by-step how Western-style diets contribute to the rapid and ongoing increase in the incidence of inflammatory bowel disease," said study author Eugene B. Chang, MD, PhD, the Martin Boyer Professor of Medicine at the University of Chicago. “We know how certain genetic differences can increase the risk for these diseases, but moving from elevated risk to the development of disease seems to require a second event which may be encountered because of our changing lifestyle."
The researchers worked with a mouse model that has many of the characteristics of human IBD. Genetically deleting a molecule, interleukin 10, which acts as a brake on the immune system’s response to intestinal bacteria, caused about 20% of mice to develop colitis when fed a low-fat diet or a diet high in polyunsaturated fats. When exposed to a diet high in saturated milk fats, the rate of disease development within six months tripled, increasing to more than 60%. In addition, the onset, severity and extent of colitis were much greater than that observed in mice fed low-fat diets.
In investigating why milk fat triggered inflammation when polyunsaturated fat did not, the researchers traced the answer to the gut microbiome, the complex mix of hundreds of bacterial strains that reside in the bowels. They found an uncommon microbe called Bilophila wadsworthia was preferentially selected in the presence of milk fat. Previous studies had found high levels of B. wadsworthia in patients with appendicitis and other intestinal inflammatory disorders, including inflammatory bowel disease.
While Bilophila wadsworthia levels were almost undetectable in mice on a low-fat or unsaturated-fat diet, the bacteria made up about 6% of all gut bacteria in mice fed a high milk-fat diet. “Here we show how the trend in consumption of Western-type diets by many societies can potentially tip the mutualistic balance between host and microbe to a state that favors the onset of disease," Chang said.
As its name implies, Bilophila wadsworthia has an affinity for bile, a substance produced by the liver and released into the intestines to help break down ingested fats. Milk fats are particularly difficult to digest and require the liver to secrete a form of bile that is rich in sulfur. B. wadsworthia thrives in the presence of sulfur. So when the bile created to dissolve milk fats reaches the colon, it enables B. wadsworthia to blossom and activate the immune system of genetically prone individuals.
The byproducts of B. wadsworthia’s interaction with bile also can amplify the effect. They serve as “gut mucosal barrier breakers," said Suzanne Devkota, PhD, a member of Chang’s laboratory and first author of the study. “By increasing the permeability of the bowel, they enhance immune-cell infiltration, and that can induce tissue damage."