High-fiber Diet Helps to Limit Bacteria in Gut That Trigger Inflammation, Animal Study Finds

A diet that is higher in fiber might benefit people with autoimmune diseases like lupus by reducing the amount of disease-causing bacteria in the gut, a new study suggests.

The study, “A Diet-Sensitive Commensal Lactobacillus Strain, Mediates TLR7-Dependent Systemic Autoimmunity,” was published in Cell Host & Microbe.

The immune system is responsible for destroying harmful invaders like bacteria, yet the body is also home to many commensal or “friendly” bacteria — organisms that normally live in places like the gut, and can be critical to good health. Yet how these commensal bacteria affect autoimmune diseases, or whether some kinds have particularly beneficial or harmful effects, remains unclear.

Investigators wondered whether these bacteria might play a role in systemic lupus erythematosus (SLE). To test this, they used mice that were engineered to develop an SLE-like disease, either through genetic changes or through giving a drug that causes irregular immune activity. They found that mice given broad-spectrum antibiotics, which kill many kinds of bacteria, including commensals, fared better than control mice.

Closer analysis revealed a number of alterations in the bacterial communities of mice with autoimmune disease. The researchers specifically honed in on the bacterium Lactobacillus reuteri. They found that giving lupus-prone mice this bacterium led to a worsening of symptoms, an effect that was not seen when the animals were given other related bacteria. L. reuteri was also found to be enriched in the gut microbiomes of SLE patients.

Further analysis revealed that L. reuteri stimulates dendritic cells and interferon signaling in lupus-prone mice. Dendritic cells are important for activating other immune cells, and interferon is a powerful stimulant of the immune system. In other words, L. reuteri could significantly increase inflammation, leading to a worsening of autoimmune disease.

Because this bacterium resides in the gut, the researchers wondered if a change in diet might be able to suppress the growth of L. reuteri, leading to an improvement in disease state. To test this, the mice were fed “resistant starch,” a diet that mimics a high-fiber diet in humans.

This starch is not absorbed in the small intestine; instead, it is fermented in the large intestine. This leads to the production of short-chain fatty acids, which, the researchers found, can inhibit the growth and activity of L. reuteri. Consistently, SLE mice fed this diet had lower levels of L. reuteri and less interferon production; they also lived longer than mice fed the control diet.

“We identified a pathway that is driving autoimmune disease and mitigated by the diet,” Martin Kriegel, the lead researcher, said in a press release, also noting that these results “may have implications beyond lupus.”

Although further research is needed to determine what patients, if any, would benefit from a similar diet change, this study is a step toward better understanding how diet can impact autoimmune diseases.

“The rapid rise of chronic immune diseases, which is paralleled by major changes in modern diets, might be related to mechanisms such as those we uncovered here,” the researchers wrote.

“A lack of dietary fiber might allow for outgrowth of [disease-causing bacteria] that promote immune pathways in genetically prone individuals. … Dietary or other targeted approaches toward the gut microbiota would restore homeostasis by restraining disease-promoting [bacteria],” they concluded.