Microbial fermentation of starches in the intestine produces short-chain fatty acids (SCFAs) that can modulate host immunity and potentially reduce susceptibility to inflammatory diseases. New work published in Cell Host & Microbe now shows that intestinal Lactobacillus reuteri contributes to disease in mouse models of systemic lupus erythematosus (SLE) and this population can be inhibited by feeding mice a diet rich in starches that are resistant to intestinal digestion and thereby available for microbial fermentation into SCFAs.

“We used transgenic mice that overexpress the innate RNA-sensing receptor TLR7 because it is a very good model to study the innate immune arm of the pathogenesis of SLE,” explains Martin Kriegel, corresponding author of the new article. “These mice develop all the hallmarks of human SLE via the increased signalling of TLR7, which activates plasmacytoid dendritic cells to secrete IFNα, a signature cytokine in SLE.”

Credit: N Tkachuk/Alamy Stock Vector

A resistant starch diet suppressed the growth of L. reuteri in these lupus-prone mice. “In addition, the diet sealed the gut barrier,” explains Kriegel. “A fluorescent dye fed to the mice was not able to leak into the systemic circulation and fewer live bacteria translocated to tissues.”

The researchers also showed that seeding the intestines of mice with L. reuteri exacerbated lupus-like disease and increased permeability of the intestinal barrier and translocation of bacteria into the lymph nodes, spleen and liver.

Kriegel now wants to study more of the underlying biology of the protection afforded by diet and how L. reuteri is pathogenic. “We would like to identify metabolites that are secreted by L. reuteri that might activate plasmacytoid dendritic cells,” he says, for example.

L. reuteri exacerbated lupus-like disease

The researchers also provide some human relevance to the study by showing that Lactobacillus species are enriched in faecal samples taken from a subset of patients with SLE. However, the main question Kriegel would like to address is whether or not a dietary intervention involving resistant starches would be therapeutically beneficial for patients with SLE.