Developing Therapeutic Strategies for Pregnant Women with Lupus

According to a new study published in Microbiome, the answer to systemic lupus erythematosus (SLE) flare ups in pregnant woman may lie in the gut microbiota.

“There are 38 trillion bacteria living in the gut of an average person, collectively called the gut microbiota,” said Xin M. Luo, associate professor of immunology in DBSP and lead author of the paper with Qinghui Mu, formerly a DBSP postdoctoral fellow and now a postdoctoral research fellow in immunology and rheumatology at Stanford University School of Medicine in a press release. “Disturbance of the gut microbiota exists in the pathogenesis of many autoimmune diseases, including lupus.” Identifying gut microbiota’s role in heightened flares among pregnant women with lupus, however, was uncharted territory.

In this study, the researcher team assessed changes made to the gut microbiota structure with or without the occurrence of pregnancy and evaluated, in an animal-model, different responses of the immune system to the same microbiota-modulating strategies in unaffected versus postpartum lupus-prone mice.

According to the results of the study, the strategies benefitting the unaffected mice exacerbated lupus in postpartum mice. “Our findings suggest that the gut microbiota may regulate lupus flares in pregnant women,” Prof. Luo said of the team’s research. “Our work helps to uncover the mechanisms underlying pregnancy-induced disease flares and offers the possibility of developing new therapeutic strategies for pregnant women with lupus.”

Prof. Lou noted that the overall goal of this research is to pinpoint beneficial and pathogenic gut bacterial species, and subsequently develop therapeutic strategies that regulate the gut microbiota community toward a beneficial effect.

“For patients with autoimmune lupus, diet and probiotics are the two relatively easy and acceptable approaches that can potentially improve disease management through modulating the gut microbiota,” Prof. Luo said. “But it is challenging to achieve this goal due to the complexity of the disease pathologies, the complexity of gut microbiota, and the differences of gut microbiota communities among individuals.”

Moving forward, the research team plans to investigate the interaction between sex hormones and gut microbiota in regulating lupus pathogenesis. “Women experience hormonal changes, which include sex hormones, during pregnancy and postpartum,” added Prof. Luo. “In addition, lupus has a strong female bias, suggesting a role for sex hormones in the disease.”

Future investigations, according to Prof. Lou, will focus on lupus nephritis, the leading cause of mortality in lupus patients, to further delineate the role of gut microbiota in the link between pregnancy and exacerbated lupus.