Docosahexaenoic acid supplementation alters the gut microbiome in a unique model of lupus flaring

Open Access
- Author:
- Wittmer, Rachael
- Area of Honors:
- Food Science
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Josephine Wee, Thesis Supervisor
Jasna Kovac, Thesis Honors Advisor - Keywords:
- lupus
microbiome
silica
total western diet - Abstract:
- Lupus is an autoimmune disease affecting at least 1.5 million Americans and 5 million more worldwide, with an additional 16,000 cases each year. Symptoms of lupus can range from a characteristic facial rash to debilitating chronic pain and life-threatening complications. It has been estimated that $50,000 in healthcare and economic productivity costs are lost annually for every patient diagnosed with lupus. While treatment exists, prolonged corticosteroids and anti-malarial treatments are costly and lead to adverse effects. There is a need to develop more specific, effective therapeutics with minimal adverse effects. While genetic predisposition is a primary driver of autoimmune disorders such as lupus, previous research suggests that environmental exposures and dietary intervention can impact the timing and severity of disease. In the NZBWF1 mouse model for lupus, exposure to crystalline silica (cSiO2) triggers lupus whereas dietary intervention with docosahexaenoic acid (DHA), an omega-3 fatty acid, mitigates immune responses from lupus triggering and decreases disease severity. The purpose of this work is to determine how environmental triggering with cSiO2 and supplementation of the diet with DHA can alter the gut microbiome composition to help explain disease severity and pathogenicity associated with lupus. We demonstrate that cSiO2-instillation resulted in elevated levels of the Lachnospiraceae bacterium 609 and dietary intervention with DHA decreased this population. Most notably, the identification of Lachnospiraceae bacterium 609 at 11 weeks of age (early timepoint) suggests that it could be a potential biomarker for disease severity. These results suggest a time-dependent effect of dietary intervention and contribute novel findings that lay the framework for the development of a cost-effective, personalized, and accessible therapeutics for lupus. Future work will focus on the role of Lachnospiraceae bacterium 609 in disease progression and severity.