Dynamics of Gut Microbiota in Autoimmune Lupus

Abstract

Gut microbiota has been recognized as an important environmental factor in health, as well as in metabolic and immunological diseases, in which perturbation of the host gut microbiota is often observed in the diseased state. However, little is known on the role of gut microbiota in systemic lupus erythematosus. We investigated the effects of host genetics, sex, age, and dietary intervention on the gut microbiome in a murine lupus model. In young, female lupus-prone mice resembling women at childbearing age, a population with the highest risk for lupus, we found marked depletion of lactobacilli, and increases in Lachnospiraceae and overall diversity compared to age-matched healthy controls. The predicted metagenomic profile in lupus-prone mice showed a significant enrichment of bacterial motility-and sporulation-related pathways. Retinoic acid as a dietary intervention restored lactobacilli that were downregulated in lupus-prone mice, and this correlated with improved symptoms. The predicted metagenomes also showed that retinoic acid reversed many lupus-associated changes in microbial functions that deviated from the control. In addition, gut microbiota of lupus-prone mice were different between sexes, and an overrepresentation of Lachnospiraceae in females was associated with an earlier onset of and/or more severe lupus symptoms. Clostridiaceae and Lachnospiraceae, both harboring butyrate-producing genera, were more abundant in the gut of lupus-prone mice at specific time points during lupus progression. Together, our results demonstrate the dynamics of gut microbiota in murine lupus and provide evidence to suggest the use of probiotic lactobacilli and retinoic acid as dietary supplements to relieve inflammatory flares in lupus patients.

Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock

“…For example, expansion of Rikenellaceae has been reported due to high-fat diet feeding (33) and during the pathological progression of inflammatory bowel disease (34). Clostridiaceae had been found to be increased in patients following ileal pouch-anal anastomosis (35), in patients with ulcerative colitis and Crohn's disease (36), and in mice during the progression of lupus (37). Decrease of Allobaculum is associated with high-fat diet feeding in mice (38).…”

MetaMIS: a metagenomic microbial interaction simulator based on microbial community profiles

“…On the other hand, several studies have noted that sex hormones and microbes together trigger a gender bias in such autoimmune diseases as type 1 diabetes (T1D) [30] and systematic lupus erythematosus (SLE) [31]. As suggested, the distribution of Enterobacteriaceae and Peptostreptococcaceae correlated strongly with the concentration of androgen as conditions in which male nonobese diabetic (NOD) mice experienced a lower risk of T1D [30].…”

Factoring the intestinal microbiome into the pathogenesis of autoimmune hepatitis

“…The intestinal microbiome can be manipulated by dietary adjustments[37,90,252], probiotic preparations[197,253,254], supplements of vitamin A and retinoic acid[255,256], antibiotics[169,257], intestinal re-colonization[33,107,109,110], pharmacological agents that decrease intestinal permeability[258-260], molecular interventions that block TLR signaling and the production of pro-inflammatory cytokines[261], molecular interventions (polysaccharide A) that stimulate anti-inflammatory responses[105,262], and short chain fatty acids that modulate signaling pathways that affect gene expression, intestinal barrier integrity, and inflammatory responses[200] (Table 3). …”