Characterization of Sex-Based Differences in Gut Microbiota That Correlate with Suppression of Lupus in Female BWF1 Mice

Systemic lupus erythematosus (SLE) is more prevalent in female mice and humans and is associated with microbiota dysbiosis. We analyzed the fecal microbiota composition in female and male NZBxNZWF1 (BWF1) mice, a model of SLE, using 16S RNA gene sequencing. Composition of gut microbiota differed between adult disease-prone female (pre-disease) and disease-resistant male mice. Transfer of male cecal contents by gavage into female mice suppressed kidney disease (decreased proteinuria) and improved survival. After our mouse colony was moved to a new barrier facility with similar housing, male cecal transplants failed to suppress disease in female recipients. After two years, the protective phenotype reemerged: male cecal transplants once again suppressed disease in female mice. We compared the gut microbiota composition in female and male BWF1 mice for the three different periods, during which the male microbiota either protected or failed to protect female recipients. In female vs. male mice and in female mice receiving male cecal transplants, we found <i>Bacteroides</i> was high, <i>Clostridium</i> was low (high <i>Bacteroides</i>/<i>Clostridium</i> ratio), and <i>Alistipes</i> was present during periods when male cecal transplants suppressed disease. These data suggest that specific bacterial populations may have opposing effects on disease suppression in a model of microbiota transplantation.