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

## TL;DR

The study found that gut bacteria in male mice can protect female mice from lupus-like kidney disease, but this effect depends on the specific bacterial composition and environment.

## Contribution

The study identifies specific gut bacterial populations associated with disease suppression in a lupus model and shows that these effects can be environment-dependent.

## Key findings

- Male cecal transplants suppressed kidney disease in female mice during certain periods.
- Bacteroides was high and Clostridium was low in protective periods, with a high Bacteroides/Clostridium ratio.
- The protective effect of male microbiota was lost when mice were moved to a new facility but returned after two years.

## Abstract

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 Bacteroides was high, Clostridium was low (high Bacteroides/Clostridium ratio), and Alistipes 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.