Gut microbiota mediated the effects of high relative humidity on lupus in female MRL/lpr mice

Abstract

Introduction The relationship between humidity and systemic lupus erythematosus (SLE) has yielded inconsistent results in prior research, while the effects of humidity on lupus in animal experiments and its underlying mechanism remain inadequately explored. Methods The present study aimed to investigate the impact of high humidity (80 ± 5%) on lupus using female and male MRL/lpr mice, with a particular focus on elucidating the role of gut microbiota in this process. To this end, fecal microbiota transplantation (FMT) was employed to transfer the gut microbiota of MRL/lpr mice under high humidity to blank MRL/lpr mice under normal humidity (50 ± 5%), allowing for an assessment of the effect of FMT on lupus. Results The study revealed that high humidity exacerbated lupus indices (serum anti-dsDNA, ANA, IL-6, and IFN- g, and renal pathology) in female MRL/lpr mice but had no significant effect on male MRL/lpr mice. The aggravation of lupus caused by high humidity may be attributed to the increased abundances of the Rikenella, Romboutsia, Turicibacter, and Escherichia-Shigella genera in female MRL/lpr mice. Furthermore, FMT also exacerbated lupus in female MRL/lpr mice but not in male MRL/lpr mice. Conclusion In summary, this study has demonstrated that high humidity exacerbated lupus by modulating gut microbiota in female MRL/lpr mice. The findings underscore the importance of considering environmental factors and gut microbiota in the development and progression of lupus, particularly among female patients.

Alterations of the gut microbiota in the lupus nephritis: a systematic review

“…( R. torques spp. ) was found to be higher in the LN group than in the control group in one (1/14) clinical study [ 28 ] and two (2/5) animal studies [ 28 , 41 ], but one (1/7) animal study [ 44 ] found a lower abundance. The genus Lactobacillus and species Lactobacillus reuteri ( L. reuteri ) were mentioned as having changes in abundance in two (2/14) clinical studies [ 32 , 38 ] and three (3/7) animal studies [ 38 , 42 , 43 ].…”

“…Two (2/14) clinical studies [ 25 , 34 ] and five (5/7) animal studies [ 38 , 40 , 41 , 43 , 44 ] reported changes in inflammatory markers and intestinal barrier dysfunction markers. In both clinical and animal studies [ 25 , 36 , 44 ], the inflammatory indicator interleukin (IL)-6 was found to be increased in patients with LN but decreased after Lactobacillus treatment [ 40 ].…”

“…Two (2/14) clinical studies [ 25 , 34 ] and five (5/7) animal studies [ 38 , 40 , 41 , 43 , 44 ] reported changes in inflammatory markers and intestinal barrier dysfunction markers. In both clinical and animal studies [ 25 , 36 , 44 ], the inflammatory indicator interleukin (IL)-6 was found to be increased in patients with LN but decreased after Lactobacillus treatment [ 40 ]. The level of calcium-protective protein, an intestinal barrier deficiency biomarker was higher in patients with LN, and the expression of the gut tight junction protein claudin-1 (Cldn1) and Zonula Occludens-1 (ZO-1) was downregulated in LN model mice compared with controls [ 41 ].…”

“…may also be important in the pathogenesis of lupus apart from R. gnavus . Although only one animal study [ 44 ] appears to have contradictory results for R. torques spp. , we believe that the variation in R. torques spp.…”