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Lupus Clinical Trials
1301 Lactobacillus spp. act in synergy to attenuate splenomegaly and lymphadenopathy in lupus- prone MRL/lpr mice
  1. Xavier Cabana-Puig1,
  2. Qinghui Mu1,
  3. Ran Lu1,
  4. Brianna Swartwout2,
  5. Leila Abdelhamid1,
  6. Jing Zhu1,
  7. Meeta Prakash3,
  8. Thomas E Cecere1,
  9. Zhuang Wang1,
  10. Sabrina Callaway1,
  11. Sha Sun4,
  12. Christopher M Reilly5,
  13. S Ansar Ahmed1 and
  14. Xin M Luo1
  1. 1Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA
  2. 2Graduate Program in Translational Biology, Medicine, and Health, Virginia Tech, Roanoke, VA, USA
  3. 3Carilion School of Medicine, Virginia Tech, Roanoke, VA, USA
  4. 4Department of Development and Cell Biology, University of California, Irvine, CA, USA
  5. 5Edward Via College of Osteopathic Medicine, Blacksburg, VA, USA

Abstract

Commensal bacteria and the immune system have a close and strong relationship that maintains a balance to control inflammation. Alterations of the microbiota, known as dysbiosis, can direct reactivity to self-antigens not only in the intestinal mucosa but also at the systemic level. Our laboratory previously reported gut dysbiosis, particularly lower abundance of bacteria in the family Lactobacillaceae, in lupus-prone MRL/lpr mice, a model of systemic autoimmunity. Restoring the microbiota with a mix of 5 different Lactobacillus species (spp.), L. reuteri, L. oris, L. johnsonii, L. gasseri and L. rhamnosus, attenuated lupus-liked clinical signs, including splenomegaly and lymphadenopathy. However, our understanding of the mechanism was limited. In this study, we used the lupus-prone MRL/lpr mouse model to delineate the mechanisms through which Lactobacillus spp. modulate lupus pathogenesis. We first investigated the effects of individual species. Surprisingly, none of the species individually recapitulated the benefits of the mix. Instead, Lactobacillus spp. acted synergistically to attenuate splenomegaly and renal lymphadenopathy through secreted factors and a CX3CR1-dependent mechanism. Interestingly, oral administration of MRS broth exerted the same benefits likely through increasing the relative abundance of endogenous Lactobacillus spp. Mechanistically, we found increased percentages of FOXP3-negative type 1 regulatory T cells with administration of the mix in both spleen and mesenteric lymph nodes. In addition, oral gavage of Lactobacillus spp. decreased the percentage of central memory T cells while increasing that of effector memory T cells in the lymphoid organs. Furthermore, a decreased percentage of double negative T cells was observed in the spleen with the mix. These results suggest that Lactobacillus spp. might act on T cells to attenuate splenomegaly and lymphadenopathy. Together, this study advances our understanding of how Lactobacillus spp. attenuate lupus in MRL/lpr mice. The synergistic action of these bacteria suggests that multiple probiotic bacteria in combination may dampen systemic autoimmunity and benefit lupus patients.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ .

https://doi.org/10.1136/lupus-2022-lupus21century.91

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