Dysregulated Intestinal Host–Microbe Interactions in Systemic Lupus Erythematosus: Insights from Patients and Mouse Models

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation that affects multiple organs, with its prevalence varying by ethnicity. Intestinal dysbiosis has been observed in both SLE patients and murine models. Additionally, intestinal barrier impairment is thou...

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Main Authors: Miki Kume, Jin Din, Daniel F. Zegarra-Ruiz
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/13/3/556
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author Miki Kume
Jin Din
Daniel F. Zegarra-Ruiz
author_facet Miki Kume
Jin Din
Daniel F. Zegarra-Ruiz
author_sort Miki Kume
collection DOAJ
description Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation that affects multiple organs, with its prevalence varying by ethnicity. Intestinal dysbiosis has been observed in both SLE patients and murine models. Additionally, intestinal barrier impairment is thought to contribute to the ability of pathobionts to evade and breach immune defenses, resulting in antigen cross-reactivity, microbial translocation, subsequent immune activation, and, ultimately, multiple organ failure. Since the detailed mechanisms underlying these processes are difficult to examine using human samples, murine models are crucial. Various SLE murine models, including genetically modified spontaneous and inducible murine models, offer insights into pathobionts and how they dysregulate systemic immune systems. Furthermore, since microbial metabolites modulate systemic immune responses, bacteria and their metabolites can be targeted for treatment. Based on human and mouse research insights, this review examines how lupus pathobionts trigger intestinal and systemic immune dysregulation. Therapeutic approaches, such as fecal microbiota transplantation and dietary adjustments, show potential as cost-effective and safe methods for preventing and treating SLE. Understanding the complex interactions between the microbiota, host factors, and immune dysregulation is essential for developing novel, personalized therapies to tackle this multifaceted disease.
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spelling doaj-art-49ebee77b68f4cbda49ea66ca2d0b9102025-08-20T02:42:22ZengMDPI AGMicroorganisms2076-26072025-03-0113355610.3390/microorganisms13030556Dysregulated Intestinal Host–Microbe Interactions in Systemic Lupus Erythematosus: Insights from Patients and Mouse ModelsMiki Kume0Jin Din1Daniel F. Zegarra-Ruiz2Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USACarter Immunology Center, University of Virginia, Charlottesville, VA 22908, USACarter Immunology Center, University of Virginia, Charlottesville, VA 22908, USASystemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation that affects multiple organs, with its prevalence varying by ethnicity. Intestinal dysbiosis has been observed in both SLE patients and murine models. Additionally, intestinal barrier impairment is thought to contribute to the ability of pathobionts to evade and breach immune defenses, resulting in antigen cross-reactivity, microbial translocation, subsequent immune activation, and, ultimately, multiple organ failure. Since the detailed mechanisms underlying these processes are difficult to examine using human samples, murine models are crucial. Various SLE murine models, including genetically modified spontaneous and inducible murine models, offer insights into pathobionts and how they dysregulate systemic immune systems. Furthermore, since microbial metabolites modulate systemic immune responses, bacteria and their metabolites can be targeted for treatment. Based on human and mouse research insights, this review examines how lupus pathobionts trigger intestinal and systemic immune dysregulation. Therapeutic approaches, such as fecal microbiota transplantation and dietary adjustments, show potential as cost-effective and safe methods for preventing and treating SLE. Understanding the complex interactions between the microbiota, host factors, and immune dysregulation is essential for developing novel, personalized therapies to tackle this multifaceted disease.https://www.mdpi.com/2076-2607/13/3/556systemic lupus erythematosusautoimmunityintestinal microbiotaintestinal barrier impairmentintestinal dysbiosispathobionts
spellingShingle Miki Kume
Jin Din
Daniel F. Zegarra-Ruiz
Dysregulated Intestinal Host–Microbe Interactions in Systemic Lupus Erythematosus: Insights from Patients and Mouse Models
Microorganisms
systemic lupus erythematosus
autoimmunity
intestinal microbiota
intestinal barrier impairment
intestinal dysbiosis
pathobionts
title Dysregulated Intestinal Host–Microbe Interactions in Systemic Lupus Erythematosus: Insights from Patients and Mouse Models
title_full Dysregulated Intestinal Host–Microbe Interactions in Systemic Lupus Erythematosus: Insights from Patients and Mouse Models
title_fullStr Dysregulated Intestinal Host–Microbe Interactions in Systemic Lupus Erythematosus: Insights from Patients and Mouse Models
title_full_unstemmed Dysregulated Intestinal Host–Microbe Interactions in Systemic Lupus Erythematosus: Insights from Patients and Mouse Models
title_short Dysregulated Intestinal Host–Microbe Interactions in Systemic Lupus Erythematosus: Insights from Patients and Mouse Models
title_sort dysregulated intestinal host microbe interactions in systemic lupus erythematosus insights from patients and mouse models
topic systemic lupus erythematosus
autoimmunity
intestinal microbiota
intestinal barrier impairment
intestinal dysbiosis
pathobionts
url https://www.mdpi.com/2076-2607/13/3/556
work_keys_str_mv AT mikikume dysregulatedintestinalhostmicrobeinteractionsinsystemiclupuserythematosusinsightsfrompatientsandmousemodels
AT jindin dysregulatedintestinalhostmicrobeinteractionsinsystemiclupuserythematosusinsightsfrompatientsandmousemodels
AT danielfzegarraruiz dysregulatedintestinalhostmicrobeinteractionsinsystemiclupuserythematosusinsightsfrompatientsandmousemodels