Mechanistic role of probiotic Lactobacillus reuteri in autoimmune lupus

益生菌罗伊氏乳杆菌在自身免疫性狼疮中的机制作用

基本信息

批准号：
10332721
负责人：
Xin M Luo
金额：
$ 33.28万
依托单位：
VIRGINIA POLYTECHNIC INST AND ST UNIV
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-03-05 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10332721
关键词：
Affect Antibodies Attenuated Autoantibodies Autoimmune Autoimmune Diseases Autoimmunity Bacteria Biological Assay Blood Circulation Cells Complex Dependence Deposition Development Diet Disease Drug Side Effects Endotoxins Epithelial Equilibrium Event Genes Genetic Transcription Goals Gut Mucosa Human Immunosuppressive Agents In Vitro Inbred MRL lpr Mice Interleukin-6 Intestinal permeability Kidney Knowledge Lactobacillus Lactobacillus reuteri Lipopolysaccharides Lupus Mediating Mus Oral Pathogenesis Pathway interactions Patients Persons Phenotype Probiotics Proteins Proteinuria RNA Regulation Regulatory T-Lymphocyte Reporting Research Role Serum Spleen Systemic Lupus Erythematosus T cell differentiation Testing Tight Junctions Up-Regulation base cost effective fecal microbiota fluorescein isothiocyanate dextran gastrointestinal epithelium gut colonization gut dysbiosis gut microbiota human disease intestinal barrier intestinal epithelium intraperitoneal mouse model neutralizing antibody new therapeutic target novel therapeutics prebiotics prevent promoter response standard of care systemic autoimmunity transcription factor transcriptome sequencing translation to humans treatment strategy zonulin

项目摘要

Project Summary Systemic lupus erythematosus (SLE) is a complex autoimmune disease with no known cure. We observed changes of gut microbiota in SLE, including a marked decrease of Lactobacillus spp., in both human and mouse. Our preliminary results showed that increasing Lactobacillus spp. in the gut is beneficial and attenuates SLE-like disease in mice. The goal of this proposal is to mechanistically define the role of a probiotic species, Lactobacillus reuteri (LR), that protects against SLE. Based on extensive preliminary observations, we hypothesize that LR attenuates lupus by strengthening the gut mucosal barrier and modulating the Th17-Treg response. In the proposed studies, we plan to achieve two specific aims to test this hypothesis. Aim 1 is focused on the impact of Lactobacillus spp. on the gut microenvironment in lupus mice. The hypothesis of this aim is that the probiotic bacteria strengthen the gut mucosal barrier by modulating the expression of tight junction proteins. Aim 2 is focused on the mechanism at the systemic level by which Lactobacillus spp. attenuate SLE. The hypothesis of this aim is that the probiotic bacteria attenuates SLE-like disease by increasing systemic TGFb and inducing renal Treg cells. The results of the proposed studies, upon translation to human disease, will identify the key events initiating the cascade that leads to human SLE, and enable development of new therapeutic targets necessary to generate treatments for the disease. Diet and probiotics/prebiotics, known to modify the gut microbiota, have the potential to become cost-effective components of SLE management strategies.

项目概要系统性红斑狼疮 (SLE) 是一种复杂的自身免疫性疾病，目前尚无治愈方法。我们观察到 SLE 患者肠道微生物群的变化，包括人和人体内乳酸菌的显着减少老鼠。我们的初步结果表明，乳酸杆菌的增加。在肠道中是有益的减轻小鼠的系统性红斑狼疮样疾病。该提案的目标是机械地定义益生菌，罗伊氏乳杆菌 (LR)，可预防系统性红斑狼疮。基于广泛的初步根据观察，我们假设 LR 通过加强肠道粘膜屏障来减轻狼疮，调节 Th17-Treg 反应。在拟议的研究中，我们计划实现两个具体目标来测试这一点假设。目标 1 重点关注乳杆菌属的影响。对狼疮小鼠肠道微环境的影响。这一目标的假设是益生菌通过调节肠道粘膜屏障来增强肠道粘膜屏障。紧密连接蛋白的表达。目标2侧重于系统层面的机制，通过该机制乳杆菌属减轻系统性红斑狼疮。这一目标的假设是益生菌可以减弱 SLE 样症状通过增加全身性 TGFb 和诱导肾 Treg 细胞来预防疾病。拟议研究的结果转化为人类疾病，将确定引发导致人类 SLE 级联反应的关键事件，以及能够开发出治疗该疾病所需的新治疗靶点。饮食和已知益生菌/益生元可以改变肠道微生物群，有可能变得具有成本效益 SLE 管理策略的组成部分。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Single-cell RNA sequencing analysis reveals the heterogeneity of IL-10 producing regulatory B cells in lupus-prone mice.

DOI：
10.3389/fimmu.2023.1282770
发表时间：
2023
期刊：
Frontiers in immunology
影响因子：
7.3
作者：
通讯作者：

Lactobacillus spp. act in synergy to attenuate splenomegaly and lymphadenopathy in lupus-prone MRL/lpr mice.

DOI：
10.3389/fimmu.2022.923754
发表时间：
2022
期刊：
FRONTIERS IN IMMUNOLOGY
影响因子：
7.3
作者：
Cabana-Puig, Xavier;Mu, Qinghui;Lu, Ran;Swartwout, Brianna;Abdelhamid, Leila;Zhu, Jing;Prakash, Meeta;Cecere, Thomas E.;Wang, Zhuang;Callaway, Sabrina;Sun, Sha;Reilly, Christopher M.;Ahmed, S. Ansar;Luo, Xin M.
通讯作者：
Luo, Xin M.

Gut Microbiota, Leaky Gut, and Autoimmune Diseases.

DOI：
10.3389/fimmu.2022.946248
发表时间：
2022
期刊：
Frontiers in immunology
影响因子：
7.3
作者：
通讯作者：

Regulation of neonatal IgA production by the maternal microbiota.

DOI：
10.1073/pnas.2015691118
发表时间：
2021-03-02
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Mu Q;Swartwout BK;Edwards M;Zhu J;Lee G;Eden K;Cabana-Puig X;McDaniel DK;Mao J;Abdelhamid L;Brock RM;Allen IC;Reilly CM;Luo XM
通讯作者：
Luo XM

Retinoic Acid, Leaky Gut, and Autoimmune Diseases.