Dataset Information

A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity.

ABSTRACT: Western lifestyle is linked to autoimmune and metabolic diseases, driven by changes in diet and gut microbiota composition. Using Toll-like receptor 7 (TLR7)-dependent mouse models of systemic lupus erythematosus (SLE), we dissect dietary effects on the gut microbiota and find that Lactobacillus reuteri can drive autoimmunity but is ameliorated by dietary resistant starch (RS). Culture of internal organs and 16S rDNA sequencing revealed TLR7-dependent translocation of L. reuteri in mice and fecal enrichment of Lactobacillus in a subset of SLE patients. L. reuteri colonization worsened autoimmune manifestations under specific-pathogen-free and gnotobiotic conditions, notably increasing plasmacytoid dendritic cells (pDCs) and interferon signaling. However, RS suppressed the abundance and translocation of L. reuteri via short-chain fatty acids, which inhibited its growth. Additionally, RS decreased pDCs, interferon pathways, organ involvement, and mortality. Thus, RS exerts beneficial effects in lupus-prone hosts through suppressing a pathobiont that promotes interferon pathways implicated in the pathogenesis of human autoimmunity.

SUBMITTER: Zegarra-Ruiz DF

PROVIDER: S-EPMC6377154 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity.

Zegarra-Ruiz Daniel F DF El Beidaq Asmaa A Iñiguez Alonso J AJ Lubrano Di Ricco Martina M Manfredo Vieira Silvio S Ruff William E WE Mubiru Derek D Fine Rebecca L RL Sterpka John J Greiling Teri M TM Dehner Carina C Kriegel Martin A MA

Cell host & microbe 20181220 1

Western lifestyle is linked to autoimmune and metabolic diseases, driven by changes in diet and gut microbiota composition. Using Toll-like receptor 7 (TLR7)-dependent mouse models of systemic lupus erythematosus (SLE), we dissect dietary effects on the gut microbiota and find that Lactobacillus reuteri can drive autoimmunity but is ameliorated by dietary resistant starch (RS). Culture of internal organs and 16S rDNA sequencing revealed TLR7-dependent translocation of L. reuteri in mice and feca ...[more]

PMID: 30581114

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Project description:BackgroundOverweight and abdominal obesity, in addition to medical conditions such as high blood pressure, high blood sugar and triglyceride levels, are typical risk factors associated with metabolic syndrome. Yet, considering the complexity of factors and underlying mechanisms leading to these inflammatory conditions, a deeper understanding of this area is still lacking. Some probiotics have a reputation of a relatively-long history of safe use, and an increasing number of studies are confirming benefits including anti-obesity effects when administered in adequate amounts. Recent reports demonstrate that probiotic functions may widely differ with reference to either intra-species or inter-species related data. Such differences do not necessarily reflect or explain strain-specific functions of a probiotic, and thus require further assessment at the intra-species level. Various anti-obesity clinical trials with probiotics have shown discrepant results and require additional consolidated studies in order to clarify the correct dose of application for reliable and constant efficacy over a long period.MethodsThree different strains of Lactobacillus sakei were administered in a high-fat diet induced obese murine model using three different doses, 1 × 1010, 1 × 109 and 1 × 108 CFUs, respectively, per day. Changes in body and organ weight were monitored, and serum chemistry analysis was performed for monitoring obesity associated biomarkers.ResultsOnly one strain of L. sakei (CJLS03) induced a dose-dependent anti-obesity effect, while no correlation with either dose or body or adipose tissue weight loss could be detected for the other two L. sakei strains (L338 and L446). The body weight reduction primarily correlated with adipose tissue and obesity-associated serum biomarkers such as triglycerides and aspartate transaminase.DiscussionThis study shows intraspecies diversity of L. sakei and suggests that anti-obesity effects of probiotics may vary in a strain- and dose-specific manner.

Dataset Information

A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity.

Publications

A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity.

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