Impact of dietary deviation on disease progression and gut microbiome composition in lupus‐prone SNF1 mice

Summary Environmental factors, including microbes and diet, play a key role in initiating autoimmunity in genetically predisposed individuals. However, the influence of gut microflora in the initiation and progression of systemic lupus erythematosus (SLE) is not well understood. In this study, we ha...

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Bibliographic Details
Published in:Clinical and experimental immunology 2015-08, Vol.181 (2), p.323-337
Main Authors: Johnson, B. M., Gaudreau, M.‐C., Al‐Gadban, M. M., Gudi, R., Vasu, C.
Format: Article
Language:English
Subjects:
Animals
Antibodies, Antinuclear - biosynthesis
autoimmunity
Bacteroides - classification
Bacteroides - immunology
Clostridium - classification
Clostridium - immunology
Crosses, Genetic
Cyanobacteria - classification
Cyanobacteria - immunology
Cytokines - biosynthesis
Disease Progression
Drinking Water - administration & dosage
drinking water pH
Female
Gastrointestinal Tract - immunology
Gastrointestinal Tract - microbiology
Gastrointestinal Tract - pathology
Genetic Predisposition to Disease
Hydrogen-Ion Concentration
immune modulation
Lactobacillus - classification
Lactobacillus - immunology
Lupus Nephritis - diet therapy
Lupus Nephritis - immunology
Lupus Nephritis - microbiology
Lupus Nephritis - pathology
Male
Mice
Mice, Inbred NZB
microbiota
Microbiota - immunology
Plasma Cells - drug effects
Plasma Cells - immunology
Plasma Cells - microbiology
Plasma Cells - pathology
RNA, Ribosomal, 16S - genetics
segmented filamentous bacteria
systemic lupus erythematosus
Th17 Cells - drug effects
Th17 Cells - immunology
Th17 Cells - microbiology
Th17 Cells - pathology
Time Factors
Translational
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Summary:Summary Environmental factors, including microbes and diet, play a key role in initiating autoimmunity in genetically predisposed individuals. However, the influence of gut microflora in the initiation and progression of systemic lupus erythematosus (SLE) is not well understood. In this study, we have examined the impact of drinking water pH on immune response, disease incidence and gut microbiome in a spontaneous mouse model of SLE. Our results show that (SWR × NZB) F1 (SNF1) mice that were given acidic pH water (AW) developed nephritis at a slower pace compared to those on neutral pH water (NW). Immunological analyses revealed that the NW‐recipient mice carry relatively higher levels of circulating autoantibodies against nuclear antigen (nAg) as well as plasma cells. Importantly, 16S rRNA gene‐targeted sequencing revealed that the composition of gut microbiome is significantly different between NW and AW groups of mice. In addition, analysis of cytokine and transcription factor expression revealed that immune response in the gut mucosa of NW recipient mice is dominated by T helper type 17 (Th17) and Th9‐associated factors. Segmented filamentous bacteria (SFB) promote a Th17 response and autoimmunity in mouse models of arthritis and multiple sclerosis. Interestingly, however, not only was SFB colonization unaffected by the pH of drinking water, but also SFB failed to cause a profound increase in Th17 response and had no significant effect on lupus incidence. Overall, these observations show that simple dietary deviations such as the pH of drinking water can influence lupus incidence and affect the composition of gut microbiome.
ISSN:0009-9104
1365-2249
DOI:10.1111/cei.12609