The Gut Microbiota and Disease: Segmented Filament Bacteria Exacerbates Kidney Disease in a Lupus Mouse Model
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Date
2018-11-01
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Abstract
Background:
Commensal organisms are a vital component to the host organism. Segmented Filament Bacteria (SFB) is a commensal bacterium found in many animal species. SFB has been shown to exacerbate inflammatory arthritis but has not been implicated in Systemic Lupus Erythematosus (SLE). The focus of our study was to understand the broader relationship between the gut microbiota and lupus.
Methods:
We used the NZM2410 lupus mouse model that is prone to developing lupus manifestations such as immune complex glomerulonephritis in order to study the effect of gut dysbiosis in lupus. NZM2410 mice were inoculated with SFB (n=10) or without SFB-containing (n=10) fecal homogenates. PCR analysis with SFB primers was used to confirm the presence of SFB after inoculation of the mice. Serum was collected monthly, and mice were euthanized at 30 weeks. Kidney damage was accessed using histopathological stains. Immunohistochemistry (IHC) was performed on kidney and small intestine tissues to assess the presence of specific immune cells as well as permeability integrity of the intestine. To analyze changes in the microbiome of SFB colonized mice, fecal bacterial DNA was analyzed using 16S rRNA sequencing.
Results:
Significantly increased glomeruli size was observed in SFB-inoculated mice using H&E staining. PAS staining showed more hyaline deposits in SFB-exposed mice, and Jones staining revealed spike formations in the glomerular basement membrane of SFB mice; all of which are indicative of lupus-like glomerulonephritis. Furthermore, we observed an increased level of fluorescence intensity of C3 and IgG in the glomeruli of SFB-inoculated mice. Inflammatory myeloid cells were also increased in the kidney of SFB mice. The tight junctions Claudin 1 and Claudin 3 were decreased in the small intestine of mice inoculated with SFB, suggesting elevated intestinal permeability better known as gut “leakiness”. There were significant differences in the intestinal microbial composition of SFB-exposed mice. These differences were evident down to the Genus taxonomic level and either indicated a disease-driven and/or SFB-influenced commensal change.
Conclusion:
These findings suggest that SFB can act as a “pathobiont” in lupus. SFB may have no role in disease in wildtype mice, but our findings suggest that gut microbiota containing SFB can exacerbate the disease progression of lupus in mice.
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Keywords
Lupus Nephritis, Gut Microbiota, Lupus Mouse Model, Segmented Filament Bacteria, Kidney Disease