Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017:2017:6519785.
doi: 10.1155/2017/6519785. Epub 2017 Dec 31.

Gut Microbiome and Inflammation: A Study of Diabetic Inflammasome-Knockout Mice

Roma Pahwa  1   2 , Miriam Balderas  3   4 , Ishwarlal Jialal  1   2 , Xinpu Chen  3   4 , Ruth Ann Luna  3   4 , Sridevi Devaraj  3   4
Affiliations

Gut Microbiome and Inflammation: A Study of Diabetic Inflammasome-Knockout Mice

Roma Pahwa et al. J Diabetes Res. 2017.

Abstract

Aims: Diabetes is a proinflammatory state, evidenced by increased pattern recognition receptors and the inflammasome (NOD-like receptor family pyrin domain (NLRP)) complex. Recent reports have elucidated the role of the gut microbiome in diabetes, but there is limited data on the gut microbiome in NLRP-KO mice and its effect on diabetes-induced inflammation.

Methods: Gut microbiome composition and biomarkers of inflammation (IL-18, serum amyloid A) were assessed in streptozotocin- (STZ-) induced diabetic mice on a NLRP3-knockout (KO) background versus wild-type diabetic mice.

Results: SAA and IL-18 levels were significantly elevated in diabetic mice (STZ) compared to control (WT) mice, and there was a significant attenuation of inflammation in diabetic NLRP3-KO mice (NLRP3-KO STZ) compared to control mice (p < 0.005). Principal coordinate analysis clearly separated controls, STZ, and NLRP3-KO STZ mice. Among the different phyla, there was a significant increase in the Firmicutes : Bacteroidetes ratio in the diabetic group compared to controls. When compared to the WT STZ group, the NLRP3-KO STZ group showed a significant decrease in the Firmicutes : Bacteroidetes ratio. Together, these findings indicate that interaction of the intestinal microbes with the innate immune system is a crucial factor that could modify diabetes and complications.

PubMed Disclaimer

Figures

Figure 1
Figure 1
(a) Rarefaction curves demonstrating the Shannon index (evenness and richness metric) of the OTUs identified for the three groups: WT control, WT STZ, and NLRP3-KO STZ. Rarefaction of the OTU table was set to 794. Curves suggest no significant differences in alpha diversity. (b) Rarefaction curve using the Chao1 index for the three groups: WT control, WT STZ, and NLRP3-KO STZ, calculated using QIIME 1.7. Rarefaction of the OTU table was set to 794. Curves suggest no differences in alpha diversity.
Figure 2
Figure 2
(a) PCoA plot of the WT group by unweighted UniFrac distances. Analyses were determined using QIIME 1.7. The axes represent the first highest discriminating axes using the Bray-Curtis distance measure. (b) PCoA plot of the treatment groups by unweighted UniFrac distances. Analyses were determined using QIIME 1.7. The axes represent the first highest discriminating axes using the Bray-Curtis distance measure.
Figure 3
Figure 3
(a) The taxonomic distribution of the WT control, WT STZ, and NLRP3-KO STZ groups is represented as the percent abundance of the identified phyla for each group. Analyses were determined using QIIME 1.7, and raw data was entered into GraphPad Prism to generate a stacked bar plot. (b) The taxonomic distribution of the WT control, WT STZ, and NLRP3-KO STZ groups is represented as the percent abundance of the identified genera for each group. Analyses were determined using QIIME 1.7, and raw data was entered into GraphPad Prism to generate a stacked bar plot.
See this image and copyright information in PMC

References

    1. Bassi R., Trevisani A., Tezza S., et al. Regenerative therapies for diabetic microangiopathy. Experimental Diabetes Research. 2012;2012:11. doi: 10.1155/2012/916560.916560 - DOI - PMC - PubMed
    1. Jialal I., Devaraj S. Anti-inflammatory strategies to prevent diabetic cardiovascular disease. Clinical Pharmacology & Therapeutics. 2015;98(2):121–123. doi: 10.1002/cpt.105. - DOI - PubMed
    1. Takeuchi O., Akira S. Pattern recognition receptors and inflammation. Cell. 2010;140(6):805–820. doi: 10.1016/j.cell.2010.01.022. - DOI - PubMed
    1. Dasu M. R., Devaraj S., Park S., Jialal I. Increased toll-like receptor (TLR) activation and TLR ligands in recently diagnosed type 2 diabetic subjects. Diabetes Care. 2010;33(4):861–868. doi: 10.2337/dc09-1799. - DOI - PMC - PubMed
    1. Devaraj S., Tobias P., Kasinath B. S., Ramsamooj R., Afify A., Jialal I. Knockout of toll-like receptor-2 attenuates both the proinflammatory state of diabetes and incipient diabetic nephropathy. Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;31(8):1796–1804. doi: 10.1161/ATVBAHA.111.228924. - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources