Comparisons of gut microbiota profiles in wild-type and gelatinase B/matrix metalloproteinase-9-deficient mice in acute DSS-induced colitis

Abstract

Gut microbiota help to educate the immune system and a number of involved immune cells were recently characterized. However, specific molecular determinants in these processes are not known, and, reciprocally, little information exists about single host determinants that alter the microbiota. Gelatinase B/matrix metalloproteinase-9 (MMP-9), an innate immune regulator and effector, has been suggested as such a host determinant. In this study, acute colitis was induced in co-housed MMP-9-/- mice (n = 10) and their wild-type (WT) littermates (n = 10) via oral administration of 3% dextran sodium sulfate (DSS) for 7 days followed by 2 days of regular drinking water. Control mice (10 WT and 10 MMP-9-/-) received normal drinking water. Fecal samples were collected at time of sacrifice and immediately frozen at −80 °C. Microbiota analysis was performed using 16S rRNA amplicon sequencing on Illumina MiSeq and taxonomic annotation was performed using the Ribosomal Database Project as reference. Statistical analysis correcting for multiple testing was done using R. No significant differences in clinical or histopathological parameters were found between both genotypes with DSS-induced colitis. Observed microbial richness at genus level and microbiota composition were not significantly influenced by host genotype. In contrast, weight loss, disease activity index, cage, and phenotype did significantly influence the intestinal microbiota composition. After multivariate analysis, cage and phenotype were identified as the sole drivers of microbiota composition variability. In conclusion, changes in fecal microbiota composition were not significantly altered in MMP-9-deficient mice compared to wild-type littermates, but instead were mainly driven by DSS-induced colonic inflammation.

Intestinal inflammation alters the antigen-specific immune response to a skin commensal

“…To explore the gut microbiome composition of adult mice subjected to colitis and S. epi-2W re-challenge, we performed V4 16S rRNA sequencing of colon-sourced stool from control or DSS mice on day 10 post-challenge. We found reduced alpha and beta diversity in DSS mice (Figures 3C and 3D) and changes in relative abundance of Bacteroides and Alloprevotella (Figures 3E, S3C, and S3D), as previously reported in this model (Bloom et al, 2011;de Bruyn et al, 2018). Prevalence of Staphylococcus spp.…”

The Compromised Mucosal Immune System of β7 Integrin-Deficient Mice Has Only Minor Effects on the Fecal Microbiota in Homeostasis

“…The major focus of the present study was to understand the impact of genotype, driving here major changes in the GALT, on the fecal microbiota structure in homeostasis. There have been many reports showing knock-out dependent differences in the gut microbiota of mice (Okubo et al, 2016; de Bruyn et al, 2018; Sun et al, 2019). However, in many cases, confounding factors that might have contributed to the differences observed have been neglected, such as breeders and cage-driven effects (Robertson et al, 2019).…”

Longitudinal Microbiome Analysis in a Dextran Sulfate Sodium-Induced Colitis Mouse Model

“…In addition, population reduction was detected in mice treated with 5% DSS for 14 days [ 31 ]. As an example, at the genus level, the increasing or decreasing abundances of Lactobacillus , Prevotella , and Parabacteroides also indicated a discrepancy between the results [ 29 , 30 , 32 , 33 , 34 ].…”