Dataset Information

Microbial ecology of the murine gut associated with the development of dextran sodium sulfate-induced colitis.

ABSTRACT: Dextran sodium sulfate (DSS) is used to induce murine colitis. Although the exact mechanism by which DSS administration causes disease is unknown, evidence suggests that the resident bacteria play a role in the development of murine DSS colitis, analogous to their role in human inflammatory bowel diseases.C57BL/6 mice received 5% DSS in the drinking water and were euthanized 3 days and 14 days after the initiation of DSS treatment. Culture-independent methods were used to follow changes in the community structure of the gut's microbiota following DSS treatment. Histologic evidence of disease and changes in host gene expression were assessed.Histologic colitis was minimal in DSS-treated animals at 3 days, but severe after 14 days. Analysis of 16S rRNA-encoding gene clone libraries demonstrated that the microbial communities in the ceca of DSS-treated mice were distinct from those in control mice. The microbiota in the cecum of DSS-treated animals was characterized by an overall decrease in microbial richness, an increase in members of the phylum Verrucomicrobia, and decrease in Tenericutes. Changes in the host's inflammatory response and microbial communities occurred before the histologic appearance of severe disease in the colon, but were seen concurrently in the cecum.DSS administration is associated with reproducible changes in the gut microbial diversity of mice. Microbial and immunological changes appeared before the development of severe inflammation in the colon. This indicates that these changes in microbial community may play role in the potentiation of the abnormal inflammatory response seen in DSS-treated animals.

SUBMITTER: Nagalingam NA

PROVIDER: S-EPMC3058753 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Microbial ecology of the murine gut associated with the development of dextran sodium sulfate-induced colitis.

Nagalingam Nabeetha A NA Kao John Y JY Young Vincent B VB

Inflammatory bowel diseases 20101108 4

<h4>Background</h4>Dextran sodium sulfate (DSS) is used to induce murine colitis. Although the exact mechanism by which DSS administration causes disease is unknown, evidence suggests that the resident bacteria play a role in the development of murine DSS colitis, analogous to their role in human inflammatory bowel diseases.<h4>Methods</h4>C57BL/6 mice received 5% DSS in the drinking water and were euthanized 3 days and 14 days after the initiation of DSS treatment. Culture-independent methods w ...[more]

PMID: 21391286

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Project description:Longitudinal studies on the gut microbiome that follow the effect of a perturbation are critical in understanding the microbiome's response and succession to disease. Here, we use a dextran sodium sulfate (DSS) mouse model of colitis as a tractable perturbation to study how gut bacteria change their physiology over the course of a perturbation. Using single-cell methods such as flow cytometry, bioorthogonal noncanonical amino acid tagging (BONCAT), and population-based cell sorting combined with 16S rRNA sequencing, we determine the diversity of physiologically distinct fractions of the gut microbiota and how they respond to a controlled perturbation. The physiological markers of bacterial activity studied here include relative nucleic acid content, membrane damage, and protein production. There is a distinct and reproducible succession in bacterial physiology, with an increase in bacteria with membrane damage and diversity changes in the translationally active fraction, both, critically, occurring before symptom onset. Large increases in the relative abundance of Akkermansia were seen in all physiological fractions, most notably in the translationally active bacteria. Performing these analyses within a detailed, longitudinal framework determines which bacteria change their physiology early on, focusing therapeutic efforts in the future to predict or even mitigate relapse in diseases like inflammatory bowel diseases. IMPORTANCE Most studies on the gut microbiome focus on the composition of this community and how it changes in disease. However, how the community transitions from a healthy state to one associated with disease is currently unknown. Additionally, common diversity metrics do not provide functional information on bacterial activity. We begin to address these two unknowns by following bacterial activity over the course of disease progression, using a tractable mouse model of colitis. We find reproducible changes in gut bacterial physiology that occur before symptom onset, with increases in the proportion of bacteria with membrane damage, and changes in community composition of the translationally active bacteria. Our data provide a framework to identify possible windows of intervention and which bacteria to target in microbiome-based therapeutics.

Dataset Information

Microbial ecology of the murine gut associated with the development of dextran sodium sulfate-induced colitis.

Publications

Microbial ecology of the murine gut associated with the development of dextran sodium sulfate-induced colitis.

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