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Burn Injury Alters the Intestinal Microbiome and Increases Gut Permeability and Bacterial Translocation.

Earley ZM, Akhtar S, Green SJ, Naqib A, Khan O, Cannon AR, Hammer AM, Morris NL, Li X, Eberhardt JM, Gamelli RL, Kennedy RH, Choudhry MA - PLoS ONE (2015)

Bottom Line: Disruption of the intestinal epithelial barrier has been shown after burn injury; this can lead to the translocation of bacteria or their products (e.g., endotoxin) from the intestinal lumen to the circulation, thereby increasing the risk for sepsis in immunocompromised individuals.Furthermore, we show that the bacteria increasing in abundance have the potential to translocate to extra-intestinal sites.This study provides an insight into how the diversity of the intestinal microbiome changes after burn injury and some of the consequences these gut bacteria can have in the host.

View Article: PubMed Central - PubMed

Affiliation: Burn & Shock Trauma Research Institute, Loyola University Chicago Health Sciences Division, Maywood, IL, 60153, United States of America; Integrative Cell Biology Program, Loyola University Chicago Health Sciences Division, Maywood, IL, 60153, United States of America.

ABSTRACT
Sepsis remains one of the leading causes of death in burn patients who survive the initial insult of injury. Disruption of the intestinal epithelial barrier has been shown after burn injury; this can lead to the translocation of bacteria or their products (e.g., endotoxin) from the intestinal lumen to the circulation, thereby increasing the risk for sepsis in immunocompromised individuals. Since the maintenance of the epithelial barrier is largely dependent on the intestinal microbiota, we examined the diversity of the intestinal microbiome of severely burned patients and a controlled mouse model of burn injury. We show that burn injury induces a dramatic dysbiosis of the intestinal microbiome of both humans and mice and allows for similar overgrowths of Gram-negative aerobic bacteria. Furthermore, we show that the bacteria increasing in abundance have the potential to translocate to extra-intestinal sites. This study provides an insight into how the diversity of the intestinal microbiome changes after burn injury and some of the consequences these gut bacteria can have in the host.

No MeSH data available.


Related in: MedlinePlus

Intestinal Permeability.Sham, burn day 1, and burn day 3 mice were gavaged with FITC-dextran and 3 hours later blood was drawn and the concentration of FITC-dextran was determined spectrophotometrically in the plasma (A). RNA was purified from the distal small (B) and large (C) intestine one day after burn, reverse transcribed and quantified with qPCR using primers for claudin (Cldn 4, and Cldn 8), in combination with endogenous control Gapdh. ΔCt values were calculated and the mean ± SEM of 10–15 animals/group was expressed relative to sham. (A), *, p<0.05 ANOVA followed by Tukey-Kramer multiple comparisons post hoc test of sham and burn day 1. (B), unpaired student t-test sham and burn day 1, * p<0.05.
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pone.0129996.g005: Intestinal Permeability.Sham, burn day 1, and burn day 3 mice were gavaged with FITC-dextran and 3 hours later blood was drawn and the concentration of FITC-dextran was determined spectrophotometrically in the plasma (A). RNA was purified from the distal small (B) and large (C) intestine one day after burn, reverse transcribed and quantified with qPCR using primers for claudin (Cldn 4, and Cldn 8), in combination with endogenous control Gapdh. ΔCt values were calculated and the mean ± SEM of 10–15 animals/group was expressed relative to sham. (A), *, p<0.05 ANOVA followed by Tukey-Kramer multiple comparisons post hoc test of sham and burn day 1. (B), unpaired student t-test sham and burn day 1, * p<0.05.

Mentions: Increased gut leakiness can result in bacterial translocation from the gut to the lymph nodes. Intestinal permeability was measured in vivo one and three days after burn with a FITC-dextran permeability assay. Sham and burn injured mice were gavaged with FITC-dextran one and three days after burn. Three hours later, the concentration of this dye was determined spectrophotometrically in the plasma. An increase in the concentration of FITC-dextran was observed in mice one day after burn, and no change was observed three days after injury relative to the sham animals (Fig 5A). In addition, gene expression of two tight junction proteins, claudin 4, and 8 were measured in the small and large intestine of sham and burn injury mice. Gene expression levels of claudin 4 and 8 decreased by ~40% in the small intestine one day after injury (Fig 5B). A smaller, and not significant, change was observed in the large intestine (Fig 5C).


Burn Injury Alters the Intestinal Microbiome and Increases Gut Permeability and Bacterial Translocation.

Earley ZM, Akhtar S, Green SJ, Naqib A, Khan O, Cannon AR, Hammer AM, Morris NL, Li X, Eberhardt JM, Gamelli RL, Kennedy RH, Choudhry MA - PLoS ONE (2015)

Intestinal Permeability.Sham, burn day 1, and burn day 3 mice were gavaged with FITC-dextran and 3 hours later blood was drawn and the concentration of FITC-dextran was determined spectrophotometrically in the plasma (A). RNA was purified from the distal small (B) and large (C) intestine one day after burn, reverse transcribed and quantified with qPCR using primers for claudin (Cldn 4, and Cldn 8), in combination with endogenous control Gapdh. ΔCt values were calculated and the mean ± SEM of 10–15 animals/group was expressed relative to sham. (A), *, p<0.05 ANOVA followed by Tukey-Kramer multiple comparisons post hoc test of sham and burn day 1. (B), unpaired student t-test sham and burn day 1, * p<0.05.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4496078&req=5

pone.0129996.g005: Intestinal Permeability.Sham, burn day 1, and burn day 3 mice were gavaged with FITC-dextran and 3 hours later blood was drawn and the concentration of FITC-dextran was determined spectrophotometrically in the plasma (A). RNA was purified from the distal small (B) and large (C) intestine one day after burn, reverse transcribed and quantified with qPCR using primers for claudin (Cldn 4, and Cldn 8), in combination with endogenous control Gapdh. ΔCt values were calculated and the mean ± SEM of 10–15 animals/group was expressed relative to sham. (A), *, p<0.05 ANOVA followed by Tukey-Kramer multiple comparisons post hoc test of sham and burn day 1. (B), unpaired student t-test sham and burn day 1, * p<0.05.
Mentions: Increased gut leakiness can result in bacterial translocation from the gut to the lymph nodes. Intestinal permeability was measured in vivo one and three days after burn with a FITC-dextran permeability assay. Sham and burn injured mice were gavaged with FITC-dextran one and three days after burn. Three hours later, the concentration of this dye was determined spectrophotometrically in the plasma. An increase in the concentration of FITC-dextran was observed in mice one day after burn, and no change was observed three days after injury relative to the sham animals (Fig 5A). In addition, gene expression of two tight junction proteins, claudin 4, and 8 were measured in the small and large intestine of sham and burn injury mice. Gene expression levels of claudin 4 and 8 decreased by ~40% in the small intestine one day after injury (Fig 5B). A smaller, and not significant, change was observed in the large intestine (Fig 5C).

Bottom Line: Disruption of the intestinal epithelial barrier has been shown after burn injury; this can lead to the translocation of bacteria or their products (e.g., endotoxin) from the intestinal lumen to the circulation, thereby increasing the risk for sepsis in immunocompromised individuals.Furthermore, we show that the bacteria increasing in abundance have the potential to translocate to extra-intestinal sites.This study provides an insight into how the diversity of the intestinal microbiome changes after burn injury and some of the consequences these gut bacteria can have in the host.

View Article: PubMed Central - PubMed

Affiliation: Burn & Shock Trauma Research Institute, Loyola University Chicago Health Sciences Division, Maywood, IL, 60153, United States of America; Integrative Cell Biology Program, Loyola University Chicago Health Sciences Division, Maywood, IL, 60153, United States of America.

ABSTRACT
Sepsis remains one of the leading causes of death in burn patients who survive the initial insult of injury. Disruption of the intestinal epithelial barrier has been shown after burn injury; this can lead to the translocation of bacteria or their products (e.g., endotoxin) from the intestinal lumen to the circulation, thereby increasing the risk for sepsis in immunocompromised individuals. Since the maintenance of the epithelial barrier is largely dependent on the intestinal microbiota, we examined the diversity of the intestinal microbiome of severely burned patients and a controlled mouse model of burn injury. We show that burn injury induces a dramatic dysbiosis of the intestinal microbiome of both humans and mice and allows for similar overgrowths of Gram-negative aerobic bacteria. Furthermore, we show that the bacteria increasing in abundance have the potential to translocate to extra-intestinal sites. This study provides an insight into how the diversity of the intestinal microbiome changes after burn injury and some of the consequences these gut bacteria can have in the host.

No MeSH data available.


Related in: MedlinePlus