Abstract
Discussion Forum (0)
ePoster
Topic: Brain Injury
Meloche-Dumas, Léamarie1,2; Le Guillan, Soazig1,2; L'Ecuyer, Sydnée1,3; Williams, Virginie2; Dion, Daniel1,2; Auger, Jérémie4; Williamson, David1,2; Rousseau, Guy1,2; Marsolais, Pierre1,2; Charbonney, Emmanuel1,2,3
1. Departement of Medicine, University of Montreal, Montreal, Canada
2. Critical Care, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada
3. Centre de Recherche du CHUM, Montreal, Canada
4. RosellR Institute for Microbiome and Probiotic by LALLEMAND, Montreal, Canada
Hôpital du Sacré-Coeur de Montréal, University of Montréal
Introduction:
Transplanted organs from neurologically deceased organ donors (NDD) have higher rates of primary dysfunction and lower survival rates compared to organs from neurologically intact donors. Systemic inflammation and stress secondary to vagal denervation contribute to this deleterious process. The impact of intestinal inflammation is described in animal models of transplantation (1) and related to organ failure in humans (2). No studies have yet investigated the status of intestine and its microbiota in human NDD. We designed the present 'proof of concept' study in a cohort of NDD, compared to elective surgery patients as controls, for which we present our preliminary data.
Objective: To characterize the intestinal alterations and microbiota in NDD.
Methods:
Prospective cohort study, enrolling 10 NDD compared to 5 elective surgery patients undergoing right hemicolectomy. Consent from all controls and NDD families was obtained prior to surgery. Comprehensive clinical data were gathered; intestinal sampling (distal ileum and colon margin) were collected once organs' retrieval (donors) and elective surgery were completed. Myeloperoxidase, cytokines, junction protein expression were measured and histology staining done. Feces were sampled in order to analyse the microbiota. Plasma samples were drawn before surgery to measure various markers of intestinal injury and LPS.
Results:
The NDD group had more males (50% vs 40%) and was younger (57 vs 70 years old). Brain injuries were from different causes (30% brain trauma, 30% brain anoxia, 30% brain hemorrhage and 10% toxic encephalopathy), 40% were hypotensive at admission and 90% were under vasopressors during their support in ICU. In the elective surgery group, 3 had open surgery and 2 laparoscopic surgery, mostly for cancers (80%). Both groups had been exposed to antibiotics, the majority to broad spectrum antibiotics, although only one dose was given to controls as prophylaxis. No difference in neutrophil infiltration measure with myeloperoxidase was noted between groups. However, the expression of junction proteins was significantly reduced in the NDD group (Fig 1) and Goblet cells were more prominent in their ileum as well (Fig 2). As for the microbiota, analyses identified significant taxonomic differences in the microbiota between the two groups (LDA score; Fig 3), and a decreased alpha diversity in NDD, but that last result was not deemed significant. Further analyses on different markers of intestinal suffering are ongoing.
Conclusion:
Intestinal alteration encompassing the mucosa and the microbiota are present in NDD. The further characterization of these factors could informe future intervention to reduce intestinal inflammation/alteration that might impact organs quality in NDD.
Image 1
Image 2
Image 3
(1) Hoeger S et al. Modulation of Brain Dead Induced Inflammation by Vagus Nerve Stimulation. American Journal of Transplantation. 2010; 10:477-489.
(2) Bansal V et al. Stimulating the central nervous system to prevent intestinal dysfunction after traumatic brain injury. J Trauma. 2010 May; 68(5):1059-64.
Topic: Brain Injury
Meloche-Dumas, Léamarie1,2; Le Guillan, Soazig1,2; L'Ecuyer, Sydnée1,3; Williams, Virginie2; Dion, Daniel1,2; Auger, Jérémie4; Williamson, David1,2; Rousseau, Guy1,2; Marsolais, Pierre1,2; Charbonney, Emmanuel1,2,3
1. Departement of Medicine, University of Montreal, Montreal, Canada
2. Critical Care, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada
3. Centre de Recherche du CHUM, Montreal, Canada
4. RosellR Institute for Microbiome and Probiotic by LALLEMAND, Montreal, Canada
Hôpital du Sacré-Coeur de Montréal, University of Montréal
Introduction:
Transplanted organs from neurologically deceased organ donors (NDD) have higher rates of primary dysfunction and lower survival rates compared to organs from neurologically intact donors. Systemic inflammation and stress secondary to vagal denervation contribute to this deleterious process. The impact of intestinal inflammation is described in animal models of transplantation (1) and related to organ failure in humans (2). No studies have yet investigated the status of intestine and its microbiota in human NDD. We designed the present 'proof of concept' study in a cohort of NDD, compared to elective surgery patients as controls, for which we present our preliminary data.
Objective: To characterize the intestinal alterations and microbiota in NDD.
Methods:
Prospective cohort study, enrolling 10 NDD compared to 5 elective surgery patients undergoing right hemicolectomy. Consent from all controls and NDD families was obtained prior to surgery. Comprehensive clinical data were gathered; intestinal sampling (distal ileum and colon margin) were collected once organs' retrieval (donors) and elective surgery were completed. Myeloperoxidase, cytokines, junction protein expression were measured and histology staining done. Feces were sampled in order to analyse the microbiota. Plasma samples were drawn before surgery to measure various markers of intestinal injury and LPS.
Results:
The NDD group had more males (50% vs 40%) and was younger (57 vs 70 years old). Brain injuries were from different causes (30% brain trauma, 30% brain anoxia, 30% brain hemorrhage and 10% toxic encephalopathy), 40% were hypotensive at admission and 90% were under vasopressors during their support in ICU. In the elective surgery group, 3 had open surgery and 2 laparoscopic surgery, mostly for cancers (80%). Both groups had been exposed to antibiotics, the majority to broad spectrum antibiotics, although only one dose was given to controls as prophylaxis. No difference in neutrophil infiltration measure with myeloperoxidase was noted between groups. However, the expression of junction proteins was significantly reduced in the NDD group (Fig 1) and Goblet cells were more prominent in their ileum as well (Fig 2). As for the microbiota, analyses identified significant taxonomic differences in the microbiota between the two groups (LDA score; Fig 3), and a decreased alpha diversity in NDD, but that last result was not deemed significant. Further analyses on different markers of intestinal suffering are ongoing.
Conclusion:
Intestinal alteration encompassing the mucosa and the microbiota are present in NDD. The further characterization of these factors could informe future intervention to reduce intestinal inflammation/alteration that might impact organs quality in NDD.
Image 1
Image 2
Image 3
(1) Hoeger S et al. Modulation of Brain Dead Induced Inflammation by Vagus Nerve Stimulation. American Journal of Transplantation. 2010; 10:477-489.
(2) Bansal V et al. Stimulating the central nervous system to prevent intestinal dysfunction after traumatic brain injury. J Trauma. 2010 May; 68(5):1059-64.
ePoster
Topic: Brain Injury
Meloche-Dumas, Léamarie1,2; Le Guillan, Soazig1,2; L'Ecuyer, Sydnée1,3; Williams, Virginie2; Dion, Daniel1,2; Auger, Jérémie4; Williamson, David1,2; Rousseau, Guy1,2; Marsolais, Pierre1,2; Charbonney, Emmanuel1,2,3
1. Departement of Medicine, University of Montreal, Montreal, Canada
2. Critical Care, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada
3. Centre de Recherche du CHUM, Montreal, Canada
4. RosellR Institute for Microbiome and Probiotic by LALLEMAND, Montreal, Canada
Hôpital du Sacré-Coeur de Montréal, University of Montréal
Introduction:
Transplanted organs from neurologically deceased organ donors (NDD) have higher rates of primary dysfunction and lower survival rates compared to organs from neurologically intact donors. Systemic inflammation and stress secondary to vagal denervation contribute to this deleterious process. The impact of intestinal inflammation is described in animal models of transplantation (1) and related to organ failure in humans (2). No studies have yet investigated the status of intestine and its microbiota in human NDD. We designed the present 'proof of concept' study in a cohort of NDD, compared to elective surgery patients as controls, for which we present our preliminary data.
Objective: To characterize the intestinal alterations and microbiota in NDD.
Methods:
Prospective cohort study, enrolling 10 NDD compared to 5 elective surgery patients undergoing right hemicolectomy. Consent from all controls and NDD families was obtained prior to surgery. Comprehensive clinical data were gathered; intestinal sampling (distal ileum and colon margin) were collected once organs' retrieval (donors) and elective surgery were completed. Myeloperoxidase, cytokines, junction protein expression were measured and histology staining done. Feces were sampled in order to analyse the microbiota. Plasma samples were drawn before surgery to measure various markers of intestinal injury and LPS.
Results:
The NDD group had more males (50% vs 40%) and was younger (57 vs 70 years old). Brain injuries were from different causes (30% brain trauma, 30% brain anoxia, 30% brain hemorrhage and 10% toxic encephalopathy), 40% were hypotensive at admission and 90% were under vasopressors during their support in ICU. In the elective surgery group, 3 had open surgery and 2 laparoscopic surgery, mostly for cancers (80%). Both groups had been exposed to antibiotics, the majority to broad spectrum antibiotics, although only one dose was given to controls as prophylaxis. No difference in neutrophil infiltration measure with myeloperoxidase was noted between groups. However, the expression of junction proteins was significantly reduced in the NDD group (Fig 1) and Goblet cells were more prominent in their ileum as well (Fig 2). As for the microbiota, analyses identified significant taxonomic differences in the microbiota between the two groups (LDA score; Fig 3), and a decreased alpha diversity in NDD, but that last result was not deemed significant. Further analyses on different markers of intestinal suffering are ongoing.
Conclusion:
Intestinal alteration encompassing the mucosa and the microbiota are present in NDD. The further characterization of these factors could informe future intervention to reduce intestinal inflammation/alteration that might impact organs quality in NDD.
Image 1
Image 2
Image 3
(1) Hoeger S et al. Modulation of Brain Dead Induced Inflammation by Vagus Nerve Stimulation. American Journal of Transplantation. 2010; 10:477-489.
(2) Bansal V et al. Stimulating the central nervous system to prevent intestinal dysfunction after traumatic brain injury. J Trauma. 2010 May; 68(5):1059-64.
Topic: Brain Injury
Meloche-Dumas, Léamarie1,2; Le Guillan, Soazig1,2; L'Ecuyer, Sydnée1,3; Williams, Virginie2; Dion, Daniel1,2; Auger, Jérémie4; Williamson, David1,2; Rousseau, Guy1,2; Marsolais, Pierre1,2; Charbonney, Emmanuel1,2,3
1. Departement of Medicine, University of Montreal, Montreal, Canada
2. Critical Care, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada
3. Centre de Recherche du CHUM, Montreal, Canada
4. RosellR Institute for Microbiome and Probiotic by LALLEMAND, Montreal, Canada
Hôpital du Sacré-Coeur de Montréal, University of Montréal
Introduction:
Transplanted organs from neurologically deceased organ donors (NDD) have higher rates of primary dysfunction and lower survival rates compared to organs from neurologically intact donors. Systemic inflammation and stress secondary to vagal denervation contribute to this deleterious process. The impact of intestinal inflammation is described in animal models of transplantation (1) and related to organ failure in humans (2). No studies have yet investigated the status of intestine and its microbiota in human NDD. We designed the present 'proof of concept' study in a cohort of NDD, compared to elective surgery patients as controls, for which we present our preliminary data.
Objective: To characterize the intestinal alterations and microbiota in NDD.
Methods:
Prospective cohort study, enrolling 10 NDD compared to 5 elective surgery patients undergoing right hemicolectomy. Consent from all controls and NDD families was obtained prior to surgery. Comprehensive clinical data were gathered; intestinal sampling (distal ileum and colon margin) were collected once organs' retrieval (donors) and elective surgery were completed. Myeloperoxidase, cytokines, junction protein expression were measured and histology staining done. Feces were sampled in order to analyse the microbiota. Plasma samples were drawn before surgery to measure various markers of intestinal injury and LPS.
Results:
The NDD group had more males (50% vs 40%) and was younger (57 vs 70 years old). Brain injuries were from different causes (30% brain trauma, 30% brain anoxia, 30% brain hemorrhage and 10% toxic encephalopathy), 40% were hypotensive at admission and 90% were under vasopressors during their support in ICU. In the elective surgery group, 3 had open surgery and 2 laparoscopic surgery, mostly for cancers (80%). Both groups had been exposed to antibiotics, the majority to broad spectrum antibiotics, although only one dose was given to controls as prophylaxis. No difference in neutrophil infiltration measure with myeloperoxidase was noted between groups. However, the expression of junction proteins was significantly reduced in the NDD group (Fig 1) and Goblet cells were more prominent in their ileum as well (Fig 2). As for the microbiota, analyses identified significant taxonomic differences in the microbiota between the two groups (LDA score; Fig 3), and a decreased alpha diversity in NDD, but that last result was not deemed significant. Further analyses on different markers of intestinal suffering are ongoing.
Conclusion:
Intestinal alteration encompassing the mucosa and the microbiota are present in NDD. The further characterization of these factors could informe future intervention to reduce intestinal inflammation/alteration that might impact organs quality in NDD.
Image 1
Image 2
Image 3
(1) Hoeger S et al. Modulation of Brain Dead Induced Inflammation by Vagus Nerve Stimulation. American Journal of Transplantation. 2010; 10:477-489.
(2) Bansal V et al. Stimulating the central nervous system to prevent intestinal dysfunction after traumatic brain injury. J Trauma. 2010 May; 68(5):1059-64.
Intestinal Loss of Junctional Proteins and Microbiota Balance in Neurologically Deceased Organ Donors
Léamarie Meloche-Dumas
Abstract
Discussion Forum (0)
ePoster
Topic: Brain Injury
Meloche-Dumas, Léamarie1,2; Le Guillan, Soazig1,2; L'Ecuyer, Sydnée1,3; Williams, Virginie2; Dion, Daniel1,2; Auger, Jérémie4; Williamson, David1,2; Rousseau, Guy1,2; Marsolais, Pierre1,2; Charbonney, Emmanuel1,2,3
1. Departement of Medicine, University of Montreal, Montreal, Canada
2. Critical Care, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada
3. Centre de Recherche du CHUM, Montreal, Canada
4. RosellR Institute for Microbiome and Probiotic by LALLEMAND, Montreal, Canada
Hôpital du Sacré-Coeur de Montréal, University of Montréal
Introduction:
Transplanted organs from neurologically deceased organ donors (NDD) have higher rates of primary dysfunction and lower survival rates compared to organs from neurologically intact donors. Systemic inflammation and stress secondary to vagal denervation contribute to this deleterious process. The impact of intestinal inflammation is described in animal models of transplantation (1) and related to organ failure in humans (2). No studies have yet investigated the status of intestine and its microbiota in human NDD. We designed the present 'proof of concept' study in a cohort of NDD, compared to elective surgery patients as controls, for which we present our preliminary data.
Objective: To characterize the intestinal alterations and microbiota in NDD.
Methods:
Prospective cohort study, enrolling 10 NDD compared to 5 elective surgery patients undergoing right hemicolectomy. Consent from all controls and NDD families was obtained prior to surgery. Comprehensive clinical data were gathered; intestinal sampling (distal ileum and colon margin) were collected once organs' retrieval (donors) and elective surgery were completed. Myeloperoxidase, cytokines, junction protein expression were measured and histology staining done. Feces were sampled in order to analyse the microbiota. Plasma samples were drawn before surgery to measure various markers of intestinal injury and LPS.
Results:
The NDD group had more males (50% vs 40%) and was younger (57 vs 70 years old). Brain injuries were from different causes (30% brain trauma, 30% brain anoxia, 30% brain hemorrhage and 10% toxic encephalopathy), 40% were hypotensive at admission and 90% were under vasopressors during their support in ICU. In the elective surgery group, 3 had open surgery and 2 laparoscopic surgery, mostly for cancers (80%). Both groups had been exposed to antibiotics, the majority to broad spectrum antibiotics, although only one dose was given to controls as prophylaxis. No difference in neutrophil infiltration measure with myeloperoxidase was noted between groups. However, the expression of junction proteins was significantly reduced in the NDD group (Fig 1) and Goblet cells were more prominent in their ileum as well (Fig 2). As for the microbiota, analyses identified significant taxonomic differences in the microbiota between the two groups (LDA score; Fig 3), and a decreased alpha diversity in NDD, but that last result was not deemed significant. Further analyses on different markers of intestinal suffering are ongoing.
Conclusion:
Intestinal alteration encompassing the mucosa and the microbiota are present in NDD. The further characterization of these factors could informe future intervention to reduce intestinal inflammation/alteration that might impact organs quality in NDD.
Image 1
Image 2
Image 3
(1) Hoeger S et al. Modulation of Brain Dead Induced Inflammation by Vagus Nerve Stimulation. American Journal of Transplantation. 2010; 10:477-489.
(2) Bansal V et al. Stimulating the central nervous system to prevent intestinal dysfunction after traumatic brain injury. J Trauma. 2010 May; 68(5):1059-64.
Topic: Brain Injury
Meloche-Dumas, Léamarie1,2; Le Guillan, Soazig1,2; L'Ecuyer, Sydnée1,3; Williams, Virginie2; Dion, Daniel1,2; Auger, Jérémie4; Williamson, David1,2; Rousseau, Guy1,2; Marsolais, Pierre1,2; Charbonney, Emmanuel1,2,3
1. Departement of Medicine, University of Montreal, Montreal, Canada
2. Critical Care, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada
3. Centre de Recherche du CHUM, Montreal, Canada
4. RosellR Institute for Microbiome and Probiotic by LALLEMAND, Montreal, Canada
Hôpital du Sacré-Coeur de Montréal, University of Montréal
Introduction:
Transplanted organs from neurologically deceased organ donors (NDD) have higher rates of primary dysfunction and lower survival rates compared to organs from neurologically intact donors. Systemic inflammation and stress secondary to vagal denervation contribute to this deleterious process. The impact of intestinal inflammation is described in animal models of transplantation (1) and related to organ failure in humans (2). No studies have yet investigated the status of intestine and its microbiota in human NDD. We designed the present 'proof of concept' study in a cohort of NDD, compared to elective surgery patients as controls, for which we present our preliminary data.
Objective: To characterize the intestinal alterations and microbiota in NDD.
Methods:
Prospective cohort study, enrolling 10 NDD compared to 5 elective surgery patients undergoing right hemicolectomy. Consent from all controls and NDD families was obtained prior to surgery. Comprehensive clinical data were gathered; intestinal sampling (distal ileum and colon margin) were collected once organs' retrieval (donors) and elective surgery were completed. Myeloperoxidase, cytokines, junction protein expression were measured and histology staining done. Feces were sampled in order to analyse the microbiota. Plasma samples were drawn before surgery to measure various markers of intestinal injury and LPS.
Results:
The NDD group had more males (50% vs 40%) and was younger (57 vs 70 years old). Brain injuries were from different causes (30% brain trauma, 30% brain anoxia, 30% brain hemorrhage and 10% toxic encephalopathy), 40% were hypotensive at admission and 90% were under vasopressors during their support in ICU. In the elective surgery group, 3 had open surgery and 2 laparoscopic surgery, mostly for cancers (80%). Both groups had been exposed to antibiotics, the majority to broad spectrum antibiotics, although only one dose was given to controls as prophylaxis. No difference in neutrophil infiltration measure with myeloperoxidase was noted between groups. However, the expression of junction proteins was significantly reduced in the NDD group (Fig 1) and Goblet cells were more prominent in their ileum as well (Fig 2). As for the microbiota, analyses identified significant taxonomic differences in the microbiota between the two groups (LDA score; Fig 3), and a decreased alpha diversity in NDD, but that last result was not deemed significant. Further analyses on different markers of intestinal suffering are ongoing.
Conclusion:
Intestinal alteration encompassing the mucosa and the microbiota are present in NDD. The further characterization of these factors could informe future intervention to reduce intestinal inflammation/alteration that might impact organs quality in NDD.
Image 1
Image 2
Image 3
(1) Hoeger S et al. Modulation of Brain Dead Induced Inflammation by Vagus Nerve Stimulation. American Journal of Transplantation. 2010; 10:477-489.
(2) Bansal V et al. Stimulating the central nervous system to prevent intestinal dysfunction after traumatic brain injury. J Trauma. 2010 May; 68(5):1059-64.
ePoster
Topic: Brain Injury
Meloche-Dumas, Léamarie1,2; Le Guillan, Soazig1,2; L'Ecuyer, Sydnée1,3; Williams, Virginie2; Dion, Daniel1,2; Auger, Jérémie4; Williamson, David1,2; Rousseau, Guy1,2; Marsolais, Pierre1,2; Charbonney, Emmanuel1,2,3
1. Departement of Medicine, University of Montreal, Montreal, Canada
2. Critical Care, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada
3. Centre de Recherche du CHUM, Montreal, Canada
4. RosellR Institute for Microbiome and Probiotic by LALLEMAND, Montreal, Canada
Hôpital du Sacré-Coeur de Montréal, University of Montréal
Introduction:
Transplanted organs from neurologically deceased organ donors (NDD) have higher rates of primary dysfunction and lower survival rates compared to organs from neurologically intact donors. Systemic inflammation and stress secondary to vagal denervation contribute to this deleterious process. The impact of intestinal inflammation is described in animal models of transplantation (1) and related to organ failure in humans (2). No studies have yet investigated the status of intestine and its microbiota in human NDD. We designed the present 'proof of concept' study in a cohort of NDD, compared to elective surgery patients as controls, for which we present our preliminary data.
Objective: To characterize the intestinal alterations and microbiota in NDD.
Methods:
Prospective cohort study, enrolling 10 NDD compared to 5 elective surgery patients undergoing right hemicolectomy. Consent from all controls and NDD families was obtained prior to surgery. Comprehensive clinical data were gathered; intestinal sampling (distal ileum and colon margin) were collected once organs' retrieval (donors) and elective surgery were completed. Myeloperoxidase, cytokines, junction protein expression were measured and histology staining done. Feces were sampled in order to analyse the microbiota. Plasma samples were drawn before surgery to measure various markers of intestinal injury and LPS.
Results:
The NDD group had more males (50% vs 40%) and was younger (57 vs 70 years old). Brain injuries were from different causes (30% brain trauma, 30% brain anoxia, 30% brain hemorrhage and 10% toxic encephalopathy), 40% were hypotensive at admission and 90% were under vasopressors during their support in ICU. In the elective surgery group, 3 had open surgery and 2 laparoscopic surgery, mostly for cancers (80%). Both groups had been exposed to antibiotics, the majority to broad spectrum antibiotics, although only one dose was given to controls as prophylaxis. No difference in neutrophil infiltration measure with myeloperoxidase was noted between groups. However, the expression of junction proteins was significantly reduced in the NDD group (Fig 1) and Goblet cells were more prominent in their ileum as well (Fig 2). As for the microbiota, analyses identified significant taxonomic differences in the microbiota between the two groups (LDA score; Fig 3), and a decreased alpha diversity in NDD, but that last result was not deemed significant. Further analyses on different markers of intestinal suffering are ongoing.
Conclusion:
Intestinal alteration encompassing the mucosa and the microbiota are present in NDD. The further characterization of these factors could informe future intervention to reduce intestinal inflammation/alteration that might impact organs quality in NDD.
Image 1
Image 2
Image 3
(1) Hoeger S et al. Modulation of Brain Dead Induced Inflammation by Vagus Nerve Stimulation. American Journal of Transplantation. 2010; 10:477-489.
(2) Bansal V et al. Stimulating the central nervous system to prevent intestinal dysfunction after traumatic brain injury. J Trauma. 2010 May; 68(5):1059-64.
Topic: Brain Injury
Meloche-Dumas, Léamarie1,2; Le Guillan, Soazig1,2; L'Ecuyer, Sydnée1,3; Williams, Virginie2; Dion, Daniel1,2; Auger, Jérémie4; Williamson, David1,2; Rousseau, Guy1,2; Marsolais, Pierre1,2; Charbonney, Emmanuel1,2,3
1. Departement of Medicine, University of Montreal, Montreal, Canada
2. Critical Care, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada
3. Centre de Recherche du CHUM, Montreal, Canada
4. RosellR Institute for Microbiome and Probiotic by LALLEMAND, Montreal, Canada
Hôpital du Sacré-Coeur de Montréal, University of Montréal
Introduction:
Transplanted organs from neurologically deceased organ donors (NDD) have higher rates of primary dysfunction and lower survival rates compared to organs from neurologically intact donors. Systemic inflammation and stress secondary to vagal denervation contribute to this deleterious process. The impact of intestinal inflammation is described in animal models of transplantation (1) and related to organ failure in humans (2). No studies have yet investigated the status of intestine and its microbiota in human NDD. We designed the present 'proof of concept' study in a cohort of NDD, compared to elective surgery patients as controls, for which we present our preliminary data.
Objective: To characterize the intestinal alterations and microbiota in NDD.
Methods:
Prospective cohort study, enrolling 10 NDD compared to 5 elective surgery patients undergoing right hemicolectomy. Consent from all controls and NDD families was obtained prior to surgery. Comprehensive clinical data were gathered; intestinal sampling (distal ileum and colon margin) were collected once organs' retrieval (donors) and elective surgery were completed. Myeloperoxidase, cytokines, junction protein expression were measured and histology staining done. Feces were sampled in order to analyse the microbiota. Plasma samples were drawn before surgery to measure various markers of intestinal injury and LPS.
Results:
The NDD group had more males (50% vs 40%) and was younger (57 vs 70 years old). Brain injuries were from different causes (30% brain trauma, 30% brain anoxia, 30% brain hemorrhage and 10% toxic encephalopathy), 40% were hypotensive at admission and 90% were under vasopressors during their support in ICU. In the elective surgery group, 3 had open surgery and 2 laparoscopic surgery, mostly for cancers (80%). Both groups had been exposed to antibiotics, the majority to broad spectrum antibiotics, although only one dose was given to controls as prophylaxis. No difference in neutrophil infiltration measure with myeloperoxidase was noted between groups. However, the expression of junction proteins was significantly reduced in the NDD group (Fig 1) and Goblet cells were more prominent in their ileum as well (Fig 2). As for the microbiota, analyses identified significant taxonomic differences in the microbiota between the two groups (LDA score; Fig 3), and a decreased alpha diversity in NDD, but that last result was not deemed significant. Further analyses on different markers of intestinal suffering are ongoing.
Conclusion:
Intestinal alteration encompassing the mucosa and the microbiota are present in NDD. The further characterization of these factors could informe future intervention to reduce intestinal inflammation/alteration that might impact organs quality in NDD.
Image 1
Image 2
Image 3
(1) Hoeger S et al. Modulation of Brain Dead Induced Inflammation by Vagus Nerve Stimulation. American Journal of Transplantation. 2010; 10:477-489.
(2) Bansal V et al. Stimulating the central nervous system to prevent intestinal dysfunction after traumatic brain injury. J Trauma. 2010 May; 68(5):1059-64.
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