Control of acute, chronic, and constitutive hyperammonemia by wild-type and genetically engineered Lactobacillus plantarum in rodents

Charles Nicaise, Deborah Prozzi, Eric Viaene, Christophe Moreno, Thierry Gustot, Eric Quertinmont, Pieter Demetter, Valérie Suain, Philippe Goffin, Jacques Devière, Pascal Hols

Research output: Contribution to journalArticle

Abstract

Hyperammonemia is a common complication of acute and chronic liver diseases. Often accompanied with side effects, therapeutic interventions such as antibiotics or lactulose are generally targeted to decrease the intestinal production and absorption of ammonia. In this study, we aimed to modulate hyperammonemia in three rodent models by administration of wild-type Lactobacillus plantarum, a genetically engineered ammonia hyperconsuming strain, and a strain deficient for the ammonia transporter. Wild-type and metabolically engineered L. plantarum strains were administered in ornithine transcarbamoylase-deficient Sparse-fur mice, a model of constitutive hyperammonemia, in a carbon tetrachloride rat model of chronic liver insufficiency and in a thioacetamide-induced acute liver failure mice model. Constitutive hyperammonemia in Sparse-fur mice and hyperammonemia in a rat model of chronic hepatic insufficiency were efficiently decreased by Lactobacillus administration. In a murine thioacetamide-induced model of acute liver failure, administration of probiotics significantly increased survival and decreased blood and fecal ammonia. The ammonia hyperconsuming strain exhibited a beneficial effect at a lower dose than its wild-type counterpart. Improved survival in the acute liver failure mice model was associated with lower blood ammonia levels but also with a decrease of astrocyte swelling in the brain cortex. Modulation of ammonia was abolished after administration of the strain deficient in the ammonium transporter. Intestinal pH was clearly lowered for all strains and no changes in gut flora were observed.
Original languageEnglish
Pages (from-to)1184-92
Number of pages9
JournalHepatology (Baltimore, Md.)
Volume48
Issue number4
DOIs
Publication statusPublished - Oct 2008

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Hyperammonemia
Lactobacillus plantarum
Ammonia
Rodentia
Acute Liver Failure
Thioacetamide
Hepatic Insufficiency
Lactulose
Ornithine
Carbon Tetrachloride
Intestinal Absorption
Brain Edema
Probiotics
Lactobacillus
Therapeutic Uses
Ammonium Compounds
Astrocytes
Liver Diseases
Chronic Disease
Anti-Bacterial Agents

Keywords

  • Acute Disease
  • Alanine
  • Ammonia
  • Animals
  • Carbon Tetrachloride
  • Chronic Disease
  • Disease Models, Animal
  • Hyperammonemia
  • Lactobacillus plantarum
  • Lactulose
  • Liver Failure
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Probiotics
  • Rats
  • Rats, Inbred Lew
  • Thioacetamide

Cite this

Nicaise, Charles ; Prozzi, Deborah ; Viaene, Eric ; Moreno, Christophe ; Gustot, Thierry ; Quertinmont, Eric ; Demetter, Pieter ; Suain, Valérie ; Goffin, Philippe ; Devière, Jacques ; Hols, Pascal. / Control of acute, chronic, and constitutive hyperammonemia by wild-type and genetically engineered Lactobacillus plantarum in rodents. In: Hepatology (Baltimore, Md.). 2008 ; Vol. 48, No. 4. pp. 1184-92.
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abstract = "Hyperammonemia is a common complication of acute and chronic liver diseases. Often accompanied with side effects, therapeutic interventions such as antibiotics or lactulose are generally targeted to decrease the intestinal production and absorption of ammonia. In this study, we aimed to modulate hyperammonemia in three rodent models by administration of wild-type Lactobacillus plantarum, a genetically engineered ammonia hyperconsuming strain, and a strain deficient for the ammonia transporter. Wild-type and metabolically engineered L. plantarum strains were administered in ornithine transcarbamoylase-deficient Sparse-fur mice, a model of constitutive hyperammonemia, in a carbon tetrachloride rat model of chronic liver insufficiency and in a thioacetamide-induced acute liver failure mice model. Constitutive hyperammonemia in Sparse-fur mice and hyperammonemia in a rat model of chronic hepatic insufficiency were efficiently decreased by Lactobacillus administration. In a murine thioacetamide-induced model of acute liver failure, administration of probiotics significantly increased survival and decreased blood and fecal ammonia. The ammonia hyperconsuming strain exhibited a beneficial effect at a lower dose than its wild-type counterpart. Improved survival in the acute liver failure mice model was associated with lower blood ammonia levels but also with a decrease of astrocyte swelling in the brain cortex. Modulation of ammonia was abolished after administration of the strain deficient in the ammonium transporter. Intestinal pH was clearly lowered for all strains and no changes in gut flora were observed.",
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Nicaise, C, Prozzi, D, Viaene, E, Moreno, C, Gustot, T, Quertinmont, E, Demetter, P, Suain, V, Goffin, P, Devière, J & Hols, P 2008, 'Control of acute, chronic, and constitutive hyperammonemia by wild-type and genetically engineered Lactobacillus plantarum in rodents', Hepatology (Baltimore, Md.), vol. 48, no. 4, pp. 1184-92. https://doi.org/10.1002/hep.22445

Control of acute, chronic, and constitutive hyperammonemia by wild-type and genetically engineered Lactobacillus plantarum in rodents. / Nicaise, Charles; Prozzi, Deborah; Viaene, Eric; Moreno, Christophe; Gustot, Thierry; Quertinmont, Eric; Demetter, Pieter; Suain, Valérie; Goffin, Philippe; Devière, Jacques; Hols, Pascal.

In: Hepatology (Baltimore, Md.), Vol. 48, No. 4, 10.2008, p. 1184-92.

Research output: Contribution to journalArticle

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T1 - Control of acute, chronic, and constitutive hyperammonemia by wild-type and genetically engineered Lactobacillus plantarum in rodents

AU - Nicaise, Charles

AU - Prozzi, Deborah

AU - Viaene, Eric

AU - Moreno, Christophe

AU - Gustot, Thierry

AU - Quertinmont, Eric

AU - Demetter, Pieter

AU - Suain, Valérie

AU - Goffin, Philippe

AU - Devière, Jacques

AU - Hols, Pascal

PY - 2008/10

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N2 - Hyperammonemia is a common complication of acute and chronic liver diseases. Often accompanied with side effects, therapeutic interventions such as antibiotics or lactulose are generally targeted to decrease the intestinal production and absorption of ammonia. In this study, we aimed to modulate hyperammonemia in three rodent models by administration of wild-type Lactobacillus plantarum, a genetically engineered ammonia hyperconsuming strain, and a strain deficient for the ammonia transporter. Wild-type and metabolically engineered L. plantarum strains were administered in ornithine transcarbamoylase-deficient Sparse-fur mice, a model of constitutive hyperammonemia, in a carbon tetrachloride rat model of chronic liver insufficiency and in a thioacetamide-induced acute liver failure mice model. Constitutive hyperammonemia in Sparse-fur mice and hyperammonemia in a rat model of chronic hepatic insufficiency were efficiently decreased by Lactobacillus administration. In a murine thioacetamide-induced model of acute liver failure, administration of probiotics significantly increased survival and decreased blood and fecal ammonia. The ammonia hyperconsuming strain exhibited a beneficial effect at a lower dose than its wild-type counterpart. Improved survival in the acute liver failure mice model was associated with lower blood ammonia levels but also with a decrease of astrocyte swelling in the brain cortex. Modulation of ammonia was abolished after administration of the strain deficient in the ammonium transporter. Intestinal pH was clearly lowered for all strains and no changes in gut flora were observed.

AB - Hyperammonemia is a common complication of acute and chronic liver diseases. Often accompanied with side effects, therapeutic interventions such as antibiotics or lactulose are generally targeted to decrease the intestinal production and absorption of ammonia. In this study, we aimed to modulate hyperammonemia in three rodent models by administration of wild-type Lactobacillus plantarum, a genetically engineered ammonia hyperconsuming strain, and a strain deficient for the ammonia transporter. Wild-type and metabolically engineered L. plantarum strains were administered in ornithine transcarbamoylase-deficient Sparse-fur mice, a model of constitutive hyperammonemia, in a carbon tetrachloride rat model of chronic liver insufficiency and in a thioacetamide-induced acute liver failure mice model. Constitutive hyperammonemia in Sparse-fur mice and hyperammonemia in a rat model of chronic hepatic insufficiency were efficiently decreased by Lactobacillus administration. In a murine thioacetamide-induced model of acute liver failure, administration of probiotics significantly increased survival and decreased blood and fecal ammonia. The ammonia hyperconsuming strain exhibited a beneficial effect at a lower dose than its wild-type counterpart. Improved survival in the acute liver failure mice model was associated with lower blood ammonia levels but also with a decrease of astrocyte swelling in the brain cortex. Modulation of ammonia was abolished after administration of the strain deficient in the ammonium transporter. Intestinal pH was clearly lowered for all strains and no changes in gut flora were observed.

KW - Acute Disease

KW - Alanine

KW - Ammonia

KW - Animals

KW - Carbon Tetrachloride

KW - Chronic Disease

KW - Disease Models, Animal

KW - Hyperammonemia

KW - Lactobacillus plantarum

KW - Lactulose

KW - Liver Failure

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Probiotics

KW - Rats

KW - Rats, Inbred Lew

KW - Thioacetamide

U2 - 10.1002/hep.22445

DO - 10.1002/hep.22445

M3 - Article

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JF - Hepatology

SN - 0270-9139

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ER -