publication . Preprint . 2015

Reduction of Alzheimer's disease beta-amyloid pathology in the absence of gut microbiota

Harach, T.; Marungruang, N.; Dutilleul, N.; Cheatham, V.; Coy, K. D. Mc; Neher, J. J.; Jucker, M.; Fåk, F.; T.; Lasser; ...
Open Access English
  • Published: 08 Sep 2015
Abstract
Alzheimer's disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer's disease is not known. We generated a germ-free mouse model of Alzheimer's disease and discovered a drastic reduction of cerebral Ab amyloid pathology when compared to control Alzheimer's disease animals with intestinal microbiota. Sequencing bacterial 16S rRNA from fecal samples revealed a remarkable shift in the gut microbiota of conventionally-raised Alzheimer's di...
Subjects
free text keywords: Quantitative Biology - Molecular Networks
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22 references, page 1 of 2

Hardy, J. & Selkoe, D. J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353-356, doi:10.1126/science.1072994 (2002).

Belkaid, Y. & Hand, T. W. Role of the microbiota in immunity and inflammation. Cell 157, 121-141, doi:10.1016/j.cell.2014.03.011 (2014).

Hooper, L. V., Littman, D. R. & Macpherson, A. J. Interactions between the microbiota and the immune system. Science 336, 1268-1273, doi:10.1126/science.1223490 (2012). [OpenAIRE]

Barrett, E., Ross, R. P., O'Toole, P. W., Fitzgerald, G. F. & Stanton, C. gamma-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol 113, 411-417, doi:10.1111/j.1365-2672.2012.05344.x (2012).

Bravo, J. A. et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences of the United States of America 108, 16050-16055, doi:10.1073/pnas.1102999108 (2011).

Murphy, E. F. et al. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut 59, 1635-1642, doi:10.1136/gut.2010.215665 (2010).

Hsiao, E. Y. et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 1451-1463, doi:10.1016/j.cell.2013.11.024 (2013).

Scheperjans, F. et al. Gut microbiota are related to Parkinson's disease and clinical phenotype. Mov Disord, doi:10.1002/mds.26069 (2014). [OpenAIRE]

Berer, K. et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 479, 538-541, doi:10.1038/nature10554 (2011). [OpenAIRE]

Radde, R. et al. Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology.

EMBO Rep 7, 940-946, doi:10.1038/sj.embor.7400784 (2006).

Bhattacharjee, S. & Lukiw, W. J. Alzheimer's disease and the microbiome. Front Cell Neurosci 7, 153, doi:10.3389/fncel.2013.00153 (2013). [OpenAIRE]

Collins, S. M., Surette, M. & Bercik, P. The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol 10, 735-742, doi:10.1038/nrmicro2876 (2012).

Nicholson, J. K. et al. Host-gut microbiota metabolic interactions. Science 336, 1262-1267, doi:10.1126/science.1223813 (2012).

Everard, A. et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls dietinduced obesity. Proceedings of the National Academy of Sciences of the United States of America 110, 9066-9071, doi:10.1073/pnas.1219451110 (2013).

22 references, page 1 of 2
Abstract
Alzheimer's disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer's disease is not known. We generated a germ-free mouse model of Alzheimer's disease and discovered a drastic reduction of cerebral Ab amyloid pathology when compared to control Alzheimer's disease animals with intestinal microbiota. Sequencing bacterial 16S rRNA from fecal samples revealed a remarkable shift in the gut microbiota of conventionally-raised Alzheimer's di...
Subjects
free text keywords: Quantitative Biology - Molecular Networks
Download from
22 references, page 1 of 2

Hardy, J. & Selkoe, D. J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353-356, doi:10.1126/science.1072994 (2002).

Belkaid, Y. & Hand, T. W. Role of the microbiota in immunity and inflammation. Cell 157, 121-141, doi:10.1016/j.cell.2014.03.011 (2014).

Hooper, L. V., Littman, D. R. & Macpherson, A. J. Interactions between the microbiota and the immune system. Science 336, 1268-1273, doi:10.1126/science.1223490 (2012). [OpenAIRE]

Barrett, E., Ross, R. P., O'Toole, P. W., Fitzgerald, G. F. & Stanton, C. gamma-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol 113, 411-417, doi:10.1111/j.1365-2672.2012.05344.x (2012).

Bravo, J. A. et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences of the United States of America 108, 16050-16055, doi:10.1073/pnas.1102999108 (2011).

Murphy, E. F. et al. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut 59, 1635-1642, doi:10.1136/gut.2010.215665 (2010).

Hsiao, E. Y. et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 1451-1463, doi:10.1016/j.cell.2013.11.024 (2013).

Scheperjans, F. et al. Gut microbiota are related to Parkinson's disease and clinical phenotype. Mov Disord, doi:10.1002/mds.26069 (2014). [OpenAIRE]

Berer, K. et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 479, 538-541, doi:10.1038/nature10554 (2011). [OpenAIRE]

Radde, R. et al. Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology.

EMBO Rep 7, 940-946, doi:10.1038/sj.embor.7400784 (2006).

Bhattacharjee, S. & Lukiw, W. J. Alzheimer's disease and the microbiome. Front Cell Neurosci 7, 153, doi:10.3389/fncel.2013.00153 (2013). [OpenAIRE]

Collins, S. M., Surette, M. & Bercik, P. The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol 10, 735-742, doi:10.1038/nrmicro2876 (2012).

Nicholson, J. K. et al. Host-gut microbiota metabolic interactions. Science 336, 1262-1267, doi:10.1126/science.1223813 (2012).

Everard, A. et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls dietinduced obesity. Proceedings of the National Academy of Sciences of the United States of America 110, 9066-9071, doi:10.1073/pnas.1219451110 (2013).

22 references, page 1 of 2
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