title: Altered Gut Microbiome Composition and Tryptic Activity of the 5xFAD Alzheimer's Mouse Model.
abstract: The regulation of physiological gut functions such as peristalsis or secretion of digestive enzymes by the central nervous system via the Nervus vagus is well known. Recent investigations highlight that pathological conditions of neurological or psychiatric disorders might directly interfere with the autonomous neuronal network of the gut - the enteric nervous system, or even derive from there. By using a murine Alzheimer's disease model, we investigated a potential influence of disease-associated changes on gastrointestinal properties. 5xFAD mice at three different ages were compared to wild type littermates in regard to metabolic parameters and enzymes of the gut by fluorimetric enzyme assay and western blotting. Overexpression of human amyloid-β protein precursor (AβPP) within the gut was assessed by qPCR and IHC; fecal microbiome analysis was conducted by 16SrRNA quantitation of selected phyla and species. While general composition of fecal samples, locomotion, and food consumption of male 5xFAD animals were not changed, we observed a reduced body weight occurring at early pathological stages. Human AβPP was not only expressed within the brain of these mice but also in gut tissue. Analysis of fecal proteins revealed a reduced trypsin amount in the 5xFAD model mice as compared to the wild type. In addition, we observed changes in fecal microbiota composition along with age. We therefore suggest that the presence of the mutated transgenes (AβPP and PS1), which are per se the basis for the genetic form of Alzheimer's disease in humans, directly interferes with gut function as shown here for the disease model mice.
authors.affiliation: Clinic of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Brandscheid
authors.affiliation: Clinic of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schuck
authors.affiliation: Clinic of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Reinhardt
authors.affiliation: Enteric Nervous System Group, University of Applied Sciences Kaiserslautern and Pediatric Surgery, Mannheim-Heidelberg, Germany.
authors.forename: Karl-Herbert
authors.initials: KH
authors.lastname: Schäfer
authors.affiliation: Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Claus U
authors.initials: CU
authors.lastname: Pietrzik
authors.affiliation: Deutsches Institut für Demenz Prävention (DIDP), Neurodegeneration and Neurobiology, Saarland University, Homburg/Saar, Germany and Experimental Neurology, Saarland University, Homburg/Saar, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Grimm
authors.affiliation: Deutsches Institut für Demenz Prävention (DIDP), Neurodegeneration and Neurobiology, Saarland University, Homburg/Saar, Germany and Experimental Neurology, Saarland University, Homburg/Saar, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hartmann
authors.affiliation: MVZ Institut für Mikroökologie GmbH, Herborn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schwiertz
authors.affiliation: Clinic of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Endres
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000201:enzymology* / Q000382:microbiology* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D003106:Colon / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D004435:Eating; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000502:physiology; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism*
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D014357:Trypsin
keywords: Alzheimer’s disease; gut; microbiome; trypsin