PMID- 28035935
OWN - NLM
STAT- MEDLINE
DCOM- 20180223
LR  - 20180605
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 56
IP  - 2
DP  - 2017
TI  - Altered Gut Microbiome Composition and Tryptic Activity of the 5xFAD Alzheimer's 
      Mouse Model.
PG  - 775-788
LID - 10.3233/JAD-160926 [doi]
AB  - 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-beta protein
      precursor (AbetaPP) 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 AbetaPP 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 (AbetaPP 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.
FAU - Brandscheid, Carolin
AU  - Brandscheid C
AD  - Clinic of Psychiatry and Psychotherapy, University Medical Center of the Johannes
      Gutenberg-University, Mainz, Germany.
FAU - Schuck, Florian
AU  - Schuck F
AD  - Clinic of Psychiatry and Psychotherapy, University Medical Center of the Johannes
      Gutenberg-University, Mainz, Germany.
FAU - Reinhardt, Sven
AU  - Reinhardt S
AD  - Clinic of Psychiatry and Psychotherapy, University Medical Center of the Johannes
      Gutenberg-University, Mainz, Germany.
FAU - Schafer, Karl-Herbert
AU  - Schafer KH
AD  - Enteric Nervous System Group, University of Applied Sciences Kaiserslautern and
      Pediatric Surgery, Mannheim-Heidelberg, Germany.
FAU - Pietrzik, Claus U
AU  - Pietrzik CU
AD  - Institute for Pathobiochemistry, University Medical Center of the Johannes
      Gutenberg-University Mainz, Mainz, Germany.
FAU - Grimm, Marcus
AU  - Grimm M
AD  - Deutsches Institut fur Demenz Pravention (DIDP), Neurodegeneration and
      Neurobiology, Saarland University, Homburg/Saar, Germany and Experimental
      Neurology, Saarland University, Homburg/Saar, Germany.
FAU - Hartmann, Tobias
AU  - Hartmann T
AD  - Deutsches Institut fur Demenz Pravention (DIDP), Neurodegeneration and
      Neurobiology, Saarland University, Homburg/Saar, Germany and Experimental
      Neurology, Saarland University, Homburg/Saar, Germany.
FAU - Schwiertz, Andreas
AU  - Schwiertz A
AD  - MVZ Institut fur Mikrookologie GmbH, Herborn, Germany.
FAU - Endres, Kristina
AU  - Endres K
AD  - Clinic of Psychiatry and Psychotherapy, University Medical Center of the Johannes
      Gutenberg-University, Mainz, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (APP protein, human)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (PSEN1 protein, human)
RN  - 0 (Presenilin-1)
RN  - EC 3.4.21.4 (Trypsin)
SB  - IM
MH  - Aging/metabolism/pathology
MH  - Alzheimer Disease/*enzymology/*microbiology/pathology
MH  - Amyloid beta-Protein Precursor/genetics/metabolism
MH  - Animals
MH  - Body Weight
MH  - Colon/enzymology/microbiology/pathology
MH  - Disease Models, Animal
MH  - Eating
MH  - Feces/chemistry/microbiology
MH  - *Gastrointestinal Microbiome/physiology
MH  - Humans
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Presenilin-1/genetics/metabolism
MH  - Trypsin/*metabolism
OTO - NOTNLM
OT  - *Alzheimer's disease
OT  - *gut
OT  - *microbiome
OT  - *trypsin
EDAT- 2016/12/31 06:00
MHDA- 2018/02/24 06:00
CRDT- 2016/12/31 06:00
PHST- 2016/12/31 06:00 [pubmed]
PHST- 2018/02/24 06:00 [medline]
PHST- 2016/12/31 06:00 [entrez]
AID - JAD160926 [pii]
AID - 10.3233/JAD-160926 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2017;56(2):775-788. doi: 10.3233/JAD-160926.