PMID- 25376667
OWN - NLM
STAT- MEDLINE
DCOM- 20150923
LR  - 20220331
IS  - 1433-7339 (Electronic)
IS  - 0941-4355 (Linking)
VI  - 23
IP  - 6
DP  - 2015 Jun
TI  - Substantial decreases in the number and diversity of microbiota during 
      chemotherapy-induced gastrointestinal mucositis in a rat model.
PG  - 1513-22
LID - 10.1007/s00520-014-2487-6 [doi]
AB  - PURPOSE: Earlier, we showed in acute myeloid leukemia (AML) patients that the 
      microbiota changes dramatically during anticancer treatment, coinciding with 
      gastrointestinal mucositis: The commensal anaerobic populations reduce in favor 
      of potential pathogens. Therefore, interventions targeting the microbiota during 
      mucositis might be interesting but can better be tested in animals than in 
      vulnerable mucositis patients. Here, we aimed to study the potential microbial 
      changes during methotrexate (MTX)-induced gastrointestinal mucositis in a 
      well-established rat model and to study whether this model can be used for future 
      microbial intervention studies. METHODS: After injection with MTX or saline (day 
      0), rats were sacrificed between days 2 and 11. Plasma citrulline level, jejunal 
      histology, and the number and diversity of intestinal bacteria in feces (using 
      fluorescence in situ hybridization (FISH)) were determined. RESULTS: Mucositis 
      was most severe on day 4 when food intake, plasma citrulline, and villus length 
      were the lowest, compared with controls (P < 0.0125). At the same time, 
      MTX-treated rats showed an overall decrease (705-fold) in most bacteria (using a 
      universal probe), compared with controls (P < 0.125). Reduced bacterial presence 
      was related with the presence of diarrhea and a reduced villus length 
      (rho = 0.38, P < 0.05). At day 4, there was an absolute and relative decrease of 
      anaerobes (13-fold and -58 %, respectively) and streptococci (296-fold and -1 %, 
      respectively) but a relative increase of Bacteroides (+49 %), compared with 
      controls (P < 0.125). CONCLUSIONS: In the mucositis rat model, we found 
      substantial decreases in the number and diversity of microbiota, resembling 
      earlier findings in humans. The model therefore seems well suited to study the 
      effects of different microbial interventions on mucositis, prior to performing 
      human studies.
FAU - Fijlstra, Margot
AU  - Fijlstra M
AD  - Department of Pediatrics, Beatrix Children's Hospital, University Medical Center 
      Groningen, University of Groningen, Groningen, The Netherlands, 
      m.fijlstra@amc.uva.nl.
FAU - Ferdous, Mithila
AU  - Ferdous M
FAU - Koning, Anne M
AU  - Koning AM
FAU - Rings, Edmond H H M
AU  - Rings EH
FAU - Harmsen, Hermie J M
AU  - Harmsen HJ
FAU - Tissing, Wim J E
AU  - Tissing WJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141108
PL  - Germany
TA  - Support Care Cancer
JT  - Supportive care in cancer : official journal of the Multinational Association of 
      Supportive Care in Cancer
JID - 9302957
RN  - 29VT07BGDA (Citrulline)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Animals
MH  - Citrulline/blood
MH  - In Situ Hybridization, Fluorescence
MH  - Intestinal Mucosa/*drug effects/*microbiology/pathology
MH  - Male
MH  - Methotrexate/*adverse effects/pharmacology
MH  - Microbiota/*drug effects
MH  - Mucositis/blood/chemically induced/*microbiology
MH  - Random Allocation
MH  - Rats
MH  - Rats, Wistar
EDAT- 2014/11/08 06:00
MHDA- 2015/09/24 06:00
CRDT- 2014/11/08 06:00
PHST- 2014/07/08 00:00 [received]
PHST- 2014/10/14 00:00 [accepted]
PHST- 2014/11/08 06:00 [entrez]
PHST- 2014/11/08 06:00 [pubmed]
PHST- 2015/09/24 06:00 [medline]
AID - 10.1007/s00520-014-2487-6 [doi]
PST - ppublish
SO  - Support Care Cancer. 2015 Jun;23(6):1513-22. doi: 10.1007/s00520-014-2487-6. Epub 
      2014 Nov 8.