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Pediatr Res

Title:		"The effects of neuroblastoma and chemotherapy on metabolism, fecal microbiome, volatile organic compounds, and gut barrier function in a murine model"
Author(s):		Castellani C; Singer G; Eibisberger M; Obermuller B; Warncke G; Miekisch W; Kolb-Lenz D; Summer G; Pauer TM; ElHaddad A; Kashofer K; Till H;
Address:		"Department of Paediatric and Adolescent Surgery, Medical University of Graz, Graz, Austria. Department of Paediatric and Adolescent Surgery, Medical University of Graz, Graz, Austria. georg.singer@medunigraz.at. Department of Biomedical Research, Medical University of Graz, Graz, Austria. Experimental Research Center, Department of Anaesthesiology and Intensive Care, University of Rostock, Rostock, Germany. Core Facility Ultra-Structure Analysis, Medical University of Graz, Graz, Austria. Institute of Pathology, Medical University of Graz, Graz, Austria"
Journal Title:		Pediatr Res
Year:		2019
Volume:		20190116
Issue:		4
Page Number:		546 - 555
DOI:		10.1038/s41390-019-0283-1
ISSN/ISBN:		1530-0447 (Electronic) 0031-3998 (Linking)
Abstract:		"BACKGROUND: Following transplantation of human neuroblastoma (NB) cells into athymic mice, we investigated the effects of tumor growth and cyclophosphamide (CTX) treatment on systemic metabolism, gut inflammation and permeability, fecal microbiome and volatile organic compounds (VOCs). METHODS: NB cells (MHH-NB11) were implanted into athymic mice (n=20); 20 healthy mice served as controls (sham). CTX was given to 20 animals (10 NB and 10 sham) after 8 and 9 weeks. Metabolic changes were measured. Ileum samples were obtained for RT-PCR (claudins 2 and 4, occludin, tight junction protein 1) and apoptosis rate determination. Fecal microbiome and VOCs were analyzed. Values were compared to sham animals. RESULTS: NB caused reduction of adipose tissue, increases of IL-6 and TNF-alpha, and decreases of TGF-beta1 and -beta2. Serum FITC-dextrane levels were increased in NB and improved under CTX. Claudin 4 expression was higher in NB versus NB + CTX and sham animals. NB caused increased apoptosis of epithelial cells. NB but also CTX led to a reduction in the abundance of Lactobacillus. NB led to alterations of the fecal VOC profile. CONCLUSIONS: NB caused a catabolic pro-inflammatory state, increased gut permeability, altered fecal VOCs and reductions of Lactobacillus. Further investigations are required to determine if modifications of the intestinal microbiome may reverse some of the observed effects"
Keywords:		"Animals Antineoplastic Agents/*pharmacology Cyclophosphamide/*pharmacology Disease Models, Animal Feces/*microbiology Gastrointestinal Microbiome/*drug effects Humans Intestinal Mucosa/*metabolism Mice Mice, Nude Neuroblastoma/*metabolism Volatile Organic;"
Notes:		"MedlineCastellani, Christoph Singer, Georg Eibisberger, Margarita Obermuller, Beate Warncke, Gert Miekisch, Wolfram Kolb-Lenz, Dagmar Summer, Gregor Pauer, Theresa M ElHaddad, Ahmed Kashofer, Karl Till, Holger eng Research Support, Non-U.S. Gov't 2019/01/31 Pediatr Res. 2019 Mar; 85(4):546-555. doi: 10.1038/s41390-019-0283-1. Epub 2019 Jan 16"