Microbiome-related metabolite changes in gut tissue, cecum content and feces of rats treated with antibiotics

C. Behr, S. Sperber, X. Jiang, V. Strauss, H. Kamp, T. Walk, M. Herold, K. Beekmann, I.M.C.M. Rietjens, B. van Ravenzwaay*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

The metabolic functionality of the gut microbiota contributes to the metabolism and well-being of its host, although detailed insight in the microbiota's metabolism is lacking. Omics technologies could facilitate unraveling metabolism by the gut microbiota. In this study, we performed metabolite profiling of different matrices of the gut, after antibiotic treatment of rats in order to evaluate metabolite changes observed at different dose levels and in different sexes, and to identify the best tissue matrix for further investigations regarding an assessment of metabolic effects of new compounds with antibiotic activity. Three different antibiotics (vancomycin, streptomycin and roxithromycin) were administered orally to rats for 28 days according to the OECD 407 guideline with a subsequent metabolic profiling in feces, cecum content and gut tissue (jejunum, ileum, cecum, colon and rectum). The data were analyzed in the MetaMap®Tox database. Treatment-related effects could be observed in the metabolite profile of feces and cecum content, but not of the different gut tissues. The metabolite profile showed compound specific effects on the microbiome. In line with the activity spectra of the antibiotics tested, vancomycin showed the largest effects, followed by roxithromycin and then by streptomycin for which changes were modest. In general, for all antibiotics the largest changes were observed for the classes of lipids (increase up to 94-fold), bile acids (increase up to 33-fold), amino acids (increase up to 200-fold) and amino acid related (increase up to 348-fold). The most relevant changes in metabolite values were similar in feces and cecum content and among sexes. The results of this targeted analysis indicate that the metabolic profiles of male and female animals in the gut microbiome are comparable. Concluding, taking other samples than feces does not add any extra information. Thus, as a non-invasive sampling method, feces provide a suitable matrix for studies on metabolism by the gut microbiota.

Original languageEnglish
Pages (from-to)198-210
JournalToxicology and Applied Pharmacology
Volume355
DOIs
Publication statusPublished - 15 Sep 2018

Fingerprint

Cecum
Microbiota
Metabolites
Feces
Rats
Metabolism
Tissue
Anti-Bacterial Agents
Roxithromycin
Streptomycin
Vancomycin
Amino Acids
Metabolome
Jejunum
Bile Acids and Salts
Ileum
Rectum
Colon
Animals
Databases

Keywords

  • Antibiotics
  • Gut content and tissue
  • Gut microbiome
  • Metabolite profiling
  • Metabolomics
  • Repeated dose oral toxicity study

Cite this

@article{649cd3adc9874bed904170e469cf7479,
title = "Microbiome-related metabolite changes in gut tissue, cecum content and feces of rats treated with antibiotics",
abstract = "The metabolic functionality of the gut microbiota contributes to the metabolism and well-being of its host, although detailed insight in the microbiota's metabolism is lacking. Omics technologies could facilitate unraveling metabolism by the gut microbiota. In this study, we performed metabolite profiling of different matrices of the gut, after antibiotic treatment of rats in order to evaluate metabolite changes observed at different dose levels and in different sexes, and to identify the best tissue matrix for further investigations regarding an assessment of metabolic effects of new compounds with antibiotic activity. Three different antibiotics (vancomycin, streptomycin and roxithromycin) were administered orally to rats for 28 days according to the OECD 407 guideline with a subsequent metabolic profiling in feces, cecum content and gut tissue (jejunum, ileum, cecum, colon and rectum). The data were analyzed in the MetaMap{\circledR}Tox database. Treatment-related effects could be observed in the metabolite profile of feces and cecum content, but not of the different gut tissues. The metabolite profile showed compound specific effects on the microbiome. In line with the activity spectra of the antibiotics tested, vancomycin showed the largest effects, followed by roxithromycin and then by streptomycin for which changes were modest. In general, for all antibiotics the largest changes were observed for the classes of lipids (increase up to 94-fold), bile acids (increase up to 33-fold), amino acids (increase up to 200-fold) and amino acid related (increase up to 348-fold). The most relevant changes in metabolite values were similar in feces and cecum content and among sexes. The results of this targeted analysis indicate that the metabolic profiles of male and female animals in the gut microbiome are comparable. Concluding, taking other samples than feces does not add any extra information. Thus, as a non-invasive sampling method, feces provide a suitable matrix for studies on metabolism by the gut microbiota.",
keywords = "Antibiotics, Gut content and tissue, Gut microbiome, Metabolite profiling, Metabolomics, Repeated dose oral toxicity study",
author = "C. Behr and S. Sperber and X. Jiang and V. Strauss and H. Kamp and T. Walk and M. Herold and K. Beekmann and I.M.C.M. Rietjens and {van Ravenzwaay}, B.",
year = "2018",
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language = "English",
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Microbiome-related metabolite changes in gut tissue, cecum content and feces of rats treated with antibiotics. / Behr, C.; Sperber, S.; Jiang, X.; Strauss, V.; Kamp, H.; Walk, T.; Herold, M.; Beekmann, K.; Rietjens, I.M.C.M.; van Ravenzwaay, B.

In: Toxicology and Applied Pharmacology, Vol. 355, 15.09.2018, p. 198-210.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Microbiome-related metabolite changes in gut tissue, cecum content and feces of rats treated with antibiotics

AU - Behr, C.

AU - Sperber, S.

AU - Jiang, X.

AU - Strauss, V.

AU - Kamp, H.

AU - Walk, T.

AU - Herold, M.

AU - Beekmann, K.

AU - Rietjens, I.M.C.M.

AU - van Ravenzwaay, B.

PY - 2018/9/15

Y1 - 2018/9/15

N2 - The metabolic functionality of the gut microbiota contributes to the metabolism and well-being of its host, although detailed insight in the microbiota's metabolism is lacking. Omics technologies could facilitate unraveling metabolism by the gut microbiota. In this study, we performed metabolite profiling of different matrices of the gut, after antibiotic treatment of rats in order to evaluate metabolite changes observed at different dose levels and in different sexes, and to identify the best tissue matrix for further investigations regarding an assessment of metabolic effects of new compounds with antibiotic activity. Three different antibiotics (vancomycin, streptomycin and roxithromycin) were administered orally to rats for 28 days according to the OECD 407 guideline with a subsequent metabolic profiling in feces, cecum content and gut tissue (jejunum, ileum, cecum, colon and rectum). The data were analyzed in the MetaMap®Tox database. Treatment-related effects could be observed in the metabolite profile of feces and cecum content, but not of the different gut tissues. The metabolite profile showed compound specific effects on the microbiome. In line with the activity spectra of the antibiotics tested, vancomycin showed the largest effects, followed by roxithromycin and then by streptomycin for which changes were modest. In general, for all antibiotics the largest changes were observed for the classes of lipids (increase up to 94-fold), bile acids (increase up to 33-fold), amino acids (increase up to 200-fold) and amino acid related (increase up to 348-fold). The most relevant changes in metabolite values were similar in feces and cecum content and among sexes. The results of this targeted analysis indicate that the metabolic profiles of male and female animals in the gut microbiome are comparable. Concluding, taking other samples than feces does not add any extra information. Thus, as a non-invasive sampling method, feces provide a suitable matrix for studies on metabolism by the gut microbiota.

AB - The metabolic functionality of the gut microbiota contributes to the metabolism and well-being of its host, although detailed insight in the microbiota's metabolism is lacking. Omics technologies could facilitate unraveling metabolism by the gut microbiota. In this study, we performed metabolite profiling of different matrices of the gut, after antibiotic treatment of rats in order to evaluate metabolite changes observed at different dose levels and in different sexes, and to identify the best tissue matrix for further investigations regarding an assessment of metabolic effects of new compounds with antibiotic activity. Three different antibiotics (vancomycin, streptomycin and roxithromycin) were administered orally to rats for 28 days according to the OECD 407 guideline with a subsequent metabolic profiling in feces, cecum content and gut tissue (jejunum, ileum, cecum, colon and rectum). The data were analyzed in the MetaMap®Tox database. Treatment-related effects could be observed in the metabolite profile of feces and cecum content, but not of the different gut tissues. The metabolite profile showed compound specific effects on the microbiome. In line with the activity spectra of the antibiotics tested, vancomycin showed the largest effects, followed by roxithromycin and then by streptomycin for which changes were modest. In general, for all antibiotics the largest changes were observed for the classes of lipids (increase up to 94-fold), bile acids (increase up to 33-fold), amino acids (increase up to 200-fold) and amino acid related (increase up to 348-fold). The most relevant changes in metabolite values were similar in feces and cecum content and among sexes. The results of this targeted analysis indicate that the metabolic profiles of male and female animals in the gut microbiome are comparable. Concluding, taking other samples than feces does not add any extra information. Thus, as a non-invasive sampling method, feces provide a suitable matrix for studies on metabolism by the gut microbiota.

KW - Antibiotics

KW - Gut content and tissue

KW - Gut microbiome

KW - Metabolite profiling

KW - Metabolomics

KW - Repeated dose oral toxicity study

U2 - 10.1016/j.taap.2018.06.028

DO - 10.1016/j.taap.2018.06.028

M3 - Article

VL - 355

SP - 198

EP - 210

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

ER -