Limits...
Panorganismal metabolic response modeling of an experimental Echinostoma caproni infection in the mouse.

Saric J, Li JV, Wang Y, Keiser J, Veselkov K, Dirnhofer S, Yap IK, Nicholson JK, Holmes E, Utzinger J - J. Proteome Res. (2009)

Bottom Line: Furthermore, altered gut microbial activity or composition was reflected by increased levels of trimethylamine in the colon.Our modeling approach facilitated in-depth appraisal of the covariation of the metabolic profiles of different biological matrices and found that urine and plasma most closely reflected changes in ileal compartments.In conclusion, an E. caproni infection not only results in direct localized (ileum and jejenum) effects, but also causes remote metabolic changes (colon and several peripheral organs), and therefore describes the panorganismal metabolic response of the infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Public Health and Epidemiology, Swiss Tropical Institute, Basel, Switzerland.

ABSTRACT
Metabolic profiling of host tissues and biofluids during parasitic infections can reveal new biomarker information and aid the elucidation of mechanisms of disease. The multicompartmental metabolic effects of an experimental Echinostoma caproni infection have been characterized in 12 outbred female mice infected orally with 30 E. caproni metacercariae each, using a further 12 uninfected animals as a control group. Mice were killed 36 days postinfection and brain, intestine (colon, ileum, jejeunum), kidney, liver, and spleen were removed. Metabolic profiles of tissue samples were measured using high-resolution magic angle spinning (1)H NMR spectroscopy and biofluids measured by applying conventional (1)H NMR spectroscopy. Spectral data were analyzed via principal component analysis, partial least-squares-derived methods and hierarchical projection analyses. Infection-induced metabolic changes in the tissues were correlated with altered metabolite concentrations in the biofluids (urine, plasma, fecal water) using hierarchical modeling and correlation analyses. Metabolic descriptors of infection were identified in liver, renal cortex, intestinal tissues but not in spleen, brain or renal medulla. The main physiological change observed in the mouse was malabsorption in the small intestine, which was evidenced by decreased levels of various amino acids in the ileum, for example, alanine, taurine, glutamine, and branched chain amino acids. Furthermore, altered gut microbial activity or composition was reflected by increased levels of trimethylamine in the colon. Our modeling approach facilitated in-depth appraisal of the covariation of the metabolic profiles of different biological matrices and found that urine and plasma most closely reflected changes in ileal compartments. In conclusion, an E. caproni infection not only results in direct localized (ileum and jejenum) effects, but also causes remote metabolic changes (colon and several peripheral organs), and therefore describes the panorganismal metabolic response of the infection.

Show MeSH

Related in: MedlinePlus

Typical 600 MHz 1H MAS NMR 1D spectra of different tissues from an uninfected control mouse, aged 8 weeks, (I) liver, (II) kidney cortex, (III) spleen, and (IV) ileum. Key: 1, β-glucose; 2, glycerophosphocholine; 3, phosphocholine; 4; lactate; 5, myo-inositol; 6, choline; 7, creatine; 8, betaine; 9, glycine; 10, taurine; 11, aspartate; 12, asparagine; 13, glutamine; 14, glutamate; 15, acetate; 16, triglyceride (CH=CH); 17, lysine; 18, alanine; 19, methionine; 20, trimethylamine-N-oxide (TMAO); 21, valine; 22, isoleucine; 23, leucine; 24, triglyceride (CH)3; 25, triglyceride (CH)2; 26, triglyceride (CH2CH2CO); 27, triglyceride (CH=CHCH2); 28, triglyceride (CH2CO).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2724024&req=5

fig1: Typical 600 MHz 1H MAS NMR 1D spectra of different tissues from an uninfected control mouse, aged 8 weeks, (I) liver, (II) kidney cortex, (III) spleen, and (IV) ileum. Key: 1, β-glucose; 2, glycerophosphocholine; 3, phosphocholine; 4; lactate; 5, myo-inositol; 6, choline; 7, creatine; 8, betaine; 9, glycine; 10, taurine; 11, aspartate; 12, asparagine; 13, glutamine; 14, glutamate; 15, acetate; 16, triglyceride (CH=CH); 17, lysine; 18, alanine; 19, methionine; 20, trimethylamine-N-oxide (TMAO); 21, valine; 22, isoleucine; 23, leucine; 24, triglyceride (CH)3; 25, triglyceride (CH)2; 26, triglyceride (CH2CH2CO); 27, triglyceride (CH=CHCH2); 28, triglyceride (CH2CO).

Mentions: The biochemical composition of the various organs and tissues analyzed in the noninfected cohort was consistent with the extant literature.20,22,23 Lactate, choline, and alanine, the branched chain amino acids (BCAAs), glutamine, glutamate, betaine, and taurine were observed in all tissue samples (Figure 1), while other metabolites were more apparent in specific tissues only. For example, liver spectra contained generally higher glucose levels than the kidney and the small intestinal tissues (ileum and jejunum), while the spleen and colon showed practically no visible glucose resonances. Furthermore, the assessed liver and ileum regions contained the highest concentration of lipid components compared to the other tissues, whereas ileum and jejunum showed the highest levels of tyrosine and phenylalanine of all measured tissues. The spleen and kidney spectra contained particularly low relative levels of both these amino acids. As expected, comparison of kidney medulla with cortical tissue showed higher concentrations of osmotically active substances, such as betaine, myo- and scyllo-inositol, and taurine, together with higher levels of glycerophosphocholine (GPC), choline, creatine, and glucose in the medulla.


Panorganismal metabolic response modeling of an experimental Echinostoma caproni infection in the mouse.

Saric J, Li JV, Wang Y, Keiser J, Veselkov K, Dirnhofer S, Yap IK, Nicholson JK, Holmes E, Utzinger J - J. Proteome Res. (2009)

Typical 600 MHz 1H MAS NMR 1D spectra of different tissues from an uninfected control mouse, aged 8 weeks, (I) liver, (II) kidney cortex, (III) spleen, and (IV) ileum. Key: 1, β-glucose; 2, glycerophosphocholine; 3, phosphocholine; 4; lactate; 5, myo-inositol; 6, choline; 7, creatine; 8, betaine; 9, glycine; 10, taurine; 11, aspartate; 12, asparagine; 13, glutamine; 14, glutamate; 15, acetate; 16, triglyceride (CH=CH); 17, lysine; 18, alanine; 19, methionine; 20, trimethylamine-N-oxide (TMAO); 21, valine; 22, isoleucine; 23, leucine; 24, triglyceride (CH)3; 25, triglyceride (CH)2; 26, triglyceride (CH2CH2CO); 27, triglyceride (CH=CHCH2); 28, triglyceride (CH2CO).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2724024&req=5

fig1: Typical 600 MHz 1H MAS NMR 1D spectra of different tissues from an uninfected control mouse, aged 8 weeks, (I) liver, (II) kidney cortex, (III) spleen, and (IV) ileum. Key: 1, β-glucose; 2, glycerophosphocholine; 3, phosphocholine; 4; lactate; 5, myo-inositol; 6, choline; 7, creatine; 8, betaine; 9, glycine; 10, taurine; 11, aspartate; 12, asparagine; 13, glutamine; 14, glutamate; 15, acetate; 16, triglyceride (CH=CH); 17, lysine; 18, alanine; 19, methionine; 20, trimethylamine-N-oxide (TMAO); 21, valine; 22, isoleucine; 23, leucine; 24, triglyceride (CH)3; 25, triglyceride (CH)2; 26, triglyceride (CH2CH2CO); 27, triglyceride (CH=CHCH2); 28, triglyceride (CH2CO).
Mentions: The biochemical composition of the various organs and tissues analyzed in the noninfected cohort was consistent with the extant literature.20,22,23 Lactate, choline, and alanine, the branched chain amino acids (BCAAs), glutamine, glutamate, betaine, and taurine were observed in all tissue samples (Figure 1), while other metabolites were more apparent in specific tissues only. For example, liver spectra contained generally higher glucose levels than the kidney and the small intestinal tissues (ileum and jejunum), while the spleen and colon showed practically no visible glucose resonances. Furthermore, the assessed liver and ileum regions contained the highest concentration of lipid components compared to the other tissues, whereas ileum and jejunum showed the highest levels of tyrosine and phenylalanine of all measured tissues. The spleen and kidney spectra contained particularly low relative levels of both these amino acids. As expected, comparison of kidney medulla with cortical tissue showed higher concentrations of osmotically active substances, such as betaine, myo- and scyllo-inositol, and taurine, together with higher levels of glycerophosphocholine (GPC), choline, creatine, and glucose in the medulla.

Bottom Line: Furthermore, altered gut microbial activity or composition was reflected by increased levels of trimethylamine in the colon.Our modeling approach facilitated in-depth appraisal of the covariation of the metabolic profiles of different biological matrices and found that urine and plasma most closely reflected changes in ileal compartments.In conclusion, an E. caproni infection not only results in direct localized (ileum and jejenum) effects, but also causes remote metabolic changes (colon and several peripheral organs), and therefore describes the panorganismal metabolic response of the infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Public Health and Epidemiology, Swiss Tropical Institute, Basel, Switzerland.

ABSTRACT
Metabolic profiling of host tissues and biofluids during parasitic infections can reveal new biomarker information and aid the elucidation of mechanisms of disease. The multicompartmental metabolic effects of an experimental Echinostoma caproni infection have been characterized in 12 outbred female mice infected orally with 30 E. caproni metacercariae each, using a further 12 uninfected animals as a control group. Mice were killed 36 days postinfection and brain, intestine (colon, ileum, jejeunum), kidney, liver, and spleen were removed. Metabolic profiles of tissue samples were measured using high-resolution magic angle spinning (1)H NMR spectroscopy and biofluids measured by applying conventional (1)H NMR spectroscopy. Spectral data were analyzed via principal component analysis, partial least-squares-derived methods and hierarchical projection analyses. Infection-induced metabolic changes in the tissues were correlated with altered metabolite concentrations in the biofluids (urine, plasma, fecal water) using hierarchical modeling and correlation analyses. Metabolic descriptors of infection were identified in liver, renal cortex, intestinal tissues but not in spleen, brain or renal medulla. The main physiological change observed in the mouse was malabsorption in the small intestine, which was evidenced by decreased levels of various amino acids in the ileum, for example, alanine, taurine, glutamine, and branched chain amino acids. Furthermore, altered gut microbial activity or composition was reflected by increased levels of trimethylamine in the colon. Our modeling approach facilitated in-depth appraisal of the covariation of the metabolic profiles of different biological matrices and found that urine and plasma most closely reflected changes in ileal compartments. In conclusion, an E. caproni infection not only results in direct localized (ileum and jejenum) effects, but also causes remote metabolic changes (colon and several peripheral organs), and therefore describes the panorganismal metabolic response of the infection.

Show MeSH
Related in: MedlinePlus