Comparison of Metabolomic Profiles of Organs in Mice of Different Strains Based on SPME-LC-HRMS

Burlikowska, Katarzyna; Stryjak, Iga; Bogusiewicz, Joanna; Kupcewicz, Bogumiła; Jaroch, Karol; Bojko, Barbara

doi:10.3390/metabo10060255

Cited by 17 publications

(12 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Changes in cellular activities are directly translated into altered metabolite patterns. Importantly, in addition to the genes encoding metabolic enzymes, the genetic background also directly influences the metabolome, especially when the metabolite pattern of single organs such as livers or brains were investigated, as was demonstrated in metabolome studies of mouse strains [8]. Similar comparative inter-strain studies have not been reported for teleost laboratory models.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Strain-Specific Liver Metabolite Profiles in Medaka

2021

View full text Add to dashboard Cite

The relationship between genetic variation and phenotypic traits is often poorly understood since specific genotypes do not always easily translate into associated phenotypes, especially for complex disorders. The genetic background has been shown to affect metabolic pathways and thus contribute to variations in the metabolome. Here, we tested the suitability of NMR metabolomics for comparative analysis of fish lines as a first step towards phenotype-genotype association studies. The Japanese rice fish, medaka (Oryzias latipes), is a widely used genetic vertebrate model with several isogenic inbred laboratory strains. We used liver extracts of medaka iCab and HO5 strains as a paradigm to test the feasibility of distinguishing the metabolome of two different inbred strains. Fifteen metabolites could be detected in uni- and multivariate analyses that showed strain-specific levels. Differences could be assigned to specific metabolic pathways. Our results show that NMR spectroscopy is a suitable method to detect variance of the metabolome caused by subtle genetic differences. Thus, it has the potential to address genotype–phenotype associations in medaka, providing an additional level of phenotypic analysis.

show abstract

Section: Discussionmentioning

confidence: 99%

“…That the metabolome highly depends on the genetic background is further demonstrated by studies of mouse strains. Distinct metabolite patterns of single organs such as the liver or brain [8], or physiological processes such as aging, [9] depended on the specific mouse strain employed in the study.…”

Section: Introductionmentioning

confidence: 99%

Strain-Specific Liver Metabolite Profiles in Medaka

2021

View full text Add to dashboard Cite

show abstract

“…Notably, several metabolite alterations demonstrated in brain tissue samples were also demonstrated in plasma. 9 However, metabolomic profiles and metabolic pathways can vary widely even among laboratory rodent strains commonly used in biomedical research, 31 and whether findings from animal models translate to humans is uncertain. 32 Nevertheless, the findings from animal studies demonstrate that there are significant metabolomic alterations associated with tinnitus and underscore the potential for human metabolomic studies to provide important insights into tinnitus pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

A Population-Based Study of Plasma Metabolomic Profiles of Persistent Tinnitus Identifies Candidate Biomarkers

Zeleznik

Welling

Stanković

et al. 2022

Preprint

View full text Add to dashboard Cite

Tinnitus, the perception of sound without the corresponding external stimulus, currently affects 15% of the US population. There is a critical need to unravel the heterogeneous etiologies underlying tinnitus and identify tailored treatment targets. Metabolomic studies have elucidated biological pathways underlying several neurodegenerative disorders and could identify metabolic perturbations that influence tinnitus development. We conducted the first large-scale metabolomic study to identify novel tinnitus biomarkers. We cross-sectionally evaluated plasma metabolite profiles and persistent tinnitus among 6477 women (488 with daily tinnitus ≥5 minutes and 5989 controls). A broad array of 466 metabolites was measured using liquid-chromatography mass spectrometry. Logistic regression was used to estimate odds ratios (OR, per 1 SD increase in metabolite values) and 95% confidence intervals (CI) for each individual metabolite while Metabolite Set Enrichment Analysis (MSEA) was used to identify metabolite classes enriched for associations with tinnitus; all models were adjusted for multiple comparisons. Compared with controls, homocitrulline (OR(95%CI)=1.32(1.16-1.50), C38:6 phosphatidylethanolamine (PE; 1.24(1.12-1.38)), C52:6 triglyceride (TAG; 1.22(1.10-1.36)), C36:4 PE (1.22(1.1-1.35)), C40:6 PE (1.22(1.09-1.35)), and C56:7 TAG (1.21(1.09-1.34)) were positively associated, whereas alpha-keto-beta-methylvalerate (0.68(0.56-0.82)) and levulinate (0.60(0.46-0.79)) were inversely associated with tinnitus (adjusted-p<0.05). Among metabolite classes, TAGs, PEs, and diglycerides (DAGs) were positively associated, while phosphatidylcholine (PC) plasmalogens, lysophosphatidylcholines (LPC), and cholesteryl esters were inversely associated with tinnitus (false discovery rate <0.05). This study identified novel plasma metabolites and metabolite classes that were significantly associated with persistent tinnitus. These findings extend our current understanding of tinnitus and could inform investigations of therapeutic targets for this challenging disorder.

show abstract

“…Seven of these excluded studies have subsequently been published. [16][17][18][19][20][21][22] The remaining six studies were included, [12][13][14][15]23,24 including our own study (Randall 2019) which comprised data from two cohorts of animals. Each of these studies has been published in a peer-reviewed journal.…”

Section: Selection Of Studiesmentioning

confidence: 99%

Gut Dysbiosis in Experimental Kidney Disease: A Meta-Analysis of Rodent Repository Data

Randall

Kieswich

Hoyles

et al. 2023

JASN

View full text Add to dashboard Cite

Significance Statement Alterations in gut microbiota contribute to the pathophysiology of a diverse range of diseases, leading to suggestions that chronic uremia may cause intestinal dysbiosis that contributes to the pathophysiology of CKD. Various small, single-cohort rodent studies have supported this hypothesis. In this meta-analysis of publicly available repository data from studies of models of kidney disease in rodents, cohort variation far outweighed any effect of experimental kidney disease on the gut microbiota. No reproducible changes in animals with kidney disease were seen across all cohorts, although a few trends observed in most experiments may be attributable to kidney disease. The findings suggest that rodent studies do not provide evidence for the existence of “uremic dysbiosis” and that single-cohort studies are unsuitable for producing generalizable results in microbiome research. Background Rodent studies have popularized the notion that uremia may induce pathological changes in the gut microbiota that contribute to kidney disease progression. Although single-cohort rodent studies have yielded insights into host-microbiota relationships in various disease processes, their relevance is limited by cohort and other effects. We previously reported finding metabolomic evidence that batch-to-batch variations in the microbiome of experimental animals are significant confounders in an experimental study. Methods To attempt to identify common microbial signatures that transcend batch variability and that may be attributed to the effect of kidney disease, we downloaded all data describing the molecular characterization of the gut microbiota in rodents with and without experimental kidney disease from two online repositories comprising 127 rodents across ten experimental cohorts. We reanalyzed these data using the DADA2 and Phyloseq packages in R, a statistical computing and graphics system, and analyzed data both in a combined dataset of all samples and at the level of individual experimental cohorts. Results Cohort effects accounted for 69% of total sample variance (P<0.001), substantially outweighing the effect of kidney disease (1.9% of variance, P=0.026). We found no universal trends in microbial population dynamics in animals with kidney disease, but observed some differences (increased alpha diversity, a measure of within-sample bacterial diversity; relative decreases in Lachnospiraceae and Lactobacillus; and increases in some Clostridia and opportunistic taxa) in many cohorts that might represent effects of kidney disease on the gut microbiota. Conclusions These findings suggest that current evidence that kidney disease causes reproducible patterns of dysbiosis is inadequate. We advocate meta-analysis of repository data as a way of identifying broad themes that transcend experimental variation.

show abstract

Comparison of Metabolomic Profiles of Organs in Mice of Different Strains Based on SPME-LC-HRMS

Cited by 17 publications

References 33 publications

Strain-Specific Liver Metabolite Profiles in Medaka

Strain-Specific Liver Metabolite Profiles in Medaka

A Population-Based Study of Plasma Metabolomic Profiles of Persistent Tinnitus Identifies Candidate Biomarkers

Gut Dysbiosis in Experimental Kidney Disease: A Meta-Analysis of Rodent Repository Data

Contact Info

Product

Resources

About