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  • Metabolomic and Transcriptomic Correlative Analyses in Germ-Free Mice Link Lacticaseibacillus rhamnosus GG-Associated Metabolites to Host Intestinal Fatty Acid Metabolism and β-Oxidation

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Title: Metabolomic and Transcriptomic Correlative Analyses in Germ-Free Mice Link Lacticaseibacillus rhamnosus GG-Associated Metabolites to Host Intestinal Fatty Acid Metabolism and β-Oxidation
Intestinal microbiota confers susceptibility to diet-induced obesity yet many probiotic species that synthesize tryptophan (trp) actually attenuate this effect, however the underlying mechanisms are unclear. We monocolonized germ-free (GF) mice with a widely consumed probiotic Lacticaseibacillus rhamnosus GG (LGG) under trp-free or -sufficient dietary conditions. We obtained untargeted metabolomics from the mouse feces and serum using liquid chromatography-mass spectrometry and obtained intestinal transcriptomic profiles via bulk-RNA sequencing. When comparing LGG-monocolonized mice with GF mice, we found a synergy between LGG and dietary trp in markedly promoting the transcriptome of fatty acid metabolism and -oxidation. Upregulation was specific and was not observed in transcriptomes of trp-fed conventional mice and mice monocolonized with Ruminococcus gnavus. Metabolomics showed that fecal and serum metabolites were also modified by LGG-host-trp interaction. We developed an R-Script based MEtabolome-TRanscriptome Correlation Analysis (METRCA) algorithm and uncovered LGG- and trp-dependent metabolites that were positively or negatively correlated with fatty acid metabolism and -oxidation gene networks. This high throughput metabolome-transcriptome correlation strategy can be used in similar investigations to reveal potential interactions between specific metabolites and functional or disease-related transcriptomic networks.  more » « less
Award ID(s):
1754783 2128307
PAR ID:
10512624
Author(s) / Creator(s):
; ; ; ; ; ; ; ;
Corporate Creator(s):
Editor(s):
Siegel
Publisher / Repository:
Nature
Date Published:
Journal Name:
Laboratory Investigation
Volume:
104
Issue:
4
ISSN:
0023-6837
Page Range / eLocation ID:
100330
Subject(s) / Keyword(s):
Lactobacillus rhamnosus lipid metabolism microbiota obesity probiotic tryptophan
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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