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

Panan Suntornsaratoon, Ronaldo P. Ferraris, Jayanth Ambat, Jayson M. Antonio, Juan Flores, Abigail Jones, Xiaoyang Su, Nan Gao, Wei Vivian Li

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Intestinal microbiota confers susceptibility to diet-induced obesity, yet many probiotic species that synthesize tryptophan (trp) actually attenuate this effect, although the underlying mechanisms are unclear. We monocolonized germ-free 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 germ-free mice, we found a synergy between LGG and dietary trp in markedly promoting the transcriptome of fatty acid metabolism and β-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 algorithm and uncovered LGG- and trp-dependent metabolites that were positively or negatively correlated with fatty acid metabolism and β-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.

Original languageEnglish (US)
Article number100330
JournalLaboratory Investigation
Volume104
Issue number4
DOIs
StatePublished - Apr 2024

All Science Journal Classification (ASJC) codes

  • General Medicine

Keywords

  • Lactobacillus rhamnosus
  • lipid metabolism
  • microbiota
  • obesity
  • probiotic
  • tryptophan

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