High-coverage metabolomics uncovers microbiota-driven biochemical landscape of interorgan transport and gut-brain communication in mice

Yunjia Lai,Kun Lu,Hongyu Ru,Yifei Yang,Yun-Chung Hsiao,Chih-Wei Liu

doi:10.1038/s41467-021-26209-8

Yunjia Lai, Kun Lu + Show 4 more

Open Access

https://doi.org/10.1038/s41467-021-26209-8

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Abstract

The mammalian gut harbors a complex and dynamic microbial ecosystem: the microbiota. While emerging studies support that microbiota regulates brain function with a few molecular cues suggested, the overall biochemical landscape of the “microbiota-gut-brain axis” remains largely unclear. Here we use high-coverage metabolomics to comparatively profile feces, blood sera, and cerebral cortical brain tissues of germ-free C57BL/6 mice and their age-matched conventionally raised counterparts. Results revealed for all three matrices metabolomic signatures owing to microbiota, yielding hundreds of identified metabolites including 533 altered for feces, 231 for sera, and 58 for brain with numerous significantly enriched pathways involving aromatic amino acids and neurotransmitters. Multicompartmental comparative analyses single out microbiota-derived metabolites potentially implicated in interorgan transport and the gut-brain axis, as exemplified by indoxyl sulfate and trimethylamine-N-oxide. Gender-specific characteristics of these landscapes are discussed. Our findings may be valuable for future research probing microbial influences on host metabolism and gut-brain communication.

Highlights

The mammalian gut harbors a complex and dynamic microbial ecosystem: the microbiota
In close proximity to numerous local neurons and immune cells, may either act on the ENS in situ to signal the central nervous system (CNS) remotely, or more likely, they synthesize or transform molecular cues that can translocate from gut lumen to systemic circulation, and possibly cross the blood-brain barrier (BBB) and affect CNS directly[9]
Using UHPLC-heated electrospray ionization (HESI)-highresolution mass spectrometry (HRMS), we detected and aligned ion features into master peak tables for each sample type based on MS1 full-scan data, generating total ion feature numbers ranging from highest 17,386 for feces to lowest 6,334 for brain tissues (Fig. 1b)

Summary

Introduction

The mammalian gut harbors a complex and dynamic microbial ecosystem: the microbiota. While emerging studies support that microbiota regulates brain function with a few molecular cues suggested, the overall biochemical landscape of the “microbiota-gut-brain axis” remains largely unclear. In close proximity to numerous local neurons and immune cells, may either act on the ENS in situ to signal the CNS remotely, or more likely, they synthesize or transform molecular cues that can translocate from gut lumen to systemic circulation, and possibly cross the blood-brain barrier (BBB) and affect CNS directly[9]. Despite such interest, surprisingly, molecular underpinnings for such microbiota-gut-brain axis are unclear. This work presents datasets from a unique multi-metabolome perspective for probing microbial influences on mammalian interorgan transport and gut-bloodbrain interaction

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