Commensal Microbiota Regulation of Metabolic Networks During Olfactory Dysfunction in Mice

Abstract

Introduction

Recently, an increasing number of studies have focused on commensal microbiota. These microorganisms have been suggested to impact human health and disease. However, only a small amount of data exists to support the assessment of the influences that commensal microbiota exert on olfactory function.

Methods

We used a buried food pellet test (BFPT) to investigate and compare olfactory functions in adult, male, germ-free (GF) and specific-pathogen-free (SPF) mice, then examined and compared the metabolomic profiles for olfactory bulbs (OBs) isolated from GF and SPF mice to uncover the mechanisms associated with olfactory dysfunction.

Results

We found that the absence of commensal microbiota was able to influence olfactory function and the metabolic signatures of OBs, with 38 metabolites presenting significant differences between the two groups. These metabolites were primarily associated with disturbances in glycolysis, the tricarboxylic acid (TCA) cycle, amino acid metabolism, and purine catabolism. Finally, the commensal microbiota regulation of metabolic networks during olfactory dysfunction was identified, based on an integrated analysis of metabolite, protein, and mRNA levels.

Conclusion

This study demonstrated that the absence of commensal microbiota may impair olfactory function and disrupt metabolic networks. These findings provide a new entry-point for understanding olfactory-associated disorders and their potential underlying mechanisms.

Keywords:

• gut microbiota
• germ-free
• olfactory bulb
• metabolomic
• gas chromatography-mass spectrometry

Acknowledgments

This study was supported by the National Key R&D Program of China (Grant no. 2017YFA0505700), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (Grant no. 2019PT320002300) and the Natural Science Foundation Project of China (Grant no. 81820108015).

Abbreviations

5ʹ-NT, 5ʹ-nucleotidase; ADSL, adenylosuccinate lyase; ADSS, adenylosuccinate synthetase; BFPT, buried food pellet test; FDR, false discovery rate; GABA, γ-Aminobutyric acid; GAD, glutamate decarboxylase; GC-MS, gas chromatography–mass spectrometry; GF, germ-free; IDH, isocitrate dehydrogenase; MDH, malate dehydrogenase; OB, olfactory bulb; OPLS–DA, pair-wise orthogonal projections to latent structures discriminant analysis; PDH, pyruvate dehydrogenase; PLS-DA, partial least squares discriminant analysis; PNP, purine-nucleoside phosphorylase; SAT, Spermidine/spermine N1-acetyl transferase; SDH, succinate dehydrogenase; SMOX, spermine oxidase; SPF, specific pathogen free; SUCL, succinate-CoA ligase; TCA, tricarboxylic acid; VIP, variable influence on projection values; XDH, xanthine dehydrogenase.

Disclosure

The authors report no conflicts of interest in this work.