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Remote Sensing Between Liver and Intestine: Importance of Microbial Metabolites

Current Pharmacology Reports volume 3, pages 101–113 (2017)Cite this article

Abstract

Purpose of Review

Recent technological advancements including metagenomics sequencing and metabolomics have allowed the discovery of critical functions of gut microbiota in obesity, malnutrition, neurological disorders, asthma, and xenobiotic metabolism. Classification of the human gut microbiome into distinct “enterotypes” has been proposed to serve as a new paradigm for understanding the interplay between microbial variation and human disease phenotypes, as many organs are affected by gut microbiota modifications during the pathogenesis of diseases. Gut microbiota remotely interacts with liver and other metabolic organs of the host through various microbial metabolites that are absorbed into the systemic circulation. The present review summarizes recent literature regarding the importance of gut microbiota in modulating the physiological and pathological responses of various host organs and describes the functions of the known microbial metabolites that are involved in this remote sensing process, with a primary focus on the gut microbiota-liver axis.

Recent Findings

Under physiological conditions, gut microbiota modulates the hepatic transcriptome, proteome, and metabolome, most notably downregulating cytochrome P450 3a-mediated xenobiotic metabolism. Gut microbiome also modulates the rhythmicity in liver gene expression, likely through microbial metabolites, such as butyrate and propionate that serve as epigenetic modifiers. Additionally, the production of host hormones such as primary bile acids and glucagon-like peptide 1 is altered by gut microbiota to modify intermediary metabolism of the host.

Summary

Dysregulation of gut microbiota is implicated in various liver diseases such as alcoholic liver disease, non-alcoholic steatohepatitis, liver cirrhosis, cholangitis, and liver cancer. Gut microbiota modifiers such as probiotics and prebiotics are increasingly recognized as novel therapeutic modalities for liver and other types of human diseases.

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Acknowledgements

This work was supported by National Institutes of Health grants ES025708, GM111381, and ES019487 and the University of Washington Center for Exposures, Diseases, Genomics, and Environment (P30 ES007033), as well as the Murphy Endowment.

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  1. Department of Environmental and Occupational Health Sciences, University of Washington, 4225 Roosevelt Way NE Suite 100, Seattle, WA, 98105, USA

    Zidong Donna Fu & Julia Yue Cui

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  1. Zidong Donna Fu
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Correspondence to Julia Yue Cui.

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This article is part of the Topical Collection on Liver & Xenobiotic Metabolism

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Fu, Z.D., Cui, J.Y. Remote Sensing Between Liver and Intestine: Importance of Microbial Metabolites. Curr Pharmacol Rep 3, 101–113 (2017). https://doi.org/10.1007/s40495-017-0087-0

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Keywords

  • Microbial metabolites
  • Intestine microbiome
  • Liver diseases
  • Bile acids
  • Short-chain fatty acids
  • Choline metabolites