Gastroenterology

Gastroenterology

Volume 146, Issue 6, May 2014, Pages 1470-1476
Gastroenterology

Basic Concepts in the Mammalian Gut Microbiome
The Intestinal Metabolome: An Intersection Between Microbiota and Host

https://doi.org/10.1053/j.gastro.2014.03.001Get rights and content

Recent advances that allow us to collect more data on DNA sequences and metabolites have increased our understanding of connections between the intestinal microbiota and metabolites at a whole-systems level. We can also now better study the effects of specific microbes on specific metabolites. Here, we review how the microbiota determines levels of specific metabolites, how the metabolite profile develops in infants, and prospects for assessing a person’s physiological state based on their microbes and/or metabolites. Although data acquisition technologies have improved, the computational challenges in integrating data from multiple levels remain formidable; developments in this area will significantly improve our ability to interpret current and future data sets.

Section snippets

Metabolomics in Assessment of Metabolic Status

Metabolomic studies analyze complex systems, including the repertoire of small molecule metabolites in the gut, using high-throughput analytical methods. Mass spectrometry and nuclear magnetic resonance spectroscopy allow robust and sensitive identification of metabolites produced by microbes and host cells in samples such as feces, urine, and tissue (see comprehensive reviews by Dettmer et al19 and Slupsky20). These tools allow researchers to determine the effects that treatments or

Effects of the Microbiome on the Metabolome

Metabolomic analyses allow for the metabolism of the gut microbiota to be directly compared with metabolic outcomes in the host. Wikoff et al29 directly tested the effect of the gut microbiota on the host by comparing the plasma metabolomic profile, obtained via untargeted mass spectrometry, between germ-free and conventionally raised mice. They found that concentrations of more than 10% of all metabolites detected in the plasma differed by at least 50% between mice with and without gut

Predictive Microbial Metagenomes

Metagenomic information can help determine how metabolism is affected by different disease states linked to dysbiosis. Studies of obesity have shown that subjects with increased adiposity have lower microbial diversity than lean subjects.33, 34 The more diverse microbiota of lean subjects contains significantly higher proportions of microbes correlated with anti-inflammatory responses, such as Faecalibacterium prausnitzii. The less diverse microbiota of obese subjects contains higher

Metabolomic Profiles of Infants

Changes to the microbiome and immune system during infancy may have lasting effects, such as contributing to the development of allergies.14, 38, 39 Distinct changes in the microbiota occur during the first 2 years of life and correlate with changes in environment and diet; these can be tracked by studying changes in infants’ fecal metabolomes. A study of infants at risk for celiac disease showed that the metabolomes of infants younger than 6 months of age were dominated by sugars, including

Xenobiotic Metabolism

In addition to diet-derived macronutrients, the microbes residing in the gastrointestinal tract may be exposed to a variety of xenobiotic compounds (antibiotics, other drugs, and diet-derived bioactive compounds). Because the gut microbiome encodes so many enzymes with different activities, it is not surprising that many of the xenobiotic compounds are often metabolized by the gut microbiota. It has been at least 40 years since we began to appreciate the contribution of microbes to xenobiotic

Computational Challenges to Discovering Correlations

Identifying statistically meaningful patterns in metabolite contingency tables (tables recording the abundance of each metabolite count in each sample) is straightforward in theory but often conducted with mathematically unfounded techniques in practice. For instance, analysis of variance and Student t test are frequently used to identify significant differences in abundances of metabolites among sample groups without establishing that the underlying data meet the distribution requirements.

Conclusion

The overall diversity and plasticity of the gut microbiota, in comparison to our human genomes, provides exciting new prospects for personalized medicine, particularly for studies to determine the mechanisms by which microbes affect production of metabolites from drugs and diet. Although there is much work to be done, especially in terms of computational methods, the experimental frameworks of metabolomics and microbial community analysis that have emerged should allow for rapid host

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    Conflicts of interest The authors disclose no conflicts.

    Funding Supported by a National Institutes of Health Signaling and Cellular Recognition Training Grant (T32 GM08759 to L.K.U.), by the Canadian Institutes of Health Research (MFE-112991 to H.J.H.), by National Research Initiative Grant 2009-55200-05197 from the USDA National Institute for Food and Agriculture (to J.V. and L.R.), and in part by the Howard Hughes Medical Institute.

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