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. 2016 Sep 20;2(9):e000080.
doi: 10.1099/mgen.0.000080. eCollection 2016 Sep.

Metagenomic data-mining reveals contrasting microbial populations responsible for trimethylamine formation in human gut and marine ecosystems

Eleanor Jameson  1 , Andrew C Doxey  2 , Ruth Airs  3 , Kevin J Purdy  1 , J Colin Murrell  4 , Yin Chen  1
Affiliations

Metagenomic data-mining reveals contrasting microbial populations responsible for trimethylamine formation in human gut and marine ecosystems

Eleanor Jameson et al. Microb Genom. .

Abstract

Existing metagenome datasets from many different environments contain untapped potential for understanding metabolic pathways and their biological impact. Our interest lies in the formation of trimethylamine (TMA), a key metabolite in both human health and climate change. Here, we focus on bacterial degradation pathways for choline, carnitine, glycine betaine and trimethylamine N-oxide (TMAO) to TMA in human gut and marine metagenomes. We found the TMAO reductase pathway was the most prevalent pathway in both environments. Proteobacteria were found to contribute the majority of the TMAO reductase pathway sequences, except in the stressed gut, where Actinobacteria dominated. Interestingly, in the human gut metagenomes, a high proportion of the Proteobacteria hits were accounted for by the genera Klebsiella and Escherichia. Furthermore Klebsiella and Escherichia harboured three of the four potential TMA-production pathways (choline, carnitine and TMAO), suggesting they have a key role in TMA cycling in the human gut. In addition to the intensive TMAO-TMA cycling in the marine environment, our data suggest that carnitine-to-TMA transformation plays an overlooked role in aerobic marine surface waters, whereas choline-to-TMA transformation is important in anaerobic marine sediments. Our study provides new insights into the potential key microbes and metabolic pathways for TMA formation in two contrasting environments.

Keywords: Marine; Trimethylamine; gut microbiome; metagenome.

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Figures

Fig. 1.
Fig. 1.
Direct formation pathways of trimethylamine (TMA). Genes encoding the key enzymes indicated were targeted for the data-mining. Key enzymes: CntAB, carnitine monooxygenase (Zhu et al., 2014); CutC, choline-TMA lyase (Craciun & Balskus, 2012); GrdH, glycine betaine reductase (Andreesen, 1994); TorA, trimethylamine N-oxide reductase (Méjean et al., 1994). Additionally the TMAO formation pathway FMO (flavin-containing monooxygenase) is indicated as it is critical to TMA cycling (Chen et al., 2011). Black arrows denote anaerobic pathways and grey arrows denote aerobic pathways.
Fig. 2.
Fig. 2.
Data-mining of TMA pathway positive hits, combined blastp and profile-HMM searches of human gut and marine metagenomes. (a–d) represent positive, phylogenetically confirmed hits, normalized to gene length (CntA, 1116 bp; GrdH, 1314 bp; CutC, 3432 bp; TorA, 2529 bp). Error bars represent sem. Bar charts (a–d) represent relative abundance of hits: (a), CntA; (b), GrdH; (c), CutC; (d), TorA. Donut charts (e–h) shown the relative abundance (per 100 000 reads) of phylum-level classification of sequences obtained from blastp and profile-HMMs combined: (e), CntA; (f), GrdH; (g), CutC; (h), TorA. The outer rings represent stressed human gut (32 datasets); the second rings, represent healthy human gut (135 datasets); the third rings marine sediment (36 datasets) and the inner rings open ocean metagenomes (18 datasets; details in Table S1).
Fig. 3.
Fig. 3.
Bar charts depicting the genus-level assignments for confirmed hits. These illustrate relative percentage abundances of phylogenetically confirmed sequence hits at genus-level classification for sequences obtained from both blastp and profile-HMM combined.
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References

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Data Bibliography

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