Potential TMA-Producing Bacteria Are Ubiquitously Found in Mammalia.

Silke Rath,Dietmar H Pieper,Tatjana Rud,Marius Vital

doi:10.3389/fmicb.2019.02966

Silke Rath, Dietmar H Pieper + Show 2 more

Open Access

https://doi.org/10.3389/fmicb.2019.02966

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Abstract

Human gut bacteria metabolize dietary components such as choline and carnitine to trimethylamine (TMA) that is subsequently oxidized to trimethylamine-N-oxide (TMAO) by hepatic enzymes. Increased plasma levels of TMAO are associated with the development of cardiovascular and renal disease. In this study, we applied gene-targeted assays in order to quantify (qPCR) and characterize (MiSeq) bacterial genes encoding enzymes responsible for TMA production, namely choline-TMA lyase (CutC), carnitine oxygenase (CntA) and betaine reductase (GrdH) in 89 fecal samples derived from various mammals spanning three dietary groups (carnivores, omnivores and herbivores) and four host orders (Carnivora, Primates, Artiodactyla and Perissodactyla). All samples contained potential TMA-producing bacteria, however, at low abundances (<1.2% of total community). The cutC gene was more abundant in omnivores and carnivores compared with herbivores. CntA was almost absent from herbivores and grdH showed lowest average abundance of all three genes. Bacteria harboring cutC and grdH displayed high diversities where sequence types affiliated with various taxa within Firmicutes dominated, whereas cntA comprised sequences primarily linked to Escherichia. Composition of TMA-forming communities was strongly influenced by diet and host taxonomy and despite their high correlation, both factors contributed uniquely to community structure. Furthermore, Random Forest (RF) models could differentiate between groups at high accuracies. This study gives a comprehensive overview of potential TMA-producing bacteria in the mammalian gut demonstrating that both diet and host taxonomy govern their abundance and composition. It highlights the role of functional redundancy sustaining potential TMA formation in distinct gut environments.

Highlights

The metabolite trimethylamine (TMA) is produced by various gut microbial taxa from dietary quaternary ammonium compounds, mainly choline (Wang et al, 2011) and carnitine (Koeth et al, 2013)
We detected potential TMA-producing communities in fecal samples from all animals tested, demonstrating that this functional group is omnipresent in the gut across Mammalia
Those bacteria occupy only a small niche as their abundance was low in all samples, except for carnitine oxygenase (cntA) that was detected at high concentrations in a few samples

Summary

Introduction

The metabolite trimethylamine (TMA) is produced by various gut microbial taxa from dietary quaternary ammonium compounds, mainly choline (Wang et al, 2011) and carnitine (Koeth et al, 2013) It is absorbed by the intestinal epithelium and oxidized by host hepatic flavin monooxygenases to trimethylamine N-oxide (TMAO), which is associated with the development of cardiovascular and kidney disease (Tang et al, 2013, 2015). The individual contribution of these factors to TMA(O) levels remain elusive, partly because quantification of TMA producers in the gut are largely lacking It is, crucial to understand the distribution of those bacteria in the gut and specify their niches in order to design effective and sustainable treatment strategies minimizing TMAO plasma concentrations (Rath et al, 2018)

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