Abstract

The methanogenic archaeon Methanomassiliicoccus luminyensis strain B10T was isolated from human feces just a few years ago. Due to its remarkable metabolic properties, particularly the degradation of trimethylamines, this strain was supposed to be used as “Archaebiotic” during metabolic disorders of the human intestine. However, there is still no data published regarding adaptations to the natural habitat of M. luminyensis as it has been shown for the other two reported mucosa-associated methanoarchaea. This study aimed at unraveling susceptibility of M. luminyensis to antimicrobial peptides as well as its immunogenicity. By using the established microtiter plate assay adapted to the anaerobic growth requirements of methanogenic archaea, we demonstrated that M. luminyensis is highly sensitive against LL32, a derivative of human cathelicidin (MIC = 2 μM). However, the strain was highly resistant against the porcine lysin NK-2 (MIC = 10 μM) and the synthetic antilipopolysaccharide peptide (Lpep) (MIC>10 μM) and overall differed from the two other methanoarchaea, Methanobrevibacter smithii and Methanosphaera stadtmanae in respect to AMP sensitivity. Moreover, only weak immunogenic potential of M. luminyensis was demonstrated using peripheral blood mononuclear cells (PBMCs) and monocyte-derived dendritic cells (moDCs) by determining release of pro-inflammatory cytokines. Overall, our findings clearly demonstrate that the archaeal gut inhabitant M. luminyensis is susceptible to the release of human-derived antimicrobial peptides and exhibits low immunogenicity towards human immune cells in vitro–revealing characteristics of a typical commensal gut microbe.

Highlights

  • The human gut microbiota is by far described to be dominated by bacteria [1], a large number of microeukaryotes, fungi, viruses as well as archaea form part of it [2]

  • Human immune cell activation in response to these two strains was investigated [5, 6] and it was shown that they are prone to the lytic effects of antimicrobial peptides, to those described for bacteria, though they differed in sensitivities [7]

  • Several strains from the newly identified methanogenic order Methanomassiliicoccales were found to inhabit the human intestine with low abundances [8,9,10] but only the strain Methanomassilii coccus luminyensis strain B10T was cultured and biochemically characterized in 2014 [11]

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Summary

Introduction

The human gut microbiota is by far described to be dominated by bacteria [1], a large number of microeukaryotes, fungi, viruses as well as archaea form part of it [2]. Several strains from the newly identified methanogenic order Methanomassiliicoccales were found to inhabit the human intestine with low abundances [8,9,10] but only the strain Methanomassilii coccus luminyensis strain B10T was cultured and biochemically characterized in 2014 [11]. This strain was shown to degrade trimethylamine (TMA) via H2-dependent reduction of methyl-compounds in the process of methanogenesis [11]. When discussing a potential use of Methanomassiliicoccales as “Archaebiotics” [12], their impact on human immune homeostasis has to be considered

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