Jean-François Brugère

Bio: Jean-François Brugère is an academic researcher from University of Auvergne. The author has contributed to research in topics: Genome & Gut flora. The author has an hindex of 21, co-authored 46 publications receiving 1965 citations. Previous affiliations of Jean-François Brugère include Joseph Fourier University & University College Cork.

Archaea and the human gut: New beginning of an old story

Abstract: Methanogenic archaea are known as human gut inhabitants since more than 30 years ago through the detection of methane in the breath and isolation of two methanogenic species belonging to the order Methanobacteriales, Methanobrevibacter smithii and Methanosphaera stadtmanae. During the last decade, diversity of archaea encountered in the human gastrointestinal tract (GIT) has been extended by sequence identification and culturing of new strains. Here we provide an updated census of the archaeal diversity associated with the human GIT and their possible role in the gut physiology and health. We particularly focus on the still poorly characterized 7th order of methanogens, the Methanomassiliicoccales, associated to aged population. While also largely distributed in non-GIT environments, our actual knowledge on this novel order of methanogens has been mainly revealed through GIT inhabitants. They enlarge the number of final electron acceptors of the gut metabolites to mono- di- and trimethylamine. Trimethylamine is exclusively a microbiota-derived product of nutrients (lecithin, choline, TMAO, L-carnitine) from normal diet, from which seems originate two diseases, trimethylaminuria (or Fish-Odor Syndrome) and cardiovascular disease through the proatherogenic property of its oxidized liver-derived form. This therefore supports interest on these methanogenic species and its use as archaebiotics, a term coined from the notion of archaea-derived probiotics.

Comparative genomics highlights the unique biology of Methanomassiliicoccales, a Thermoplasmatales-related seventh order of methanogenic archaea that encodes pyrrolysine

Abstract: A seventh order of methanogens, the Methanomassiliicoccales, has been identified in diverse anaerobic environments including the gastrointestinal tracts (GIT) of humans and other animals and may contribute significantly to methane emission and global warming Methanomassiliicoccales are phylogenetically distant from all other orders of methanogens and belong to a large evolutionary branch composed by lineages of non-methanogenic archaea such as Thermoplasmatales, the Deep Hydrothermal Vent Euryarchaeota-2 (DHVE-2, Aciduliprofundum boonei) and the Marine Group-II (MG-II) To better understand this new order and its relationship to other archaea, we manually curated and extensively compared the genome sequences of three Methanomassiliicoccales representatives derived from human GIT microbiota, “Candidatus Methanomethylophilus alvus", “Candidatus Methanomassiliicoccus intestinalis” and Methanomassiliicoccus luminyensis Comparative analyses revealed atypical features, such as the scattering of the ribosomal RNA genes in the genome and the absence of eukaryotic-like histone gene otherwise present in most of Euryarchaeota genomes Previously identified in Thermoplasmatales genomes, these features are presently extended to several completely sequenced genomes of this large evolutionary branch, including MG-II and DHVE2 The three Methanomassiliicoccales genomes share a unique composition of genes involved in energy conservation suggesting an original combination of two main energy conservation processes previously described in other methanogens They also display substantial differences with each other, such as their codon usage, the nature and origin of their CRISPRs systems and the genes possibly involved in particular environmental adaptations The genome of M luminyensis encodes several features to thrive in soil and sediment conditions suggesting its larger environmental distribution than GIT Conversely, “Ca M alvus” and “Ca M intestinalis” do not present these features and could be more restricted and specialized on GIT Prediction of the amber codon usage, either as a termination signal of translation or coding for pyrrolysine revealed contrasted patterns among the three genomes and suggests a different handling of the Pyl-encoding capacity This study represents the first insights into the genomic organization and metabolic traits of the seventh order of methanogens It suggests contrasted evolutionary history among the three analyzed Methanomassiliicoccales representatives and provides information on conserved characteristics among the overall methanogens and among Thermoplasmata

Phylogenomic Data Support a Seventh Order of Methylotrophic Methanogens and Provide Insights into the Evolution of Methanogenesis

Abstract: Increasing evidence from sequence data from various environments, including the human gut, suggests the existence of a previously unknown putative seventh order of methanogens. The first genomic data from members of this lineage, Methanomassiliicoccus luminyensis and “Candidatus Methanomethylophilus alvus,” provide insights into its evolutionary history and metabolic features. Phylogenetic analysis of ribosomal proteins robustly indicates a monophyletic group independent of any previously known methanogenic order, which shares ancestry with the Marine Benthic Group D, the Marine Group II, the DHVE2 group, and the Thermoplasmatales. This phylogenetic position, along with the analysis of enzymes involved in core methanogenesis, strengthens a single ancient origin of methanogenesis in the Euryarchaeota and indicates further multiple independent losses of this metabolism in nonmethanogenic lineages than previously suggested. Genomic analysis revealed an unprecedented loss of the genes coding for the first six steps of methanogenesis from H2/CO2 and the oxidative part of methylotrophic methanogenesis, consistent with the fact that M. luminyensis and “Ca. M. alvus” are obligate H2-dependent methylotrophic methanogens. Genomic data also suggest that these methanogens may use a large panel of methylated compounds. Phylogenetic analysis including homologs retrieved from environmental samples indicates that methylotrophic methanogenesis (regardless of dependency on H2) is not restricted to gut representatives but may be an ancestral characteristic of the whole order, and possibly also of ancient origin in the Euryarchaeota. 16S rRNA and McrA trees show that this new order of methanogens is very diverse and occupies environments highly relevant for methane production, therefore representing a key lineage to fully understand the diversity and evolution of methanogenesis.

Archaebiotics: Proposed therapeutic use of archaea to prevent trimethylaminuria and cardiovascular disease

Abstract: Trimethylamine (TMA) is produced by gut bacteria from dietary ingredients. In individuals with a hereditary defect in flavin-containing monooxygenase 3, bacterial TMA production is believed to contribute to the symptoms of trimethylaminuria (TMAU; fish-odor syndrome). Intestinal microbiota TMA metabolism may also modulate atherosclerosis risk by affecting trimethylamine oxide (TMAO) production levels. We propose that reducing TMA formation in the gut by converting it to an inert molecule could be used to prevent or limit these human diseases, while avoiding the major drawbacks of other clinical interventions. Reducing TMA levels by microbiological interventions could also be helpful in some vaginoses. Particular members of a recently discovered group of methanogens, that are variably present in the human gut, are unusual in being apparently restricted to utilizing only methyl compounds including TMA as substrates. We confirmed experimentally that one of these strains tested, Methanomassiliicoccus luminyensis B10, is able to deplete TMA, by reducing it with H2 for methanogenesis. We therefore suggest that members of this archaeal lineage could be used as treatments for metabolic disorders.

Genome Sequence of “Candidatus Methanomethylophilus alvus” Mx1201, a Methanogenic Archaeon from the Human Gut Belonging to a Seventh Order of Methanogens

Abstract: We report the draft genome sequence of "Candidatus Methanomethylophilus alvus" Mx1201, a methanogen present in the human gut. It was enriched from human feces under anaerobic conditions with methanol as the substrate. Its circular genome, of around 1.7 Mb, contains genes needed for methylotrophic methanogenesis from methanol and tri-, di-, and monomethylamine.

The Microbiota-Gut-Brain Axis

Abstract: The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within ...

The role of the gut microbiota in nutrition and health

Abstract: The microbial communities that colonize different regions of the human gut influence many aspects of health. In the healthy state, they contribute nutrients and energy to the host via the fermentation of nondigestible dietary components in the large intestine, and a balance is maintained with the host's metabolism and immune system. Negative consequences, however, can include acting as sources of inflammation and infection, involvement in gastrointestinal diseases, and possible contributions to diabetes mellitus and obesity. Major progress has been made in defining some of the dominant members of the microbial community in the healthy large intestine, and in identifying their roles in gut metabolism. Furthermore, it has become clear that diet can have a major influence on microbial community composition both in the short and long term, which should open up new possibilities for health manipulation via diet. Achieving better definition of those dominant commensal bacteria, community profiles and system characteristics that produce stable gut communities beneficial to health is important. The extent of interindividual variation in microbiota composition within the population has also become apparent, and probably influences individual responses to drug administration and dietary manipulation. This Review considers the complex interplay between the gut microbiota, diet and health.

Population-level analysis of gut microbiome variation

Abstract: Fecal microbiome variation in the average, healthy population has remained under-investigated. Here, we analyzed two independent, extensively phenotyped cohorts: the Belgian Flemish Gut Flora Project (FGFP; discovery cohort; N = 1106) and the Dutch LifeLines-DEEP study (LLDeep; replication; N = 1135). Integration with global data sets (N combined = 3948) revealed a 14-genera core microbiota, but the 664 identified genera still underexplore total gut diversity. Sixty-nine clinical and questionnaire-based covariates were found associated to microbiota compositional variation with a 92% replication rate. Stool consistency showed the largest effect size, whereas medication explained largest total variance and interacted with other covariate-microbiota associations. Early-life events such as birth mode were not reflected in adult microbiota composition. Finally, we found that proposed disease marker genera associated to host covariates, urging inclusion of the latter in study design.

Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi

Abstract: Microsporidia are obligate intracellular parasites infesting many animal groups. Lacking mitochondria and peroxysomes, these unicellular eukaryotes were first considered a deeply branching protist lineage that diverged before the endosymbiotic event that led to mitochondria. The discovery of a gene for a mitochondrial-type chaperone combined with molecular phylogenetic data later implied that microsporidia are atypical fungi that lost mitochondria during evolution. Here we report the DNA sequences of the 11 chromosomes of the approximately 2.9-megabase (Mb) genome of Encephalitozoon cuniculi (1,997 potential protein-coding genes). Genome compaction is reflected by reduced intergenic spacers and by the shortness of most putative proteins relative to their eukaryote orthologues. The strong host dependence is illustrated by the lack of genes for some biosynthetic pathways and for the tricarboxylic acid cycle. Phylogenetic analysis lends substantial credit to the fungal affiliation of microsporidia. Because the E. cuniculi genome contains genes related to some mitochondrial functions (for example, Fe-S cluster assembly), we hypothesize that microsporidia have retained a mitochondrion-derived organelle.