A humanized gnotobiotic mouse model of host–archaeal–bacterial mutualism

Abstract

Our colons harbor trillions of microbes including a prominent archaeon, Methanobrevibacter smithii. To examine the contributions of Archaea to digestive health, we colonized germ-free mice with Bacteroides thetaiotaomicron, an adaptive bacterial forager of the polysaccharides that we consume, with or without M. smithii or the sulfate-reducing bacterium Desulfovibrio piger. Wholegenome transcriptional profiling of B. thetaiotaomicron, combined with mass spectrometry, revealed that, unlike D. piger, M. smithii directs B. thetaiotaomicron to focus on fermentation of dietary fructans to acetate, whereas B. thetaiotaomicron-derived formate is used by M. smithii for methanogenesis. B. thetaiotaomicron-M. smithii cocolonization produces a significant increase in host adiposity compared with monoassociated, or B. thetaiotaomicron-D. piger biassociated, animals. These findings demonstrate a link between this archaeon, prioritized bacterial utilization of polysaccharides commonly encountered in our modern diets, and host energy balance. adiposity ͉ energy homeostasis ͉ gut microbial ecology ͉ polysaccharide metabolism ͉ Methanobrevibacter smithii T he role of Archaea in human health remains unclear (1). One site where their influence may be profound is the gut. Hydrogen-consuming methanogenic archaeons are present in the intestinal tracts of many invertebrate and vertebrate species (2-4). Our adult intestine contains 10 trillion to 100 trillion microbial cells and is dominated by members of just two divisions of Bacteria, the Bacteroidetes and the Firmicutes (5). Archaea, the only known producers of methane, are present at high levels in 50-85% of humans (6-8). Concordance rates for methane production are equivalent for both monozygotic and dizygotic twins, underscoring the importance of family environment (mothers) in acquisition of methanogens (9). The most comprehensive enumeration of the adult human colonic microbiota reported to date (5) found a single predominant archaeal species, Methanobrevibacter smithii. This Euryarchaeote can comprise up to 10% of all anaerobes in the colons of healthy adults, while Methanosphaera stadtmanae and Crenarchaeotes can be minor members (10, 11).One manifestation of the mutualism between humans and their distal gut microbiota is that the latter extracts energy that would be lost from otherwise indigestible dietary polysaccharides (fiber). Fermentation of dietary fiber is accomplished by syntrophic interactions between microbes linked in a metabolic food web and is a major energy-producing pathway for members of the Bacteroidetes and the Firmicutes. These primary bacterial fermentors generate short-chain fatty acids (SCFAs), principally acetate, propionate, and butyrate, as well as other organic acids (e.g., formate) and gases [e.g., hydrogen (H 2 ) and carbon dioxide (CO 2 )]. Accumulation of H 2 inhibits bacterial NADH dehydrogenases, thereby reducing the yield of ATP. Studies in man-made bioreactors have shown that removal of H 2 by means of archaeal methanogenesis improves ferment...

Olfaction in the kidney: ‘smelling’ gut microbial metabolites

“…Sodium‐coupled monocarboxylate transporters absorb SCFAs from the colon into the plasma (Natarajan & Pluznick, 2014), where they have been reported to be in the 0.1–10 m m range (Le Poul et al . 2003; Samuel & Gordon, 2006; Maslowski et al . 2009; Trompette et al .…”

“…While plasma SCFAs range between 0.1 and 10 m m (Le Poul et al . 2003; Samuel & Gordon, 2006; Maslowski et al . 2009; Trompette et al .…”

Ça « chat » entre la microflore intestinale et l’hôte

“…Les techniques de microfabrication par photolithographie et les traitements de surface permettent aujourd'hui d'imprimer des protéines d'adhérence cellulaire selon des motifs qui ont la taille des cellules et d'entourer ces motifs de polymè-res anti-adhésifs [4,5]. En contrôlant la géométrie de leur patron adhésif, on peut contrôler individuellement la forme des cellules en culture [5].…”

“…En contrôlant la géométrie de leur patron adhésif, on peut contrôler individuellement la forme des cellules en culture [5]. Ainsi, il a pu être montré que l'allongement dans une direction privilégiée de la forme de la cellule (anisotropie) était un facteur géométrique capable d'influencer l'orientation de la polarité cellulaire [6].…”

“…Les relations hôte/microflore ont été examinées par deux approches. La première a utilisé des modèles murins sans microflore intestinale (germ-free), ceux-ci ayant été ensuite colonisés par l'apport de différentes espèces bacté-riennes cultivables provenant de l'intestin de rongeurs (modèle conventionnel), ou « humanisés » par l'apport de bacté-ries cultivables issues de la microflore intestinale humaine [5,6]. La seconde approche a utilisé la bactérie à Gram négatif, anaérobie, Bacteroides thetaiotaomicron [6][7][8].…”