Dissecting the in Vivo Metabolic Potential of Two Human Gut Acetogens
ABSTRACT Fermenting microbial communities generate hydrogen; its removal through the production of acetate, methane, or hydrogen sulfide modulates the efficiency of energy extraction from available nutrients in many ecosystems. We noted that pathway components for acetogenesis are more abundantly and consistently represented in the gut microbiomes of monozygotic twins and their mothers than components for methanogenesis or sulfate reduction and subsequently analyzed the metabolic potential of two sequenced human gut acetogens, Blautia hydrogenotrophica and Marvinbryantia formatexigens in vitro and in the intestines of gnotobiotic mice harboring a prominent saccharolytic bacterium. To do so, we developed a generally applicable method for multiplex sequencing of expressed microbial mRNAs (microbial RNA-Seq) and, together with mass spectrometry of metabolites, showed that these organisms have distinct patterns of substrate utilization. B. hydrogenotrophica targets aliphatic and aromatic amino acids. It increases the efficiency of fermentation by consuming reducing equivalents, thereby maintaining a high NAD(+)/NADH ratio and boosting acetate production. In contrast, M. formatexigens consumes oligosaccharides, does not impact the redox state of the gut, and boosts the yield of succinate. These findings have strategic implications for those who wish to manipulate the hydrogen economy of gut microbial communities in ways that modulate energy harvest.
- SourceAvailable from: Tamir Gonen
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- "Members of this phylum generally act as mutualists by aiding in the digestion of complex carbohydrates, promoting gut development , modulating the immune system, and protecting against colonization by pathogens (Round and Mazmanian, 2009; Smith et al., 2006; Thomas et al., 2011). As metabolically pliable organisms, Bacteroidetes also help to support a diverse gut community through syntrophic interactions with other microbes (Fischbach and Sonnenburg, 2011; Rey et al., 2010). Evidence suggests that the capacity of a bacterium to survive in a polymicrobial environment is related to the elaboration of interbacterial antagonistic factors. "
ABSTRACT: Bacteroidetes are a phylum of Gram-negative bacteria abundant in mammalian-associated polymicrobial communities, where they impact digestion, immunity, and resistance to infection. Despite the extensive competition at high cell density that occurs in these settings, cell contact-dependent mechanisms of interbacterial antagonism, such as the type VI secretion system (T6SS), have not been defined in this group of organisms. Herein we report the bioinformatic and functional characterization of a T6SS-like pathway in diverse Bacteroidetes. Using prominent human gut commensal and soil-associated species, we demonstrate that these systems localize dynamically within the cell, export antibacterial proteins, and target competitor bacteria. The Bacteroidetes system is a distinct pathway with marked differences in gene content and high evolutionary divergence from the canonical T6S pathway. Our findings offer a potential molecular explanation for the abundance of Bacteroidetes in polymicrobial environments, the observed stability of Bacteroidetes in healthy humans, and the barrier presented by the microbiota against pathogens.
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- "sibility of evaluating more simplified , defined communities on the host metabolomic profile is a promising avenue to gain mechanistic insights . Simplified and defined model systems have been used extensively to study functional properties of common gut residents in vivo ( Sonnenburg et al . , 2006 ; Samuel et al . , 2007 ; Marco et al . , 2010 ; Rey et al . , 2010 ; Faith et al . , 2011 ) . Our use of one - and two - member model communities indicates that there are aspects of the host metabolome that are conserved between these simplified ecosystems and an entire human micro - biota , specifically the common depletion of meta - bolites that are present in GF mice . An important remaining questio"
ABSTRACT: Defining the functional status of host-associated microbial ecosystems has proven challenging owing to the vast number of predicted genes within the microbiome and relatively poor understanding of community dynamics and community-host interaction. Metabolomic approaches, in which a large number of small molecule metabolites can be defined in a biological sample, offer a promising avenue to 'fingerprint' microbiota functional status. Here, we examined the effects of the human gut microbiota on the fecal and urinary metabolome of a humanized (HUM) mouse using an optimized ultra performance liquid chromatography-mass spectrometry-based method. Differences between HUM and conventional mouse urine and fecal metabolomic profiles support host-specific aspects of the microbiota's metabolomic contribution, consistent with distinct microbial compositions. Comparison of microbiota composition and metabolome of mice humanized with different human donors revealed that the vast majority of metabolomic features observed in donor samples are produced in the corresponding HUM mice, and individual-specific features suggest 'personalized' aspects of functionality can be reconstituted in mice. Feeding the mice a defined, custom diet resulted in modification of the metabolite signatures, illustrating that host diet provides an avenue for altering gut microbiota functionality, which in turn can be monitored via metabolomics. Using a defined model microbiota consisting of one or two species, we show that simplified communities can drive major changes in the host metabolomic profile. Our results demonstrate that metabolomics constitutes a powerful avenue for functional characterization of the intestinal microbiota and its interaction with the host.The ISME Journal advance online publication, 6 June 2013; doi:10.1038/ismej.2013.89.The ISME Journal 06/2013; 7(10). DOI:10.1038/ismej.2013.89 · 9.27 Impact Factor
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- "Additionally, the augmented B. thetaiotaomicron levels lead to increased production of short-chain fatty acids, which can be used as source of nutrition by the human host. Alternatively, gut communities that lack methanogens can instead process excess H 2 through acetogenesis (Rey et al. 2010). In this case the acetogen Bacteroides hydrogenotrophica fills the role of H 2 consumer, with similar benefits to both the microbes involved in the syntrophic interaction and the host. "
ABSTRACT: The human body is inhabited by billions of microbial cells and these microbial symbionts play critical roles in human health. Human-associated microbial communities are diverse, and the structure of these communities is variable across body habitats, through time, and between individuals. We can apply concepts developed by plant and animal ecologists to better understand and predict the spatial and temporal patterns in these communities. Due to methodological limitations and the largely unknown natural history of most microbial taxa, this integration of ecology into research on the human microbiome is still in its infancy. However, such integration will yield a deeper understanding of the role of the microbiome in human health and an improved ability to test ecological concepts that are more difficult to test in plant and animal systems.Annual Review of Ecology Evolution and Systematics 11/2012; 43:137-155. DOI:10.1146/annurev-ecolsys-110411-160307 · 10.98 Impact Factor