scholarly journals Design of synthetic human gut microbiome assembly and function

2020 ◽  
Author(s):  
Ryan L. Clark ◽  
Bryce M. Connors ◽  
David M. Stevenson ◽  
Susan E. Hromada ◽  
Joshua J. Hamilton ◽  
...  
Keyword(s):  
Experimental Design ◽  
Microbial Communities ◽  
Gut Microbiome ◽  
Species Interactions ◽  
Molecular Mechanisms ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Flexible Framework ◽  
And Function ◽  
Butyrate Production

ABSTRACTThe assembly of microbial communities and functions emerge from a complex and dynamic web of interactions. A major challenge in microbiome engineering is identifying organism configurations with community-level behaviors that achieve a desired function. The number of possible subcommunities scales exponentially with the number of species in a system, creating a vast experimental design space that is challenging to even sparsely traverse. We develop a model-guided experimental design framework for microbial communities and apply this method to explore the functional landscape of the health-relevant metabolite butyrate using a 25-member synthetic human gut microbiome community. Based on limited experimental measurements, our model accurately forecasts community assembly and butyrate production at every possible level of complexity. Our results elucidate key ecological and molecular mechanisms driving butyrate production including inter-species interactions, pH and hydrogen sulfide. Our model-guided iterative approach provides a flexible framework for understanding and predicting community functions for a broad range of applications.

scholarly journals The Glycine Lipids ofBacteroides thetaiotaomicronAre Important for Fitness during GrowthIn VivoandIn Vitro

2018 ◽  
Vol 85 (10) ◽  
Author(s):  
Alli Lynch ◽  
Seshu R. Tammireddy ◽  
Mary K. Doherty ◽  
Phillip D. Whitfield ◽  
David J. Clarke
Keyword(s):  
Amino Acid ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Cellular Membrane ◽  
Bacteroides Thetaiotaomicron ◽  
Human Gut ◽  
Acyltransferase Activity ◽  
Content Type ◽  
Health And Disease ◽  
And Function

ABSTRACTAcylated amino acids function as important components of the cellular membrane in some bacteria. Biosynthesis is initiated by theN-acylation of the amino acid, and this is followed by subsequentO-acylation of the acylated molecule, resulting in the production of the mature diacylated amino acid lipid. In this study, we use both genetics and liquid chromatography-mass spectrometry (LC-MS) to characterize the biosynthesis and function of a diacylated glycine lipid (GL) species produced inBacteroides thetaiotaomicron. We, and others, have previously reported the identification of a gene, namedglsBin this study, that encodes anN-acyltransferase activity responsible for the production of a monoacylated glycine calledN-acyl-3-hydroxy-palmitoyl glycine (or commendamide). In all of theBacteroidalesgenomes sequenced so far, theglsBgene is located immediately downstream from a gene, namedglsA, that is also predicted to encode a protein with acyltransferase activity. We use LC-MS to show that the coexpression ofglsBandglsAresults in the production of GL inEscherichia coli. We constructed a deletion mutant of theglsBgene inB. thetaiotaomicron, and we confirm thatglsBis required for the production of GL inB. thetaiotaomicron. Moreover, we show thatglsBis important for the ability ofB. thetaiotaomicronto adapt to stress and colonize the mammalian gut. Therefore, this report describes the genetic requirements for the biosynthesis of GL, a diacylated amino acid species that contributes to fitness in the human gut bacteriumB. thetaiotaomicron.IMPORTANCEThe gut microbiome has an important role in both health and disease of the host. The mammalian gut microbiome is often dominated by bacteria from theBacteroidales, an order that includesBacteroidesandPrevotella. In this study, we have identified an acylated amino acid, called glycine lipid, produced byBacteroides thetaiotaomicron, a beneficial bacterium originally isolated from the human gut. In addition to identifying the genes required for the production of glycine lipids, we show that glycine lipids have an important role during the adaptation ofB. thetaiotaomicronto a number of environmental stresses, including exposure to either bile or air. We also show that glycine lipids are important for the normal colonization of the murine gut byB. thetaiotaomicron. This work identifies glycine lipids as an important fitness determinant inB. thetaiotaomicronand therefore increases our understanding of the molecular mechanisms underpinning colonization of the mammalian gut by beneficial bacteria.

scholarly journals Antioxidants maintain Butyrate production by Human GutClostridiain the presence of Oxygen

2019 ◽  
Author(s):  
Matthieu Million ◽  
Nicholas Armstrong ◽  
Saber Khelaifia ◽  
Elodie Guilhot ◽  
Magali Richez ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Severe Acute Malnutrition ◽  
Methanogenic Archaea ◽  
Fatty Acid Esters ◽  
Acute Malnutrition ◽  
Human Gut ◽  
Clostridium Sporogenes ◽  
Human Gut Microbiome ◽  
Clostridium Subterminale ◽  
Butyrate Production

ABSTRACTBackgroundOxygen diffused from the human gut mucosa and shape the microbiota with a radial gradient of microbes according to their oxygen tolerance, while microbial and chemical oxygen consumption maintains the lumen in a deeply anaerobic state. Uncontrolled oxidative stress and hyperoxygenation have been reported as a pathogenic mechanism inSalmonellaorCitrobacter rodentiuminfection, in patients with HIV and in severe acute malnutrition. We recently found that antioxidants allow strict anaerobes, including methanogenic archaea, to thrive in an oxidative environment (aerobic). Here, we tested the metabolomics switching of the 3 most odorous anaerobic microbes isolated from human gut when grown in aerobiosis with antioxidants.MethodsThree human gut Clostridia,Clostridium sporogenes, Clostridium lituseburenseandClostridium subterminale, isolated by culturomics, were grown in anaerobiosis or in aerobiosis with antioxidants. Gaz and liquid chromatography-Mass spectrometry (GC/MS and LC/MS) were used for metabolomics analysis.ResultsAn unexpected global dichotomic metabolomic switching from thiols, alcohols and short-chain fatty acid esters to a specific aerobic metabolic repertoire with the production of alkanes, cycloheptatriene and, paradoxically, increased butyrate production, was observed. Analysis of polar metabolites confirmed the discovery of an unexplored aerobic metabolic repertoire, including the production of specific dipeptides and several lysophospholipids, thus unraveling unsuspected human gut microbiome capacities.ConclusionsAntioxidants unraveled an unexplored aerobic metabolic repertoire of human gutClostridia. The increased production of butyrate suggests that antioxidants contribute to the maintenance and the active resilience of the human gut microbiome against oxidative aggression, as duringSalmonellainfection.

scholarly journals Examining the Effects of an Anti-Salmonella Bacteriophage Preparation, BAFASAL®, on Ex-Vivo Human Gut Microbiome Composition and Function Using a Multi-Omics Approach

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1734
Author(s):  
Janice Mayne ◽  
Xu Zhang ◽  
James Butcher ◽  
Krystal Walker ◽  
Zhibin Ning ◽  
...  
Keyword(s):  
Food Chain ◽  
Gut Microbiome ◽  
Food Industry ◽  
Ex Vivo ◽  
Human Gut ◽  
Microbiome Composition ◽  
Human Gut Microbiome ◽  
And Function ◽  
The Impact

Salmonella infections (salmonellosis) pose serious health risks to humans, usually via food-chain contamination. This foodborne pathogen causes major food losses and human illnesses, with significant economic impacts. Overuse of antibiotics in the food industry has led to multidrug-resistant strains of bacteria, and governments are now restricting their use, leading the food industry to search for alternatives to secure food chains. Bacteriophages, viruses that infect and kill bacteria, are currently being investigated and used as replacement treatments and prophylactics due to their specificity and efficacy. They are generally regarded as safe alternatives to antibiotics, as they are natural components of the ecosystem. However, when specifically used in the industry, they can also make their way into humans through our food chain or exposure, as is the case for antibiotics. In particular, agricultural workers could be repeatedly exposed to bacteriophages supplemented to animal feeds. To our knowledge, no studies have investigated the effects of such exposure to bacteriophages on the human gut microbiome. In this study, we used a novel in-vitro assay called RapidAIM to investigate the effect of a bacteriophage mixture, BAFASAL®, used in poultry farming on five individual human gut microbiomes. Multi-omics analyses, including 16S rRNA gene sequencing and metaproteomic, revealed that ex-vivo human gut microbiota composition and function were unaffected by BAFASAL® treatment, providing an additional measure for its safety. Due to the critical role of the gut microbiome in human health and the known role of bacteriophages in regulation of microbiome composition and function, we suggest assaying the impact of bacteriophage-cocktails on the human gut microbiome as a part of their safety assessment.

scholarly journals Microbe-seq: high-throughput, single-microbe genomics with strain resolution, applied to a human gut microbiome

2020 ◽  
Author(s):  
Wenshan Zheng ◽  
Shijie Zhao ◽  
Yehang Yin ◽  
Huidan Zhang ◽  
David M. Needham ◽  
...  
Keyword(s):  
Microbial Communities ◽  
High Throughput ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Microbial Interactions ◽  
Single Individual ◽  
Human Gut ◽  
Single Strain ◽  
Human Gut Microbiome

AbstractWe present Microbe-seq, a high-throughput single-microbe method that yields strain-resolved genomes from complex microbial communities. We encapsulate individual microbes into droplets with microfluidics and liberate their DNA, which we amplify, tag with droplet-specific barcodes, and sequence. We use Microbe-seq to explore the human gut microbiome; we collect stool samples from a single individual, sequence over 20,000 microbes, and reconstruct nearly-complete genomes of almost 100 bacterial species, including several with multiple subspecies strains. We use these genomes to probe genomic signatures of microbial interactions: we reconstruct the horizontal gene transfer (HGT) network within the individual and observe far greater exchange within the same bacterial phylum than between different phyla. We probe bacteria-virus interactions; unexpectedly, we identify a significant in vivo association between crAssphage, an abundant bacteriophage, and a single strain of Bacteroides vulgatus. Microbe-seq contributes high-throughput culture-free capabilities to investigate genomic blueprints of complex microbial communities with single-microbe resolution.

scholarly journals Bacterial associations in the healthy human gut microbiome across populations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mark Loftus ◽  
Sayf Al-Deen Hassouneh ◽  
Shibu Yooseph
Keyword(s):  
Gut Microbiome ◽  
Sequence Data ◽  
Bacterial Species ◽  
Human Populations ◽  
Human Gut ◽  
Healthy Human ◽  
Human Gut Microbiome ◽  
Genome Shotgun Sequence ◽  
Bacterial Associations ◽  
And Function

AbstractIn a microbial community, associations between constituent members play an important role in determining the overall structure and function of the community. The human gut microbiome is believed to play an integral role in host health and disease. To understand the nature of bacterial associations at the species level in healthy human gut microbiomes, we analyzed previously published collections of whole-genome shotgun sequence data, totaling over 1.6 Tbp, generated from 606 fecal samples obtained from four different healthy human populations. Using a Random Forest Classifier, we identified 202 signature bacterial species that were prevalent in these populations and whose relative abundances could be used to accurately distinguish between the populations. Bacterial association networks were constructed with these signature species using an approach based on the graphical lasso. Network analysis revealed conserved bacterial associations across populations and a dominance of positive associations over negative associations, with this dominance being driven by associations between species that are closely related either taxonomically or functionally. Bacterial species that form network modules, and species that constitute hubs and bottlenecks, were also identified. Functional analysis using protein families suggests that much of the taxonomic variation across human populations does not foment substantial functional or structural differences.

scholarly journals Resident microbial communities inhibit growth and antibiotic-resistance evolution of Escherichia coli in human gut microbiome samples

PLoS Biology ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. e3000465 ◽  
Author(s):  
Michael Baumgartner ◽  
Florian Bayer ◽  
Katia R. Pfrunder-Cardozo ◽  
Angus Buckling ◽  
Alex R. Hall
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Microbial Communities ◽  
Gut Microbiome ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Resistance Evolution

scholarly journals Resident microbial communities inhibit growth and antibiotic resistance evolution of Escherichia coli in human gut microbiome samples

2019 ◽  
Author(s):  
Michael Baumgartner ◽  
Florian Bayer ◽  
Katia R. Pfrunder-Cardozo ◽  
Angus Buckling ◽  
Alex R. Hall
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Microbial Communities ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
Individual Species ◽  
Human Gut ◽  
E Coli ◽  
Human Gut Microbiome ◽  
Resistance Evolution

AbstractCountering the rise of antibiotic resistant pathogens requires improved understanding of how resistance emerges and spreads in individual species, which are often embedded in complex microbial communities such as the human gut microbiome. Interactions with other microorganisms in such communities might suppress growth and resistance evolution of individual species (e.g. via resource competition), but could also potentially accelerate resistance evolution via horizontal transfer of resistance genes. It remains unclear how these different effects balance out, partly because it is difficult to observe them directly. Here, we used a gut microcosm approach to quantify the effect of three human gut microbiome communities on growth and resistance evolution of a focal strain of Escherichia coli. We found the resident microbial communities not only suppressed growth and colonization by focal E. coli, they also prevented it from evolving antibiotic resistance upon exposure to a beta-lactam antibiotic. With samples from all three human donors, our focal E. coli strain only evolved antibiotic resistance in the absence of the resident microbial community, even though we found resistance genes, including a highly effective resistance plasmid, in resident microbial communities. We identified physical constraints on plasmid transfer that can explain why our focal strain failed to acquire some of these beneficial resistance genes, and we found some chromosomal resistance mutations were only beneficial in the absence of the resident microbiota. This suggests, depending on in situ gene transfer dynamics, interactions with resident microbiota can inhibit antibiotic resistance evolution of individual species.

scholarly journals Examining the effects of an anti-Salmonella bacteriophage preparation, BAFASAL, on ex vivo human gut microbiome composition and function using a multi-omics approach

2021 ◽  
Author(s):  
Janice Mayne ◽  
Xu Zhang ◽  
James Butcher ◽  
Krystal Walker ◽  
Zhibin Ning ◽  
...  
Keyword(s):  
Food Chain ◽  
Gut Microbiome ◽  
Ex Vivo ◽  
Human Gut ◽  
Microbiome Composition ◽  
Human Gut Microbiome ◽  
Salmonella Infections ◽  
And Function ◽  
The Impact

Salmonella infections (salmonellosis) pose serious health risks to humans, usually via contamination in our food chain. This foodborne pathogen causes major food losses and human illnesses that result in significant economic impacts. Pathogens such as Salmonella have traditionally been kept at bay through the use of antibiotics, but antibiotic overuse within the food industry has led to the development of numerous multidrug-resistant bacterial strains. Thus, governments are now restricting antibiotic use, forcing the industry to search for alternatives to secure safe food chains. Bacteriophages, viruses that infect and kill bacteria, are currently being investigated and used as replacement treatments and prophylactics due to their specificity and efficacy. They are generally regarded as safe alternatives to antibiotics as they are natural components of the ecosystem. One example is BAFASEL, a commercial bacteriophage mixture that specifically targets Salmonella and is currently approved for use in poultry farming. However, when specifically used in the industry they can also make their way into humans through our food chain or exposure as is the case for antibiotics. In particular, agricultural workers could be repeatedly exposed to bacteriophages supplemented in animal feeds. To the best of our knowledge, no studies have investigated the effects of such exposure to bacteriophages on the human gut microbiome. In this study, we used a novel in vitro assay called RapidAIM to investigate BAFASAL's potential impact on five individual human gut microbiomes. Multi-omics analyses, including 16S rRNA gene sequencing and metaproteomic, revealed that ex vivo human gut microbiota composition and function were unaffected by BAFASAL treatment providing an additional measure for its safety. Due to the critical role of the gut microbiome in human health and the known role of bacteriophages in regulation of microbiome composition and function, we suggest assaying the impact of bacteriophage-cocktails on the human gut microbiome as a part of their safety assessment.

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