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 Characterization of the role of glycine lipids inBacteroides thetaiotaomicron

2018 ◽  
Author(s):  
Alli Lynch ◽  
Seshu R. Tammireddy ◽  
Mary K. Doherty ◽  
Phillip D. Whitfield ◽  
David J. Clarke
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Deletion Mutant ◽  
Cellular Membrane ◽  
Liquid Chromatography Mass Spectrometry ◽  
Human Gut ◽  
Acyltransferase Activity ◽  
And Function

AbstractAcylated amino acids function as important components of the cellular membrane in some bacteria. Biosynthesis is initiated by the N-acylation of the amino acid and this is followed by subsequent O-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 novel diacylated glycine lipid (GL) species inBacteroides thetaiotaomicron. We, and others, have previously reported the identification of a gene, namedglsBin this study, that encodes a N-acyltransferase activity responsible for the production of a monoacylated glycine called N-acyl-3-hydroxy-palmitoyl glycine (or commendamide). In all of theBacteroidalesgenomes so far sequenced theglsBgene is located immediately downstream from a gene, namedglsA, also predicted to encode a protein with acyltransferase activity. We use LC-MS to show that co-expression ofglsBandglsAresults in the production of GL inEscherichia coli. We constructed a deletion mutant of theglsBgene inB. thetaiotaomicronand 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 is the first to describe the genetic requirements for the biosynthesis of GL, a novel diacylated amino acids species that contributes to fitness in the human gut bacterium,B. thetaiotaomicron.

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 Differential Metabolism of Exopolysaccharides from Probiotic Lactobacilli by the Human Gut Symbiont Bacteroides thetaiotaomicron

2015 ◽  
Vol 81 (12) ◽  
pp. 3973-3983 ◽  
Author(s):  
Alicia Lammerts van Bueren ◽  
Aakanksha Saraf ◽  
Eric C. Martens ◽  
Lubbert Dijkhuizen
Keyword(s):  
Gastrointestinal Tract ◽  
Carbohydrate Metabolism ◽  
Lactobacillus Reuteri ◽  
Bacterial Species ◽  
Transport Systems ◽  
Bacteroides Thetaiotaomicron ◽  
Human Gut ◽  
Positive Health ◽  
Content Type ◽  
Commensal Species

ABSTRACTProbiotic microorganisms are ingested as food or supplements and impart positive health benefits to consumers. Previous studies have indicated that probiotics transiently reside in the gastrointestinal tract and, in addition to modulating commensal species diversity, increase the expression of genes for carbohydrate metabolism in resident commensal bacterial species. In this study, it is demonstrated that the human gut commensal speciesBacteroides thetaiotaomicronefficiently metabolizes fructan exopolysaccharide (EPS) synthesized by probioticLactobacillus reuteristrain 121 while only partially degrading reuteran and isomalto/malto-polysaccharide (IMMP) α-glucan EPS polymers.B. thetaiotaomicronmetabolized these EPS molecules via the activation of enzymes and transport systems encoded by dedicated polysaccharide utilization loci specific for β-fructans and α-glucans. Reduced metabolism of reuteran and IMMP α-glucan EPS molecules may be due to reduced substrate binding by components of the starch utilization system (sus). This study reveals that microbial EPS substrates activate genes for carbohydrate metabolism inB. thetaiotaomicronand suggests that microbially derived carbohydrates provide a carbohydrate-rich reservoir forB. thetaiotaomicronnutrient acquisition in the gastrointestinal tract.

scholarly journals Role of Biological Sex in the Cardiovascular-Gut Microbiome Axis

2022 ◽  
Vol 8 ◽  
Author(s):  
Shuangyue Li ◽  
Georgios Kararigas
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Microbial Composition ◽  
Biological Sex ◽  
Technological Advances ◽  
Host Health ◽  
Health And Disease ◽  
And Function ◽  
Insight Into

There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.

Global and temporal state of the human gut microbiome in health and disease

2021 ◽  
Author(s):  
Saeed Shoaie ◽  
Sunjae Lee ◽  
Mathieu Almeida ◽  
Gholamreza Bidkhori ◽  
Nicolas Pons ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Integrative Analysis ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Health And Disease ◽  
One Year ◽  
The Stability ◽  
Clinical Phenotyping ◽  
Sampling Times

Abstract The role of gut microbiota in humans is of great interest, and metagenomics provided the possibilities for extensively analysing bacterial diversity in health and disease. Here we explored the human gut microbiome samples across 19 countries, performing compositional, functional and integrative analysis. To complement these data and analyse the stability of the microbiome, we followed 86 healthy Swedish individuals over one year, with four sampling times and extensive clinical phenotyping. The integrative analysis of temporal microbiome changes shows the existence of two types of species with a tendency to vary in abundance with time, here called outflow and inflow species. Importantly, the former tends to be enriched in disease, while the latter is enriched in health. We suggest that the decrease of disease-associated outflow and the increase of health-associated inflow species with time may be a fundamental albeit previously unrecognized aspect of the homeostasis maintenance in a healthy microbiome.

Role of Human Gut Microbiome in Health and Disease

2021 ◽  
pp. 101-112
Author(s):  
Nazar Reehana ◽  
Mohamed Yousuff Mohamed Imran ◽  
Nooruddin Thajuddin ◽  
D. Dhanasekaran
Keyword(s):  
Gut Microbiome ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Health And Disease

scholarly journals Metabolic Feedback Inhibition Influences Metabolite Secretion by the Human Gut Symbiont Bacteroides thetaiotaomicron

mSystems ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Jennie L. Catlett ◽  
Jonathan Catazaro ◽  
Mikaela Cashman ◽  
Sean Carr ◽  
Robert Powers ◽  
...  
Keyword(s):  
Amino Acids ◽  
Phenotypic Plasticity ◽  
Energy Conservation ◽  
Organic Acids ◽  
Feedback Inhibition ◽  
Bacteroides Thetaiotaomicron ◽  
Human Gut ◽  
Content Type ◽  
Abundant Taxon ◽  
Metabolic Interactions

Bacteroides is a highly abundant taxon in the human gut, and Bacteroides thetaiotaomicron (B. theta) is a ubiquitous human symbiont that colonizes the host early in development and persists throughout its life span. The phenotypic plasticity of keystone organisms such as B. theta is important to understand in order to predict phenotype(s) and metabolic interactions under changing nutrient conditions such as those that occur in complex gut communities. Our study shows B. theta prioritizes energy conservation and suppresses secretion of “overflow metabolites” such as organic acids and amino acids when concentrations of acetate are high. Secreted metabolites, especially amino acids, can be a source of nutrients or signals for the host or other microbes in the community. Our study suggests that when metabolically stressed by acetate, B. theta stops sharing with its ecological partners.

scholarly journals Human genetic determinants of the gut microbiome and their associations with health and disease: a phenome-wide association study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hilde E. Groot ◽  
Yordi J. van de Vegte ◽  
Niek Verweij ◽  
Erik Lipsic ◽  
Jacco C. Karper ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Healthy Aging ◽  
Total Sample ◽  
Causal Link ◽  
Small Scale ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Health And Disease

Abstract Small-scale studies have suggested a link between the human gut microbiome and highly prevalent diseases. However, the extent to which the human gut microbiome can be considered a determinant of disease and healthy aging remains unknown. We aimed to determine the spectrum of diseases that are linked to the human gut microbiome through the utilization of its genetic determinants as a proxy for its composition. 180 single nucleotide polymorphisms (SNPs) known to influence the human gut microbiome were used to assess the association with health and disease outcomes in 422,417 UK Biobank participants. Potential causal estimates were obtained using a Mendelian randomization (MR) approach. From the total sample analysed (mean age was 57 ± 8 years), 194,567 (46%) subjects were male. Median exposure was 66-person years (interquartile range 59–72). Eleven SNPs were significantly associated with 28 outcomes (Bonferroni corrected P value < 4.63·10−6) including food intake, hypertension, atopy, COPD, BMI, and lipids. Multiple SNP MR pointed to a possible causal link between Ruminococcus flavefaciens and hypertension, and Clostridium and platelet count. Microbiota and their metabolites might be of importance in the interplay between overlapping pathophysiological processes, although challenges remain in establishing causal relationships.

scholarly journals Microbe-Metabolite Associations Linked to the Rebounding Murine Gut Microbiome Postcolonization with Vancomycin-Resistant Enterococcus faecium

mSystems ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Andre Mu ◽  
Glen P. Carter ◽  
Lucy Li ◽  
Nicole S. Isles ◽  
Alison F. Vrbanac ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Enterococcus Faecium ◽  
Molecular Mechanisms ◽  
Microbial Community Composition ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Content Type ◽  
Functional Roles ◽  
Specific Pathogen ◽  
Vancomycin Resistant

ABSTRACT Vancomycin-resistant Enterococcus faecium (VREfm) is an emerging antibiotic-resistant pathogen. Strain-level investigations are beginning to reveal the molecular mechanisms used by VREfm to colonize regions of the human bowel. However, the role of commensal bacteria during VREfm colonization, in particular following antibiotic treatment, remains largely unknown. We employed amplicon 16S rRNA gene sequencing and metabolomics in a murine model system to try and investigate functional roles of the gut microbiome during VREfm colonization. First-order taxonomic shifts between Bacteroidetes and Tenericutes within the gut microbial community composition were detected both in response to pretreatment using ceftriaxone and to subsequent VREfm challenge. Using neural networking approaches to find cooccurrence profiles of bacteria and metabolites, we detected key metabolome features associated with butyric acid during and after VREfm colonization. These metabolite features were associated with Bacteroides, indicative of a transition toward a preantibiotic naive microbiome. This study shows the impacts of antibiotics on the gut ecosystem and the progression of the microbiome in response to colonization with VREfm. Our results offer insights toward identifying potential nonantibiotic alternatives to eliminate VREfm through metabolic reengineering to preferentially select for Bacteroides. IMPORTANCE This study demonstrates the importance and power of linking bacterial composition profiling with metabolomics to find the interactions between commensal gut bacteria and a specific pathogen. Knowledge from this research will inform gut microbiome engineering strategies, with the aim of translating observations from animal models to human-relevant therapeutic applications.

scholarly journals Superresolution Imaging Captures Carbohydrate Utilization Dynamics in Human Gut Symbionts

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Krishanthi S. Karunatilaka ◽  
Elizabeth A. Cameron ◽  
Eric C. Martens ◽  
Nicole M. Koropatkin ◽  
Julie S. Biteen
Keyword(s):  
Outer Membrane ◽  
Human Health ◽  
Outer Membrane Proteins ◽  
Live Cells ◽  
Human Gut ◽  
Uptake Mechanism ◽  
Complex Assembly ◽  
Content Type ◽  
Superresolution Imaging ◽  
And Function

ABSTRACTGut microbes play a key role in human health and nutrition by catabolizing a wide variety of glycans via enzymatic activities that are not encoded in the human genome. The ability to recognize and process carbohydrates strongly influences the structure of the gut microbial community. While the effects of diet on the microbiota are well documented, little is known about the molecular processes driving metabolism. To provide mechanistic insight into carbohydrate catabolism in gut symbionts, we studied starch processing in real time in the modelBacteroides thetaiotaomicronstarch utilization system (Sus) by single-molecule fluorescence. Although previous studies have explored Sus protein structure and function, the transient interactions, assembly, and collaboration of these outer membrane proteins have not yet been elucidated in live cells. Our live-cell superresolution imaging reveals that the polymeric starch substrate dynamically recruits Sus proteins, serving as an external scaffold for bacterial membrane assembly of the Sus complex, which may promote efficient capturing and degradation of starch. Furthermore, by simultaneously localizing multiple Sus outer membrane proteins on theB. thetaiotaomicroncell surface, we have characterized the dynamics and stoichiometry of starch-induced Sus complex assembly on the molecular scale. Finally, based on Sus protein knockout strains, we have discerned the mechanism of starch-induced Sus complex assembly in live anaerobic cells with nanometer-scale resolution. Our insights into the starch-induced outer membrane protein assembly central to this conserved nutrient uptake mechanism pave the way for the development of dietary or pharmaceutical therapies to controlBacteroidetesin the intestinal tract to enhance human health and treat disease.IMPORTANCEIn this study, we used nanometer-scale superresolution imaging to reveal dynamic interactions between the proteins involved in starch processing by the prominent human gut symbiontBacteroides thetaiotaomicronin real time in live cells. These results represent the first working model of starch utilization system (Sus) complex assembly and function during glycan catabolism and are likely to describe aspects of how other Sus-like systems function in human gutBacteroidetes. Our results provide unique mechanistic insights into a glycan catabolism strategy that is prevalent within the human gut microbial community. Proper understanding of this conserved nutrient uptake mechanism is essential for the development of dietary or pharmaceutical therapies to control intestinal tract microbial populations, to enhance human health, and to treat disease.

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