scholarly journals A Distinct Contractile Injection System Found in a Majority of Adult Human Microbiomes

2019 ◽  
Author(s):  
Maria I. Rojas ◽  
Giselle S. Cavalcanti ◽  
Katelyn McNair ◽  
Sean Benler ◽  
Amanda T. Alker ◽  
...  
Keyword(s):  
The United States ◽  
Injection System ◽  
Grand Challenge ◽  
Human Gut ◽  
Adult Human ◽  
Host Health ◽  
Significant Barrier ◽  
Health And Disease ◽  
Bacterial Groups ◽  
A Current

ABSTRACTAn imbalance of normal bacterial groups such as Bacteroidales within the human gut is correlated with diseases like obesity. A current grand challenge in the microbiome field is to identify factors produced by normal microbiome bacteria that cause these observed health and disease correlations. While identifying factors like a bacterial injection system could provide a missing explanation for why Bacteroidales correlates with host health, no such factor has been identified to date. The lack of knowledge about these factors is a significant barrier to improving therapies like fecal transplants that promote a healthy microbiome. Here we show that a previously ill-defined Contractile Injection System is carried in the gut microbiome of 99% of individuals from the United States and Europe. This type of Contractile Injection System, we name here Bacteroidales Injection System (BIS), is related to the contractile tails of bacteriophage (viruses of bacteria) and have been described to mediate interactions between bacteria and diverse eukaryotes like amoeba, insects and tubeworms. Our findings that BIS are ubiquitous within adult human microbiomes suggest that they shape host health by mediating interactions between Bacteroidales bacteria and the human host or its microbiome.

scholarly journals A Distinct Contractile Injection System Gene Cluster Found in a Majority of Healthy Adult Human Microbiomes

mSystems ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Maria I. Rojas ◽  
Giselle S. Cavalcanti ◽  
Katelyn McNair ◽  
Sean Benler ◽  
Amanda T. Alker ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gene Cluster ◽  
Bowel Disease ◽  
Human Microbiome ◽  
Gene Clusters ◽  
The United States ◽  
Injection System ◽  
Human Gut ◽  
Human Host ◽  
Inflammatory Bowel

ABSTRACT Many commensal bacteria antagonize each other or their host by producing syringe-like secretion systems called contractile injection systems (CIS). Members of the Bacteroidales family have been shown to produce only one type of CIS—a contact-dependent type 6 secretion system that mediates bacterium-bacterium interactions. Here, we show that a second distinct cluster of genes from Bacteroidales bacteria from the human microbiome may encode yet-uncharacterized injection systems that we term Bacteroidales injection systems (BIS). We found that BIS genes are present in the gut microbiomes of 99% of individuals from the United States and Europe and that BIS genes are more prevalent in the gut microbiomes of healthy individuals than in those individuals suffering from inflammatory bowel disease. Gene clusters similar to that of the BIS mediate interactions between bacteria and diverse eukaryotes, like amoeba, insects, and tubeworms. Our findings highlight the ubiquity of the BIS gene cluster in the human gut and emphasize the relevance of the gut microbiome to the human host. These results warrant investigations into the structure and function of the BIS and how they might mediate interactions between Bacteroidales bacteria and the human host or microbiome. IMPORTANCE To engage with host cells, diverse pathogenic bacteria produce syringe-like structures called contractile injection systems (CIS). CIS are evolutionarily related to the contractile tails of bacteriophages and are specialized to puncture membranes, often delivering effectors to target cells. Although CIS are key for pathogens to cause disease, paradoxically, similar injection systems have been identified within healthy human microbiome bacteria. Here, we show that gene clusters encoding a predicted CIS, which we term Bacteroidales injection systems (BIS), are present in the microbiomes of nearly all adult humans tested from Western countries. BIS genes are enriched within human gut microbiomes and are expressed both in vitro and in vivo. Further, a greater abundance of BIS genes is present within healthy gut microbiomes than in those humans with with inflammatory bowel disease (IBD). Our discovery provides a potentially distinct means by which our microbiome interacts with the human host or its microbiome.

scholarly journals Gut Microbiota Metabolism and Interaction with Food Components

2020 ◽  
Vol 21 (10) ◽  
pp. 3688 ◽  
Author(s):  
Pamela Vernocchi ◽  
Federica Del Chierico ◽  
Lorenza Putignani
Keyword(s):  
Gut Microbiota ◽  
Disease Onset ◽  
Human Gut ◽  
Food Components ◽  
Host Health ◽  
Wide Variability ◽  
Gut Microbe ◽  
A Cell ◽  
Health And Disease ◽  
Biochemical Mechanisms

The human gut contains trillions of microbes that play a central role in host biology, including the provision of key nutrients from the diet. Food is a major source of precursors for metabolite production; in fact, diet modulates the gut microbiota (GM) as the nutrients, derived from dietary intake, reach the GM, affecting both the ecosystem and microbial metabolic profile. GM metabolic ability has an impact on human nutritional status from childhood. However, there is a wide variability of dietary patterns that exist among individuals. The study of interactions with the host via GM metabolic pathways is an interesting field of research in medicine, as microbiota members produce myriads of molecules with many bioactive properties. Indeed, much evidence has demonstrated the importance of metabolites produced by the bacterial metabolism from foods at the gut level that dynamically participate in various biochemical mechanisms of a cell as a reaction to environmental stimuli. Hence, the GM modulate homeostasis at the gut level, and the alteration in their composition can concur in disease onset or progression, including immunological, inflammatory, and metabolic disorders, as well as cancer. Understanding the gut microbe–nutrient interactions will increase our knowledge of how diet affects host health and disease, thus enabling personalized therapeutics and nutrition.

scholarly journals Metabolic functions of the human gut microbiota: the role of metalloenzymes

2019 ◽  
Vol 36 (4) ◽  
pp. 593-625 ◽  
Author(s):  
Lauren J. Rajakovich ◽  
Emily P. Balskus
Keyword(s):  
Gut Microbiota ◽  
Human Gut ◽  
Human Gut Microbiota ◽  
Metabolic Functions ◽  
Host Health ◽  
Health And Disease

Metalloenzymes play central roles in metabolic functions of the human gut microbiota that are associated with host health and disease.

MRI Research Proposals Involving Child Subjects: Concerns Hindering Research Ethics Boards from Approving Them and a Checklist to Help Evaluate Them

2011 ◽  
Vol 20 (1) ◽  
pp. 115-129 ◽  
Author(s):  
J. DEBORAH SHILOFF ◽  
BRYAN MAGWOOD ◽  
KRISZTINA L. MALISZA
Keyword(s):  
United States ◽  
Research Ethics ◽  
Gold Standard ◽  
The United States ◽  
Institutional Review Boards ◽  
Scientific Review ◽  
Initial Development ◽  
Institutional Review ◽  
Research Ethics Boards ◽  
A Current

The process of research is often lengthy and can be extremely arduous. It may take many years to proceed from the initial development of an idea through to the comparison of the new modalities against a current gold-standard practice. Each step along the way involves rigorous scientific review, where protocols are scrutinized by multiple scientists not only in the specific field at hand but related fields as well. In addition to scientific review, most countries require a further review by a panel that will specifically address the ethics of the proposed research. In Canada, those panels are referred to as Research Ethics Boards (REB), with the United States counterparts known as Institutional Review Boards (IRB).

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 A previously undescribed highly prevalent phage identified in a Danish enteric virome catalogue

2021 ◽  
Author(s):  
Lore Van Espen ◽  
Emilie Glad Bak ◽  
Leen Beller ◽  
Lila Close ◽  
Ward Deboutte ◽  
...  
Keyword(s):  
Viral Genome ◽  
De Novo ◽  
Human Gut ◽  
Host Genus ◽  
Faecal Samples ◽  
High Prevalence ◽  
Paediatric Cohort ◽  
Health And Disease ◽  
Wet Lab ◽  
Public Datasets

Abstract Background: Gut viruses are important players in the complex human gut microbial ecosystem. Recently, the number of human gut virome studies is steadily increasing, however we are still only scratching the surface of the immense viral diversity as many wet lab and bio-informatics challenges remain. In this study, 254 virus-enriched faecal metagenomes from 204 Danish subjects were used to generate a Danish Enteric Virome Catalogue (DEVoC) of 12,986 non-redundant viral genome sequences encoding 190,029 viral genes, which formed 67,921 orthologous groups. The DEVoC was used to characterize the composition of the healthy DEVoC gut viromes from 46 children and adolescents (6-18 years old) and 45 adults (40 -73 years old).Results: The majority of DEVoC viral sequences (67.3 %) and proteins (61.6 %) were not present in other (human gut) viral genome databases. Gut viromes of healthy Danish subjects mostly consisted of phages. While 39 phage genomes (PGs) were present in more than 10 healthy subjects, the degree of viral individuality was high. Among the 39 prevalent PGs, one was significantly more prevalent in the paediatric cohort, whereas two were more prevalent in adults. In 1,880 gut virome samples of 27 studies from across the world, the 39 prevalent PGs reveal several age-, geography- and disease-related prevalence patterns. Two PGs also showed a remarkably high prevalence worldwide – a crAss-like phage (20.6% prevalence), belonging to the tentative AlphacrAssvirinae subfamily, genus I; and a previously undescribed circular temperate phage (14.4% prevalence), named LoVEphage (because it encodes Lots of Viral Elements). A de novo assembly of selected public datasets generated an additional 18 circular LoVEphage-like genomes (67.9-72.4 kb). CRISPR spacer analysis suggested Bacteroides as a host genus for the LoVEphage, and a closely related prophage was identified in Bacteroides dorei, further confirming the host.Conclusions: The DEVoC, the largest human gut virome catalogue generated from consistently processed faecal samples, facilitated analysis of healthy Danish human gut viromes and we foresee that it will benefit future analysis on the roles of gut viruses in human health and disease. The identification of a previously undescribed prevalent phage illustrates the usefulness of developing a virome catalogue.

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