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Publications in this journal

• Bacterial symbioses of the medicinal leech Hirudo verbana.

  Authors: Michael Nelson, Joerg Graf

  Gut microbes. 3(4).

  Gastrointestinal microbiomes play important roles in the health and nutrition of animals and humans. The medicinal leech, Hirudo verbana, serves as a powerful model for the study of microbialGastrointestinal microbiomes play important roles in the health and nutrition of animals and humans. The medicinal leech, Hirudo verbana, serves as a powerful model for the study of microbial symbioses of the gut, due to its naturally limited microbiome compared with other popular models, the ability to cultivate the most abundant microbes, and genetically manipulate one of them, Aeromonas veronii. This review covers the relevance and application of leeches in modern medicine as well as recent discoveries detailing the nature of the gut microbiome. Additionally, the dual life-style of A. veronii allows one to do direct comparisons between colonization factors for beneficial and pathogenic associations, and relevant findings are detailed with respect to their role within the host and pathogenicity to other animals.

• Gut-associated microbes of Drosophila melanogaster.

  Authors: Nichole Broderick, Bruno Lemaitre

  Gut microbes. 3(4).

  There is growing interest in using Drosophila melanogaster to elucidate mechanisms that underlie the complex relationships between a host and its microbiota. In addition to the many genetic resourcesThere is growing interest in using Drosophila melanogaster to elucidate mechanisms that underlie the complex relationships between a host and its microbiota. In addition to the many genetic resources and tools Drosophila provides, its associated microbiota is relatively simple (1-30 taxa), in contrast to the complex diversity associated with vertebrates (> 500 taxa). These attributes highlight the potential of this system to dissect the complex cellular and molecular interactions that occur between a host and its microbiota. In this review, we summarize what is known regarding the composition of gut-associated microbes of Drosophila and their impact on host physiology. We also discuss these interactions in the context of their natural history and ecology and describe some recent insights into mechanisms by which Drosophila and its gut microbiota interact. "Workers with Drosophila have been considered fortunate in that they deal with the first multicellular invertebrate to be cultured monoxenically (Delcourt and Guyenot, 1910); the first to be handled axenically on a semisynthetic diet (Guyenot, 1917); and the first to be grown on a defined diet (Schultz et al., 1946). This list of advantages is somewhat embarrassing, since it implies an interest in nutrition that, in reality, was only secondary. The very first studies were concerned with the reduction of variability in genetic experiments (Delcourt and Guyenot, 1910) and standardization of the nutritional environment." -James Sang, 1959 Ann NY Acad ( 1).

• Composition of the early intestinal microbiota

  Authors: Fiona Fouhy, R. Paul Ross, Gerald Fitzgerald, Catherine Stanton, Paul D. Cotter

  Gut Microbes.

• Host-microbiota interactions in inflammatory bowel disease.

  Authors: Charles O Elson, Yingzi Cong

  Gut microbes. 3(4).

  The interaction of the host with its abundant intestinal microbiota is complex and engages most of the cells in the intestinal mucosa. The inflammatory bowel diseases appear to be disorders of theThe interaction of the host with its abundant intestinal microbiota is complex and engages most of the cells in the intestinal mucosa. The inflammatory bowel diseases appear to be disorders of the host immune response to the microbiota. This is supported by data from induced gene mutations in mice and more recently by the identification of gene variants in humans that result in IBD or IBD susceptibility. These genetic studies have provided insights into the cells and molecular pathways involved in the host-microbiota dialog. This review discusses the innate, adaptive, and regulatory immune response to the microbiota in the context of the mouse and human genes that are involved in maintaining intestinal homeostasis and preventing inflammation. These data continue to support the hypothesis that inflammatory bowel disease results from a dysregulated adaptive immune response, particularly a CD4 T-cell response, to the microbiota. The microbiota itself is an active participant in these homeostatic processes. The microbiota composition is perturbed during inflammation, resulting in a dysbiosis that may induce or perpetuate inflammation. However, host genotype and the environment have a major impact on the shape of such dysbiosis, as well as upon which members of the microbiota stimulate pathogenic immune responses.

• Microbial degradation of complex carbohydrates in the gut.

  Authors: Harry Flint, Karen Scott, Sylvia Duncan, Petra Louis, Evelyne Forano

  Gut microbes. 3(4).

  Bacteria that colonize the mammalian intestine collectively possess a far larger repertoire of degradative enzymes and metabolic capabilities than their hosts. Microbial fermentation of complexBacteria that colonize the mammalian intestine collectively possess a far larger repertoire of degradative enzymes and metabolic capabilities than their hosts. Microbial fermentation of complex non-digestible dietary carbohydrates and host-derived glycans in the human intestine has important consequences for health. Certain dominant species, notably among the Bacteroidetes, are known to possess very large numbers of genes that encode carbohydrate active enzymes and can switch readily between different energy sources in the gut depending on availability. Nevertheless, more nutritionally specialized bacteria appear to play critical roles in the community by initiating the degradation of complex substrates such as plant cell walls, starch particles and mucin. Examples are emerging from the Firmicutes, Actinobacteria and Verrucomicrobium phyla, but more information is needed on these little studied groups. The impact of dietary carbohydrates, including prebiotics, on human health requires understanding of the complex relationship between diet composition, the gut microbiota and metabolic outputs.

• Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity.

  Authors: Patrice Cani, Melania Osto, Lucie Geurts, Amandine Everard

  Gut microbes. 3(4).

  Obesity is associated with metabolic alterations related to glucose homeostasis and cardiovascular risk factors. These metabolic alterations are associated with low-grade inflammation thatObesity is associated with metabolic alterations related to glucose homeostasis and cardiovascular risk factors. These metabolic alterations are associated with low-grade inflammation that contributes to the onset of these diseases. We and others have provided evidence that gut microbiota participate in whole-body metabolism by affecting energy balance, glucose metabolism, and low-grade inflammation associated with obesity and related metabolic disorders. Recently, we defined gut microbiota-derived lipopolysaccharide (LPS) (and metabolic endotoxemia) as a factor involved in the onset and progression of inflammation and metabolic diseases. In this review, we discuss mechanisms involved in the development of metabolic endotoxemia such as the gut permeability. We also discuss our latest discoveries demonstrating a link between the gut microbiota, endocannabinoid system tone, leptin resistance, gut peptides (glucagon-like peptide-1 and -2), and metabolic features. Finally, we will introduce the role of the gut microbiota in specific dietary treatments (prebiotics and probiotics) and surgical interventions (gastric bypass).

• Portrait of an immunoregulatory Bifidobacterium.

  Authors: Patrycja Konieczna, Cezmi A Akdis, Eamonn Mm Quigley, Fergus Shanahan, Liam O'Mahony

  Gut microbes. 3(3).

  There is increasing interest in the administration of microbes or microbial metabolites for the prevention and treatment of aberrant inflammatory activity. The protective effects associated withThere is increasing interest in the administration of microbes or microbial metabolites for the prevention and treatment of aberrant inflammatory activity. The protective effects associated with these microbes are mediated by multiple mechanisms involving epithelial cells, DCs and T cells, but most data are derived from animal models. In this addendum, we summarize our recent data, showing that oral consumption of Bifidobacterium infantis 35624 is associated with enhanced IL-10 secretion and Foxp3 expression in human peripheral blood. In addition, we discuss the potential DC subset-specific mechanisms, which could contribute to DCREG and TREG programming by specific gut microbes.

• Composition of the early intestinal microbiota: Knowledge, knowledge gaps and the use of high-throughput sequencing to address these gaps.

  Authors: Fiona Fouhy, R Paul Ross, Gerald Fitzgerald, Catherine Stanton, Paul D Cotter

  Gut microbes. 3(3).

  The colonization, development and maturation of the newborn gastrointestinal tract that begins immediately at birth and continues for two years, is modulated by numerous factors including mode ofThe colonization, development and maturation of the newborn gastrointestinal tract that begins immediately at birth and continues for two years, is modulated by numerous factors including mode of delivery, feeding regime, maternal diet/weight, probiotic and prebiotic use and antibiotic exposure pre-, peri- and post-natally. While in the past, culture-based approaches were used to assess the impact of these factors on the gut microbiota, these have now largely been replaced by culture-independent DNA-based approaches and most recently, high-throughput sequencing-based forms thereof. The aim of this review is to summarize recent research into the modulatory factors that impact on the acquisition and development of the infant gut microbiota, to outline the knowledge recently gained through the use of culture-independent techniques and, in particular, highlight advances in high-throughput sequencing and how these technologies have, and will continue to, fill gaps in our knowledge with respect to the human intestinal microbiota.

• Comparative evaluation of establishing a human gut microbial community within rodent models.

  Authors: Melissa Wos-Oxley, André Bleich, Andrew P A Oxley, Silke Kahl, Lydia Janus, Anna Smoczek, Hannes Nahrstedt, Marina Pils, Stefan Taudien, Matthias Platzer, Hans-Jürgen Hedrich, Eva Medina, Dietmar Pieper

  Gut microbes. 3(3).

  The structure of the human gut microbial community is determined by host genetics and environmental factors, where alterations in its structure have been associated with the onset of differentThe structure of the human gut microbial community is determined by host genetics and environmental factors, where alterations in its structure have been associated with the onset of different diseases. Establishing a defined human gut microbial community within inbred rodent models provides a means to study microbial-related pathologies, however, an in-depth comparison of the established human gut microbiota in the different models is lacking. We compared the efficiency of establishing the bacterial component of a defined human microbial community within germ-free (GF) rats, GF mice, and antibiotic-treated specific pathogen-free mice. Remarkable differences were observed between the different rodent models. While the majority of abundant human-donor bacterial phylotypes were established in the GF rats, only a subset was present in the GF mice. Despite the fact that members of the phylum Bacteriodetes were well established in all rodent models, mice enriched for phylotypes related to species of Bacteroides. In contrary to the efficiency of Clostridiales to populate the GF rat in relative proportions to that of the human-donor, members of Clostridia cluster IV only poorly colonize the mouse gut. Thus, the genetic background of the different recipient rodent systems (that is, rats and mice) strongly influences the nature of the populating human gut microbiota, determining each model's biological suitability.

• Retraction of enteropathogenic E. coli type IV pili promotes efficient host cell colonization, effector translocation and tight junction disruption.

  Authors: Benjamin Aroeti, Gil Friedman, Efrat Zlotkin-Rivkin, Michael Donnenberg

  Gut microbes. 3(3).

  Type IV pili (Tfp) play a primary role in mediating the adherence of pathogenic bacteria to their hosts. The pilus filament can retract with an immense force. However, the role of this activity inType IV pili (Tfp) play a primary role in mediating the adherence of pathogenic bacteria to their hosts. The pilus filament can retract with an immense force. However, the role of this activity in microbial pathogenesis has not been rigorously explored. Experiments performed on volunteers suggested that the retraction capacity of enteropathogenic Escherichia coli (EPEC) Tfp is required for full virulence. Here we review our recent study ( 1) in which we showed that the retraction capacity of the EPEC Tfp facilitates tight-junction disruption and actin-rich pedestal formation by promoting efficient bacterial protein effector translocation into epithelial host cells. We also present new data using live imaging confocal microscopy suggesting that EPEC adheres to monolayers in microcolonies and that Tfp retraction facilitates significant changes in the microcolony shape, which may be critical for efficient effector delivery. Our studies hence suggest novel insights into the role of pili retraction in EPEC pathogenesis.

• Naming names: Eponyms and biological history.

  Authors: Gayatri Vedantam, V K Viswanathan

  Gut microbes. 3(3).

  The constraints imposed by available experimental data, and the need for precision, typically limits the eloquence of researchers. Scientists, however, indulge in their literary and poetic selves inThe constraints imposed by available experimental data, and the need for precision, typically limits the eloquence of researchers. Scientists, however, indulge in their literary and poetic selves in the names that they bestow on genes and proteins, on organisms and diseases. We briefly review some familiar names in the Inside Passage, and explore their historical antecedents.

• Microbes-induced EMT at the crossroad of inflammation and cancer.

  Authors: Paul Hofman, Valérie Vouret-Craviari

  Gut microbes. 3(3).

  It is noteworthy that bacterial or viral infections, and the resulting chronic inflammation, have been shown to predispose individuals to certain types of cancer. Remarkably, these microbesIt is noteworthy that bacterial or viral infections, and the resulting chronic inflammation, have been shown to predispose individuals to certain types of cancer. Remarkably, these microbes upregulated some transcription factors involved in the regulation of the epithelial to mesenchymal transition, referred herein as EMT. EMT is a cellular process that consists in the conversion of epithelial cell phenotype to a mesenchymal phenotype. Under physiological conditions EMT is clearly important for embryogenesis, organ development, wound repair and tissue remodeling. However, EMT may also be activated under pathologic conditions, more particularly in carcinogenesis and metastatic progression. In this review, we make a parallel between microbes- and growth factors- induced transcription factors. A unifying EMT model then emerges that may help in understanding the development of microbial pathogenesis and in defining new potential future therapeutic strategy in treating diseases linked to infections.

• The gut microbiota and its relationship to diet and obesity: New insights.

  Authors: Siobhan Clarke, Eileen Murphy, Kanishka Nilaweera, Paul Ross, Fergus Shanahan, Paul W O'Toole, Paul D Cotter

  Gut microbes. 3(3).

  Obesity develops from a prolonged imbalance of energy intake and energy expenditure. However, the relatively recent discovery that the composition and function of the gut microbiota impacts onObesity develops from a prolonged imbalance of energy intake and energy expenditure. However, the relatively recent discovery that the composition and function of the gut microbiota impacts on obesity has lead to an explosion of interest in what is now a distinct research field. Here, research relating to the links between the gut microbiota, diet and obesity will be reviewed under five major headings: (1) the gut microbiota of lean and obese animals, (2) the composition of the gut microbiota of lean and obese humans, (3) the impact of diet on the gut microbiota, (4) manipulating the gut microbiota and (5) the mechanisms by which the gut microbiota can impact on weight gain.

• Study on the association of Helicobacter species with viral hepatitis-induced hepatocellular carcinoma.

  Authors: Alexander Krüttgen, Hans-Peter Horz, Josefine Weber-Heynemann, Mihael Vucur, Christian Trautwein, Gerhard Haase, Tom Luedde, Christoph Roderburg

  Gut microbes. 3(3).

  Helicobacter species are important pathogens and previous studies in mice suggested a link between colonization by Helicobacter hepaticus (H. hepaticus) and hepatocellular carcinoma (HCC). This studyHelicobacter species are important pathogens and previous studies in mice suggested a link between colonization by Helicobacter hepaticus (H. hepaticus) and hepatocellular carcinoma (HCC). This study aimed at corroborating this potential link in human patients. We used a sensitive and specific Helicobacter ssp PCR assay to screen stool samples from a collective of patients with viral-induced HCC (hepatitis B or hepatitis C) and a control group for presence of Helicobacter ssp DNA. Although retrieving DNA of H. pylori and H. canadensis from stool samples of non-HCC patients, we found no evidence indicating the presence of H. hepaticus in HCC-patients with chronic hepatitis B or hepatitis C. Interestingly we found H. canadensis in a stool sample of a patient presenting with diarrhea. Taken together, our data argue against a pathogenic role of H. hepaticus in viral-induced HCC. Yet, our results do not exclude a role of H. hepaticus in those HCC cases caused by other carcinogens, such as aflatoxin. Moreover, we speculate that H. canadensis might be a novel gastrointestinal pathogen.

• Gut Balance, a synbiotic supplement, increases fecal Lactobacillus paracasei but has little effect on immunity in healthy physically active individuals.

  Authors: Nicholas West, David Pyne, Allan Cripps, Claus Christophersen, Michael A Conlon, Peter Fricker

  Gut microbes. 3(3).

  Synbiotic supplements, which contain multiple functional ingredients, may enhance the immune system more than the use of individual ingredients alone. A double blind active controlled parallel trialSynbiotic supplements, which contain multiple functional ingredients, may enhance the immune system more than the use of individual ingredients alone. A double blind active controlled parallel trial over a 21 d exercise training period was conducted to evaluate the effect of Gut Balance™, which contains Lactobacillus paracasei subsp. paracasei (L. casei 431®), Bifidobacterium animalis ssp. lactis (BB-12®), Lactobacillus acidophilus (LA-5®), Lactobacillus rhamnosus (LGG®), two prebiotics (raftiline and raftilose) and bovine whey derived lactoferrin and immunoglobulins with acacia gum on fecal microbiota, short chain fatty acids (SCFA), gut permeability, salivary lactoferrin and serum cytokines. All subjects randomized were included in the analysis. There was a 9-fold (1.2-fold to 64-fold; 95% confidence intervals p = 0.03) greater increase in fecal L. paracasei numbers with Gut Balance™ compared with acacia gum supplementation. Gut Balance™ was associated with a 50% (-12% to 72%; p = 0.02) smaller increase in the concentration of serum IL-16 in comparison to acacia gum from pre- to post-study. No substantial effects of either supplement were evident in fecal SCFA concentrations, measures of mucosal immunity or GI permeability. Clinical studies are now required to determine whether Gut Balance™ may exert beneficial GI health effects by increasing the recovery of fecal L. paracasei. Both supplements had little effect on immunity. Twenty two healthy physically active male subjects (mean age = 33.9 ± 6.5y) were randomly allocated to either daily prebiotic or synbiotic supplementation for 21 d. Saliva, blood, urine and fecal samples were collected pre-, mid and post-intervention. Participants recorded patterns of physical activity on a self-reported questionnaire.

• Helicobacter pylori DNA's anti-inflammatory effect on experimental colitis.

  Authors: Stephanie Owyang, Jay Luther, Christopher Owyang, Min Zhang, John Y Kao

  Gut microbes. 3(2).

  Our laboratory has demonstrated a clinical inverse association between H. pylori infection and inflammatory bowel disease (IBD). In our most recent work we described a possible mechanism by which H.Our laboratory has demonstrated a clinical inverse association between H. pylori infection and inflammatory bowel disease (IBD). In our most recent work we described a possible mechanism by which H. pylori can reduce the risk for developing IBD. Specifically, we were able to demonstrate the immuno-regulatory properties of the H. pylori genome and its ability to downregulate inflammatory responses through interaction with mucosal dendritic cells both in an in-vitro and in-vivo model. Furthermore, we were able to demonstrate the ability of H. pylori DNA to downregulate dendritic cell production of IL-12 and type I interferon, two pro-inflammatory cytokines. In the present work, we conducted further studies to examine the unique properties of the H. pylori genome and the exact mechanism in which it interacts with dendritic cells. Our data highlight a specific immuno-regulatory sequence (IRS), TTTAGGG, which occurs significantly more frequently as compared with other IRS sequences and is unique to the H. pylori genome. Additionally, we illustrate that H. pylori DNA has no effect on modulating the TLR-4 dependent LPS-induction of dendritic cell IL-12 production. This indicates that the inhibitory effect of H. pylori genomic DNA is restricted to the TLR-9 signaling pathway that senses bacterial DNA. In conclusion, the findings of this addendum strengthen the unique properties of H. pylori genome and revealed the importance of TLR-9 mediated mechanism in the pathogenesis of IBD.

• Clostridium difficile infection: Toxins and non-toxin virulence factors, and their contributions to disease establishment and host response.

  Authors: Gayatri Vedantam, Andrew Clark, Michele Chu, Rebecca McQuade, Michael Mallozzi, V K Viswanathan

  Gut microbes. 3(2).

  Clostridium difficile infection is the leading cause of antibiotic- and healthcare-associated diarrhea, and its containment and treatment imposes a significant financial burden, estimated to be overClostridium difficile infection is the leading cause of antibiotic- and healthcare-associated diarrhea, and its containment and treatment imposes a significant financial burden, estimated to be over $3 billion in the USA alone. Since the year 2000, CDI epidemics/outbreaks have occurred in North America, Europe and Asia. These outbreaks have been variously associated with, or attributed to, the emergence of Clostridium difficile strains with increased virulence, an increase in resistance to commonly used antimicrobials such as the fluoroquinolones, or host susceptibilities, including the use of gastric acid suppressants, to name a few. Efforts to elucidate C. difficile pathogenic mechanisms have been hampered by a lack of molecular tools, manipulatable animal models, and genetic intractability of clinical C. difficile isolates. However, in the past 5 y, painstaking efforts have resulted in the unraveling of multiple C. difficile virulence-associated pathways and mechanisms. We have recently reviewed the disease, its associated risk factors, transmission and interventions (Viswanathan, Gut Microbes 2010). This article summarizes genetics, non-toxin virulence factors, and host-cell biology associated with C. difficile pathogenesis as of 2011, and highlights those findings/factors that may be of interest as future intervention targets.

• Models for the study of Clostridium difficile infection.

  Authors: Emma Best, Jane Freeman, Mark Wilcox

  Gut microbes. 3(2).

  Models of Clostridium difficile infection (C. difficile) have been used extensively for Clostridium difficile (C. difficile) research. The hamster model of C. difficile infection has been mostModels of Clostridium difficile infection (C. difficile) have been used extensively for Clostridium difficile (C. difficile) research. The hamster model of C. difficile infection has been most extensively employed for the study of C. difficile and this has been used in many different areas of research, including the induction of C. difficile, the testing of new treatments, population dynamics and characterization of virulence. Investigations using in vitro models for C. difficile introduced the concept of colonization resistance, evaluated the role of antibiotics in C. difficile development, explored population dynamics and have been useful in the evaluation of C. difficile treatments. Experiments using models have major advantages over clinical studies and have been indispensible in furthering C. difficile research. It is important for future study programs to carefully consider the approach to use and therefore be better placed to inform the design and interpretation of clinical studies.

• Special Edition of Gut Microbes.

  Authors: Beth McCormick, Brett Finlay

  Gut microbes. 3(2).

• Shigella: A model of virulence regulation in vivo.

  Authors: Benoit Marteyn, Anastasia Gazi, Philippe Sansonetti

  Gut microbes. 3(2).

  Much is known about the molecular effectors of pathogenicity of gram-negative enteric pathogens, among which Shigella can be considered a model. This is due to its capacity to recapitulate theMuch is known about the molecular effectors of pathogenicity of gram-negative enteric pathogens, among which Shigella can be considered a model. This is due to its capacity to recapitulate the multiple steps required for a pathogenic microbe to survive close to its mucosal target, colonize and then invade its epithelial surface, cause its inflammatory destruction and simultaneously regulate the extent of the elicited innate response to likely survive the encounter and achieve successful subsequent transmission. These various steps of the infectious process represent an array of successive environmental conditions to which the bacteria need to successfully adapt. These conditions represent the selective pressure that triggered the "arms race" in which Shigella acquired the genetic and molecular effectors of its pathogenic armory, including the regulatory hierarchies that regulate the expression and function of these effectors. They also represent cues through which Shigella achieves the temporo-spatial expression and regulation of its virulence effectors. The role of such environmental cues has recently become obvious in the case of the major virulence effector of Shigella, the type three secretion system (T3SS) and its dedicated secreted virulence effectors. It needs to be better defined for other major virulence components such as the LPS and peptidoglycan which are used as examples here, in addition to the T3SS as models of regulation as it relates to the assembly and functional regulation of complex macromolecular systems of the bacterial surface. This review also stresses the need to better define what the true and relevant environmental conditions can be at the various steps of the progression of infection. The "identity" of the pathogen differs depending whether it is cultivated under in vitro or in vivo conditions. Moreover, this "identity" may quickly change during its progression into the infected tissue. Novel concepts and relevant tools are needed to address this challenge in microbial pathogenesis.

• Infection strategies of enteric pathogenic E. coli.

  Authors: Abigail Clements, Joanna Young, Nicholas Constantinou, Gad Frankel

  Gut microbes. 3(2).

  Enteric Escherichia coli (E. coli) are both natural flora of humans and important pathogens causing significant morbidity and mortality worldwide. Traditionally enteric E. coli have been divided intoEnteric Escherichia coli (E. coli) are both natural flora of humans and important pathogens causing significant morbidity and mortality worldwide. Traditionally enteric E. coli have been divided into 6 pathotypes, with further pathotypes often proposed. In this review we suggest expansion of the enteric E. coli into 8 pathotypes to include the emerging pathotypes of adherent invasive E. coli (AIEC) and Shiga-toxin producing enteroaggregative E. coli (STEAEC). The molecular mechanisms that allow enteric E. coli to colonize and cause disease in the human host are examined and for two of the pathotypes that express a type 3 secretion system (T3SS) we discuss the complex interplay between translocated effectors and manipulation of host cell signaling pathways that occurs during infection.

• How a sugary bug gets through the day: Recent developments in understanding fundamental processes impacting Campylobacter jejuni pathogenesis.

  Authors: Christine M Szymanski, Erin Gaynor

  Gut microbes. 3(2).

  Campylobacter jejuni is a highly prevalent yet fastidious bacterial pathogen that poses a significant health burden worldwide. Lacking many hallmark virulence factors, it is becoming increasinglyCampylobacter jejuni is a highly prevalent yet fastidious bacterial pathogen that poses a significant health burden worldwide. Lacking many hallmark virulence factors, it is becoming increasingly clear that C. jejuni pathogenesis involves different strategies compared with other well-characterized enteric organisms. This includes the involvement of basic biological processes and cell envelope glycans in a number of aspects related to pathogenesis. The past few years have seen significant progress in the understanding of these pathways and how they relate to C. jejuni fundamental biology, stress survival, colonization, and virulence attributes. This review focuses on recent studies in three general areas where "pathogenesis" and "basic biology" overlap: physiology, stress responses, and glycobiology.

• Signature tagged mutagenesis in the functional genetic analysis of gastrointestinal pathogens.

  Authors: Joanne Cummins, Cormac G M Gahan

  Gut microbes. 3(2).

  Signature tagged mutagenesis is a genetic approach that was developed to identify novel bacterial virulence factors. It is a negative selection method in which unique identification tags allowSignature tagged mutagenesis is a genetic approach that was developed to identify novel bacterial virulence factors. It is a negative selection method in which unique identification tags allow analysis of pools of mutants in mixed populations. The approach is particularly well suited to functional genetic analysis of the gastrointestinal phase of infection in foodborne pathogens and has the capacity to guide the development of novel vaccines and therapeutics. In this review we outline the technical principles underpinning signature-tagged mutagenesis as well as novel sequencing-based approaches for transposon mutant identification such as TraDIS (transposon directed insertion-site sequencing). We also provide an analysis of screens that have been performed in gastrointestinal pathogens which are a global health concern (Escherichia coli, Listeria monocytogenes, Helicobacter pylori, Vibrio cholerae and Salmonella enterica). The identification of key virulence loci through the use of signature tagged mutagenesis in mice and relevant larger animal models is discussed.

• Leptin signaling protects the gut from Entamoeba histolytica infection.

  Authors: Gayatri Vedantam, V K Viswanathan

  Gut microbes. 3(1).

  The role of the adipose-derived hormone leptin, and leptin receptors, in signaling satiety to the central nervous system and regulating energy balance is well recognized. But leptin also acts onThe role of the adipose-derived hormone leptin, and leptin receptors, in signaling satiety to the central nervous system and regulating energy balance is well recognized. But leptin also acts on peripheral tissues such as skeletal muscles, adipose tissues, pancreas, liver, intestine and the immune system. The existence of different splice variants of leptin receptor and the numerous intracellular signaling pathways triggered by leptin make this a truly versatile system. Two recent studies explore the link between malnutrition, leptin signaling and susceptibility to amebic infection. These studies point to important and novel aspects of leptin signaling in maintaining gut homeostasis and warding off infections.

• The role of gut microbiota in immune homeostasis and autoimmunity.

  Authors: Hsin-Jung Wu, Eric Wu

  Gut microbes. 3(1).

  Keeping a delicate balance in the immune system by eliminating invading pathogens, while still maintaining self-tolerance to avoid autoimmunity, is critical for the body's health. The gut microbiotaKeeping a delicate balance in the immune system by eliminating invading pathogens, while still maintaining self-tolerance to avoid autoimmunity, is critical for the body's health. The gut microbiota that resides in the gastrointestinal tract provides essential health benefits to its host, particularly by regulating immune homeostasis. Moreover, it has recently become obvious that alterations of these gut microbial communities can cause immune dysregulation, leading to autoimmune disorders. Here we review the advances in our understanding of how the gut microbiota regulates innate and adaptive immune homeostasis, which in turn can affect the development of not only intestinal but also systemic autoimmune diseases. Exploring the interaction of gut microbes and the host immune system will not only allow us to understand the pathogenesis of autoimmune diseases but will also provide us new foundations for the design of novel immuno- or microbe-based therapies.

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