Table of Contents

Volume 3, Issue 1

  January/February 2012

  Pages 1 - 60

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EDITOR'S CORNER

Open Access Article

Letter from the Editor

Gail Hecht and Eva Riedmann
Page 1
http://dx.doi.org/10.4161/gmic.19150
Full Text | PDF




THE INSIDE PASSAGE

Leptin signaling protects the gut from Entamoeba histolytica infection

Gayatri Vedantam and V. K. Viswanathan
Pages 2 - 3
http://dx.doi.org/10.4161/gmic.19424
Abstract | Full Text | PDF

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 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.




REVIEW

The role of gut microbiota in immune homeostasis and autoimmunity

Hsin-Jung Wu and Eric Wu
Pages 4 - 14
http://dx.doi.org/10.4161/gmic.19320
Abstract | Full Text | PDF

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 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.




RESEARCH PAPER

Characterization of Lactobacillus gasseri isolates from a breast-fed infant

Luciana Rodrigues da Cunha, Célia L.L. Fortes Ferreira, Evelyn Durmaz, Yong Jun Goh, Rosemary Sanozky-Dawes and Todd Klaenhammer
Pages 15 - 24
http://dx.doi.org/10.4161/gmic.19489
Abstract | Full Text | PDF

The potential health benefits of probiotic bacteria have led to the isolation of new microbial strains for incorporation into food products. However, newly isolated candidate probiotic organisms do not automatically share the “generally recognized as safe” (GRAS) status of traditional lactic acid bacteria (LAB). Before their introduction into food products, the safety of new isolates has to be evaluated. The objective of this study was to characterize LAB isolates from the stool of a newborn infant, and evaluate their safety and probiotic potential, in vitro. Thirty colonies were identified as Lactobacillus gasseri through sequencing of 16S rDNA. Pulsed Field Gel Electrophoresis using restriction enzymes SmaI and Apa I revealed that 29 of the L. gasseri were nearly identical, however one isolate exhibited a distinctive DNA fingerprint. All 30 L. gasseri were evaluated for resistance to antibiotics, bile tolerance, hemolytic activity and antagonism toward selected pathogens. All 30 strains harbored three plasmids, with one strain that showed strong tolerance to 0.5% of bile and harbored a unique fourth plasmid encoding a putative multidrug resistance transporter protein (LmrB). No hemolytic activity or antagonism, beyond acid inhibition was observed. Three selected strains UFVCC1083, 1091 and 1112 showed strong resistance to simulated small intestinal and gastric juices and adhered in vitro to mucin and two intestinal epithelial cell lines, Caco-2 and HT-29. This study identified and characterized recently isolated L. gasseri strains from faeces of a breast fed infant as potential probiotic candidates for use in the human milk banks in Brazil.




ARTICLE ADDENDA

Characterization of a probiotic-derived soluble protein which reveals a mechanism of preventive and treatment effects of probiotics on intestinal inflammatory diseases

Fang Yan and D. Brent Polk
Pages 25 - 28
http://dx.doi.org/10.4161/gmic.19245
Abstract | Full Text | PDF

The beneficial effects of probiotics have been demonstrated in many diseases, such as inflammatory bowel disease. The known mechanisms for probiotic action include blocking pathogenic bacterial effects, enhancing the innate immunity and decreasing pathogen-induced inflammation, and promoting intestinal epithelial cell survival, barrier function, and protective responses. We purified and cloned a Lactobacillus rhamnosus GG (LGG)-derived soluble protein, p40. This protein ameliorated cytokine-induced apoptosis in intestinal epithelial cells through activation of the EGF receptor and its down-stream target, Akt. By using special hydrogel beads to protect p40 from degradation, we showed that p40 reduced intestinal epithelial apoptosis and preserved barrier function in the colon epithelium in an EGF receptor-dependent manner, thereby preventing and treating intestinal inflammation in mouse models of colitis. Further works regarding structural analysis of p40, regulation of EGF receptor activation and immunoregulatory effects by p40 are discussed. These results may provide insights into the clinical application of probiotics for intestinal inflammatory disorders.

Prebiotic fiber modulation of the gut microbiota improves risk factors for obesity and the metabolic syndrome

Jill A. Parnell and Raylene A. Reimer
Pages 29 - 34
http://dx.doi.org/10.4161/gmic.19246
Abstract | PDF

Prebiotic fibers are non-digestible carbohydrates that promote the growth of beneficial bacteria in the gut. Prebiotic consumption may benefit obesity and associated co-morbidities by improving or normalizing the dysbiosis of the gut microbiota. We evaluated the dose response to a prebiotic diet on the gut microbiota, body composition and obesity associated risk factors in lean and genetically obese rats. Prebiotic fibers increased Firmicutes and decreased Bacteroidetes, a profile often associated with a leaner phenotype. Bifidobacteria and Lactobacillus numbers also increased. Changes in the gut microbiota correlated with energy intake, glucose, insulin, satiety hormones, and hepatic cholesterol and triglyceride accumulation. Here we provide a comprehensive analysis evaluating the results through the lens of the gut microbiota. Salient, new developments impacting the interpretation and significance of our data are discussed. We propose that prebiotic fibers have promise as a safe and cost-effective means of modulating the gut microbiota to promote improved host:bacterial interactions in obesity and insulin resistance. Human clinical trials should be undertaken to confirm these effects.

Clostridial toxins: Sensing a target in a hostile gut environment

Numan Oezguen, Trevor D. Power, Petri Urvil, Hanping Feng, Charalabos Pothoulakis, Jonathan S. Stamler, Werner Braun and Tor C. Savidge
Pages 35 - 41
http://dx.doi.org/10.4161/gmic.19250
Abstract | Full Text | PDF

The current global outbreak of Clostridium difficile infection exemplifies the major public health threat posed by clostridial glucosylating toxins. In the western world, C. difficile infection is one of the most prolific causes of bacterial-induced diarrhea and potentially fatal colitis. Two pathogenic enterotoxins, TcdA and TcdB, cause the disease. Vancomycin and metronidazole remain readily available treatment options for C. difficile infection, but neither is fully effective as is evident by high clinical relapse and fatality rates. Thus, there is an urgent need to find an alternative therapy that preferentially targets the toxins and not the drug-resistant pathogen. Recently, we addressed these critical issues in a Nature Medicine letter, describing a novel host defense mechanism for subverting toxin virulence that we translated into prototypic allosteric therapy for C. difficile infection. In this addendum article, we provide a continued perspective of this antitoxin mechanism and consider the broader implications of therapeutic allostery in combating gut microbial pathogenesis.

Systemic antibody responses to gut microbes in health and disease

Kathrin Zimmermann, Anna Haas and Annette Oxenius
Pages 42 - 47
http://dx.doi.org/10.4161/gmic.19344
Abstract | Full Text | PDF

Gastrointestinal commensal microbes usually exist in mutualistic relationship with their mammalian host. This relationship exists even though the mammalian host immune system is equipped with exquisite sensors for microbial chemical structures which trigger powerful immune defense mechanisms. Such beneficial mutualism is specifically maintained at the gut mucosal interface by a variety of physical and bioactive barriers as well as specific immunregulatory mechanisms. In addition, there is a strict compartmentalization between systemic and gut mucosal immunity—at least in inbred mice—which focuses adaptive immunity to gut microbes specifically to the gut tissue and the gut lumen. Only in circumstances of increased gut microbial exposure due to elevated gut epithelial permeability, due to genetic deficiencies in local defense mechanisms, due to imbalances in local immune regulation or in case of gastrointestinal pathogenic bacterial infections this compartmentalization is broken and systemic immune responses to gut microbes are induced, which manifest for example as systemic antibody responses specific for gut microbial antigens. Here we briefly discuss the abundance of systemic antibody responses to commensal gut bacteria in healthy humans and how it is altered in situations with chronic enteropathies such as in inflammatory bowel disease and HIV-1 infection or infection with gut bacterial pathogens.

Spermine oxidase, a polyamine catabolic enzyme that links Helicobacter pylori CagA and gastric cancer risk

Rupesh Chaturvedi, Thibaut de Sablet, Richard M. Peek and Keith T. Wilson
Pages 48 - 56
http://dx.doi.org/10.4161/gmic.19345
Abstract | Full Text | PDF

We have recently reported that Helicobacter pylori strains expressing the virulence factor cytotoxin-associated gene A (CagA) stimulate increased levels of spermine oxidase (SMO) in gastric epithelial cells, while cagA^– strains did not. SMO catabolizes the polyamine spermine and produces H₂O₂ that results in both apoptosis and DNA damage. Exogenous overexpression of CagA confirmed these findings, and knockdown or inhibition of SMO blocked CagA-mediated apoptosis and DNA damage. The strong association of SMO, apoptosis, and DNA damage was also demonstrated in humans infected with cagA⁺, but not cagA^– strains. In infected gerbils and mice, DNA damage was CagA-dependent and only present in epithelial cells that expressed SMO. We also discovered SMO^high gastric epithelial cells from infected animals with dysplasia that are resistant to apoptosis despite high levels of DNA damage. Inhibition of polyamine synthesis or SMO could abrogate the development of this cell population that may represent precursors for neoplastic transformation.

Effect of prebiotics on the human gut microbiota of elderly persons

Ruth Toward, Samantha Montandon, Gemma Walton and Glenn R. Gibson
Pages 57 - 60
http://dx.doi.org/10.4161/gmic.19411
Abstract | Full Text | PDF

The colonic microbiota undergoes certain age related changes that may affect health. For example, above the age of 55–65 y, populations of bifidobacteria are known to decrease markedly. Bifidobacteria are known inhibitors of pathogenic microbes and a decrease in their activities may increase susceptibility to infections. There is therefore interest in trying to reverse their decline in aged persons. As the gut microbiota responds to dietary intervention, both probiotics and prebiotics have been tested in this regard. Probiotics are live microbes in the diet, whereas prebiotics are fermentable ingredients that specifically target components of the indigenous microbiota seen to be beneficial. We have published a recent paper demonstrating that prebiotic galactooligosaccharides can exert power effects upon bifidobacteria in the gut flora of elderly persons (both in vivo and in vitro). This addendum summarizes research that led up to this study and discusses the possible impact of prebiotics in impacting upon the gut health of aged persons.