Showing papers by "Rustam Aminov published in 2017"

Potential Effects of Horizontal Gene Exchange in the Human Gut.

Abstract: Many essential functions of the human body are dependent on the symbiotic microbiota, which is present at especially high numbers and diversity in the gut. This intricate host-microbe relationship is a result of the long-term coevolution between the two. While the inheritance of mutational changes in the host evolution is almost exclusively vertical, the main mechanism of bacterial evolution is horizontal gene exchange. The gut conditions, with stable temperature, continuous food supply, constant physicochemical conditions, extremely high concentration of microbial cells and phages, and plenty of opportunities for conjugation on the surfaces of food particles and host tissues, represent one of the most favorable ecological niches for horizontal gene exchange. Thus, the gut microbial system genetically is very dynamic and capable of rapid response, at the genetic level, to selection, for example, by antibiotics. There are many other factors to which the microbiota may dynamically respond including lifestyle, therapy, diet, refined food, food additives, consumption of pre- and probiotics, and many others. The impact of the changing selective pressures on gut microbiota, however, is poorly understood. Presumably, the gut microbiome responds to these changes by genetic restructuring of gut populations, driven mainly via horizontal gene exchange. Thus, our main goal is to reveal the role played by horizontal gene exchange in the changing landscape of the gastrointestinal microbiome and potential effect of these changes on human health in general and autoimmune diseases in particular.

Human Gut Symbiont Roseburia hominis Promotes and Regulates Innate Immunity

Abstract: Acknowledgments The authors would like to thank Andrew Gewirtz (Georgia State University, Atlanta, GA, USA) and Adam Cunningham (University of Birmingham, Edgbaston, Birmingham, UK) for generously providing the germ-free and conventional TLR5KO mice, respectively. The authors also wish to acknowledge a significant contribution to the inception of the work, experimental work, interpretation of results, and writing of the manuscript by Denise Kelly, as well as the support from RESAS (Rural and Environmental Science and Analytical Services) of the Scottish Government. EM and VF were supported by the Marie Curie Initial training network Fellowships funded by the EU (grant #215532). The authors acknowledge a generous support of Prof. Harry Flint and Dr. Sylvia Duncan in the microbiological part of this work. The skilled technical support of Gillian Campbell and Pauline Young at RINH Genomics is also gratefully acknowledged.

Transglutaminases in Dysbiosis As Potential Environmental Drivers of Autoimmunity

Abstract: Protein-glutamine γ-glutamyltransferases (transglutaminases) belong to the class of transferases. They catalyze the formation of an isopeptide bond between the acyl group at the end of the side chain of protein- or peptide-bound glutamine residues and the first order e-amine groups of protein- or peptide-bound lysine. The transglutaminases are considered to be universal protein cross-linkers, and they play an essential role in a number of human diseases. In this review, we discuss mainly the bacterial transglutaminases in terms of the functionality of the enzymes and a potential role they may play in bacterial survival. Since microbial transglutaminases are functionally similar to the human homologs, they may be involved in the human disease provocation. We suggest here a potential involvement of transglutaminases in the pathologies such as autoimmune diseases. In this hypothesis, the endogenous microbial transglutaminases that are secreted by the gut microbiota, especially in a dysbiotic configuration, are potential drivers of systemic autoimmunity, via the enzymatic posttranslational modification of peptides in the gut lumen. These microbial transglutaminase activities directed towards cross-linking of naive proteins can potentially generate neo-epitopes that are not only immunogenic but may also activate some immune response cascades leading to the pathological autoimmune processes.

Application of bacteriophages

Abstract: The emergence of antibiotic-resistant bacteria and decrease in the discovery rate of novel antibiotics takes mankind back to the ‘pre-antibiotic era’ and search for alternative treatments. Bacteriophages have been one of promising alternative agents which can be utilised for medicinal and biological control purposes in agriculture and related fields. The idea to treat bacterial infections with phages came out of the pioneering work of Felix d‘Herelle but this was overshadowed by the success of antibiotics. Recent renewed interest in phage therapy is dictated by its advantages most importantly by their specificity against the bacterial targets. This prevents complications such as antibiotic-induced dysbiosis and secondary infections. This article is compiled by the participants of the Expert Round Table conference ‘Bacteriophages as tools for therapy, prophylaxis and diagnostics’ (19–21 October 2015) at the Eliava Institute of Bacteriophage, Microbiology and Virology, Tbilisi, Georgia. The first paper from the Round Table was published in the Biotechnology Journal1. This In Focus article expands from this paper and includes recent developments reported since then by the Expert Round Table participants, including the implementation of the Nagoya Protocol for the applications of bacteriophages.

Editorial: Microbial and Environmental Factors in Autoimmune and Inflammatory Diseases.

Abstract: Pathogenesis of many autoinflammatory and autoimmune diseases is largely driven by inappropriate or inadequate immune responses toward environmental challenges. Most of them are multifactorial. For example, assessment of disease risk factors in rheumatoid arthritis (RA) brings the share of genetic predisposition to 50–60%, with the rest attributed to environmental factors (1). Thus, the diseases such as RA are well defined by Meda et al. (2) as comprising of both genetic and epigenetic components: \" the disease of bad genes and bad luck. \" While genetic predisposition to RA and other autoimmune and autoinflammatory diseases has been a subject of very extensive research in recent years, the role of environmental factors remains less explored. The research topic articles address the role of various environmental factors that may contribute to the onset of autoinflammatory and autoimmune disorders. They are presented in the following order: purely environmental factors, dysbiotic conditions, and infections of bacterial, fungal, and viral nature. In their comprehensive review, Anaya et al. discuss what they call the \" autoimmune ecology, \" which includes all levels involved, from the ecosphere to the environmental factors and to the molecular mechanisms of interaction of these factors with the human immune system. The role of microbiota and vaccines, lifestyle habits and socioeconomic status, organic solvents, ultraviolet, and other factors is discussed in the context of how these factors may interact with the innate immunity via the toll-like receptor signaling pathway, B-cell activation, the T helper 17, and regulatory T (Treg) cells, posttranslational modifications of self-antigens, and epigenetic modifications. This is a formidable attempt to synthetize the current knowledge of how various environmental factors (collectively called exposome) may interact with the immune system leading to differential outcomes including autoimmune disease. In the perspective article by Pollard, the silica-induced trigger mechanisms in the pathogenesis of inflammatory and autoimmune diseases are overviewed. Despite the proven epidemiological link between the silica exposure and autoimmune diseases, very little is known about the mecha-nistic factors leading to this disease. Based on currently available human and animal studies, a putative chain of events is proposed, which begins with activation of the innate immune system and then leads to proinflammatory cytokine production, pulmonary inflammation, activation of adaptive immunity, breaking of tolerance, autoantibody production, and tissue damage. Animal models of the silica exposure, which are used to mimic human autoimmunity, are also discussed.