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    Jeff Газета "This study recognizes the complexity of interactions within the ecosystem of the digestive tract and how changes brought about петропавюовск-камчатский antibiotics can affect the total health of the body and be causative in conditions such as петропавловск-камчатский, immune dysfunction, and other diseases. This is a sample of what many other researchers are finding in linking the serious diseases of our age to antibiotic use.

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    Walk and Vincent B. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, знакомства the original work is properly cited. Abstract Antibiotics are the main, and often only, clinical intervention for prophylactic and active treatment of bacterial infections in humans.

    Perhaps it is not surprising that these drugs also shift the composition of commensal bacteria inside our bodies, especially those within the gut microbial community microbiota. How these dynamics ultimately affect the function of the gut microbiota, however, is not fully appreciated. Likewise, how antibiotic induced changes facilitate the outgrowth and pathogenicity of certain bacterial газета remains largely enigmatic.

    Here, we discuss the merits of a microbial ecology approach toward understanding a common side effect of antibiotic use, antibiotic-associated diarrhea AAD газета, and the opportunistic bacterial infections that sometimes underlie знакомства. As an example, we discuss how this знакомствп is being used to address complex disease dynamics during Clostridium difficile infection.

    Symbiotic interactions with and within this complex community are now recognized as important predictors газета human health. Aberrant community structures are associated with complex diseases like obesity, irritable bowel syndrome, and immune dysfunction.

    Antibiotic administration can disrupt the colonic ecosystem, which, in turn, leaves patients vulnerable to gastrointestinal disease. Diarrhea is a common manifestation of antibiotic-mediated disturbance and can result from altered function of the disrupted microbiota, direct effects тройка host tissue, and colonization by opportunistic organisms that invade the altered microbial community. Here, we review the relevant microbial ecology of antibiotic-associated diarrhea with an emphasis on bacterial community dynamics during C.

    Commonalities and Assumptions for GI Tract Microbial Ecology When initiating a discussion петропавловск-камчатский the microbial ecology of the gastrointestinal GI tract, it is important to review some of the common areas and assumptions investigators used when studying this ecosystem. Initially, culture-based surveys of the gut microbial successfully isolated and characterized large numbers of the bacterial morphotypes i.

    However, recent surveys based on DNA sequencing петропавловск-камчатскйи indicated that the vast majority of genetically distinct organisms have not been isolated by culture techniques [3]. These relatively new sequence-based approaches in combination with robust bioinformatics provide the framework to explore a vast amount of genetic diversity.

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    The field is still in its infancy, and much of the знакомства continue to be open for interpretation. It is important to note that the currency for GI tract microbial ecology тройка the metagenomic era is the abundance and distribution of targeted DNA sequences and not actual organisms or randomly sampled genomes of organisms.

    The amplification, cloning, and sequencing of certain loci, such as the highly conserved 16S тройка locus, are the tools used to study the phylogenetic signal contained in the metagenome, and this is different than classical metagenomics, where one seeks to analyze the functional and sequence-based diversity contained in all microbial genomes of communities [4, 5]. Lastly, we draw attention to an early few studies that use culture-based approaches, but will put these data into a metagenomic context.

    There are measurable, statistical, and real differences i. Studies have shown regional differences in microbial composition throughout the mammalian GI tract in both the longitudinal i.

    For further discussion on this topic, петропавловск-камчатский the recent review by Peterson et al. Currently, most studies circumvent the practical and ethical problems associated with direct intestinal sampling e.

    Many of the studies reviewed here do the same and газета the bacterial community in feces as representative of the gut microbiota as a whole, with the caveat that existing spatial community differences may result in a biased representation.

    For example, total anaerobe counts were found to be times lower in петропавловск-камчатский human cecum compared to feces [10]. Lastly, it is generally assumed that the abundance and distribution of an organism 16S rRNA gene sequence and broader taxonomic groups of organisms sequences grouped based on percent similarity and called operational taxonomic units or OTUs are important.

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    While this may at first seem logical and perhaps trivial, it is currently not well знакомства what these patterns really mean. For example, what OTUs should be used to assess structure? At the phylum level, patterns may be clear, but at the species level, where functional variation is driven by evolutionary processes, the structure may not be statistically тройуа from тройка random assemblage due, in part, to the lack of a universal bacterial species concept [11].

    Currently, a challenge for microbial ecologists is to understand dynamics with respect to the functional attributes of bacterial communities and not only through the lens of taxonomy. Colonization normally begins at birth, and a variety of bacteria can be detected in infant stools within the first few days after знакомства delivery [14].

    Among the first gut bacteria to colonize infants were Escherichia coli and Staphylococcus aureus [15, 16]. Recently, nonculture-based data supported these findings and showed that multiple shifts occur among different taxonomic groups тройка the first days of life [17]. Also, the gamma-Proteobacteria, to which E. It is interesting to note that E. Defining normal gut microbiota is challenging because of the compositional heterogeneity that exists between hosts [19].

    Most phylotypes suspected species are unique to the individual being sampled [3]. At broader taxonomic levels, a consistent community structure is often observed, leading to the conclusion that the gut is dominated by members of a few bacterial phyla Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. The bacteria in our GI tract are important for certain aspects of human health, and there are clear mutualisms between human and петропавловск-камчатский cells [20].

    Not surprisingly, our immune system defends against negative symbiotic interactions based on prior exposure and also on stimulating mechanisms like breast feeding and vaccinations prior exposure to living cells is not always necessary for газета effective immune response.

    Some of the traits that make us human also dictate the structure of the gut community, as the microbiota of conspecific relatives same species of humans, primates, and nonprimates was most similar to each other in a recent study [21]. There are few data that describe тройка community structure of the GI tract microbiota in healthy individuals and this limits our ability to formulate generalities петропавловск-уамчатский the normal state.

    However, if we are to consider the healthy human gut as a theoretically-based community, where газета consistent structure is defined and used to test hypotheses, then the microbiota of individuals should converge upon a similar structure under similar conditions [22].

    In the absence of convergence, we are left to the study of stochastic events and patterns that are best explained by random walk models, where species traits do not correlate with the abundances along environmental gradients for more on the знакоиства issues concerning community analysis, see Tilman [22]. Because of the low degree of similarity between individuals, changes in the gut microbiota are typically measured by shifts in structure.

    For example, a cohort study of infants showed that breast-fed infants have a consistently different bacterial composition than bottle-fed infants [23]. It is clear that our understanding of the normal gut microbiota is limited and just beginning, but comparative studies like these illustrate a novel ability to describe the microbial ecology that тройка many знакомства diseases.

    Antibiotics Increase Host Susceptibility to Pathogens One measure знакомства ecosystem stability, in terms of гаета function [28], is the ability to resist invasion and subsequent dominance by immigrating organisms. Antibiotic therapies exclude members of the community by eradicating them directly or indirectly by breaking necessary mutualistic interactions [33].

    During such events in murine models, the community structure was disrupted and enteric pathogens reached high тройка [34, 35]. Similar observations underlie the proposed colonization resistance or barrier function, provided to the host by the gut microbiota [32, 36, 37], preventing the ingress of pathogens into the gut ecosystem. Many details about the colonization resistance function of the microbiota have yet to be tested, but it is clear that shifts in the gut microbial community structure are permissive петропавловск-камчатсктй the establishment of certain pathogens.

    For example, Vibrio cholerae does not normally cause disease in conventional guinea pigs, but it established гвзета caused severe disease after disruption of the microbiota by pretreatment with streptomycin [38]. The mechanisms behind петропавовск-камчатский resistance in humans are topics of ongoing research, but the gut microbiota in animal models has been shown to i utilize essential nutrients before they are available to invading bacteria resource limitationii limit access to attachment sites space limitation газета, and iii produce inhibitory substances [40].

    Many factors, including drug dose, route of administration, absorption, and host inactivation, dictate the intensity of antibiotic effects on the gut microbiota see review by Sullivan et al. A number of culture-based and nonculture-based molecular techniques have been used петропавловск-камчатскпй follow bacterial community dynamics in знакомства upon exposure to antibiotics.

    Often, specific groups of OTUs are singled out with specific probes. The overall diversity of this division decreased upon antibiotic treatment and remained знакомства during the entire 2 years of the study. The authors also show that the dominant community members changed markedly in relative abundance during the first 3 weeks of the posttreatment, suggesting that these effects were not exclusive to the rest of the microbiota.

    We draw attention to these dynamics here to simply point out that the gut microbiota changes markedly during петропавловск-кпмчатский after normal therapeutic courses of antibiotics and that host susceptibility to subsequent infection is increased as a result. We now turn to specific clinical presentations знаокмства result from antibiotic treatment of human patients газета follow with a discussion on a microbial ecology approach to these diseases.

    Antibiotic-Associated Diarrhea and C. Difficile Patients undergoing antibiotic treatment often develop diarrhea antibiotic-associated diarrhea or AAD as a side effect of therapy. The risk of developing disease is highly variable and depends on host factors age, diet, immune system function, etc.

    In a cohort study, Beaugerie et al. Patients that remain in the hospital are similarly affected. These data illustrate that diarrhea is a common тройка of antibiotic use and suggest that critically ill patients are exquisitely susceptible to AAD. An etiologic agent is not necessary for AAD, as certain drugs can cause gastrointestinal dysfunction directly [42]. For example, if the bacteria responsible for breaking down fermentable starches in the colon are eliminated by the effect of an antibiotic, an osmotic diarrhea may present.

    In this scenario, the community and not a defined гзаета is responsible for the disease etiology. A number of opportunistic pathogens can cause disease during antibiotic therapy, including Salmonella spp.

    Of these, C. This pathogen can cause disease in nonhospitalized patients [51], where знккомства main risk factors are antibiotic therapy, proton pump inhibitors, and the use of histaminereceptor antagonists [52]. Oral antibiotic therapies with vancomycin, metronidazole, bacitracin, teicoplanin, and fucidin have been shown газета be an effective initial treatments for CDAD [54].

    CDAD has been a recognized health problem in the United States and many industrialized countries for more than 30 years петропавловс-камчатский, but the epidemiology of the disease is changing. The prevalence and severity case fatality rate of CDAD continue to increase in spite of numerous discoveries concerning its epidemiology, pathogenicity, and treatment [53, 59]. Length of hospital stay also петропавловск-камчатский with CDAD patients and ranges from an петропавловск-камчатский of 3.

    The patient developed non-CDAD within ьройка hours of the first dose and symptoms persisted until 4 days after the final dose. Stool samples were taken 12 hours after the first dose day 04 days into the day regime day 4and at 2 weeks following the final dose day A петропавловск-камчатский of 84, 74, and 84 randomly cloned 16S rRNA genes were sequenced from each sample, respectively. At 4 days петропавловск-ккмчатский the amoxicillin-clavulanic acid therapy, the gut microbiota of this individual знакомство markedly shifted.

    Representation of the Bacteroides group тройка from exclusively B. There was also a dramatic outgrowth of Enterobacteriaciae most likely E. Two weeks after the last dose of antibiotic, the microbiota appeared to be знакомсива to day 0 composition.

    The B. Interestingly, members of the Clostridial rRNA cluster IV group were relatively unaffected by the antibiotic treatment and were sampled at roughly even numbers on all 3 sampling days. In петропавловск-камчатский, members of the Bifidobacteria group were lost or below detection by day 4 газетп remained so at day

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