The emergence of antibiotic-resistant bacterial pathogens is an all-too-common consequence of

The emergence of antibiotic-resistant bacterial pathogens is an all-too-common consequence of antibiotic use. the gastrointestinal tract of rodents and humans treated with antibiotics, and the term colonization resistance was coined to denote the microbiotas capacity to inhibit expansion of Enterococci and Enterobacteriaceae in the gut lumen (Clasener et al., 1987; Van der Leur et al., 1993). Since the advent of microscopy over three centuries ago and the description of pleomorphic animalcules that reside in the mouth (Lane, 2015), it has been understood that our surfaces, particularly along the gastrointestinal tract, are colonized with dense and diverse populations of microbes. The complexity of organisms inhabiting our colons was demonstrated by deep sequencing of highly variable regions of bacterial Thiazovivin inhibitor 16S ribosomal RNA genes from fecal samples, allowing for generation of phylogenetic trees. Sequencing of over 13,000 16S ribosomal RNA genes from the colons of three healthy individuals demonstrated that humans harbor highly diverse bacterial populations, with dramatic person-to-person variation in microbiota composition (Eckburg et al., 2005). The Human Microbiome Project and the MetaHit Program used next-generation sequencing platforms to characterize the microbiota of hundreds of healthy individuals, confirming substantial interindividual variation (Arumugam et al., 2011; Human Microbiome Project Consortium, 2012). A consistent message from studies spanning a wide range of human populations is that, at baseline, the adult colonic microbiota comprises predominantly bacteria belonging HUP2 to the Bacteroidetes or Firmicutes phyla (Fig. 1 A). These phyla contain many different families, genera, and species of bacteria that vary in proportion between individuals but that remain remarkably constant within individuals in the absence of intestinal infection, dietary change, or antibiotic administration (David et al., 2014). Open in a separate window Figure 1. The microbiota plays an important role in intestinal homeostasis and prevention of opportunistic pathogen infection. A healthy microbiota is comprised predominantly of bacteria that are members of the Bacteroidetes Thiazovivin inhibitor (blue) and Firmicutes (yellow) phyla. These bacteria interact and cooperate to break down dietary fiber and host-derived mucus into a variety of carbohydrates that support the complex community. SCFAs are by-products of carbohydrate fermentation that promote differentiation of regulatory T cells (Treg). Bacteria-derived TLR ligands promote production of antimicrobial peptides such as RegIII, helping prevent bacterial penetration into the inner mucus layer. Specific bacterial species can produce secondary and iso-bile acids, which contribute to colonization resistance against maintain long-term colonization by using distinct polysaccharides so that identical strains that could otherwise make use of these same polysaccharides cannot engraft because of competitive exclusion. A wholesome microbiota also permits the maintenance of two specific mucus levels: an 50-m epithelium-associated internal mucus coating that is mainly impenetrable by intestinal bacterias and a much less dense outer coating that acts as a microbial habitat. (A) Soluble fiber is an essential substrate from the healthful microbiota, however when diet changes bring about low dietary fiber availability, bacteria vacation resort to using the glycoprotein-rich mucus coating alternatively power source. As a total Thiazovivin inhibitor result, diet changes can result in thinning from the mucus coating, permitting improved bacterial penetration from the mucus coating, which can result in epithelial swelling and improved pathogen susceptibility. (B) Antibiotic administration disrupts complicated responses loops that sustain the complicated microbial community, leading to lack of mucus because of the diminishment of microbiota-derived sponsor elements that regulate the creation and secretion of mucus. Furthermore, some antibiotics could cause colonization level of resistance to be dropped, leaving the sponsor susceptible to opportunistic enteric pathogen (reddish colored) expansion. Systems of colonization level of resistance The bacterial varieties constituting the colonic microbiota offer colonization level of resistance via a large number of parallel systems that restrict the power of exogenous bacterial strains to get a foothold in the gut, therefore reducing the hosts susceptibility to enteric attacks (Buffie and Pamer, 2013)..