Emerging Insights into Antibiotic-Associated Diarrhea and Clostridium difficile Infection through the Lens of Microbial Ecology

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 strains 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), and the opportunistic bacterial infections that sometimes underlie it. As an example, we discuss how this approach is being used to address complex disease dynamics during Clostridium difficile infection

Characterization of the cryptic Escherichia lineages: rapid identification and prevalence

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86967/1/j.1462-2920.2011.02519.x.pd

Vaginal biogenic amines: biomarkers of bacterial vaginosis or precursors to vaginal dysbiosis?

Bacterial vaginosis (BV) is the most common vaginal disorder among reproductive age women. One clinical indicator of BV is a "fishy" odor. This odor has been associated with increases in several biogenic amines (BAs) that may serve as important biomarkers. Within the vagina, BA production has been linked to various vaginal taxa, yet their genetic capability to synthesize BAs is unknown. Using a bioinformatics approach, we show that relatively few vaginal taxa are predicted to be capable of producing BAs. Many of these taxa (Dialister, Prevotella, Parvimonas, Megasphaera, Peptostreptococcus, and Veillonella spp.) are more abundant in the vaginal microbial community state type (CST) IV, which is depleted in lactobacilli. Several of the major Lactobacillus species (L. crispatus, L. jensenii, and L. gasseri) were identified as possessing gene sequences for proteins predicted to be capable of putrescine production. Finally, we show in a small cross sectional study of 37 women that the BAs putrescine, cadaverine and tyramine are significantly higher in CST IV over CSTs I and III. These data support the hypothesis that BA production is conducted by few vaginal taxa and may be important to the outgrowth of BV-associated (vaginal dysbiosis) vaginal bacteria

Correlation between Tick Density and Pathogen Endemicity, New Hampshire

To assess the endemicity of tick-borne pathogens in New Hampshire, we surveyed adult tick vectors. Pathogens were more prevalent in areas of high tick density, suggesting a correlation between tick establishment and pathogen endemicity. Infection rates in ticks correlated with disease frequency in humans

Emergence of carbapenemase-producing Klebsiella pneumoniae of sequence type 258 in Michigan, USA

The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) in our hospital increased beginning in 2009. We aimed to study the clinical and molecular epidemiology of these emerging isolates. We performed a retrospective review of all adult patients with clinical cultures confirmed as CPE by positive modified Hodge test from 5/2009-5/2010 at the University of Michigan Health System (UMHS). Clinical information was obtained from electronic medical records. Available CPE isolates were analyzed by polymerase chain reaction (PCR) and sequencing of the 16S rRNA encoding gene and blaKPC locus. Multilocus sequence typing (MLST) was used to characterize Klebsiella pneumoniae isolates. Twenty six unique CPE isolates were obtained from 25 adult patients. The majority were Klebsiella pneumoniae (n=17). Other isolates included K. oxytoca (n=3), Citrobacter freundii (n=2), Enterobacter cloacae (n=2), Enterobacter aerogenes (n=1) and Escherichia coli (n=1). Molecular characterization of 19 available CPE isolates showed that 13 (68%) carried the KPC-3 allele and 6 (32%) carried the KPC-2 allele. Among 14 available K. pneumoniae strains, 12 (86%) carried the KPC-3 allele and belonged to a common lineage, sequence type (ST) 258. The other 2 (14%) K. pneumoniae isolates carried the KPC-2 allele and belonged to two unique STs. Among these ST 258 strains, 67% were isolated from patients with prior exposures to health care settings outside of our institution. In contrast, all CPE isolates carrying the KPC-2 allele and all non ST 258 CPE isolates had acquisition attributable to our hospital. Molecular epidemiology of carbapenemase producing K. pneumoniae suggests that KPC-3 producing K. pneumoniae isolates of a common lineage, sequence type (ST 258), are emerging in our hospital. While ST 258 is a dominant sequence type throughout the United States, this study is the first to report its presence in Michigan

Clostridium difficile ribotype diversity at six health care institutions in the United States

Capillary-based PCR ribotyping was used to quantify the presence/absence and relative abundance of 98 Clostridium difficile ribotypes from clinical cases of disease at health care institutions in six states of the United States. Regionally important ribotypes were identified, and institutions in close proximity did not necessarily share more ribotype diversity than institutions that were farther apart

Alteration of the murine gut microbiota during infection with the parasitic helminth Heligmosomoides polygyrus

Background: In a murine model of inflammatory bowel disease (IBD), treatment of colitis in IL-10 gene-deficient mice with the parasitic helminth Heligmosomoides polygyrus ameliorates colonic inflammation. The cellular and molecular mechanisms driving this therapeutic host response are being studied vigorously. One proposed mechanism is that H. polygyrus infection favors the outgrowth or suppression of certain bacteria, which in turn help modulate host immunity. Methods: To quantify the effect of H. polygyrus infection on the composition of the gastrointestinal (GI) tract microbiota, we conducted two independent microbial ecology analyses of C57BL/6 mice. We obtained and analyzed 3,353 bacterial 16S rRNA encoding gene sequences from the ileum and cecum of infected and uninfected mice as well as incective H. polygyrus larvae at the outset of the second experiment and adult worms taken directly from the mouse duodenum at the end of the second experiment. Results: We found that a significant shift in the abundance and relative distribution of bacterial species in the ileum of mice is associated with H. polygyrus infection. Members of the bacterial family Lactobacillaceae significantly increased in abundance in the ileum of infected mice reproducibly in two independent experiments despite having different microbiotas present at the outset of each experiment. Conclusions: These data support the concept that helminth infection shifts the composition of intestinal bacteria. The clinical consequences of these shifts in intestinal flora are yet to be explored. (Inflamm Bowel Dis 2010)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78230/1/21299_ftp.pd

Alcator C-Mod: research in support of ITER and steps beyond

This paper presents an overview of recent highlights from research on Alcator C-Mod. Significant progress has been made across all research areas over the last two years, with particular emphasis on divertor physics and power handling, plasma–material interaction studies, edge localized mode-suppressed pedestal dynamics, core transport and turbulence, and RF heating and current drive utilizing ion cyclotron and lower hybrid tools. Specific results of particular relevance to ITER include: inner wall SOL transport studies that have led, together with results from other experiments, to the change of the detailed shape of the inner wall in ITER; runaway electron studies showing that the critical electric field required for runaway generation is much higher than predicted from collisional theory; core tungsten impurity transport studies reveal that tungsten accumulation is naturally avoided in typical C-Mod conditions.United States. Department of Energy (DE-FC02-99ER54512-CMOD)United States. Department of Energy (DE-AC02-09CH11466)United States. Department of Energy (DE-FG02-96ER-54373)United States. Department of Energy (DE-FG02-94ER54235

Healthy human gut phageome

The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20-50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health.Peer reviewe