Publications by authors named "Doyle V Ward"

46 Publications

The Urinary Microbiome of Older Adults Residing in a Nursing Home Varies with Duration of Residence and Shows Increases in Potential Pathogens.

J Gerontol A Biol Sci Med Sci 2021 Nov 13. Epub 2021 Nov 13.

Department of Emergency Medicine, UMass Memorial Medical Center and University of Massachusetts Medical School, Worcester, MA.

The community of bacteria that colonize the urinary tract, the urinary microbiome, is hypothesized to influence a wide variety of urinary tract conditions. Older adults that reside in nursing homes are frequently diagnosed and treated for urinary tract conditions such as urinary tract infection (UTI). We investigated the urinary microbiome of older adults residing in a nursing home to determine if there are features of the urinary microbiome that are associated specific conditions and exposure in this population. We were also interested in the stability of urinary microbiome over time and in similarities between the urinary and gastrointestinal microbiome. Urine samples were prospectively collected over a period of 10 months from a cohort of 26 older adults (age > 65 years) residing in single nursing home located in Central Massachusetts. Serial samples were obtained from 6 individuals over 10 months and 5 participants were concurrently enrolled in a study of the gastrointestinal microbiome. Information collected on participants included demographics, medical history, duration of residence in the nursing home, frailty, dementia symptoms, urinary symptoms, antibiotic treatment, urinary catherization, and hospitalizations over a 10-month period. Clean catch mid-stream urine samples were collected and stored at -80C. DNA was extracted and 16S rRNA gene sequencing performed. The length of stay in the nursing facility and the Clinical Frailty Scale correlated with significant changes in microbiome composition. An increase in the relative abundance of a putative urinary pathogen, Aerococcus urinae, was the largest factor influencing change that occurred over duration of residence.
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http://dx.doi.org/10.1093/gerona/glab345DOI Listing
November 2021

Gut microbiota regulation of P-glycoprotein in the intestinal epithelium in maintenance of homeostasis.

Microbiome 2021 09 7;9(1):183. Epub 2021 Sep 7.

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, 01605, USA.

Background: P-glycoprotein (P-gp) plays a critical role in protection of the intestinal epithelia by mediating efflux of drugs/xenobiotics from the intestinal mucosa into the gut lumen. Recent studies bring to light that P-gp also confers a critical link in communication between intestinal mucosal barrier function and the innate immune system. Yet, despite knowledge for over 10 years that P-gp plays a central role in gastrointestinal homeostasis, the precise molecular mechanism that controls its functional expression and regulation remains unclear. Here, we assessed how the intestinal microbiome drives P-gp expression and function.

Results: We have identified a "functional core" microbiome of the intestinal gut community, specifically genera within the Clostridia and Bacilli classes, that is necessary and sufficient for P-gp induction in the intestinal epithelium in mouse models. Metagenomic analysis of this core microbial community revealed that short-chain fatty acid and secondary bile acid production positively associate with P-gp expression. We have further shown these two classes of microbiota-derived metabolites synergistically upregulate P-gp expression and function in vitro and in vivo. Moreover, in patients suffering from ulcerative colitis (UC), we find diminished P-gp expression coupled to the reduction of epithelial-derived anti-inflammatory endocannabinoids and luminal content (e.g., microbes or their metabolites) with a reduced capability to induce P-gp expression.

Conclusion: Overall, by means of both in vitro and in vivo studies as well as human subject sample analysis, we identify a mechanistic link between cooperative functional outputs of the complex microbial community and modulation of P-gp, an epithelial component, that functions to suppress overactive inflammation to maintain intestinal homeostasis. Hence, our data support a new cross-talk paradigm in microbiome regulation of mucosal inflammation. Video abstract.
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http://dx.doi.org/10.1186/s40168-021-01137-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425172PMC
September 2021

Inflammation-type dysbiosis of the oral microbiome associates with the duration of COVID-19 symptoms and long COVID.

JCI Insight 2021 10 22;6(20). Epub 2021 Oct 22.

Department of Microbiology and Physiological Systems.

In the COVID-19 pandemic, caused by SARS-CoV-2, many individuals experience prolonged symptoms, termed long-lasting COVID-19 symptoms (long COVID). Long COVID is thought to be linked to immune dysregulation due to harmful inflammation, with the exact causes being unknown. Given the role of the microbiome in mediating inflammation, we aimed to examine the relationship between the oral microbiome and the duration of long COVID symptoms. Tongue swabs were collected from patients presenting with COVID-19 symptoms. Confirmed infections were followed until resolution of all symptoms. Bacterial composition was determined by metagenomic sequencing. We used random forest modeling to identify microbiota and clinical covariates that are associated with long COVID symptoms. Of the patients followed, 63% developed ongoing symptomatic COVID-19 and 37% went on to long COVID. Patients with prolonged symptoms had significantly higher abundances of microbiota that induced inflammation, such as members of the genera Prevotella and Veillonella, which, of note, are species that produce LPS. The oral microbiome of patients with long COVID was similar to that of patients with chronic fatigue syndrome. Altogether, our findings suggest an association with the oral microbiome and long COVID, revealing the possibility that dysfunction of the oral microbiome may have contributed to this draining disease.
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http://dx.doi.org/10.1172/jci.insight.152346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564890PMC
October 2021

The Nursing Home Older Adult Gut Microbiome Composition Shows Time-dependent Dysbiosis and Is Influenced by Medication Exposures, Age, Environment, and Frailty.

J Gerontol A Biol Sci Med Sci 2021 10;76(11):1930-1938

Program in Microbiome Dynamics, University of Massachusetts Medical School, Worcester, USA.

Older adults in nursing homes (NHs) have increased frailty, medication, and antimicrobial exposures, all factors that are known to affect the composition of gut microbiota. Our objective was to define which factors have the greatest association with the NH resident gut microbiota, explore patterns of dysbiosis and compositional changes in gut microbiota over time in this environment. We collected serial stool samples from NH residents. Residents were assessed using the Mini Nutritional Assessment tool and Clinical Frailty Scale. Bacterial composition of resident stool samples was determined by metagenomic sequencing. We used mixed-effect random forest modeling to identify clinical covariates that associate with microbiota. We enrolled and followed 166 residents from 5 NHs collecting 512 stool samples and following 15 residents for > 1 year. Medications, particularly psychoactive and antihypertensive medications, had the greatest effect on the microbiota. Age and frailty also contributed, and were associated with increased and decreased diversity, respectively. The microbiota of residents who had lived in the NH for > 1 year were enriched in inflammatory and pathogenic species and reduced in anti-inflammatory and symbiotic species. We observed intraindividual stability of the microbiome among older adults who had lived in the NH already for >1 year followed with sample collections 1 year apart. Older adult NH gut microbiome is heavily influenced by medications, age, and frailty. This microbiome is influenced by the length of NH residency with dysbiosis becoming evident at 12 months, however, after this point there is demonstrated relative stability over time.
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http://dx.doi.org/10.1093/gerona/glab167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514073PMC
October 2021

The high prevalence of among nursing home elders associates with a dysbiotic microbiome.

Gut Microbes 2021 Jan-Dec;13(1):1-15

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.

disproportionally affects the elderly living in nursing homes (NHs). Our objective was to explore the prevalence of in NH elders, over time and to determine whether the microbiome or other clinical factors are associated with colonization.We collected serial stool samples from NH residents. prevalence was determined by quantitative polymerase-chain reaction detection of Toxin genes and ; microbiome composition was determined by shotgun metagenomic sequencing. We used mixed-effect random forest modeling machine to determine bacterial taxa whose abundance is associated with prevalence while controlling for clinical covariates including demographics, medications, and past medical history.We enrolled 167 NH elders who contributed 506 stool samples. Of the 123 elders providing multiple samples, 30 (24.4%) elders yielded multiple samples in which was detected and 78 (46.7%) had at least one positive sample. Elders with positive samples were characterized by increased abundances of pathogenic or inflammatory-associated bacterial taxa and by lower abundances of taxa with anti-inflammatory or symbiotic properties. Proton pump inhibitor (PPI) use is associated with lower prevalence of (Odds Ratio 0.46; 95%CI, 0.22-0.99) and the abundance of bacterial species with known beneficial effects was higher in PPI users and markedly lower in elders with high prevalence. is prevalent among NH elders and a dysbiotic gut microbiome associates with colonization status. Manipulating the gut microbiome may prove to be a key strategy in the reduction of in the NH.
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http://dx.doi.org/10.1080/19490976.2021.1897209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007149PMC
March 2021

Associations between Diet, the Gut Microbiome, and Short-Chain Fatty Acid Production among Older Caribbean Latino Adults.

J Acad Nutr Diet 2020 12 12;120(12):2047-2060.e6. Epub 2020 Aug 12.

Background: Caribbean Latino adults have disproportionately high prevalence of chronic disease; however, underlying mechanisms are unknown. Unique gut microbiome profiles and relation to dietary quality may underlie health disparities.

Objectives: To examine the dietary quality of an underrepresented group of Caribbean Latino older adults with high prevalence of chronic disease; characterize gut microbiome profiles in this cohort; determine associations between dietary quality, gut microbiome composition, and short-chain fatty acid (SCFA) production; examine associations of clinical factors (body mass index, type 2 diabetes [T2D] status, and laxative use) with gut microbiome composition.

Design: The study design was cross-sectional.

Participants/setting: Recruitment and interviews occurred at the Senior Center in Lawrence, MA, from September 2016-September 2017. A total of 20 adults aged ≥50 years, self-identified of Caribbean Latino origin, without use of antibiotics in 6 months or intestinal surgery were included in the study.

Exposure And Outcome Measures: Diet was assessed by two, 24-hour recalls and dietary quality was calculated using the Healthy Eating Index 2015 and the Mediterranean Diet Score. The gut microbiome was assessed by 16S rRNA sequencing and fecal SCFA content. Anthropometrics (ie, weight and height) were measured by a trained interviewer, and self-reported laxative use, and other self-report health outcomes (ie, T2D status) were assessed by questionnaire.

Statistical Analyses: Faith Phylogenetic Diversity (alpha diversity) and unique fraction metric, or UniFrac (beta diversity) and nonphylogenetic metrics, including Shannon diversity index (alpha diversity) were calculated. Spearman correlations and group comparisons using Kruskal-Wallis test between alpha diversity indexes and nutrient intakes were calculated. Patterns in the microbiome were estimated using a partitioning around medoids with estimation of number of clusters, with optimum average silhouette width. Log odds were calculated to compare predefined nutrients and diet score components between microbiome clusters using multivariable logistic regression, controlling for age and sex. Pearson correlation was used to relate SCFA fecal content to individual nutrients and diet indexes. Final models were additionally adjusted for laxative use. Differences in lifestyle factors by gut microbiome cluster were tested by Fisher's exact test.

Results: Generally, there was poor alignment of participant's diets to either the Mediterranean Diet score or Healthy Eating Index 2015. Range in the Healthy Eating Index 2015 was 36 to 90, where only 5% (n=1) of the sample showed high adherence to the Dietary Guidelines for Americans. Mediterranean Diet scores suggested low conformance with a Mediterranean eating pattern (score range=2 to 8, where 45% scored ≤3 [poor adherence]). The gut microbiome separated into two clusters by difference in a single bacterial taxon: Prevotella copri (P copri) (permutational multivariate analysis of variance [PERMANOVA] R=0.576, ADONIS function P=0.001). Significantly lower P copri abundance was observed in cluster 1 compared with cluster 2 (Mann-Whitney P<0.0001). Samples in the P copri dominated cluster 2 showed significantly lower alpha diversity compared with P copri depleted cluster 1 (Shannon diversity index P=0.01). Individuals in the P copri dominated cluster showed a trend toward higher 18:3 α-linolenic fatty acid intakes (P=0.09). Percentage of energy from total fat intake was significantly, positively correlated with fecal acetate (r=0.46; P=0.04), butyrate (r=0.50; P=0.03) and propionate (r=0.52; P=0.02). Associations between dietary intake and composition of the gut microbiome were attenuated by self-report recent laxative use. Individuals with T2D exhibited a significantly greater abundance of the Enterobacteriales (P=0.01) and a trend toward lower fecal content of butyric acid compared to subjects without T2D (P=0.08). Significant beta diversity differences were observed by weight (Mantel P<0.003) and body mass index (Mantel P<0.07).

Conclusions: Two unique microbiome profiles, identified by abundance of P copri, were identified among Caribbean Latino adults. Microbiome profiles and SCFA content were associated with diet, T2D, and lifestyle. Further research is needed to determine the role of P copri and SCFA production in the risk for chronic disease and associated lifestyle predictors.
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http://dx.doi.org/10.1016/j.jand.2020.04.018DOI Listing
December 2020

Dysbiosis in a canine model of human fistulizing Crohn's disease.

Gut Microbes 2020 11 30;12(1):1785246. Epub 2020 Jul 30.

Cummings School of Veterinary Medicine, Tufts University , North Grafton, MA, USA.

Crohn's disease (CD) is a chronic immune-mediated inflammatory condition caused by the loss of mucosal tolerance toward the commensal microbiota. On average, 29.5% and 42.7% CD patients experience perianal complications at 10 and 20 y after diagnosis, respectively. Perianal CD (pCD) result in high disease burden, diminished quality of life, and elevated health-care costs. Overall pCD are predictors of poor long-term outcomes. Animal models of gut inflammation have failed to fully recapitulate the human manifestations of fistulizing CD. Here, we evaluated dogs with spontaneous canine anal furunculosis (CAF), a disease with clinical similarities to pCD, as a surrogate model for understanding the microbial contribution of human pCD pathophysiology. By comparing the gut microbiomes between dogs suffering from CAF (CAF dogs) and healthy dogs, we show CAF-dog microbiomes are either very dissimilar (dysbiotic) or similar (healthy-like), yet unique, to healthy dog's microbiomes. Compared to healthy or healthy-like CAF microbiomes, dysbiotic CAF microbiomes showed an increased abundance of and and a decreased abundance of species and . Our results mirror what have been reported in previous microbiome studies of patients with CD; particularly, CAF dogs exhibited two distinct microbiome composition: dysbiotic and healthy-like, with determinant bacterial taxa such as and that overlap what it has been found on their human counterpart. Thus, our results support the use of CAF dogs as a surrogate model to advance our understanding of microbial dynamics in pCD.
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http://dx.doi.org/10.1080/19490976.2020.1785246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524328PMC
November 2020

Anaerobic Antibiotics and the Risk of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Biol Blood Marrow Transplant 2020 11 17;26(11):2053-2060. Epub 2020 Jul 17.

Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, North Carolina. Electronic address:

Certain anaerobic bacteria are important for maintenance of gut barrier integrity and immune tolerance and may influence the risk of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a single-center retrospective cohort study of allogeneic HSCT recipients to evaluate associations between receipt of antibiotics with an anaerobic spectrum of activity and GVHD outcomes. We identified 1214 children and adults who developed febrile neutropenia between 7 days before and 28 days after HSCT and compared GVHD risk and mortality among patients who received anaerobic antibiotics (piperacillin-tazobactam or carbapenems; n = 491) to patients who received only antibiotics with minimal activity against anaerobes (aztreonam, cefepime, or ceftazidime; n = 723). We performed metagenomic sequencing of serial fecal samples from 36 pediatric patients to compare the effects of specific antibiotics on the gut metagenome. Receipt of anaerobic antibiotics was associated with higher hazards of acute gut/liver GVHD (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.03 to 1.54) and acute GVHD mortality (HR, 1.63; 95% CI, 1.08 to 2.46), but not chronic GVHD diagnosis (HR, 1.04; 95% CI: .84 to 1.28) or chronic GVHD mortality (HR, .88; 95% CI, .53 to 1.45). Anaerobic antibiotics resulted in decreased gut bacterial diversity, reduced abundances of Bifidobacteriales and Clostridiales, and loss of bacterial genes encoding butyrate biosynthesis enzymes from the gut metagenome. Acute gut/liver GVHD was preceded by a sharp decline in bacterial butyrate biosynthesis genes with antibiotic treatment. Our findings demonstrate that exposure to anaerobic antibiotics is associated with increased risks of acute gut/liver GVHD and acute GVHD mortality after allogeneic HSCT. Use of piperacillin-tazobactam or carbapenems should be reserved for febrile neutropenia cases in which anaerobic or multidrug-resistant infections are suspected.
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http://dx.doi.org/10.1016/j.bbmt.2020.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609492PMC
November 2020

Upper Gastrointestinal Perforations: A Possible Danger of Antibiotic Overuse.

J Gastrointest Surg 2020 12 16;24(12):2730-2736. Epub 2019 Dec 16.

Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Background: The role of changes in gut microflora on upper gastrointestinal (UGI) perforations is not known. We conducted a retrospective case-control study to examine the relationship between antibiotic exposure-a proxy for microbiome modulation-and UGI perforations in a national sample.

Methods: We queried a 5% random sample of Medicare (2009-2013) to identify patients ≥ 65 years old hospitalized with UGI (stomach or small intestine) perforations using International Classification of Diseases diagnosis codes. Cases with UGI perforations were matched with 4 controls, each based on age and sex. Exposure to outpatient antibiotics (0-30, 31-60, 61-90 days) prior to case patients' index hospitalization admission data was determined with Part D claims. Univariate and multivariable regression analyses were performed to evaluate the effect of antibiotic exposure on UGI perforation.

Results: Overall, 504 cases and 2016 matched controls were identified. Compared to controls, more cases had antibiotic exposure 0-30 days (19% vs. 3%, p < 0.001) and 31-60 days (5% vs. 2%, p < 0.001) prior to admission. In adjusted analyses, antibiotic exposure 0-30 days prior to admission was associated with 6.8 increased odds of an UGI perforation (95% CI 4.8, 9.8); 31-60 days was associated with 1.9 increased odds (95% CI 1.1, 3.3); and 61-90 days was associated with 3.7 increased odds (95% CI 2.0, 6.9).

Conclusions: Recent outpatient antibiotic use, in particular in the preceding 30 days, is associated with UGI perforation among Medicare beneficiaries. Exposure to antibiotics, one of the most modifiable determinants of the microbiome, should be minimized in the outpatient setting.
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http://dx.doi.org/10.1007/s11605-019-04473-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133306PMC
December 2020

Gut Colonization Preceding Mucosal Barrier Injury Bloodstream Infection in Pediatric Hematopoietic Stem Cell Transplantation Recipients.

Biol Blood Marrow Transplant 2019 11 18;25(11):2274-2280. Epub 2019 Jul 18.

Division of Pediatric Infectious Diseases, Ann & Robert H. Lurie Children's Hospital, Chicago, Illinois.

The gastrointestinal tract is the predicted reservoir for most bloodstream infections (BSIs) after hematopoietic stem cell transplantation (HSCT). Whole-genome sequencing and comparative genomics have the potential to improve our understanding of the dynamics of gut colonization that precede BSI in HSCT recipients. Within a prospective cohort study of children (age <18 years) undergoing HSCT, 9 subjects met criteria for mucosal barrier injury BSI. We performed whole-genome sequencing of the blood culture isolate and weekly fecal samples preceding the BSI to compare the genetic similarity of BSI isolates to fecal strains. We evaluated temporal associations between antibiotic exposures and the abundances of BSI strains in the gut microbiota and correlated the detection of antibiotic resistance genes with the phenotypic antibiotic resistance of these strains. The median patient age was 2.6 years, and 78% were male. BSIs were caused by Escherichia coli (n = 5), Enterococcus faecium (n = 2), Enterobacter cloacae (n = 1), and Rothia mucilaginosa (n = 1). In the 6 BSI episodes with evaluable comparative genomics, the fecal strains were identical to the blood culture isolate (>99.99% genetic similarity). Gut domination by these strains preceded only 4 of 7 E. coli or E. faecium BSIs by a median of 17 days (range, 6 to 21 days). Increasing abundances of the resulting BSI strains in the gut microbiota were frequently associated with specific antibiotic exposures. E. cloacae and R. mucilaginosa were not highly abundant in fecal samples preceding BSIs caused by these species. The detection of antibiotic resistance genes for β-lactam antibiotics and vancomycin predicted phenotypic resistance in BSI strains. Bacterial strains causing mucosal barrier injury BSI in pediatric HSCT recipients were observed in the gut microbiota before BSI onset, and changes in the abundances of these strains within the gut preceded most BSI episodes. However, frequent sampling of the gut microbiota and sampling of other ecological niches is likely necessary to effectively predict BSI in HSCT recipients.
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http://dx.doi.org/10.1016/j.bbmt.2019.07.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861666PMC
November 2019

Cognitive and Microbiome Impacts of Experimental Ancylostoma ceylanicum Hookworm Infections in Hamsters.

Sci Rep 2019 05 27;9(1):7868. Epub 2019 May 27.

Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Suite 219, Worcester, MA, 01605, USA.

Hookworms are one of the most prevalent and important parasites, infecting ~500 million people worldwide. Hookworm disease is among the leading causes of iron-deficiency anemia in the developing world and is associated with significant growth stunting and malnutrition. In humans, hookworms appear to impair memory and other forms of cognition, although definitive data are hard to come by. Here we study the impact of a human hookworm parasite, Ancylostoma ceylanicum, on cognition in hamsters in a controlled laboratory setting. We developed tests that measure long-term memory in hamsters. We find that hookworm-infected hamsters were fully capable of detecting a novel object. However, hookworm-infected hamsters were impaired in detecting a displaced object. Defects could be discerned at even at low levels of infection, whereas at higher levels of infection, hamsters were statistically unable to distinguish between displaced and non-displaced objects. These spatial memory deficiencies could not be attributed to defects in infected hamster mobility or to lack of interest. We also found that hookworm infection resulted in reproducible reductions in diversity and changes in specific taxanomic groups in the hamster gut microbiome. These data demonstrate that human hookworm infection in a laboratory mammal results in a specific, rapid, acute, and measurable deficit in spatial memory, and we speculate that gut alterations could play some role in these cognitive deficits. Our findings highlight the importance of hookworm elimination and suggest that finer tuned spatial memory studies be carried out in humans.
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http://dx.doi.org/10.1038/s41598-019-44301-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536493PMC
May 2019

Alzheimer's Disease Microbiome Is Associated with Dysregulation of the Anti-Inflammatory P-Glycoprotein Pathway.

mBio 2019 05 7;10(3). Epub 2019 May 7.

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

The microbiota-gut-brain axis is a bidirectional communication system that is poorly understood. Alzheimer's disease (AD), the most common cause of dementia, has long been associated with bacterial infections and inflammation-causing immunosenescence. Recent studies examining the intestinal microbiota of AD patients revealed that their microbiome differs from that of subjects without dementia. In this work, we prospectively enrolled 108 nursing home elders and followed each for up to 5 months, collecting longitudinal stool samples from which we performed metagenomic sequencing and T84 intestinal epithelial cell functional assays for P-glycoprotein (P-gp) expression, a critical mediator of intestinal homeostasis. Our analysis identified clinical parameters as well as numerous microbial taxa and functional genes that act as predictors of AD dementia in comparison to elders without dementia or with other dementia types. We further demonstrate that stool samples from elders with AD can induce lower P-gp expression levels those samples from elders without dementia or with other dementia types. We also paired functional studies with machine learning approaches to identify bacterial species differentiating the microbiome of AD elders from that of elders without dementia, which in turn are accurate predictors of the loss of dysregulation of the P-gp pathway. We observed that the microbiome of AD elders shows a lower proportion and prevalence of bacteria with the potential to synthesize butyrate, as well as higher abundances of taxa that are known to cause proinflammatory states. Therefore, a potential nexus between the intestinal microbiome and AD is the modulation of intestinal homeostasis by increases in inflammatory, and decreases in anti-inflammatory, microbial metabolism. Studies of the intestinal microbiome and AD have demonstrated associations with microbiome composition at the genus level among matched cohorts. We move this body of literature forward by more deeply investigating microbiome composition via metagenomics and by comparing AD patients against those without dementia and with other dementia types. We also exploit machine learning approaches that combine both metagenomic and clinical data. Finally, our functional studies using stool samples from elders demonstrate how the c microbiome of AD elders can affect intestinal health via dysregulation of the P-glycoprotein pathway. P-glycoprotein dysregulation contributes directly to inflammatory disorders of the intestine. Since AD has been long thought to be linked to chronic bacterial infections as a possible etiology, our findings therefore fill a gap in knowledge in the field of AD research by identifying a nexus between the microbiome, loss of intestinal homeostasis, and inflammation that may underlie this neurodegenerative disorder.
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http://dx.doi.org/10.1128/mBio.00632-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509190PMC
May 2019

Integration of genomic and clinical data augments surveillance of healthcare-acquired infections.

Infect Control Hosp Epidemiol 2019 06 23;40(6):649-655. Epub 2019 Apr 23.

Department of Microbiology and Physiological Systems,University of Massachusetts Medical School,Worcester,Massachusetts.

Background: Determining infectious cross-transmission events in healthcare settings involves manual surveillance of case clusters by infection control personnel, followed by strain typing of clinical/environmental isolates suspected in said clusters. Recent advances in genomic sequencing and cloud computing now allow for the rapid molecular typing of infecting isolates.

Objective: To facilitate rapid recognition of transmission clusters, we aimed to assess infection control surveillance using whole-genome sequencing (WGS) of microbial pathogens to identify cross-transmission events for epidemiologic review.

Methods: Clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, and Klebsiella pneumoniae were obtained prospectively at an academic medical center, from September 1, 2016, to September 30, 2017. Isolate genomes were sequenced, followed by single-nucleotide variant analysis; a cloud-computing platform was used for whole-genome sequence analysis and cluster identification.

Results: Most strains of the 4 studied pathogens were unrelated, and 34 potential transmission clusters were present. The characteristics of the potential clusters were complex and likely not identifiable by traditional surveillance alone. Notably, only 1 cluster had been suspected by routine manual surveillance.

Conclusions: Our work supports the assertion that integration of genomic and clinical epidemiologic data can augment infection control surveillance for both the identification of cross-transmission events and the inclusion of missed and exclusion of misidentified outbreaks (ie, false alarms). The integration of clinical data is essential to prioritize suspect clusters for investigation, and for existing infections, a timely review of both the clinical and WGS results can hold promise to reduce HAIs. A richer understanding of cross-transmission events within healthcare settings will require the expansion of current surveillance approaches.
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http://dx.doi.org/10.1017/ice.2019.75DOI Listing
June 2019

The influence of payor status on outcomes associated with surgical repair of upper gastrointestinal perforations due to peptic ulcer disease in the United States.

Am J Surg 2019 01 2;217(1):121-125. Epub 2018 Jul 2.

Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Background: An association between lack of insurance and inferior outcomes has been well described for a number of surgical emergencies, yet little is known about the relationship of payor status and outcomes of patients undergoing emergent surgical repair for upper gastrointestinal (UGI) perforations. We evaluated the association of payor status and in-hospital mortality for patients undergoing emergency surgery for UGI perforations in the United States.

Methods: Nationwide Inpatient Sample (NIS) was queried to identify patients between 18 and 64 years of age who underwent emergent (open or laparoscopic) repair for UGI perforations secondary to peptic ulcer disease (2010-2014). Primary outcome was in-hospital mortality. Secondary outcomes were major and minor postoperative complications. The main predictor outcome was insurance status (Private, Medicaid, Uninsured). Univariate and multivariable regression analyses were performed. Data were weighted to provide national estimates.

Results: 21,005 patients underwent surgical repair for UGI perforations. Patients with private insurance represented the largest payor group (47%). After adjustment of other factors, payor status was not a statistically significant predictor of in-hospital mortality (Medicaid vs. Private: [OR] 1.1; 95% [CI] 0.67-1.81; Uninsured vs. Private: OR 0.9, 95% CI 0.52-1.61). However, payor status remained a statistically significant predictor of major postoperative complications (Medicaid vs. Private [OR] 1.4; 95% CI 1.1, 1.8; Uninsured vs. Private [OR]1.2, 95% CI 0.9, 1.5) and minor postoperative complications (Medicaid vs. Private [OR] 1.4; 95% CI 1.1, 1.9; Uninsured vs. Private [OR]1.2, 95% CI 0.9, 1.6).

Conclusions: Emergency surgery for UGI perforations is associated with high mortality and morbidity across all payor classes; however, Medicaid is a predictor for both major and minor postoperative complications. Preventing perforation through preventative measures will be key to reducing the burden of peptic ulcer disease across all populations.
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http://dx.doi.org/10.1016/j.amjsurg.2018.06.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889867PMC
January 2019

Variability of indoor fungal microbiome of green and non-green low-income homes in Cincinnati, Ohio.

Sci Total Environ 2018 Jan 10;610-611:212-218. Epub 2017 Aug 10.

University of Cincinnati, Department of Environmental Health, P.O. Box 670056, Cincinnati, OH, USA. Electronic address:

"Green" housing is designed to use low-impact materials, increase energy efficiency and improve occupant health. However, little is known about the indoor mycobiome of green homes. The current study is a subset of a multicenter study that aims to investigate the indoor environment of green homes and the respiratory health of asthmatic children. In the current study, the mycobiome in air, bed dust and floor dust was compared between green (study site) and non-green (control site), low-income homes in Cincinnati, Ohio. The samples were collected at baseline (within four months following renovation), and 12months after the baseline at the study site. Parallel sample collection was conducted in non-green control homes. Air samples were collected by PM2.5 samplers over 5-days. Bed and floor dust samples were vacuumed after the air sampling was completed. The DNA sample extracts were analyzed using ITS amplicon sequencing. Analysis indicated that there was no clear trend in the fungal communities between green and non-green homes. Instead, fungal community differences were greatest between sample types - air, bed, and floor. Microbial communities also changed substantially between sampling intervals in both green and non-green homes for all sample types, potentially indicating that there was very little stability in the mycobiomes. Research gaps remain regarding how indoor mycobiome fluctuates over time. Longer follow-up periods might elucidate the effect of green renovation on microbial load in buildings.
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http://dx.doi.org/10.1016/j.scitotenv.2017.07.274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728913PMC
January 2018

Intestinal organoids model human responses to infection by commensal and Shiga toxin producing Escherichia coli.

PLoS One 2017 14;12(6):e0178966. Epub 2017 Jun 14.

Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio, United States of America.

Infection with Shiga toxin (Stx) producing Escherichia coli O157:H7 can cause the potentially fatal complication hemolytic uremic syndrome, and currently only supportive therapy is available. Lack of suitable animal models has hindered study of this disease. Induced human intestinal organoids (iHIOs), generated by in vitro differentiation of pluripotent stem cells, represent differentiated human intestinal tissue. We show that iHIOs with addition of human neutrophils can model E. coli intestinal infection and innate cellular responses. Commensal and O157:H7 introduced into the iHIO lumen replicated rapidly achieving high numbers. Commensal E. coli did not cause damage, and were completely contained within the lumen, suggesting defenses, such as mucus production, can constrain non-pathogenic strains. Some O157:H7 initially co-localized with cellular actin. Loss of actin and epithelial integrity was observed after 4 hours. O157:H7 grew as filaments, consistent with activation of the bacterial SOS stress response. SOS is induced by reactive oxygen species (ROS), and O157:H7 infection increased ROS production. Transcriptional profiling (RNAseq) demonstrated that both commensal and O157:H7 upregulated genes associated with gastrointestinal maturation, while infection with O157:H7 upregulated inflammatory responses, including interleukin 8 (IL-8). IL-8 is associated with neutrophil recruitment, and infection with O157:H7 resulted in recruitment of human neutrophils into the iHIO tissue.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0178966PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5470682PMC
September 2017

Recovery of ethanol-induced depletion ameliorates alcoholic liver disease.

Gut 2018 05 26;67(5):891-901. Epub 2017 May 26.

Department of Internal Medicine I, Gastroenterology, Endocrinology & Metabolism, Medical University Innsbruck, Innsbruck, Austria.

Objective: Alcoholic liver disease (ALD) is a global health problem with limited therapeutic options. Intestinal barrier integrity and the microbiota modulate susceptibility to ALD. , a Gram-negative intestinal commensal, promotes barrier function partly by enhancing mucus production. The aim of this study was to investigate microbial alterations in ALD and to define the impact of administration on the course of ALD.

Design: The intestinal microbiota was analysed in an unbiased approach by 16S ribosomal DNA (rDNA) sequencing in a Lieber-DeCarli ALD mouse model, and faecal abundance was determined in a cohort of patients with alcoholic steatohepatitis (ASH). The impact of on the development of experimental acute and chronic ALD was determined in a preventive and therapeutic setting, and intestinal barrier integrity was analysed.

Results: Patients with ASH exhibited a decreased abundance of faecal when compared with healthy controls that indirectly correlated with hepatic disease severity. Ethanol feeding of wild-type mice resulted in a prominent decline in abundance. Ethanol-induced intestinal depletion could be restored by oral supplementation. Furthermore, administration when performed in a preventive setting decreased hepatic injury, steatosis and neutrophil infiltration. also protected against ethanol-induced gut leakiness, enhanced mucus thickness and tight-junction expression. In already established ALD, used therapeutically ameliorated hepatic injury and neutrophil infiltration.

Conclusion: Ethanol exposure diminishes intestinal abundance in both mice and humans and can be recovered in experimental ALD by oral supplementation. promotes intestinal barrier integrity and ameliorates experimental ALD. Our data suggest that patients with ALD might benefit from supplementation.
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http://dx.doi.org/10.1136/gutjnl-2016-313432DOI Listing
May 2018

Alcohol-related changes in the intestinal microbiome influence neutrophil infiltration, inflammation and steatosis in early alcoholic hepatitis in mice.

PLoS One 2017 28;12(3):e0174544. Epub 2017 Mar 28.

Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.

Background: Alcohol-induced intestinal dysbiosis disrupts homeostatic gut-liver axis function and is essential in the development of alcoholic liver disease. Here, we investigate changes in enteric microbiome composition in a model of early alcoholic steatohepatitis and dissect the pathogenic role of intestinal microbes in alcohol-induced liver pathology.

Materials And Methods: Wild type mice received a 10-day diet that was either 5% alcohol-containing or an isocaloric control diet plus a single binge. 16S rDNA sequencing defined the bacterial communities in the cecum of alcohol- and pair-fed animals. Some mice were treated with an antibiotic cocktail prior to and throughout alcohol feeding. Liver neutrophils, cytokines and steatosis were evaluated.

Results: Acute-on-chronic alcohol administration induced shifts in various bacterial phyla in the cecum, including increased Actinobacteria and a reduction in Verrucomicrobia driven entirely by a reduction in the genus Akkermansia. Antibiotic treatment reduced the gut bacterial load and circulating bacterial wall component lipopolysaccharide (LPS). We found that bacterial load suppression prevented alcohol-related increases in the number of myeloperoxidase- (MPO) positive infiltrating neutrophils in the liver. Expression of liver mRNA tumor necrosis factor alpha (Tnfα), C-X-C motif chemokine ligand 1 (Cxcl1) and circulating protein monocyte chemoattractant protein-1 (MCP-1) were also reduced in antibiotic-treated alcohol-fed mice. Alcohol-induced hepatic steatosis measured by Oil-Red O staining was significantly reduced in antibiotic treated mice. Genes regulating lipid production and storage were also altered by alcohol and antibiotic treatment. Interestingly, antibiotic treatment did not protect from alcohol-induced increases in serum aminotransferases (ALT/AST).

Conclusions: Our data indicate that acute-on-chronic alcohol feeding alters the microflora at multiple taxonomic levels and identifies loss of Akkermansia as an early marker of alcohol-induced gut dysbiosis. We conclude that gut microbes influence liver inflammation, neutrophil infiltration and liver steatosis following alcohol consumption and these data further emphasize the role of the gut-liver axis in early alcoholic liver disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0174544PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370121PMC
August 2017

Strain-level microbial epidemiology and population genomics from shotgun metagenomics.

Nat Methods 2016 05 21;13(5):435-8. Epub 2016 Mar 21.

Centre for Integrative Biology, University of Trento, Trento, Italy.

Identifying microbial strains and characterizing their functional potential is essential for pathogen discovery, epidemiology and population genomics. We present pangenome-based phylogenomic analysis (PanPhlAn; http://segatalab.cibio.unitn.it/tools/panphlan), a tool that uses metagenomic data to achieve strain-level microbial profiling resolution. PanPhlAn recognized outbreak strains, produced the largest strain-level population genomic study of human-associated bacteria and, in combination with metatranscriptomics, profiled the transcriptional activity of strains in complex communities.
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http://dx.doi.org/10.1038/nmeth.3802DOI Listing
May 2016

Metagenomic Sequencing with Strain-Level Resolution Implicates Uropathogenic E. coli in Necrotizing Enterocolitis and Mortality in Preterm Infants.

Cell Rep 2016 Mar 17;14(12):2912-24. Epub 2016 Mar 17.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Necrotizing enterocolitis (NEC) afflicts approximately 10% of extremely preterm infants with high fatality. Inappropriate bacterial colonization with Enterobacteriaceae is implicated, but no specific pathogen has been identified. We identify uropathogenic E. coli (UPEC) colonization as a significant risk factor for the development of NEC and subsequent mortality. We describe a large-scale deep shotgun metagenomic sequence analysis of the early intestinal microbiome of 144 preterm and 22 term infants. Using a pan-genomic approach to functionally subtype the E. coli, we identify genes associated with NEC and mortality that indicate colonization by UPEC. Metagenomic multilocus sequence typing analysis further defined NEC-associated strains as sequence types often associated with urinary tract infections, including ST69, ST73, ST95, ST127, ST131, and ST144. Although other factors associated with prematurity may also contribute, this report suggests a link between UPEC and NEC and indicates that further attention to these sequence types as potential causal agents is needed.
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http://dx.doi.org/10.1016/j.celrep.2016.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819403PMC
March 2016

Prophages of the genus Bifidobacterium as modulating agents of the infant gut microbiota.

Environ Microbiol 2016 07 18;18(7):2196-213. Epub 2016 Jan 18.

Laboratory of Probiogenomics, Department of Life Sciences, University of Parma, Parma, Italy.

Phage predation is one of the key forces that shape genetic diversity in bacterial genomes. Phages are also believed to act as modulators of the microbiota composition and, consequently, as agents that drive bacterial speciation in complex bacterial communities. Very little is known about the occurrence and genetic variability of (pro)phages within the Bifidobacterium genus, a dominant bacterial group of the human infant microbiota. Here, we performed cataloguing of the predicted prophage sequences from the genomes of all currently recognized bifidobacterial type strains. We analysed their genetic diversity and deduced their evolutionary development, thereby highlighting an intriguing origin. Furthermore, we assessed infant gut microbiomes for the presence of (pro)phage sequences and found compelling evidence that these viral elements influence the composition of bifidobacterial communities in the infant gut microbiota.
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http://dx.doi.org/10.1111/1462-2920.13154DOI Listing
July 2016

Bifidobacteria exhibit social behavior through carbohydrate resource sharing in the gut.

Sci Rep 2015 Oct 28;5:15782. Epub 2015 Oct 28.

Laboratory of Probiogenomics, Department of Life Sciences, University of Parma, Italy.

Bifidobacteria are common and frequently dominant members of the gut microbiota of many animals, including mammals and insects. Carbohydrates are considered key carbon sources for the gut microbiota, imposing strong selective pressure on the complex microbial consortium of the gut. Despite its importance, the genetic traits that facilitate carbohydrate utilization by gut microbiota members are still poorly characterized. Here, genome analyses of 47 representative Bifidobacterium (sub)species revealed the genes predicted to be required for the degradation and internalization of a wide range of carbohydrates, outnumbering those found in many other gut microbiota members. The glycan-degrading abilities of bifidobacteria are believed to reflect available carbon sources in the mammalian gut. Furthermore, transcriptome profiling of bifidobacterial genomes supported the involvement of various chromosomal loci in glycan metabolism. The widespread occurrence of bifidobacterial saccharolytic features is in line with metagenomic and metatranscriptomic datasets obtained from human adult/infant faecal samples, thereby supporting the notion that bifidobacteria expand the human glycobiome. This study also underscores the hypothesis of saccharidic resource sharing among bifidobacteria through species-specific metabolic specialization and cross feeding, thereby forging trophic relationships between members of the gut microbiota.
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http://dx.doi.org/10.1038/srep15782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623478PMC
October 2015

Center Variation in Intestinal Microbiota Prior to Late-Onset Sepsis in Preterm Infants.

PLoS One 2015 25;10(6):e0130604. Epub 2015 Jun 25.

Perinatal Institute, Cincinnati Children's Hospital, Cincinnati, Ohio, United States of America.

Objective: Late onset sepsis (LOS) contributes to mortality and morbidity in preterm infants. We tested the hypotheses that microbes causing LOS originate from the gut, and that distortions in the gut microbial community increases subsequent risk of LOS.

Study Design: We examined the gut microbial community in prospectively collected stool samples from preterm infants with LOS and an equal number of age-matched controls at two sites (Cincinnati, OH and Birmingham, AL), by sequencing the bacterial 16S rDNA. We confirmed our findings in a subset of infants by whole genome shotgun sequencing, and analyzed the data using R and LEfSe.

Results: Infants with LOS in Cincinnati, as compared to controls, had less abundant Actinobacteria in the first samples after birth (median 18 days before sepsis onset), and less abundant Pseudomonadales in the last samples collected prior to LOS (median 8 days before sepsis onset). Infants with LOS in Birmingham, as compared to controls, had no differences identified in the first sample microbial communities, but Lactobacillales was less abundant in the last samples prior to LOS (median 4 days before sepsis onset). Sequencing identified detectable levels of the sepsis-causative organism in stool samples prior to disease onset for 82% of LOS cases.

Conclusions: Translocation of gut microbes may account for the majority of LOS cases. Distortions in the fecal microbiota occur prior to LOS, but the form of distortion depends on timing and site. The microbial composition of fecal samples does not predict LOS onset in a generalizable fashion.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130604PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482142PMC
April 2016

16S community profiling identifies proton pump inhibitor related differences in gastric, lung, and oropharyngeal microflora.

J Pediatr 2015 Apr 4;166(4):917-23. Epub 2015 Feb 4.

Department of Microbiology, Brigham and Women's Hospital, Boston, MA.

Objectives: To test the hypothesis that proton pump inhibitor (PPI) use results in changes in gastric microflora which, through full column reflux, results in lung and oropharyngeal microflora changes.

Study Design: We performed a prospective, cross-sectional cohort study of 116 children (57 off and 59 on PPIs) undergoing simultaneous bronchoscopy and upper endoscopy for the evaluation of chronic cough. We performed 16S sequencing on gastric, bronchoalveolar lavage, and oropharyngeal fluid. Fifty patients also underwent multichannel intraluminal impedance testing.

Results: Streptococcus was more abundant in the gastric fluid of patients taking PPIs, and there was a significant correlation with PPI dose (mg/kg/d) and abundance of gastric Streptococcus (P = .01). There was also a significant difference in the abundance of oropharyngeal Streptococcus in patients treated with PPI. Eight unique bacterial genera were found in the gastric and lung fluid but not in the oropharyngeal suggesting exchange between the 2 sites and 2 of the 8 (Lactococcus, Acinetobacter) were more abundant in patients with more full column reflux, suggesting direct aspiration. Principal component analysis revealed greater overlap between gastric and lung than oropharyngeal microflora.

Conclusions: PPI use was associated with differences in gastric, lung, and oropharyngeal microflora. Although microflora exchange can occur between all 3 sites, gastric and lung microflora are more closely related, and the mechanism of exchange between sites may be aspiration of full column reflux.
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http://dx.doi.org/10.1016/j.jpeds.2014.12.067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380592PMC
April 2015

Intestinal microbiota of preterm infants differ over time and between hospitals.

Microbiome 2014 1;2:36. Epub 2014 Oct 1.

Department Pediatrics, Perinatal Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., MLC 7009, Cincinnati, OH 45229, USA ; Department of Environmental Health, University of Cincinnati College of Medicine, 3223 Eden Ave., Cincinnati, OH 45267, USA ; Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA.

Background: Intestinal microbiota are implicated in risk of necrotizing enterocolitis (NEC) and sepsis, major diseases of preterm infants in neonatal intensive care units (NICUs). Rates of these diseases vary over time and between NICUs, but time and NICU comparisons of the intestinal microbiota of preterm infants are lacking.

Methods: We included 66 singleton infants <29 weeks gestational age with stool samples collected between postnatal days 3 to 21 of life who survived free of NEC and sepsis. Infants were enrolled during 2010 and 2011. Twenty-six infants were enrolled at hospital 1 in Cincinnati, OH, and 40 infants were enrolled at hospital 2 in Birmingham, AL. Samples collected from days 3-9 ("week 1") and days 10-16 ("week 2") were compared between years and hospitals. Microbial succession was compared between hospitals in 28 infants with samples from the first 3 weeks of life. DNA extracted from stool was used to sequence the 16S rRNA gene by Illumina MiSeq using universal primers. Resulting operational taxonomic unit tables were analyzed for differences between years and hospitals using linear discriminant analysis effect size algorithm (LEfSe; significance, p < 0.05).

Results: Significant variation was observed in infant microbiota by year and hospital. Among hospital 1 infants, week 1 samples had more phylum Firmicutes (class Bacilli, families Clostridiaceae and Enterococcaceae) in 2010 and more phylum Proteobacteria (family Enterobacteriaceae) in 2011; week 2 samples did not significantly vary over time. However, among hospital 2 infants, the week 1 shift was nearly opposite, with more Proteobacteria (Enterobacteriaceae) in 2010 and more Firmicutes (Bacilli) in 2011; week 2 samples exhibited the same pattern. Regression analysis of clinical covariates found that antibiotic use had an important influence but did not explain these observed shifts in microbiota over time and between hospitals. Microbial succession also differed by hospital, with greater change in microbiota in hospital 1 than hospital 2 infants (p < 0.01, Jaccard distance).

Conclusion: Colonizing microbiota differ over time and between NICUs in ways that could be relevant to disease. Multi-site, longitudinal studies are needed to reliably define the impact of intestinal microbiota on adverse outcomes of preterm infants.
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http://dx.doi.org/10.1186/2049-2618-2-36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203463PMC
October 2014

Draft genome sequences of six enterohepatic helicobacter species isolated from humans and one from rhesus macaques.

Genome Announc 2014 Sep 11;2(5). Epub 2014 Sep 11.

Draft genome sequences of seven enterohepatic Helicobacter species, H. bilis, H. canadensis, H. canis, H. cinaedi, H. winghamensis, H. pullorum, and H. macacae, are presented. These isolates were obtained from clinical patients and a nonhuman primate. Due to potential zoonotic risks, we characterized antibiotic resistance markers and Helicobacter virulence factors.
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http://dx.doi.org/10.1128/genomeA.00857-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161742PMC
September 2014

16S rRNA gene survey of microbial communities in Winogradsky columns.

PLoS One 2014 7;9(8):e104134. Epub 2014 Aug 7.

Department of Biology, Vassar College, Poughkeepsie, New York, United States of America.

A Winogradsky column is a clear glass or plastic column filled with enriched sediment. Over time, microbial communities in the sediment grow in a stratified ecosystem with an oxic top layer and anoxic sub-surface layers. Winogradsky columns have been used extensively to demonstrate microbial nutrient cycling and metabolic diversity in undergraduate microbiology labs. In this study, we used high-throughput 16s rRNA gene sequencing to investigate the microbial diversity of Winogradsky columns. Specifically, we tested the impact of sediment source, supplemental cellulose source, and depth within the column, on microbial community structure. We found that the Winogradsky columns were highly diverse communities but are dominated by three phyla: Proteobacteria, Bacteroidetes, and Firmicutes. The community is structured by a founding population dependent on the source of sediment used to prepare the columns and is differentiated by depth within the column. Numerous biomarkers were identified distinguishing sample depth, including Cyanobacteria, Alphaproteobacteria, and Betaproteobacteria as biomarkers of the soil-water interface, and Clostridia as a biomarker of the deepest depth. Supplemental cellulose source impacted community structure but less strongly than depth and sediment source. In columns dominated by Firmicutes, the family Peptococcaceae was the most abundant sulfate reducer, while in columns abundant in Proteobacteria, several Deltaproteobacteria families, including Desulfobacteraceae, were found, showing that different taxonomic groups carry out sulfur cycling in different columns. This study brings this historical method for enrichment culture of chemolithotrophs and other soil bacteria into the modern era of microbiology and demonstrates the potential of the Winogradsky column as a model system for investigating the effect of environmental variables on soil microbial communities.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104134PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125166PMC
April 2015

Standardized metadata for human pathogen/vector genomic sequences.

PLoS One 2014 17;9(6):e99979. Epub 2014 Jun 17.

Broad Institute, Cambridge, Massachusetts, United States of America.

High throughput sequencing has accelerated the determination of genome sequences for thousands of human infectious disease pathogens and dozens of their vectors. The scale and scope of these data are enabling genotype-phenotype association studies to identify genetic determinants of pathogen virulence and drug/insecticide resistance, and phylogenetic studies to track the origin and spread of disease outbreaks. To maximize the utility of genomic sequences for these purposes, it is essential that metadata about the pathogen/vector isolate characteristics be collected and made available in organized, clear, and consistent formats. Here we report the development of the GSCID/BRC Project and Sample Application Standard, developed by representatives of the Genome Sequencing Centers for Infectious Diseases (GSCIDs), the Bioinformatics Resource Centers (BRCs) for Infectious Diseases, and the U.S. National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), informed by interactions with numerous collaborating scientists. It includes mapping to terms from other data standards initiatives, including the Genomic Standards Consortium's minimal information (MIxS) and NCBI's BioSample/BioProjects checklists and the Ontology for Biomedical Investigations (OBI). The standard includes data fields about characteristics of the organism or environmental source of the specimen, spatial-temporal information about the specimen isolation event, phenotypic characteristics of the pathogen/vector isolated, and project leadership and support. By modeling metadata fields into an ontology-based semantic framework and reusing existing ontologies and minimum information checklists, the application standard can be extended to support additional project-specific data fields and integrated with other data represented with comparable standards. The use of this metadata standard by all ongoing and future GSCID sequencing projects will provide a consistent representation of these data in the BRC resources and other repositories that leverage these data, allowing investigators to identify relevant genomic sequences and perform comparative genomics analyses that are both statistically meaningful and biologically relevant.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099979PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061050PMC
February 2015

Draft genome sequences of the altered schaedler flora, a defined bacterial community from gnotobiotic mice.

Genome Announc 2014 Apr 10;2(2). Epub 2014 Apr 10.

Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.

The altered Schaedler flora (ASF) is a bacterial community that supports normal growth and development of gnotobiotic mice. We report here the draft genome sequences of the 8 bacteria that comprise the ASF.
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http://dx.doi.org/10.1128/genomeA.00287-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983311PMC
April 2014
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