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Cuts Both Ways: Proteases Modulate Virulence of Enterohemorrhagic .
Palmer LD, Skaar EP
(2019) MBio 10:
MeSH Terms: Enterohemorrhagic Escherichia coli, Escherichia coli Proteins, Humans, Microbiota, Peptide Hydrolases, Virulence
Show Abstract · Added April 2, 2019
Enterohemorrhagic (EHEC) is a major cause of foodborne gastrointestinal illness. EHEC uses a specialized type III secretion system (T3SS) to form attaching and effacing lesions in the colonic epithelium and outcompete commensal gut microbiota to cause disease. A recent report in (E. A. Cameron, M. M. Curtis, A. Kumar, G. M. Dunny, et al., mBio 9:e02204-18, 2018, https://doi.org/10.1128/mBio.02204-18) describes a new role for gut commensals in potentiating disease caused by EHEC. Proteases produced by EHEC and the prevalent human commensal cleave proteins in the EHEC T3SS translocon that modulate T3SS function. protease activity promotes translocation of bacterial effectors required for lesion formation. These results describe a new role for the microbiota in gastrointestinal disease that could uncover future treatments to prevent the spread of gastroenteritis.
Copyright © 2019 Palmer and Skaar.
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Distinct mucosal microbial communities in infants with surgical necrotizing enterocolitis correlate with age and antibiotic exposure.
Romano-Keeler J, Shilts MH, Tovchigrechko A, Wang C, Brucker RM, Moore DJ, Fonnesbeck C, Meng S, Correa H, Lovvorn HN, Tang YW, Hooper L, Bordenstein SR, Das SR, Weitkamp JH
(2018) PLoS One 13: e0206366
MeSH Terms: Age Factors, Anti-Bacterial Agents, Biodiversity, Enterocolitis, Necrotizing, Female, Humans, Infant, Infant, Newborn, Intestinal Mucosa, Male, Microbiota, Pregnancy
Show Abstract · Added October 27, 2018
OBJECTIVE - Necrotizing enterocolitis (NEC) is the most common surgical emergency in preterm infants, and pathogenesis associates with changes in the fecal microbiome. As fecal samples incompletely represent microbial communities in intestinal mucosa, we sought to determine the NEC tissue-specific microbiome and assess its contribution to pathogenesis.
DESIGN - We amplified and sequenced the V1-V3 hypervariable region of the bacterial 16S rRNA gene extracted from intestinal tissue and corresponding fecal samples from 12 surgical patients with NEC and 14 surgical patients without NEC. Low quality and non-bacterial sequences were removed, and taxonomic assignment was made with the Ribosomal Database Project. Operational taxonomic units were clustered at 97%. We tested for differences between NEC and non-NEC samples in microbiome alpha- and beta-diversity and differential abundance of specific taxa between NEC and non-NEC samples. Additional analyses were performed to assess the contribution of other demographic and environmental confounding factors on the infant tissue and fecal microbiome.
RESULTS - The fecal and tissue microbial communities were different. NEC was associated with a distinct microbiome, which was characterized by low diversity, higher abundances of Staphylococcus and Clostridium_sensu_stricto, and lower abundances of Actinomyces and Corynebacterium. Infant age and vancomycin exposure correlated with shifts in the tissue microbiome.
CONCLUSION - The observed low diversity in NEC tissues suggests that NEC is associated with a bacterial bloom and a distinct mucosal bacterial community. The exact bacterial species that constitute the bloom varied by infant and were strongly influenced by age and exposure to vancomycin.
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12 MeSH Terms
Interpreting heterogeneity in intestinal tuft cell structure and function.
Banerjee A, McKinley ET, von Moltke J, Coffey RJ, Lau KS
(2018) J Clin Invest 128: 1711-1719
MeSH Terms: Animals, Goblet Cells, Humans, Immunity, Intestinal Mucosa, Microbiota, Microvilli
Show Abstract · Added October 16, 2018
Intestinal tuft cells are a morphologically unique cell type, best characterized by striking microvilli that form an apical tuft. These cells represent approximately 0.5% of gut epithelial cells depending on location. While they are known to express chemosensory receptors, their function has remained unclear. Recently, numerous groups have revealed startling insights into intestinal tuft cell biology. Here, we review the latest developments in understanding this peculiar cell type's structure and function. Recent advances in volumetric microscopy have begun to elucidate tuft cell ultrastructure with respect to its cellular neighbors. Moreover, single-cell approaches have revealed greater diversity in the tuft cell population than previously appreciated and uncovered novel markers to characterize this heterogeneity. Finally, advanced model systems have revealed tuft cells' roles in mucosal healing and orchestrating type 2 immunity against eukaryotic infection. While much remains unknown about intestinal tuft cells, these critical advances have illuminated the physiological importance of these previously understudied cells and provided experimentally tractable tools to interrogate this rare cell population. Tuft cells act as luminal sensors, linking the luminal microbiome to the host immune system, which may make them a potent clinical target for modulating host response to a variety of acute or chronic immune-driven conditions.
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7 MeSH Terms
Nasopharyngeal Lactobacillus is associated with a reduced risk of childhood wheezing illnesses following acute respiratory syncytial virus infection in infancy.
Rosas-Salazar C, Shilts MH, Tovchigrechko A, Schobel S, Chappell JD, Larkin EK, Gebretsadik T, Halpin RA, Nelson KE, Moore ML, Anderson LJ, Peebles RS, Das SR, Hartert TV
(2018) J Allergy Clin Immunol 142: 1447-1456.e9
MeSH Terms: Acute Disease, Child, Preschool, Cohort Studies, Female, Humans, Infant, Lactobacillus, Male, Microbiota, Nasopharynx, RNA, Ribosomal, 16S, Respiratory Sounds, Respiratory Syncytial Virus Infections, Risk
Show Abstract · Added March 14, 2018
BACKGROUND - Early life acute respiratory infection (ARI) with respiratory syncytial virus (RSV) has been strongly associated with the development of childhood wheezing illnesses, but the pathways underlying this association are poorly understood.
OBJECTIVE - To examine the role of the nasopharyngeal microbiome in the development of childhood wheezing illnesses following RSV ARI in infancy.
METHODS - We conducted a nested cohort study of 118 previously healthy, term infants with confirmed RSV ARI by RT-PCR. We used next-generation sequencing of the V4 region of the 16S ribosomal RNA gene to characterize the nasopharyngeal microbiome during RSV ARI. Our main outcome of interest was 2-year subsequent wheeze.
RESULTS - Of the 118 infants, 113 (95.8%) had 2-year outcome data. Of these, 46 (40.7%) had parental report of subsequent wheeze. There was no association between the overall taxonomic composition, diversity, and richness of the nasopharyngeal microbiome during RSV ARI with the development of subsequent wheeze. However, the nasopharyngeal detection and abundance of Lactobacillus was consistently higher in infants who did not develop this outcome. Lactobacillus also ranked first among the different genera in a model distinguishing infants with and without subsequent wheeze.
CONCLUSIONS - The nasopharyngeal detection and increased abundance of Lactobacillus during RSV ARI in infancy are associated with a reduced risk of childhood wheezing illnesses at age 2 years.
Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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14 MeSH Terms
Power and sample size calculations for high-throughput sequencing-based experiments.
Li CI, Samuels DC, Zhao YY, Shyr Y, Guo Y
(2018) Brief Bioinform 19: 1247-1255
MeSH Terms: Chromatin Immunoprecipitation, Genome-Wide Association Study, Heterozygote, High-Throughput Nucleotide Sequencing, Humans, Microbiota, Mutation, Poisson Distribution, Sequence Analysis, RNA
Show Abstract · Added April 3, 2018
Power/sample size (power) analysis estimates the likelihood of successfully finding the statistical significance in a data set. There has been a growing recognition of the importance of power analysis in the proper design of experiments. Power analysis is complex, yet necessary for the success of large studies. It is important to design a study that produces statistically accurate and reliable results. Power computation methods have been well established for both microarray-based gene expression studies and genotyping microarray-based genome-wide association studies. High-throughput sequencing (HTS) has greatly enhanced our ability to conduct biomedical studies at the highest possible resolution (per nucleotide). However, the complexity of power computations is much greater for sequencing data than for the simpler genotyping array data. Research on methods of power computations for HTS-based studies has been recently conducted but is not yet well known or widely used. In this article, we describe the power computation methods that are currently available for a range of HTS-based studies, including DNA sequencing, RNA-sequencing, microbiome sequencing and chromatin immunoprecipitation sequencing. Most importantly, we review the methods of power analysis for several types of sequencing data and guide the reader to the relevant methods for each data type.
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9 MeSH Terms
Association of oral microbiome with type 2 diabetes risk.
Long J, Cai Q, Steinwandel M, Hargreaves MK, Bordenstein SR, Blot WJ, Zheng W, Shu XO
(2017) J Periodontal Res 52: 636-643
MeSH Terms: Actinobacteria, Actinomyces, Adult, Aged, Bifidobacterium, Case-Control Studies, Corynebacterium, Diabetes Mellitus, Type 2, Female, High-Throughput Nucleotide Sequencing, Humans, Male, Microbiota, Middle Aged, Mouth, Obesity, RNA, Ribosomal, 16S, Risk Factors
Show Abstract · Added April 10, 2018
BACKGROUND AND OBJECTIVE - The oral microbiome may help to maintain systemic health, including how it affects blood glucose levels; however, direct evidence linking the oral microbiome with diabetes is lacking.
MATERIAL AND METHODS - We compared the oral microbiome profiles of 98 participants with incident diabetes, 99 obese non-diabetics and 97 normal weight non-diabetics, via deep sequencing of the 16S rRNA gene.
RESULTS - We found that the phylum Actinobacteria was present significantly less abundant among patients with diabetes than among the controls (p = 3.9 × 10 ); the odds ratio (OR) and 95% confidence interval (CI) was 0.27 (0.11-0.66) for those individuals who had relative abundance higher than the median value. Within this phylum, five families and seven genera were observed, and most of them were less abundant among patients with diabetes. Notably, genera Actinomyces and Atopobium were associated with 66% and 72% decreased risk of diabetes with p-values of 8.9 × 10 and 7.4 × 10 , respectively. Stratified analyses by race showed that most taxa in this phylum were associated with diabetes in both black and white participants. This phylum was also less abundant among non-diabetic obese subjects compared to normal weight individuals, particularly genera Mobiluncus, Corynebacterium and Bifidobacterium, which showed p < 0.05.
CONCLUSION - Our study revealed that multiple bacteria taxa in the phylum Actinobacteria are associated with the risk of type 2 diabetes. Some are also associated with the prevalence of obesity, suggesting that the oral microbiome may play an important role in diabetes etiology.
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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The human intestinal microbiota of constipated-predominant irritable bowel syndrome patients exhibits anti-inflammatory properties.
Gobert AP, Sagrestani G, Delmas E, Wilson KT, Verriere TG, Dapoigny M, Del'homme C, Bernalier-Donadille A
(2016) Sci Rep 6: 39399
MeSH Terms: Animals, Anti-Inflammatory Agents, Colitis, Cytokines, Dextran Sulfate, Dysbiosis, Gastrointestinal Microbiome, Humans, Inflammation, Intestines, Irritable Bowel Syndrome, Mice, Mice, Inbred C57BL, Microbiota, Rats
Show Abstract · Added December 17, 2016
The intestinal microbiota of patients with constipated-predominant irritable bowel syndrome (C-IBS) displays chronic dysbiosis. Our aim was to determine whether this microbial imbalance instigates perturbation of the host intestinal mucosal immune response, using a model of human microbiota-associated rats (HMAR) and dextran sulfate sodium (DSS)-induced experimental colitis. The analysis of the microbiota composition revealed a decrease of the relative abundance of Bacteroides, Roseburia-Eubacterium rectale and Bifidobacterium and an increase of Enterobacteriaceae, Desulfovibrio sp., and mainly Akkermansia muciniphila in C-IBS patients compared to healthy individuals. The bacterial diversity of the gut microbiota of healthy individuals or C-IBS patients was maintained in corresponding HMAR. Animals harboring a C-IBS microbiota had reduced DSS colitis with a decreased expression of pro-inflammatory cytokines from innate, Th1, and Th17 responses. The pre-treatment of conventional C57BL/6 mice or HMAR with A. muciniphila, but not with Escherichia coli, prior exposure to DSS also resulted in a reduction of colitis severity, highlighting that the anti-inflammatory effect of the gut microbiota of C-IBS patients is mediated, in part, by A. muciniphila. This work highlights a novel aspect of the crosstalk between the gut microbiota of C-IBS patients and host intestinal homeostasis.
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15 MeSH Terms
Differences in the Nasopharyngeal Microbiome During Acute Respiratory Tract Infection With Human Rhinovirus and Respiratory Syncytial Virus in Infancy.
Rosas-Salazar C, Shilts MH, Tovchigrechko A, Schobel S, Chappell JD, Larkin EK, Shankar J, Yooseph S, Nelson KE, Halpin RA, Moore ML, Anderson LJ, Peebles RS, Das SR, Hartert TV
(2016) J Infect Dis 214: 1924-1928
MeSH Terms: Bacteria, DNA, Ribosomal, Female, Humans, Infant, Male, Microbiota, Nasopharynx, Picornaviridae Infections, Prospective Studies, RNA, Ribosomal, 16S, Respiratory Syncytial Virus Infections, Respiratory Tract Infections, Sequence Analysis, DNA
Show Abstract · Added March 14, 2018
Respiratory viruses alter the nasopharyngeal microbiome and may be associated with a distinct microbial signature. To test this hypothesis, we compared the nasopharyngeal microbiome of 135 previously healthy infants with acute respiratory infection due to human rhinovirus (HRV; n = 52) or respiratory syncytial virus (RSV; n = 83). The nasopharyngeal microbiome was assessed by sequencing the V4 region of the 16S ribosomal RNA. Respiratory viruses were identified by quantitative reverse-transcription polymerase chain reaction. We found significant differences in the overall taxonomic composition and abundance of certain bacterial genera between infants infected with HRV and those infected with RSV. Our results suggest that respiratory tract viral infections are associated with different nasopharyngeal microbial profiles.
© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
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14 MeSH Terms
Neither vaginal nor buccal administration of 800 μg misoprostol alters mucosal and systemic immune activation or the cervicovaginal microbiome: a pilot study.
Kalams SA, Rogers LM, Smith RM, Barnett L, Crumbo K, Sumner S, Prashad N, Rybczyk K, Milne G, Dowd SE, Chong E, Winikoff B, Aronoff DM
(2016) Eur J Contracept Reprod Health Care 21: 436-442
MeSH Terms: Abortifacient Agents, Nonsteroidal, Administration, Buccal, Administration, Intravaginal, Cervix Uteri, Cross-Over Studies, Elafin, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immune System, Lymphocytes, Microbiota, Misoprostol, Pilot Projects, United States, Vagina
Show Abstract · Added June 2, 2017
OBJECTIVES - The aim of the study was to assess the extent to which misoprostol alters mucosal or systemic immune responses following either buccal or vaginal administration.
METHODS - This was a prospective, crossover pilot study of 15 healthy, reproductive-age women. Women first received 800 μg misoprostol either via buccal or vaginal administration and were crossed over 1 month later to receive the drug via the other route. Cervicovaginal lavage samples, cervical Cytobrush samples, cervicovaginal swabs, urine and blood were obtained immediately prior to drug administration and the following day. Parameters assessed included urine and cervicovaginal misoprostol levels, whole blood cytokine responses (by ELISA) to immune stimulation with lipopolysaccharide, peripheral blood and cervical lymphocyte phenotyping by flow cytometry, cervicovaginal antimicrobial peptide measurement by ELISA and vaginal microbial ecology assessment by 16S rRNA sequencing.
RESULTS - Neither buccal nor vaginal misoprostol significantly altered local or systemic immune and microbiological parameters.
CONCLUSION - In this pilot study, we did not observe significant alteration of mucosal or systemic immunology or vaginal microbial ecology 1 day after drug administration following either the buccal or vaginal route.
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16 MeSH Terms
The Role of the Microbiome in Gastrointestinal Cancer.
Wroblewski LE, Peek RM, Coburn LA
(2016) Gastroenterol Clin North Am 45: 543-56
MeSH Terms: Adenocarcinoma, Animals, Carcinogenesis, Cell Proliferation, Colonic Polyps, Colorectal Neoplasms, Diet, Disease Models, Animal, Esophageal Neoplasms, Gastrointestinal Microbiome, Gastrointestinal Neoplasms, Gastrointestinal Tract, Helicobacter Infections, Helicobacter pylori, Humans, Inflammation, Microbiota, Stem Cells, Stomach Neoplasms
Show Abstract · Added April 6, 2017
Humans are host to complex microbial communities previously termed normal flora and largely overlooked. However, resident microbes contribute to both health and disease. Investigators are beginning to define microbes that contribute to the development of gastrointestinal malignancies and the mechanisms by which this occurs. Resident microbes can induce inflammation, leading to cell proliferation and altered stem cell dynamics, which can lead to alterations in DNA integrity and immune regulation and promote carcinogenesis. Studies in human patients and rodent models of cancer have identified alterations in the microbiota of the stomach, esophagus, and colon that increase the risk for malignancy.
Published by Elsevier Inc.
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19 MeSH Terms