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Bibliography on: Microbiome

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ESP: PubMed Auto Bibliography 23 May 2019 at 01:43 Created: 

Microbiome

It has long been known that every multicellular organism coexists with large prokaryotic ecosystems — microbiomes — that completely cover its surfaces, external and internal. Recent studies have shown that these associated microbiomes are not mere contamination, but instead have profound effects upon the function and fitness of the multicellular organism. We now know that all MCEs are actually functional composites, holobionts, composed of more prokaryotic cells than eukaryotic cells and expressing more prokaryotic genes than eukaryotic genes. A full understanding of the biology of "individual" eukaryotes will now depend on an understanding of their associated microbiomes.

Created with PubMed® Query: microbiome[tiab] NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

RevDate: 2019-05-22

Shi X, Shao C, Luo C, et al (2019)

Microfluidics-Based Enrichment and Whole-Genome Amplification Enable Strain-Level Resolution for Airway Metagenomics.

mSystems, 4(4): pii:4/4/e00198-19.

Dysbiosis of airway microbiomes has been found in various respiratory diseases, but its molecular details in terms of taxonomic profile, metabolic characteristics, defensive function, and inhabit adaption are far from clear. Shotgun metagenome sequencing provides detailed information for microbes, whereas its application is rather limited in airways due to host DNA contaminants that overwhelm a minute amount of microbial content. Here, we describe a microfluidics-based enrichment device and an emulsion-based whole-genome amplification procedure (MEEA) for the preparation of DNA from sputa for shotgun sequencing in a metagenomics study. The two protocols coupled in MEEA are first separately assayed with mock samples and are both promising in efficiency and bias. The efficiency and consistency of MEEA are further evaluated in six clinical sputum samples against direct sequencing without enrichment, and MEEA enables 2 to 14 times enrichment for microbial reads, which take 14.68% to 33.52% of total reads. The dominant pathogens detected in MEEA are in excellent agreement with those from clinical etiological tests. Meanwhile, MEEA presents much more microbiome complexity and genome information at a strain level than direct sequencing, exhibiting high sensitivity for identifying prophages and DNA viruses. MEEA provides better microbiome profiling than direct sequencing without a preference for specific microorganisms. The more detailed functional and taxonomic characterization of their species constituents, including both bacterium and virus, facilitates metagenomics studies on the pathogenesis of respiratory microbiomes.IMPORTANCE The airway microbial community, which takes important pathogenic roles for respiratory diseases, is far from clear in terms of taxonomy and gene functions. One of the critical reasons is the heavy contamination of host cell/DNA in airway samples, which hinders the subsequent sequencing of the whole genomic contents of the microbial community-the metagenome. Here, we describe a protocol for airway sample preparation which couples a microbe enrichment microfluidic device and a DNA amplification method performed in numerous droplets. When evaluated with mock and clinical sputum samples, the microfluidics-based enrichment device and emulsion-based whole-genome amplification (MEEA) procedure efficiently removes host cells, amplifies the microbial genome, and shows no obvious bias among microbes. The efficiency of MEEA makes it a promising method in research of respiratory microbial communities and their roles in diseases.

RevDate: 2019-05-22

Amato KR (2019)

Missing Links: the Role of Primates in Understanding the Human Microbiome.

mSystems, 4(3): pii:4/3/e00165-19.

The gut microbiome can influence host energy balances and metabolic programming. While this information is valuable in a disease context, it also has important implications for understanding host energetics from an ecological and evolutionary perspective. Here I argue that gut microbial influences on host life history-the timing of events that make up an organism's life-are an overlooked but robust area of study given that variation in life history is linked directly to host energetic budgets and allocation patterns. Additionally, while cultural influences on life history complicate the exploration of these links in humans, nonhuman primates represent an alternative system in which more robust associations can be made. By integrating human and nonhuman primate microbiome research within the context of life history theory, we will be able to more effectively pinpoint microbial contributions to host phenotypes. This information will improve our understanding of host-microbe interactions in health and disease and will transform the fields of ecology and evolution more generally.

RevDate: 2019-05-22

Kleiner M (2019)

Metaproteomics: Much More than Measuring Gene Expression in Microbial Communities.

mSystems, 4(3): pii:4/3/e00115-19.

Metaproteomics is the large-scale identification and quantification of proteins from microbial communities and thus provides direct insight into the phenotypes of microorganisms on the molecular level. Initially, metaproteomics was mainly used to assess the "expressed" metabolism and physiology of microbial community members. However, recently developed metaproteomic tools allow quantification of per-species biomass to determine community structure, in situ carbon sources of community members, and the uptake of labeled substrates by community members. In this perspective, I provide a brief overview of the questions that we can currently address, as well as new metaproteomics-based approaches that we and others are developing to address even more questions in the study of microbial communities and plant and animal microbiota. I also highlight some areas and technologies where I anticipate developments and potentially major breakthroughs in the next 5 years and beyond.

RevDate: 2019-05-22

Nagai K, Tokita KI, Ono H, et al (2019)

Hindgut Bacterial Flora Analysis in Oriental Honey Buzzard (Pernis ptilorhynchus).

Zoological science, 36(1):77-81.

The intestinal microbiome is known to affect host health through various effects on nutrition and immunity. The oriental honey buzzard (OHB) is a raptor that feeds on bees and wasps. Due to its restricted diet, we reasoned that the OHB may have a unique microbiome. The aim of this study was to characterize the structure of the intestinal flora of oriental honey buzzards and to investigate the difference of intestinal bacterial flora between individuals in the wild and those reared in captivity. We investigated the intestinal microbiome of seven wild buzzards (Wild), one zoo-reared (Zoo), and one individual reared in captivity for one month (Rearing). Average operational taxonomic units in Wild and Rearing were 69.4 and 113, respectively. Diversity indices such as ACE, Chao 1, Shannon, and Alpha were significantly lower in the Wild than in the Rearing samples. These results suggest that the variety of Wild microbiome is remarkably low. At the phylum level, the composition of the microbiome was similar in all three groups, with firmicutes and bacteroidetes predominating. The third most abundant bacterium in Wild was Proteobacteria, whereas it was Actinobacteria in Rearing and unclassified bacteria in Zoo. Thus, microbiome composition is affected even with just one month of human rearing.

RevDate: 2019-05-22

Holman DB, KE Gzyl (2019)

A meta-analysis of the bovine gastrointestinal tract microbiota.

FEMS microbiology ecology pii:5497297 [Epub ahead of print].

The bovine gastrointestinal (GI) tract microbiota has important influences on animal health and production. Presently, a large number of studies have used high-throughput sequencing of the archaeal and bacteria 16S rRNA gene to characterize these microbiota under various experimental parameters. By aggregating publically available archaeal and bacterial 16S rRNA gene datasets from 53 studies we were able to determine taxa that are common to nearly all microbiota samples from the bovine GI tract as well as taxa that are strongly linked to either the rumen or feces. The methanogenic genera Methanobrevibacter and Methanosphaera were identified in nearly all fecal and rumen samples (> 99.1%), as were the bacterial genera Prevotella and Ruminococcus (≥ 92.9%). Bacterial genera such as Alistipes, Bacteroides, Clostridium, Faecalibacterium, and Escherichia/Shigella were associated with feces and Fibrobacter, Prevotella, Ruminococcus, and Succiniclasticum with the rumen. As expected, individual study strongly affected the bacterial community structure, however, fecal and rumen samples did appear separated from each other. This meta-analysis provides the first comparison of high-throughput sequencing 16S rRNA gene datasets generated from the bovine GI tract by multiple studies and may serve as a foundation for improving future microbial community research with cattle.

RevDate: 2019-05-22

Ma A, Sun M, McDermaid A, et al (2019)

MetaQUBIC: a computational pipeline for gene-level functional profiling of metagenome and metatranscriptome.

Bioinformatics (Oxford, England) pii:5497255 [Epub ahead of print].

MOTIVATION: Metagenomic and metatranscriptomic analyses can provide an abundance of information related to microbial communities. However, straightforward analysis of this data does not provide optimal results, with a required integration of data types being needed to thoroughly investigate these microbiomes and their environmental interactions.

RESULTS: Here, we present MetaQUBIC, an integrated biclustering-based computational pipeline for gene module detection that integrates both metagenomic and metatranscriptomic data. Additionally, we used this pipeline to investigate 735 paired DNA and RNA human gut microbiome samples, resulting in a comprehensive hybrid gene expression matrix of 2.3 million cross-species genes in the 735 human faecal samples and 155 functional enriched gene modules. We believe both the MetaQUBIC pipeline and the generated comprehensive human gut hybrid expression matrix will facilitate further investigations into multiple levels of microbiome studies.

AVAILABILITY: The package is freely available at https://github.com/OSU-BMBL/metaqubic.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RevDate: 2019-05-22

Revolinski SL, LS Munoz-Price (2019)

Clostridioides difficile in transplant patients: early diagnosis, treatment, and prevention.

Current opinion in infectious diseases [Epub ahead of print].

PURPOSE OF REVIEW: Clostridioides difficile infection is common in solid organ transplant and hematopoietic stem-cell transplant recipients and is associated with significant morbidity and mortality. These populations are also underrepresented in clinical trials, making optimal management difficult. Because of this, management of these populations follows national guideline recommendations. This review aims to summarize the recent relevant literature pertaining to the clinical management of C. difficile infection in transplant patients, with a particular focus on diagnosis, treatment, and prevention.

RECENT FINDINGS: Early diagnosis of C. difficile colonization may mitigate both horizontal and vertical transmission (progression from colonization to colitis) of infection. Once diagnosed, recent literature suggests antibiotic treatment should align with that recommended by national guidelines. Fecal microbiota transplant is an emerging therapy for recurrent C. difficile infection, and recent data have demonstrated safety and efficacy. Prevention strategies including antimicrobial stewardship, probiotic administration, antibiotic administration, and bezlotoxumab may be beneficial in transplant populations, but more data are needed to confirm recent findings.

SUMMARY: Studies evaluating C. difficile infection in transplant patients are only recently starting to emerge. Further research is needed to identify optimal treatment and prevention strategies, and to examine novel strategies such as microbiome manipulation.

RevDate: 2019-05-22

Hsu PI, Pan CY, Kao JY, et al (2019)

Short-term and long-term impacts of Helicobacter pylori eradication with reverse hybrid therapy on the gut microbiota.

Journal of gastroenterology and hepatology [Epub ahead of print].

BACKGROUND AND AIMS: Anti-H. pylori therapy may lead to the growth of pathogenic or antibiotic-resistant bacteria in the gut. The study aimed to investigate the short-term and long-term impacts of H. pylori eradication with reverse hybrid therapy on the components and macrolide resistance of the gut microbiota.

METHODS: H. pylori-related gastritis patients were administered a 14-day reverse hybrid therapy. Fecal samples were collected before treatment and at the end of week 2, week 8, and week 48. The V3-V4 region of the bacterial 16S rRNA gene in fecal specimens was amplified by polymerase chain reaction and sequenced on Illumina Miseq platform. Additionally, amplification of erm(B) gene (encoding erythromycin resistance methylase) was performed.

RESULTS: Reverse hybrid therapy resulted in decreased relative abundances of Firmicutes (from 62.0% to 30.7%; P < 0.001) and Actinobacteria (from 3.4% to 0.6%; 0.032) at the end of therapy. In contrast, the relative abundance of Proteobacteria increased from 10.2% to 49.1% (0.002). These microbiota alterations did not persist but returned to the initial levels at week 8 and week 48. The amount of erm(B) gene in fecal specimens was comparable to the pretreatment level at week 2 but increased at week 8 (0.025) and then returned to the pretreatment level by week 48.

CONCLUSIONS: H. pylori eradication with reverse hybrid therapy can lead to short-term gut dysbiosis. The amount of erm(B) gene in the stool increased transiently after treatment and returned to the pretreatment level 1-year post-treatment.

RevDate: 2019-05-22

Bento-Silva A, Koistinen VM, Mena P, et al (2019)

Factors affecting intake, metabolism and health benefits of phenolic acids: do we understand individual variability?.

European journal of nutrition pii:10.1007/s00394-019-01987-6 [Epub ahead of print].

INTRODUCTION: Phenolic acids are important phenolic compounds widespread in foods, contributing to nutritional and organoleptic properties.

The bioavailability of these compounds depends on their free or conjugated presence in food matrices, which is also affected by food processing. Phenolic acids undergo metabolism by the host and residing intestinal microbiota, which causes conjugations and structural modifications of the compounds. Human responses, metabolite profiles and health responses of phenolics, show considerable individual variation, which is affected by absorption, metabolism and genetic variations of subjects.

OPINION: A better understanding of the gut-host interplay and microbiome biochemistry is becoming highly relevant in understanding the impact of diet and its constituents. It is common to study metabolism and health benefits separately, with some exceptions; however, it should be preferred that health responders and non-responders are studied in combination with explanatory metabolite profiles and gene variants. This approach could turn interindividual variation from a problem in human research to an asset for research on personalized nutrition.

RevDate: 2019-05-22

Sarris J (2019)

Nutritional Psychiatry: From Concept to the Clinic.

Drugs pii:10.1007/s40265-019-01134-9 [Epub ahead of print].

The field of 'nutritional psychiatry' has evolved with rapidity over the past several years, with an increasing amount of dietary or nutrient-based (nutraceutical) intervention studies being initiated, and more preclinical and epidemiological data being available. This emergent paradigm involves the clinical consideration (where appropriate) of prescriptive dietary modification/improvement, and/or the select judicious use of nutrient-based supplementation to prevent or manage psychiatric disorders. In the last several years, significant links have increasingly been established between dietary quality and mental health (although not all data are supportive). Maternal and early-life nutrition may also affect the mental health outcomes in offspring. In respect to nutraceutical research, like with many recent conventional drug studies, results are fairly mixed across the board, and in many cases there is not emphatic evidence to support the use of nutraceuticals in various psychiatric disorders. This may in part be due to a preponderance of recent studies within the field revealing marked placebo effects. Due to current indicators pointing towards mental disorders having an increasing burden of disease, bold and innovative approaches on a societal level are now required. In light of the widespread use of nutrient supplements by those with and without mental disorders, it is also critical that scientifically rigorous methodologies be brought to bear on the assessment of the efficacy of these supplements, and to determine if, or what dose of, a nutrient supplement is required, for whom, and when, and under what circumstances. More simple studies of additional isolated nutrients are not of great benefit to the field (unless studied in supra-dosage in an individualised, biomarker-guided manner), nor, based on recent data, is the research of 'shotgun' formulations of nutraceuticals. The next critical step for the field is to design psychiatric interventional studies for both dietary modification and nutraceuticals, based on more of a personalised medicine approach, using biomarkers (e.g. nutrient deficiencies, inflammatory cytokine levels, genomic assessment, microbiome analysis) and a person's dietary patterns and individual macro/micronutrient requirements.

RevDate: 2019-05-22

de Assumpção PP, Araújo TMT, de Assumpção PB, et al (2019)

Suicide journey of H. pylori through gastric carcinogenesis: the role of non-H. pylori microbiome and potential consequences for clinical practice.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology pii:10.1007/s10096-019-03564-5 [Epub ahead of print].

Despite being one of the most studied cancer-related infections, the relationship between Helicobacter pylori infection and gastric adenocarcinoma (GC) remains, in some points, obscure. Based on a critical analysis of the available literature regarding stomach microbiota, we aimed to shed light to a possible new interpretation of the current understanding about the Helicobacter pylori-related GC carcinogenesis. We analyzed data from the literature on Helicobacter pylori and other potential carcinogenic pathogens, in both benignant conditions and gastric adenocarcinoma. Helicobacter pylori is the dominant microorganism in benignant conditions as non-complicated gastritis. In atrophic gastritis, metaplasia and, mainly, in gastric adenocarcinoma, a strong reduction in Helicobacter pylori abundance, and increased occurrence of other microorganisms is strongly demonstrated by metagenomic experiments. While causing peptic disease and keeping the stomach's high acidity, Helicobacter pylori infection avoids gastric infection by carcinogenic intestinal microbiota. Nevertheless, Helicobacter pylori persistence may also provoke an atrophic gastritis, a condition that causes its own decline, due to a microenvironment modification, including reduced acidity, resulting in Helicobacter pylori substitution by a cancer-prone microbiota. This new interpretation might result in a dramatic modification on clinical management of Helicobacter pylori-related gastric disease.

RevDate: 2019-05-22

Avram O, Rapoport D, Portugez S, et al (2019)

M1CR0B1AL1Z3R-a user-friendly web server for the analysis of large-scale microbial genomics data.

Nucleic acids research pii:5494765 [Epub ahead of print].

Large-scale mining and analysis of bacterial datasets contribute to the comprehensive characterization of complex microbial dynamics within a microbiome and among different bacterial strains, e.g., during disease outbreaks. The study of large-scale bacterial evolutionary dynamics poses many challenges. These include data-mining steps, such as gene annotation, ortholog detection, sequence alignment and phylogeny reconstruction. These steps require the use of multiple bioinformatics tools and ad-hoc programming scripts, making the entire process cumbersome, tedious and error-prone due to manual handling. This motivated us to develop the M1CR0B1AL1Z3R web server, a 'one-stop shop' for conducting microbial genomics data analyses via a simple graphical user interface. Some of the features implemented in M1CR0B1AL1Z3R are: (i) extracting putative open reading frames and comparative genomics analysis of gene content; (ii) extracting orthologous sets and analyzing their size distribution; (iii) analyzing gene presence-absence patterns; (iv) reconstructing a phylogenetic tree based on the extracted orthologous set; (v) inferring GC-content variation among lineages. M1CR0B1AL1Z3R facilitates the mining and analysis of dozens of bacterial genomes using advanced techniques, with the click of a button. M1CR0B1AL1Z3R is freely available at https://microbializer.tau.ac.il/.

RevDate: 2019-05-22

Day RL, Harper AJ, Woods RM, et al (2019)

Probiotics: current landscape and future horizons.

Future science OA, 5(4):FSO391.

In recent years there has been a rapid rise in interest for the application of probiotic supplements to act as mediators in health and disease. This appeal is predominantly due to ever-increasing evidence of the interaction of the microbiota and pathophysiological processes of disease within the human host. This narrative review considers the current landscape of the probiotic industry and its research, and discusses current pitfalls in the lack of translation from laboratory science to clinical application. Future considerations into how industry and academia must adapt probiotic research to maximize success are suggested, including more targeted application of probiotic strains dependent on individual capabilities as well as application of multiple advanced analytical technologies to further understand and accelerate microbiome science.

RevDate: 2019-05-22

Heaney LM, Davies OG, NM Selby (2019)

Gut microbial metabolites as mediators of renal disease: do short-chain fatty acids offer some hope?.

Future science OA, 5(4):FSO384.

RevDate: 2019-05-22

R Wardill H (2019)

Early career interview: Hannah Wardill.

Future science OA, 5(4):FSO382.

RevDate: 2019-05-22

Kuhbandner K, Hammer A, Haase S, et al (2019)

MAdCAM-1-Mediated Intestinal Lymphocyte Homing Is Critical for the Development of Active Experimental Autoimmune Encephalomyelitis.

Frontiers in immunology, 10:903.

Lymphocyte homing into the intestine is mediated by binding of leukocytes to mucosal addressin cell adhesion molecule 1 (MAdCAM-1), expressed on endothelial cells. Currently, the immune system of the gut is considered a major modulator not only of inflammatory bowel disease, but also of extra-intestinal autoimmune disorders, including multiple sclerosis (MS). Despite intense research in this field, the exact role of the intestine in the pathogenesis of (neuro-)inflammatory disease conditions remains to be clarified. This prompted us to investigate the role of MAdCAM-1 in immunological processes in the intestine during T cell-mediated autoimmunity of the central nervous system (CNS). Using the experimental autoimmune encephalomyelitis model of MS, we show that MAdCAM-1-deficient (MAdCAM-1-KO) mice are less susceptible to actively MOG35-55-induced disease. Protection from disease was accompanied by decreased numbers of immune cells in the lamina propria and Peyer's patches as well as reduced immune cell infiltration into the spinal cord. MOG35-55-recall responses were intact in other secondary lymphoid organs of MAdCAM-1-KO mice. The composition of specific bacterial groups within the microbiome did not differ between MAdCAM-1-KO mice and controls, while MAdCAM-1-deficiency severely impaired migration of MOG35-55-activated lymphocytes to the gut. Our data indicate a critical role of MAdCAM-1 in the development of CNS inflammation by regulating lymphocyte homing to the intestine, and may suggest a role for the intestinal tract in educating lymphocytes to become encephalitogenic.

RevDate: 2019-05-22

Haussner F, Chakraborty S, Halbgebauer R, et al (2019)

Challenge to the Intestinal Mucosa During Sepsis.

Frontiers in immunology, 10:891.

Sepsis is a complex of life-threating organ dysfunction in critically ill patients, with a primary infectious cause or through secondary infection of damaged tissues. The systemic consequences of sepsis have been intensively examined and evidences of local alterations and repercussions in the intestinal mucosal compartment is gradually defining gut-associated changes during sepsis. In the present review, we focus on sepsis-induced dysfunction of the intestinal barrier, consisting of an increased permeability of the epithelial lining, which may facilitate bacterial translocation. We discuss disturbances in intestinal vascular tonus and perfusion and coagulopathies with respect to their proposed underlying molecular mechanisms. The consequences of enzymatic responses by pancreatic proteases, intestinal alkaline phosphatases, and several matrix metalloproteases are also described. We conclude our insight with a discussion on novel therapeutic interventions derived from crucial aspects of the gut mucosal dynamics during sepsis.

RevDate: 2019-05-22

Martinez-Fernandez G, Denman SE, CS McSweeney (2019)

Sample Processing Methods Impacts on Rumen Microbiome.

Frontiers in microbiology, 10:861.

The standardization of collection and processing methods for rumen samples is crucial to reduce the level of errors that may affect the analysis and interpretation of the data. The aim of this study was to compare two processing methods and their impacts on the microbial community composition analysis, from material that was either immediately frozen or samples that were stored as cell pellets after removing the supernatant prior to freezing. Eight rumen-fistulated Brahman steers received chloroform as an antimethanogenic compound for 21 days. Rumen fluid samples (60 mL per animal) were collected using a probe covered with two layers of cheesecloth at 3 h post feeding at day 0 prior-treatment (control period) and day 21 of treatment. One sub-set of samples were placed in dry ice and stored at -80°C (Method 1) for subsequent DNA extraction, while a second subset of samples was centrifuged, the supernatant removed and the microbial pellet and rumen contents placed in dry ice and stored at -80°C (Method 2) prior to DNA extractions. Phylogenetic based methods (Illumina Miseq) targeting the 16S rRNA gene were used to characterize the bacterial and archaeal communities from both collection methods for the control and treatment periods. The results from this study showed that the chloroform treatment was significantly different for all beta diversity measures regardless of the processing method used. Significant differences in the relative abundances of some bacteria and archaea, such as Elusimicrobia, Fibrobacteres, Lentisphaerae, Spirochaetes, and Verrucomicrobia and Methanomassiliicoccaceae, were observed at higher levels in the Method 2. These microbial populations are known to have fragile cell wall structures and are susceptible to cell lysis. Regardless of the processing method used, both identified the key microbial groups and can be used to compare the relative shifts in the rumen microbiome between treatments. However, immediately freezing samples might alter the abundance of material from species that are more readily lysed and will not be suitable for studies that aim to assign absolute abundance values to these species within the rumen.

RevDate: 2019-05-22

Ryan PM, Stanton C, Ross RP, et al (2019)

Paediatrician's perspective of infant gut microbiome research: current status and challenges.

Archives of disease in childhood pii:archdischild-2019-316891 [Epub ahead of print].

Due to its innately intriguing nature and recent genomic technological advances, gut microbiome research has been at the epicentre of medical research for over a decade now. Despite the degree of publicisation, a comprehensive understanding and, therefore, acceptance of the area as a whole may be somewhat lacking within the broader medical community. This paper summarises the main analytical techniques and tools currently applied to compositional microbiome research. In addition, we outline five major lessons learnt from a decade of infant microbiome research, along with the current research gaps. Finally, we aim to provide an introduction and general guidelines relating to infant gut microbiome research for the practising paediatrician.

RevDate: 2019-05-22

Bedognetti D, Ceccarelli M, Galluzzi L, et al (2019)

Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop.

Journal for immunotherapy of cancer, 7(1):131 pii:10.1186/s40425-019-0602-4.

Tumor immunology has changed the landscape of cancer treatment. Yet, not all patients benefit as cancer immune responsiveness (CIR) remains a limitation in a considerable proportion of cases. The multifactorial determinants of CIR include the genetic makeup of the patient, the genomic instability central to cancer development, the evolutionary emergence of cancer phenotypes under the influence of immune editing, and external modifiers such as demographics, environment, treatment potency, co-morbidities and cancer-independent alterations including immune homeostasis and polymorphisms in the major and minor histocompatibility molecules, cytokines, and chemokines. Based on the premise that cancer is fundamentally a disorder of the genes arising within a cell biologic process, whose deviations from normality determine the rules of engagement with the host's response, the Society for Immunotherapy of Cancer (SITC) convened a task force of experts from various disciplines including, immunology, oncology, biophysics, structural biology, molecular and cellular biology, genetics, and bioinformatics to address the complexity of CIR from a holistic view. The task force was launched by a workshop held in San Francisco on May 14-15, 2018 aimed at two preeminent goals: 1) to identify the fundamental questions related to CIR and 2) to create an interactive community of experts that could guide scientific and research priorities by forming a logical progression supported by multiple perspectives to uncover mechanisms of CIR. This workshop was a first step toward a second meeting where the focus would be to address the actionability of some of the questions identified by working groups. In this event, five working groups aimed at defining a path to test hypotheses according to their relevance to human cancer and identifying experimental models closest to human biology, which include: 1) Germline-Genetic, 2) Somatic-Genetic and 3) Genomic-Transcriptional contributions to CIR, 4) Determinant(s) of Immunogenic Cell Death that modulate CIR, and 5) Experimental Models that best represent CIR and its conversion to an immune responsive state. This manuscript summarizes the contributions from each group and should be considered as a first milestone in the path toward a more contemporary understanding of CIR. We appreciate that this effort is far from comprehensive and that other relevant aspects related to CIR such as the microbiome, the individual's recombined T cell and B cell receptors, and the metabolic status of cancer and immune cells were not fully included. These and other important factors will be included in future activities of the taskforce. The taskforce will focus on prioritization and specific actionable approach to answer the identified questions and implementing the collaborations in the follow-up workshop, which will be held in Houston on September 4-5, 2019.

RevDate: 2019-05-22

Keskin M, Goksan Pabuccu E, Sahin O, et al (2019)

Oral antibiotic prophylaxis in elective cesarean deliveries: pilot analysis in tertiary Care Hospital.

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians [Epub ahead of print].

INTRODUCTION: Puerperal infection remains a significant cause of maternal morbidity and mortality. Those infections occur more likely after cesarean delivery (CD). Prophylactic antibiotics are administered at the time of CD to prevent complications. In addition to intraoperative prophylaxis; prescription of antibiotics during hospital discharge to prevent surgical site infections (SSI) is quite common. Purpose of this study is to determine the utility of prophylactic oral antibiotic prescription in a cohort of low-risk women undergoing CD.

MATERIALS AND METHODS: A prospective observational study was conducted between 2014 and 2018 at Ufuk University School of Medicine, Department of Obstetrics and Gynaecology. Total of 389 low risk elective cesarean deliveries were selected. All cases received intraoperative prophylaxis. In group I (157 subjects), no further antibiotics were given and in group II (232 cases), oral cephuroxime 500 mg was given during hospital discharge. Primary outcome was SSI. Secondary outcomes were endometritis and other infectious conditions.

RESULTS: Overall SSI rate was 2.5%. Only 2 SSIs were noted in group 1 (1.2%) compared to eight in group II (3.4%). There was no statistical difference in SSI rate between two groups. Secondary outcomes were also comparable.

CONCLUSION: In this study we failed to reveal any beneficial effect of oral antibiotic prescription during hospital discharge in low risk elective CDs. Therefore, use of oral antibiotics in addition to intraoperative prophylaxis should be questioned in terms of increased costs, emergence of bacterial resistance and long term effects on new born as a consequence of changes in gut microbiome.

RevDate: 2019-05-22

Lew KN, Starkweather A, Cong X, et al (2019)

A Mechanistic Model of Gut-Brain Axis Perturbation and High-Fat Diet Pathways to Gut Microbiome Homeostatic Disruption, Systemic Inflammation, and Type 2 Diabetes.

Biological research for nursing [Epub ahead of print].

Type 2 diabetes (T2D) is a highly prevalent metabolic disease, affecting nearly 10% of the American population. Although the etiopathogenesis of T2D remains poorly understood, advances in DNA sequencing technologies have allowed for sophisticated interrogation of the human microbiome, providing insight into the role of the gut microbiome in the development and progression of T2D. An emerging body of research reveals that gut-brain axis (GBA) perturbations and a high-fat diet (HFD), along with other modifiable and nonmodifiable risk factors, contribute to gut microbiome homeostatic imbalance. Homeostatic imbalance or disruption increases gut wall permeability and facilitates translocation of endotoxins (lipopolysaccharides) into the circulation with resultant systemic inflammation. Chronic, low-grade systemic inflammation ensues with pro-inflammatory pathways activated, contributing to obesity, insulin resistance (IR), pancreatic β-cell decline, and, thereby, T2D. While GBA perturbations and HFD are implicated in provoking these conditions, prior mechanistic models have tended to examine HFD and GBA pathways exclusively without considering their shared pathways to T2D. Addressing this gap, this article proposes a mechanistic model informed by animal and human studies to advance scientific understanding of (1) modifiable and nonmodifiable risk factors for gut microbiome homeostatic disruption, (2) HFD and GBA pathways contributing to homeostatic disruption, and (3) shared GBA and HFD pro-inflammatory pathways to obesity, IR, β-cell decline, and T2D. The proposed mechanistic model, based on the extant literature, proposes a framework for studying the complex relationships of the gut microbiome to T2D to advance study in this promising area of research.

RevDate: 2019-05-21

Claudel JP, Auffret N, Leccia MT, et al (2019)

Staphylococcus epidermidis: A Potential New Player in the Physiopathology of Acne?.

Dermatology (Basel, Switzerland) pii:000499858 [Epub ahead of print].

BACKGROUND: Cutibacterium acnes has been identified as one of the main triggers of acne. However, increasing knowledge of the human skin microbiome raises questions about the role of other skin commensals, such as Staphylococcus epidermidis, in the physiopathology of this skin disease.

SUMMARY: This review provides an overview of current knowledge of the potential role of S. epidermidis in the physiopathology of acne. Recent research indicates that acne might be the result of an unbalanced equilibrium between C. acnes and S. epidermidis,according to dedicated interactions. Current treatments act on C. acnesonly. Other treatment options may be considered, such as probiotics derived from S. epidermidis to restore the naturally balanced microbiota or through targeting the regulation of the host's AMP mediators. Key Messages: Research seems to confirm the beneficial role of S. epidermidis in acne by limiting C. acnes over-colonisation and inflammation.

RevDate: 2019-05-21

Gopinath D, Menon RK, Banerjee M, et al (2019)

Culture-independent studies on bacterial dysbiosis in oral and oropharyngeal squamous cell carcinoma: A systematic review.

Critical reviews in oncology/hematology, 139:31-40 pii:S1040-8428(18)30324-X [Epub ahead of print].

Imbalance within the resident bacterial community (dysbiosis), rather than the presence and activity of a single organism, has been proposed to be associated with, and to influence, the development and progression of various diseases; however, the existence and significance of dysbiosis in oral/oropharyngeal cancer is yet to be clearly established. A systematic search (conducted on 25/01/2018 and updated on 25/05/2018) was performed on three databases (Pubmed, Web of Science & Scopus) to identify studies employing culture-independent methods which investigated the bacterial community in oral/oropharyngeal cancer patients compared to control subjects. Of the 1546 texts screened, only fifteen publications met the pre-determined selection criteria. Data extracted from 731 cases and 809 controls overall, could not identify consistent enrichment of any particular taxon in oral/oropharyngeal cancers, although common taxa could be identified between studies. Six studies reported the enrichment of Fusobacteria in cancer at different taxonomic levels whereas four studies reported an increase in Parvimonas. Changes in microbial diversity remained inconclusive, with four studies showing a higher diversity in controls, three studies showing a higher diversity in tumors and three additional studies showing no difference between tumors and controls. Even though most studies identified a component of dysbiosis in oral/oropharyngeal cancer, methodological and analytical variations prevented a standardized summary, which highlights the necessity for studies of superior quality and magnitude employing standardized methodology and reporting. Indeed an holistic metagenomic approach is likely to be more meaningful, as is understanding of the overall metabolome, rather than a mere enumeration of the organisms present.

RevDate: 2019-05-21

Nathalie M, de Wiele Tom V, Fiona F, et al (2019)

Gut microbiome patterns depending on children's psychosocial stress: reports versus biomarkers.

Brain, behavior, and immunity pii:S0889-1591(18)31214-5 [Epub ahead of print].

AIM: Chronic stress increases disease vulnerability factors including inflammation, a pathological characteristic potentially regulated by the gut microbiota. We checked the association between the gut microbiome and psychosocial stress in children/adolescents and investigated which stress parameter (negative versus positive emotion, self-report versus parental report, events versus emotions, biomarker cortisol versus parasympathetic activity) is the most relevant indicator herein.

METHODS: Gut microbiome sequencing was completed in fecal samples from 93 Belgian 8-16y olds. Stress measures included negative events, negative emotions, emotional problems reported by parents, happiness, hair cortisol and heart rate variability (pnn50 parameter reflecting parasympathetic activity). Alpha diversity, beta diversity and linear discriminant analysis were the unadjusted analyses. Age, sex, socio-economic status, diet, physical activity, sleep and weight status were adjusted for via a redundancy analysis and differential abundance via zero-inflated negative binomial regression.

RESULTS: High stress as reflected by low pnn50 and more negative events were associated with a lower alpha diversity as indicated by the Simpson index. Happiness and pnn50 showed significant differences between high and low stress groups based on weighted UniFrac distance, and this remained significant after confounder adjustment. Adjusted and unadjusted taxonomic differences were also most pronounced for happiness and pnn50 being associated respectively with 24 OTU (=11.8% of bacterial counts) and 31 OTU (=13.0%). As a general pattern, high stress was associated with lower Firmicutes at the phylum level and higher Bacteroides, Parabacteroides, Rhodococcus, Methanobrevibacter and Roseburia but lower Phascolarctobacterium at genus level. Several genera gave conflicting results between different stress measures e.g. Ruminococcaceae UCG014, Tenericutes, Eubacterium coprostanoligenes, Prevotella 9 and Christensenellaceae R7. Differential results in preadolescents versus adolescents were also evident.

CONCLUSION: Even in this young healthy population, stress parameters were cross-sectionally associated with gut microbial composition but this relationship was instrument specific. Positive emotions and parasympathetic activity appeared the strongest parameters and should be integrated in future microbiota projects amongst other stress measures.

RevDate: 2019-05-21

Chang AM, Liu Q, Hajjar AM, et al (2019)

Toll-like receptor 2 and toll-like receptor 4 responses regulate neutrophil infiltration into the junctional epithelium and significantly contribute to the composition of the oral microbiota.

Journal of periodontology [Epub ahead of print].

BACKGROUND: Oral gingival tissue, especially the junctional epithelium (JE), is constantly exposed to sub-gingival plaque. A key component of gingival health is the regulation of the number of neutrophils that migrate into the gingival crevice to counteract its harmful effects. This report investigates the contribution of innate defense receptors, Toll-like receptor 2 (TLR), TLR4 and both (TLR2/4) to the maintenance of neutrophil homeostasis in the JE.

METHODS: Bacterial composition was analyzed from whole oral swabs collected from 12-14-week-old TLR2, TLR4, TLR2/4 double knock-out (KO) mice using a MiSeq platform targeting the V3-V4 region of the 16S ribosomal RNA gene. Mandibles were histologically examined for quantification of neutrophils in the JE and bone loss. Lastly, total bacterial load was quantitated using quantitative real-time PCR.

RESULTS: Compared to wild-type (WT), all TLR KO mice displayed significantly increased recruitment of neutrophils (p = 0.0079) into the JE. In addition, TLR4 and TLR2/4 KO mice demonstrated a significant increase in the number of bacteria (p = 0.022 and p = 0.0152, respectively). Lastly, comparative compositional analyses of the oral microbiome revealed that each KO strain harbored unique microbial communities that are distinct from each other but maintained similar levels of alveolar bone.

CONCLUSIONS: Neutrophil migration into healthy mouse JE does not require TLR2 or TLR4. However, a significant increase in the number of neutrophils as well as a significant change in the oral microbial composition in both TLR2 and TLR4 KO mice demonstrate that these TLRs contribute to the homeostatic relationship between bacteria and the host in healthy mice periodontal tissue. This article is protected by copyright. All rights reserved.

RevDate: 2019-05-21

Keller MJ, Huber A, Espinoza L, et al (2019)

Impact of Herpes Simplex Virus Type 2 and Human Immunodeficiency Virus Dual Infection on Female Genital Tract Mucosal Immunity and the Vaginal Microbiome.

The Journal of infectious diseases pii:5481045 [Epub ahead of print].

BACKGROUND: Mechanisms linking herpes simplex virus type 2 (HSV-2) with human immunodeficiency virus (HIV) are not fully defined. We tested the hypothesis that HSV-2 and HIV dual infection is associated with cervicovaginal inflammation and/or vaginal dysbiosis.

METHODS: Genital tract samples were obtained weekly over a 12-week period from 30 women seropositive (+) for HIV and HSV-2 and 15 women each who were seropositive for one or seronegative (-) for both viruses. Immune mediators, antimicrobial activity, and microbial composition and diversity were compared.

RESULTS: Significant differences in the concentrations of interferon-γ (P = .002), tumor necrosis factor-α (P = .03), human beta defensin 1 (P = .001), secretory leukocyte protease inhibitor (P = .01), and lysozyme (P = .03) were observed across the 4 groups (Kruskal-Wallis). There were also significant differences in vaginal microbial alpha diversity (Simpson index) (P = .0046). Specifically, when comparing HIV-1+/HSV-2+ to HIV-1-/HSV-2- women, a decrease in Lactobacillus crispatus and increase in diverse anaerobes was observed. The number of genital HSV outbreaks was greater in HIV+ versus HIV- women (39 versus 12) (P = .04), but there were no significant differences when comparing outbreak to non-outbreak visits.

CONCLUSIONS: Increased microbial diversity and cervicovaginal inflammation in HIV and HSV-2 dually infected women may adversely impact genital health and, in the absence of antiretroviral therapy, facilitate HIV shedding.

RevDate: 2019-05-21

Little RF, TS Uldrick (2019)

Are There Clues to Oral KSHV Shedding and Kaposi Sarcoma Oncogenesis in the Oral Microbiome?.

The Journal of infectious diseases pii:5491268 [Epub ahead of print].

RevDate: 2019-05-21

Reiger M, Schwierzeck V, C Traidl-Hoffmann (2019)

[Atopic eczema and microbiome].

Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete pii:10.1007/s00105-019-4424-6 [Epub ahead of print].

BACKGROUND: Atopic eczema is a chronic inflammatory skin disease characterized by skin barrier disruption, inflammation and dysbiosis. Furthermore, atopic eczema is associated with other diseases of the atopic group, such as allergies, rhinoconjunctivitis and asthma. The skin microbiome consists of bacteria, viruses and fungi. Patients suffering from atopic eczema often show an imbalance (dysbiosis) of the microbiome.

OBJECTIVE: It is not yet completely clarified what influence dysbiosis and the cutaneous microbiome have on the development and severity of atopic eczema. Modern sequencing methods will be used to investigate the role of the skin microbiome in the pathogenesis of atopic eczema in the future.

MATERIAL AND METHODS: This article presents and discusses the results of current basic research.

RESULTS: The human skin microbiome differs according to body region, age and gender. It interacts with the skin barrier and the cutaneous immune system. Patients suffering from atopic eczema develop dysbiosis consisting of an increased load of Staphylococcus aureus and a reduction of commensal skin bacteria. The altered skin microbiome in patients suffering from atopic eczema may also affect skin barrier function and inflammatory reactions.

CONCLUSION: Knowledge of the skin microbiome has improved in recent years. This will certainly improve the understanding of the pathogenesis causing atopic eczema. These findings may also form the foundation of new treatment and prevention strategies for atopic eczema in the future.

RevDate: 2019-05-21

Boix-Amorós A, Collado MC, Van't Land B, et al (2019)

Reviewing the evidence on breast milk composition and immunological outcomes.

Nutrition reviews pii:5492496 [Epub ahead of print].

A large number of biologically active components have been found in human milk (HM), and in both human and animal models, studies have provided some evidence suggesting that HM composition can be altered by maternal exposures, subsequently influencing health outcomes for the breastfed child. Evidence varies from the research studies on whether breastfeeding protects the offspring from noncommunicable diseases, including those associated with immunological dysfunction. It has been hypothesized that the conflicting evidence results from HM composition variations, which contain many immune active molecules, oligosaccharides, lactoferrin, and lysozyme in differing concentrations, along with a diverse microbiome. Determining the components that influence infant health outcomes in terms of both short- and long-term sequelae is complicated by a lack of understanding of the environmental factors that modify HM constituents and thereby offspring outcomes. Variations in HM immune and microbial composition (and the differing infantile responses) may in part explain the controversies that are evidenced in studies that aim to evaluate the prevalence of allergy by prolonged and exclusive breastfeeding. HM is a "mixture" of immune active factors, oligosaccharides, and microbes, which all may influence early immunological outcomes. This comprehensive review provides an in-depth overview of existing evidence on the studied relationships between maternal exposures, HM composition, vaccine responses, and immunological outcomes.

RevDate: 2019-05-21

Chowdhry R, Singh N, Sahu DK, et al (2019)

Dysbiosis and Variation in Predicted Functions of the Granulation Tissue Microbiome in HPV Positive and Negative Severe Chronic Periodontitis.

BioMed research international, 2019:8163591.

Retrospective analysis has already shown correlation between severe Chronic Periodontitis (CP) cases with human papiloma virus (HPV). Hence, we aimed to explore deep-seated infected granulation tissue removed during periodontal flap surgery procedures for residential bacterial species between HPV+ and HVP- CP cases, which may serve as good predisposition marker for oral cancer. All CP-granulation samples showed the prominence of Firmicutes, Proteobacteria, and Bacteroidetes phyla with an abundance of gram negative anaerobes, except Streptococcus. In Beta diversity nonmetric multidimensional scaling plot, the random distribution of species was observed between HPV+ and HPV- CP granulation-samples. However, an abundance of Capnocytophaga ochracea was observed in HPV+ CP samples (p<0.05), while Porphyromonas endodontalis, Macellibacteroides fermentas, Treponema phagedenis, and Campylobacter rectus species were highly abundant in HPV- CP samples (p<0.05). The differential species richness leads altered functions related to mismatch-repair and nucleotide excision-repair and cytoskeleton-proteins. Hence, differential abundance of gram negative bacterial species between HPV+ and HPV- granulation-samples under anaerobic conditions may release virulence factors which may alter pathways favouring carcinogenesis. Hence, these species may serve as good predisposition marker for oral-cancer.

RevDate: 2019-05-21

Rizzato C, Torres J, Kasamatsu E, et al (2019)

Potential Role of Biofilm Formation in the Development of Digestive Tract Cancer With Special Reference to Helicobacter pylori Infection.

Frontiers in microbiology, 10:846.

Bacteria are highly social organisms that communicate via signaling molecules and can assume a multicellular lifestyle to build biofilm communities. Until recently, complications from biofilm-associated infection have been primarily ascribed to increased bacterial resistance to antibiotics and host immune evasion, leading to persistent infection. In this theory and hypothesis article we present a relatively new argument that biofilm formation has potential etiological role in the development of digestive tract cancer. First, we summarize recent new findings suggesting the potential link between bacterial biofilm and various types of cancer to build the foundation of our hypothesis. To date, evidence has been particularly convincing for colorectal cancer and its precursor, i.e., polyps, pointing to several key individual bacterial species, such as Bacteroides fragilis, Fusobacterium nucleatum, and Streptococcus gallolyticus subsp. Gallolyticus. Then, we further extend this hypothesis to one of the most common bacterial infection in humans, Helicobacter pylori (Hp), which is considered a major cause of gastric cancer. Thus far, there has been no direct evidence linking in vivo Hp gastric biofilm formation to gastric carcinogenesis. Yet, we synthesize the information to support an argument that biofilm associated-Hp is potentially more carcinogenic, summarizing biological characteristics of biofilm-associated bacteria. We also discuss mechanistic pathways as to how Hp or other biofilm-associated bacteria control biofilm formation and highlight recent findings on Hp genes that influence biofilm formation, which may lead to strain variability in biofilm formation. This knowledge may open a possibility of developing targeted intervention. We conclude, however, that this field is still in its infancy. To test the hypothesis rigorously and to link it ultimately to gastric pathologies (e.g., premalignant lesions and cancer), studies are needed to learn more about Hp biofilms, such as compositions and biological properties of extracellular polymeric substance (EPS), presence of non-Hp microbiome and geographical distribution of biofilms in relation to gastric gland types and structures. Identification of specific Hp strains with enhanced biofilm formation would be helpful not only for screening patients at high risk for sequelae from Hp infection, but also for development of new antibiotics to avoid resistance, regardless of its association with gastric cancer.

RevDate: 2019-05-21

Deo PN, R Deshmukh (2019)

Oral microbiome: Unveiling the fundamentals.

Journal of oral and maxillofacial pathology : JOMFP, 23(1):122-128.

The oral cavity has the second largest and diverse microbiota after the gut harboring over 700 species of bacteria. It nurtures numerous microorganisms which include bacteria, fungi, viruses and protozoa. The mouth with its various niches is an exceptionally complex habitat where microbes colonize the hard surfaces of the teeth and the soft tissues of the oral mucosa. In addition to being the initiation point of digestion, the oral microbiome is crucial in maintaining oral as well as systemic health. Because of the ease of sample collection, it has become the most well-studied microbiome till date. Previously, studying the microbiome was limited to the conventional culture-dependent techniques, but the abundant microflora present in the oral cavity could not be cultured. Hence, studying the microbiome was difficult. The emergence of new genomic technologies including next-generation sequencing and bioinformatics has revealed the complexities of the oral microbiome. It has provided a powerful means of studying the microbiome. Understanding the oral microbiome in health and disease will give further directions to explore the functional and metabolic alterations associated with the diseased states and to identify molecular signatures for drug development and targeted therapies which will ultimately help in rendering personalized and precision medicine. This review article is an attempt to explain the different aspects of the oral microbiome in health.

RevDate: 2019-05-21

Wei MY, Shi S, Liang C, et al (2019)

The microbiota and microbiome in pancreatic cancer: more influential than expected.

Molecular cancer, 18(1):97 pii:10.1186/s12943-019-1008-0.

Microbiota is just beginning to be recognized as an important player in carcinogenesis and the interplay among microbes is greater than expected. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease for which mortality closely parallels incidence. Early detection would provide the best opportunity to increase survival rates. Specific well-studied oral, gastrointestinal, and intrapancreatic microbes and some kinds of hepatotropic viruses and bactibilia may have potential etiological roles in pancreatic carcinogenesis, or modulating individual responses to oncotherapy. Concrete mechanisms mainly involve perpetuating inflammation, regulating the immune system-microbe-tumor axis, affecting metabolism, and altering the tumor microenvironment. The revolutionary technology of omics has generated insight into cancer microbiomes. A better understanding of the microbiota in PDAC might lead to the establishment of screening or early-stage diagnosis methods, implementation of cancer bacteriotherapy, adjustment of therapeutic efficacy even alleviating the adverse effects, creating new opportunities and fostering hope for desperate PDAC patients.

RevDate: 2019-05-21

Olmedo-Martín RV, González-Molero I, Olveira G, et al (2019)

Vitamin D in inflammatory bowel disease: Biological, clinical and therapeutic aspects.

Current drug metabolism pii:CDM-EPUB-98551 [Epub ahead of print].

BACKGROUND: Vitamin D has an immunoregulatory action in inflammatory bowel disease (IBD) as well as other immune-mediated disorders. Its influence on intestinal permeability, innate and adaptive immunity, and the composition and diversity of the microbiota contribute to the maintenance of intestinal homeostasis. Patients with IBD have a greater prevalence of vitamin D deficiency than the general population and a possible association between this deficit and a worse course of the disease. However, intervention studies in patients with IBD have proved inconclusive.

OBJECTIVE: To review all the evidence concerning the role of vitamin D as an important factor in the pathophysiology of IBD, review the associations found between its deficiency and the prognosis of the disease, and draw conclusions for the practical application from the main intervention studies undertaken.

METHOD: Structured search and review of basic, epidemiological, clinical and intervention studies evaluating the influence of vitamin D in IBD, following the basic principles of scientific data.

RESULTS: Vitamin D deficiency is associated with disease activity, quality of life, the consumption of social and healthcare resources, and the durability of anti-TNFα biological treatment. The determination of new metabolites of vitamin D, the measurement of its absorption capacity and questionnaires about sun exposure could help identify groups of IBD patients with a special risk of vitamin D deficiency.

CONCLUSION: Well-designed intervention studies are needed in IBD, with probably higher objective plasma doses of vitamin D to establish its efficacy as a therapeutic agent with immunomodulatory properties. Meanwhile, vitamin D deficiency should be screened for and corrected in affected patients in order to achieve adequate bone and phosphocalcic metabolism.

RevDate: 2019-05-21

Shikano A, Kuda T, Shibayama J, et al (2019)

Effects of Lactobacillus plantarum Uruma-SU4 fermented green loofah on plasma lipid levels and gut microbiome of high-fat diet fed mice.

Food research international (Ottawa, Ont.), 121:817-824.

To clarify the effect of loofah Luffa cylindrica and fermented loofah on hyperlipidemia, the in vitro bile acid lowering capacity and blood lipid levels of ddY mice fed high-fat diet supplemented with loofah were determined. Furthermore, the caecal microbiomes patterns were analysed using 16S rDNA amplicon sequencing with a next generation sequencer (MiSeq) system. Green loofah was homogenized and autoclaved (LH), and subsequently fermented with Lactobacillus plantarum Uruma-SU4 (FL). In vitro bile acid (taurocholic, glycocholic and deoxycholic acids (DCA)) lowering capacity was significantly high in FL. The levels of plasma triacylglyceride in mice which were fed a high-fat diet containing 17% beef tallow was lowered by 5% dried FL (FLD) and was unaffected by dried LH (LHD). Caecal Lactobacillus johnsonii and Clostridium disporicum known as predominant lactic acid bacteria in mice gut and urso-DCA producer, respectively, were increased by FLD. On the other hand, Flintibacter butyricus was lowered by both LHD and FLD. These results suggest that if green loofah cannot be consumed as a fresh vegetable, lactic acid fermentation may be useful in generating effective nutritional supplements and functional foods.

RevDate: 2019-05-20

Regar RK, Gaur VK, Bajaj A, et al (2019)

Comparative microbiome analysis of two different long-term pesticide contaminated soils revealed the anthropogenic influence on functional potential of microbial communities.

The Science of the total environment, 681:413-423 pii:S0048-9697(19)32108-4 [Epub ahead of print].

Microbial communities play a crucial role in bioremediation of pollutants in contaminated ecosystem. In addition to pure culture isolation and bacterial 16S rRNA based community studies, the focus has now shifted employing the omics technologies enormously for understanding the microbial diversity and functional potential of soil samples. Our previous report on two pesticide-contaminated sites revealed the diversity of both culturable and unculturable bacteria. In the present study, we have observed distinct taxonomic and functional communities in contaminated soil with respect to an uncontaminated soil as control by using shotgun metagenomic sequencing method. Our data demonstrated that Proteobacteria, Actinobacteria, Firmicutes, Bacteroidetes, and Acidobacteria significantly dominated the microbial diversity with their cumulative abundance percentage in the range of 98.61, 87.38, and 80.52 for Hindustan Insecticides Limited (HIL), India Pesticides Limited (IPL), and control respectively. Functional gene analysis demonstrated the presence of large number of both substrate specific upper pathway and common lower pathway degradative genes. Relatively lower number of genes was found encoding the degradation of styrene, atrazine, bisphenol, dioxin, and naphthalene. When three bacteria were augumentated with rhamnolipid (20-100 μM) and Triton X-100 (84-417 μM) surfactants in HIL soil, an enhanced degradation to 76%, 70%, and 58% of HCH, Endosulfan, and DDT respectively was achieved. The overall data obtained from two heavily contaminated soil suggest the versatility of the microbial communities for the xenobiotic pollutant degradation which may help in exploiting their potential applications in bioremediation.

RevDate: 2019-05-20

Zeng Q, Junli Gong , Liu X, et al (2019)

Gut dysbiosis and lack of short chain fatty acids in a Chinese cohort of patients with multiple sclerosis.

Neurochemistry international pii:S0197-0186(18)30616-8 [Epub ahead of print].

BACKGROUND: Recent studies, mostly conducted in Western countries, showed that gut microbes are involved in the pathogenesis of multiple sclerosis (MS).

OBJECTIVE: The aim of this study was to investigate whether gut dysbiosis is relevant to the initiation and progression of MS in a Chinese population.

METHODS: Next-generation sequencing (NGS) and gas chromatography (GC) were integrated and used to compare the fecal bacterial communities and the short-chain fatty acid (SCFA) levels among relapsing-remitting MS (RRMS) patients (n = 34), neuromyelitis optica spectrum disorder (NMOSD) patients (n = 34), and healthy controls (HCs) (n = 34). T-cell profile analyses were performed by flow cytometry for MS patients and matched controls (n = 12).

RESULTS: (1) The gut microbiome of MS patients was characterized by an increase of Streptococcus and a decrease of Prevotella_9; additionally, compared to NMOSD patients, Prevotella_9 was found to be much more abundant in MS patients. (2) A striking depletion of fecal acetate, propionate, and butyrate was observed in MS patients compared to HCs. (3) The abundance of Streptococcus was negatively correlated with the proportion of pTregs (P < 0.05) and positively correlated with Th17 cells (P < 0.05) in the peripheral blood, while the abundance of Prevotella_9 was negatively correlated with the Th17 cell frequency (P < 0.01), and the fecal SCFA level was positively correlated with pTreg frequency (P < 0.05).

CONCLUSIONS: Gut dysbiosis and a lack of SCFAs exist in Chinese MS patients, which might be related to an aberrant immune response of MS; this relationship may have a diagnostic and therapeutic value for patients with MS.

RevDate: 2019-05-20

Herbert RA, Eng T, Martinez U, et al (2019)

Rhizobacteria mediate the phytotoxicity of a range of biorefinery-relevant compounds.

Environmental toxicology and chemistry [Epub ahead of print].

Advances in engineering biology have expanded the list of renewable compounds that can be produced at scale via biological routes from plant biomass. In most cases, these chemical products have not been evaluated for effects on biological systems, defined here as bioactivity, that may be relevant to their manufacture. For sustainable chemical and fuel production, the industry needs to transition from fossil to renewable carbon sources, resulting in unprecedented expansion in the production and environmental distribution of chemicals used in biomanufacturing. Further, while some chemicals have been assessed for mammalian toxicity, environmental and agricultural hazards are largely unknown. We assessed six compounds that are representative of the emerging biofuel and bioproduct manufacturing process for their effect on model plants (Arabidopsis thaliana, Sorghum bicolor) and show that several alter plant seedling physiology at sub-millimolar concentrations. However, these responses change in the presence of individual bacterial species from the A. thaliana root microbiome. We identified two individual microbes that change the effect of chemical treatment on root architecture, and a pooled microbial community with different effects relative to its constituents individually. Our findings indicate that screening industrial chemicals for bioactivity on model organisms in the presence of their microbiomes is important for biologically and ecologically relevant risk analyses. This article is protected by copyright. All rights reserved.

RevDate: 2019-05-20

Duvallet C, Larson K, Snapper S, et al (2019)

Aerodigestive sampling reveals altered microbial exchange between lung, oropharyngeal, and gastric microbiomes in children with impaired swallow function.

PloS one, 14(5):e0216453 pii:PONE-D-18-20128.

BACKGROUND: Children with oropharyngeal dysphagia have impaired airway protection mechanisms and are at higher risk for pneumonia and other pulmonary complications. Aspiration of gastric contents is often implicated as a cause for these pulmonary complications, despite being supported by little evidence. The goal of this study is to determine the relative contribution of oropharyngeal and gastric microbial communities to perturbations in the lung microbiome of children with and without oropharyngeal dysphagia and aspiration.

METHODS: We conducted a prospective cohort study of 220 patients consecutively recruited from a tertiary aerodigestive center undergoing simultaneous esophagogastroduodenoscopy and flexible bronchoscopy. Bronchoalveolar lavage, gastric and oropharyngeal samples were collected from all recruited patients and 16S sequencing was performed. A subset of 104 patients also underwent video fluoroscopic swallow studies to assess swallow function and were categorized as aspiration/no aspiration. To ensure the validity of the results, we compared the microbiome of these aerodigestive patients to the microbiome of pediatric patients recruited to a longitudinal cohort study of children with suspected GERD; patients recruited to this study had oropharyngeal, gastric and/or stool samples available. The relationships between microbial communities across the aerodigestive tract were described by analyzing within- and between-patient beta diversities and identifying taxa which are exchanged between aerodigestive sites within patients. These relationships were then compared in patients with and without aspiration to evaluate the effect of aspiration on the aerodigestive microbiome.

RESULTS: Within all patients, lung, oropharyngeal and gastric microbiomes overlap. The degree of similarity is the lowest between the oropharynx and lungs (median Jensen-Shannon distance (JSD) = 0.90), and as high between the stomach and lungs as between the oropharynx and stomach (median JSD = 0.56 for both; p = 0.6). Unlike the oropharyngeal microbiome, lung and gastric communities are highly variable across people and driven primarily by person rather than body site. In patients with aspiration, the lung microbiome more closely resembles oropharyngeal rather than gastric communities and there is greater prevalence of microbial exchange between the lung and oropharynx than between gastric and lung sites (p = 0.04 and 4x10-5, respectively).

CONCLUSIONS: The gastric and lung microbiomes display significant overlap in patients with intact airway protective mechanisms while the lung and oropharynx remain distinct. In patients with impaired swallow function and aspiration, the lung microbiome shifts towards oropharyngeal rather than gastric communities. This finding may explain why antireflux surgeries fail to show benefit in pediatric pulmonary outcomes.

RevDate: 2019-05-20

Mainali K, Bewick S, Vecchio-Pagan B, et al (2019)

Detecting interaction networks in the human microbiome with conditional Granger causality.

PLoS computational biology, 15(5):e1007037 pii:PCOMPBIOL-D-18-00900 [Epub ahead of print].

Human microbiome research is rife with studies attempting to deduce microbial correlation networks from sequencing data. Standard correlation and/or network analyses may be misleading when taken as an indication of taxon interactions because "correlation is neither necessary nor sufficient to establish causation"; environmental filtering can lead to correlation between non-interacting taxa. Unfortunately, microbial ecologists have generally used correlation as a proxy for causality although there is a general consensus about what constitutes a causal relationship: causes both precede and predict effects. We apply one of the first causal models for detecting interactions in human microbiome samples. Specifically, we analyze a long duration, high resolution time series of the human microbiome to decipher the networks of correlation and causation of human-associated microbial genera. We show that correlation is not a good proxy for biological interaction; we observed a weak negative relationship between correlation and causality. Strong interspecific interactions are disproportionately positive, whereas almost all strong intraspecific interactions are negative. Interestingly, intraspecific interactions also appear to act at a short time-scale causing vast majority of the effects within 1-3 days. We report how different taxa are involved in causal relationships with others, and show that strong interspecific interactions are rarely conserved across two body sites whereas strong intraspecific interactions are much more conserved, ranging from 33% between the gut and right-hand to 70% between the two hands. Therefore, in the absence of guiding assumptions about ecological interactions, Granger causality and related techniques may be particularly helpful for understanding the driving factors governing microbiome composition and structure.

RevDate: 2019-05-20

Rendina DN, Lubach GR, Phillips GJ, et al (2019)

Maternal and Breast Milk Influences on the Infant Gut Microbiome, Enteric Health and Growth Outcomes of Rhesus Monkeys.

Journal of pediatric gastroenterology and nutrition [Epub ahead of print].

OBJECTIVES: Gut bacteria play an essential role during infancy and are strongly influenced by the mode of birth and feeding. A primate model was used to investigate the benefits of exposure to the mother or conversely the negative impact of early nursery rearing on microbial colonization.

METHOD: Rectal swabs were obtained from rhesus macaques born vaginally and mother-reared (MR, N = 35) or delivered primarily via cesarean-section and human-reared (HR, N = 19). Microbiome composition was determined by rRNA gene amplicon sequencing at 2, 4 and 8 weeks of age and KEGG orthologs used to assess influences on functional metabolic pathways in the gut. Growth trajectories and incidence of diarrheic symptoms were evaluated.

RESULTS: The microbial community structure was different between MR and HR infants with respect to phylogeny and abundance at all 3 ages. When examining dominant phyla, HR infants had a higher Firmicutes-to-Bacteroidetes ratio. At the genus level, breast milk-dependent commensal taxa and adult-typical genera were more abundant in MR infants. This difference resulted in a corresponding shift in the predicted metabolic effects, specifically for microbial genes associated with metabolism and immune function. HR infants had faster growth trajectories (p < 0.001), but more diarrheic symptoms by 6 months postnatal (p = 0.008).

CONCLUSIONS: MR infants acquired adult-typical microbiota more quickly, and had higher levels of several beneficial commensal taxa. Cesarean-delivered and formula-fed infants had different developmental trajectories of bacterial colonization. Establishment of the gut microbiome was associated with an infant's growth trajectory, and implicated in the subsequent vulnerability to Campylobacter infections associated with diarrhea in infant monkeys.

RevDate: 2019-05-20

Hiremath G, Shilts MH, Boone HH, et al (2019)

The Salivary Microbiome Is Altered in Children With Eosinophilic Esophagitis and Correlates With Disease Activity.

Clinical and translational gastroenterology [Epub ahead of print].

OBJECTIVES: Eosinophilic esophagitis (EoE) is an allergen-mediated inflammatory disease affecting the esophagus. Although microbial communities may affect the host immune responses, little is known about the role of the microbiome in EoE. We compared the composition of the salivary microbiome in children with EoE with that of non-EoE controls to test the hypotheses that the salivary microbiome is altered in children with EoE and is associated with disease activity.

METHODS: Saliva samples were collected from 26 children with EoE and 19 non-EoE controls comparable for age and ethnicity. The salivary microbiome was profiled using 16S rRNA gene sequencing. Disease activity was assessed using the Eosinophilic Esophagitis Endoscopic Reference Score and the Eosinophilic Esophagitis Histologic Scoring System (EoEHSS).

RESULTS: A trend toward lower microbial richness and alpha diversity was noted in children with EoE. Although the overall salivary microbiome composition was similar between children with and without EoE, specific taxa such as Streptococcus (q value = 0.06) tended to be abundant in children with active EoE compared with non-EoE controls. Haemophilus was significantly abundant in children with active EoE compared with inactive EoE (q value = 0.0008) and increased with the increasing EoEHSS and Eosinophilic Esophagitis Histology Scoring System (q value = 5e-10). In addition, 4 broad salivary microbial communities correlated with the EoEHSS.

DISCUSSION: The composition of the salivary microbiome community structure can be altered in children with EoE. A relative abundance of Haemophilus positively correlates with the disease activity. These findings indicate that perturbations in the salivary microbiome may have a role in EoE pathobiology and could serve as a noninvasive marker of disease activity.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

RevDate: 2019-05-20

Lunjani N, Hlela C, L O'Mahony (2019)

Microbiome and skin biology.

Current opinion in allergy and clinical immunology [Epub ahead of print].

PURPOSE OF REVIEW: The skin is home to a diverse milieu of bacteria, fungi, viruses, bacteriophages, and archaeal communities. The application of culture-independent approaches has revolutionized the characterization of the skin microbiome and have revealed a previously underappreciated phylogenetic and functional granularity of skin-associated microbes in both health and disease states.

RECENT FINDINGS: The physiology of a given skin-niche drives the site-specific differences in bacterial phyla composition of healthy skin. Changes in the skin microbiome have consistently been associated with atopic dermatitis. In particular, Staphylococcus aureus overgrowth with concomitant decline in Staphylococcus epidermidis is a general feature associated with atopic dermatitis and is not restricted to eczematous lesions. Changes in fungal species are now also being described. Changes in the composition and metabolic activity of the gut microbiota are associated with skin health.

SUMMARY: We are now beginning to appreciate the intimate and intricate interactions between microbes and skin health. Multiple studies are currently focused on the manipulation of the skin or gut microbiome to explore their therapeutic potential in the prevention and treatment of skin inflammation.

RevDate: 2019-05-20

Ogunrinde E, Zhou Z, Luo Z, et al (2019)

A link between plasma microbial translocation, microbiome, and autoantibody development in first-degree relatives of systemic lupus erythematosus patients.

Arthritis & rheumatology (Hoboken, N.J.) [Epub ahead of print].

OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by antibody production against self-antigens. However, the events underlying autoantibody formation in SLE remains unclear. This study investigated the role of plasma autoantibody levels, microbial translocation, and the microbiome in SLE.

METHODS: Plasma samples from two cohorts, one with 18 unrelated healthy controls (UHCs) and 18 first-degree relatives (FDRs) and the other with 19 healthy controls and 21 SLE patients were assessed for autoantibody levels by autoantigen microarrays, lipopolysaccharide (LPS) levels by limulus amebocyte assay and microbiome composition by microbial 16S rDNA sequencing.

RESULTS: FDRs and SLE patients exhibited increased plasma autoantibodies compared to their control groups. Parents and children of lupus patients exhibited elevated plasma LPS levels in comparison to controls (p = 0.02). Plasma LPS levels positively correlated with plasma anti-dsDNA IgG levels in FDRs (r=0.51, p=0.03) but not in SLE patients. Circulating microbiome analysis revealed that FDRs (Observed species, p=0.004; Chao1 index, p=0.005) but not patients had significantly reduced microbiome diversity compared to their controls. The majority of differentially abundant bacteria identified between UHCs and FDRs were in the Firmicutes phylum, while bacteria from several different phyla were identified between HCs and SLE patients. Bacteria in the Paenibacillus genus was the only overlapping differentially abundant bacteria in both cohorts, and it was reduced in FDRs (p.adj = 2.13 x 10-12) and SLE patients (p.adj = 0.008) but elevated in controls.

CONCLUSIONS: These results indicate a possible role for plasma microbial translocation and microbiome composition in influencing autoantibody development in SLE. This article is protected by copyright. All rights reserved.

RevDate: 2019-05-20

Petrullo L, Jorgensen MJ, Snyder-Mackler N, et al (2019)

Composition and stability of the vervet monkey milk microbiome.

American journal of primatology [Epub ahead of print].

The human milk microbiome is vertically transmitted to offspring during the postnatal period and has emerged as a critical driver of infant immune and metabolic development. Despite this importance in humans, the milk microbiome of nonhuman primates remains largely unexplored. This dearth of comparative work precludes our ability to understand how species-specific differences in the milk microbiome may differentially drive maternal effects and limits how translational models can be used to understand the role of vertically transmitted milk microbes in human development. Here, we present the first culture-independent data on the milk microbiome of a nonhuman primate. We collected milk and matched fecal microbiome samples at early and late lactation from a cohort of captive lactating vervet monkeys (N = 15). We found that, similar to humans, the vervet monkey milk microbiome comprises a shared community of taxa that are universally present across individuals. However, unlike in humans, this shared community is dominated by the genera Lactobacillus, Bacteroides, and Prevotella. We also found that, in contrast to previous culture-dependent studies in humans, the vervet milk microbiome exhibits greater alpha-diversity than the gut microbiome across lactation. Finally, we did not find support for the translocation of microbes from the gut to the mammary gland within females (i.e., "entero-mammary pathway"). Taken together, our results show that the vervet monkey milk microbiome is taxonomically diverse, distinct from the gut microbiome, and largely stable. These findings demonstrate that the milk microbiome is a unique substrate that may selectively favor the establishment and persistence of particular microbes across lactation and highlights the need for future experimental studies on the origin of microbes in milk.

RevDate: 2019-05-20

Zhong S, Zhou Z, Liang Y, et al (2019)

Targeting strategies for chemotherapy-induced peripheral neuropathy: does gut microbiota play a role?.

Critical reviews in microbiology [Epub ahead of print].

Chemotherapy-induced peripheral neuropathy (CIPN) is a progressive, often irreversible condition that produces severe neurological deficits. Emerging data suggest that chemotherapy also exerts detrimental effects on gut microbiota composition and intestinal permeability, contributing to dysbiosis and inflammation. Compared with other complications associated with chemotherapy, such as diarrhoea and mucositis, CIPN is of particular concern because it is the most common reason for terminating or suspending treatment. However, specific and effective curative treatment strategies are lacking. In this review, we provide an update on current preclinical and clinical understandings about the role of gut microbiota in CIPN. The gut microbiota serves as an intersection between the microbiome-gut-brain and the neuroimmune-endocrine axis, forming a complex network that can directly or indirectly affect key components involved in the manifestations of CIPN. Herein, we discuss several potential mechanisms within the context of the networks and summarize alterations in gut microbiome induced by chemotherapeutic drugs, providing great potential for researchers to target pathways associated with the gut microbiome and overcome CIPN.

RevDate: 2019-05-20

Montironi R, Santoni M, Cimadamore A, et al (2019)

Editorial: Emerging Biomarkers in Genitourinary Tumors.

Frontiers in oncology, 9:326.

RevDate: 2019-05-20

Sakai Y, Seki N, Hamano H, et al (2019)

A study of the prebiotic effect of lactulose at low dosages in healthy Japanese women.

Bioscience of microbiota, food and health, 38(2):69-72.

To investigate the prebiotic effect of lactulose at low dosages, we assessed changes in defaecation frequency following ingestion of 1, 2, or 3 g/day of lactulose for 2 weeks. Each test was carried out after a 2-week washout period. This was an open-label, before-after trial that enrolled 26 healthy Japanese women. The defaecation frequency, number of defaecation days, and number of faecal bifidobacteria increased significantly compared with before ingestion of 1, 2, and 3 g/day of lactulose. These results suggest that even 1 g/day of lactulose could have a prebiotic effect.

RevDate: 2019-05-20

Xiao Y, Xiao G, Liu H, et al (2019)

Captivity causes taxonomic and functional convergence of gut microbial communities in bats.

PeerJ, 7:e6844 pii:6844.

Background: Diet plays a crucial role in sculpting microbial communities. Similar diets appear to drive convergence of gut microbial communities between host species. Captivity usually provides an identical diet and environment to different animal species that normally have similar diets. Whether different species' microbial gut communities can be homogenized by a uniform diet in captivity remains unclear.

Methods: In this study, we compared gut microbial communities of three insectivorous bat species (Rhinolophus ferrumequinum, Vespertilio sinensis, and Hipposideros armiger) in captivity and in the wild using 16S rDNA sequencing. In captivity, R. ferrumequinum and V. sinensis were fed yellow mealworms, while H. armiger was fed giant mealworms to rule out the impact of an identical environment on the species' gut microbial communities.

Results: We found that the microbial communities of the bat species we studied clustered by species in the wild, while the microbial communities of R. ferrumequinum and V. sinensis in captivity clustered together. All microbial functions found in captive V. sinensis were shared by R. ferrumequinum. Moreover, the relative abundances of all metabolism related KEGG pathways did not significantly differ between captive R. ferrumequinum and V. sinensis; however, the relative abundance of "Glycan Biosynthesis and Metabolism" differed significantly between wild R. ferrumequinum and V. sinensis.

Conclusion: Our results suggest that consuming identical diets while in captivity tends to homogenize the gut microbial communities among bat species. This study further highlights the importance of diet in shaping animal gut microbiotas.

RevDate: 2019-05-20

Cicatelli A, Ferrol N, Rozpadek P, et al (2019)

Editorial: Effects of Plant-Microbiome Interactions on Phyto- and Bio-Remediation Capacity.

Frontiers in plant science, 10:533.

RevDate: 2019-05-20

Wang J, Lang T, Shen J, et al (2019)

Core Gut Bacteria Analysis of Healthy Mice.

Frontiers in microbiology, 10:887.

Previous studies revealed that there existed great individual variations of gut microbiota in mice, and the gut bacteria of mice were changed with the occurrence and development of diseases. To identify the core gut bacteria in healthy mice and explore their relationships with the host phenotypes would help to understand the underlying mechanisms. In this study, we identified 37 genus-level core bacteria from feces of 101 healthy mice with different ages, sexes, and mouse strains in three previous studies. They collectively represented nearly half of the total sequences, and predominantly included carbohydrate- and amino acids-metabolizing bacteria and immunomodulatory bacteria. Among them, Anaerostipes indwelt the gut of all healthy mice. Co-abundance analysis showed that these core genera were clustered into five groups (Group C1-C5), which were ecologically related. For example, the abundances of Group C2 including probiotics Bifidobacterium and Lactobacillus slightly positively correlated with those of Group C1. Principal component analysis (PCA) and multivariate analysis of variance test revealed that these core gut genera were distinguished with age and sex, and also associated with their health/disease state. Linear discriminant analysis effect size (LEfSe) method showed that bacteria in Group C1 and C2/C3 increased with the age in infancy and early adulthood, and were more abundant in female mice than in male ones. The metabolic syndrome (MS) induced by high fat diet (HFD) and accelerated postnatal growth would decrease Group C2 genera, whereas probiotics intervention would reverse HFD-induced reduction of Group C2. Spearman correlation analysis indicated that the principal components based on the abundance of the 37 core genera were significantly correlated with host characteristic parameters of MS. These results demonstrated that the 37 core genera in five co-abundance groups from healthy mice were related to host phenotypes. It was indicated that these prevalent gut bacterial genera could be representative of the healthy gut microbiome in gnotobiotic animal models, and might also be candidates of probiotics and fecal microbiota transplantation.

RevDate: 2019-05-20

Fuertes A, Pérez-Burillo S, Apaolaza I, et al (2019)

Adaptation of the Human Gut Microbiota Metabolic Network During the First Year After Birth.

Frontiers in microbiology, 10:848.

Predicting the metabolic behavior of the human gut microbiota in different contexts is one of the most promising areas of constraint-based modeling. Recently, we presented a supra-organismal approach to build context-specific metabolic networks of bacterial communities using functional and taxonomic assignments of meta-omics data. In this work, this algorithm is applied to elucidate the metabolic changes induced over the first year after birth in the gut microbiota of a cohort of Spanish infants. We used metagenomics data of fecal samples and nutritional data of 13 infants at five time points. The resulting networks for each time point were analyzed, finding significant alterations once solid food is introduced in the diet. Our work shows that solid food leads to a different pattern of output metabolites that can be potentially released from the gut microbiota to the host. Experimental validation is presented for ferulate, a neuroprotective metabolite involved in the gut-brain axis.

RevDate: 2019-05-20

Calon TGA, Trobos M, Johansson ML, et al (2019)

Microbiome on the Bone-Anchored Hearing System: A Prospective Study.

Frontiers in microbiology, 10:799.

The bone-anchored hearing system (BAHS) has evolved to a common treatment option for various types of hearing revalidation. The BAHS consists of an implant in the skull that breeches the skin. Soft tissue reactions are a common complication associated with BAHS and are generally poorly understood. This study aims to investigate the influence of BAHS and associated skin reactions around the implant. A total of 45 patients were prospectively followed from implantation up to at least 1 year. Swabs were obtained at baseline, 12 weeks follow-up and during cases of inflammation (Holgers score ≥2). The microbiota was assessed using IS-proTM, a bacterial profiling method based on the interspace region between the 16S-23S rRNA genes. Detection of operational taxonomic units, the Shannon Diversity Index, sample similarity analyses and Partial Least Squares Discriminant Analysis (PLS-DA) were employed. Staphylococcus epidermidis, Streptococcus pneumoniae/mitis, Propionibacterium acnes, Staphylococcus capitis, Staphylococcus hominis, Bifidobacterium longum, Haemophilus parainfluenzae, Lactobacillus rhamnosus, Bordetella spp., Streptococcus sanguinis, Peptostreptococcus anaerobius, Staphylococcus aureus, Lactococcus lactis, Enterobacter cloacae, and Citrobacter koseri were the most commonly found bacterial species. S. pneumoniae/mitis was significantly more often observed after implantation, whereas P. acnes was significantly less observed after implantation compared with baseline. The relative abundance of S. epidermidis (17%) and S. aureus (19.4%) was the highest for the group of patients with inflammation. The Shannon Diversity Index was significantly increased after implantation compared with pre-surgical swabs for Firmicutes, Actinobacteria, Fusobacteria, Verrucomicrobia (FAFV), but not for other phyla. When combining all phyla, there was no significant increase in the Shannon Diversity Index. The diversity index was similar post-surgically for patients experiencing inflammation and for patients without inflammation. With a supervised classifier (PLS-DA), patients prone to inflammation could be identified at baseline with an accuracy of 91.7%. In addition, PLS-DA could classify post-surgical abutments as non-inflamed or inflamed with an accuracy of 97.7%. This study shows the potential of using IS-proTM to describe and quantify the microbiota associated with the percutaneous BAHS. Furthermore, the results indicate the possibility of an early identification of patients susceptible to adverse skin reaction following implantation. Both S. aureus and S. epidermidis should be considered as relevant bacteria for BAHS-associated inflammation.

RevDate: 2019-05-20

Shurney D (2019)

The Gut Microbiome: Unleashing the Doctor Within.

American journal of lifestyle medicine, 13(3):265-268 pii:10.1177_1559827619826551.

RevDate: 2019-05-20

Gyongyosi B, Cho Y, Lowe P, et al (2019)

Alcohol-induced IL-17A production in Paneth cells amplifies endoplasmic reticulum stress, apoptosis, and inflammasome-IL-18 activation in the proximal small intestine in mice.

Mucosal immunology pii:10.1038/s41385-019-0170-4 [Epub ahead of print].

Gut microbial translocation contributes to alcoholic hepatitis. Using a mouse model of alcoholic hepatitis, we investigated the effects of chronic alcohol plus binge and found increased abundance of Paneth cells and IL-17A in the proximal small intestine (PSI). Alcohol increased IL-17A production and pro-apoptotic signaling evidenced by Bax, Bim, caspase-3, and caspase-8 increases via endoplasmic reticulum (ER) stress indicated by C/EBP homologous protein (CHOP) upregulation; this was prevented by the ER stress inhibitor, 4-PBA, in isolated crypts in vitro and in vivo. Mechanistically, IL-17 augmented alcohol-induced ER stress in isolated crypts. In vivo IL-17A blocking antibody administration in alcohol-treated mice attenuated ER stress-mediated apoptosis and IL-18 induction and prevented alcohol-induced impairment of tight junctions in the PSI and LPS translocation to the liver. Acute-on-chronic alcohol resulted in inflammasome activation, caspase-1 cleavage, and IL-18 production in the PSI. In vivo treatment with antibiotics or 4-PBA prevented CHOP upregulation and inflammasome activation. Our data suggest that alcohol upregulates innate immune mechanisms by increasing Paneth cell numbers and IL-17A release contributing to apoptosis amplification, inflammasome activation, and gut leakiness in the PSI. Binge alcohol-induced Paneth cell expansion, ER stress, and inflammasome activation in the PSI are modulated by the gut microbiome.

RevDate: 2019-05-20

Zeineldin M, Lowe J, B Aldridge (2019)

Contribution of the Mucosal Microbiota to Bovine Respiratory Health.

Trends in microbiology pii:S0966-842X(19)30098-8 [Epub ahead of print].

Recognizing the respiratory tract as a dynamic and complex ecosystem has enhanced our understanding of the pathophysiology of bovine respiratory disease (BRD). There is widespread evidence showing that disease-predisposing factors often disrupt the respiratory microbial ecosystem, provoking atypical colonization patterns and a progressive dysbiosis. The ecological factors that shape the respiratory microbiota, and the influence of these complex communities on bovine respiratory health, are a rich area for research exploration. Here, we review the current status of understanding of the bovine respiratory microbiota, the factors that influence its development and stability, its role in maintaining mucosal homeostasis, and ultimately its contribution to bovine health and disease. Finally, we explore the limitations of current research approaches to the microbiome and discuss potential directions for future research that can help us better understand the role of the respiratory microbiota in the health, welfare, and productivity of livestock.

RevDate: 2019-05-19

Gottlieb A, Bechmann L, A Canbay (2018)

The Presence and Severity of Nonalcoholic Steatohepatitis Is Associated with Specific Changes in Circulating Bile Acids.

Annals of hepatology, 17(3):341-342.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease nowadays with currently no approved therapies for the disease. The liver plays a pivotal role in lipid and glucose metabolism. The interactions of molecular mechanisms on the gut for example influences the development still needs to be understood. Bile acids (BA) have been shown to impact metabolic homeostasis and insulin sensitivity. Here, we comment on a study analyzing BA profiles in NAFLD patients addressing novel pathways involved in NAFLD progression.

RevDate: 2019-05-19

Li P, Wu H, Jin Y, et al (2019)

Exploring the diversity and dynamic of bacterial community vertically distributed in Tongguling National Nature Reserve in Hainan Island, China.

Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] pii:10.1007/s42770-019-00078-2 [Epub ahead of print].

National nature reserves are important for preserving ecological resources and constructing national ecological security barriers. Tongguling National Nature Reserve (TNNR) is known for its unique tropical island ecosystem and abundant biological resources. This study was conducted to characterize and compare its bacterial community diversity and composition in soils from 10, 20, and 30 cm in depth using high-throughput sequencing of 16S rDNA genes. We found that soils from 20 cm had the highest diversity and might serve as a "middle bridge" to the dynamic distribution between the 10- and 30-cm soil samples. The diversity pattern indicated that the main abundant groups varied distinctly and significantly among soils of different depths. Moreover, Chloroflexi was the most dynamic group in TNNR soils, together with another abundant but rarely reported group, Verrucomicrobia, which greatly enhanced the microbial diversity of TNNR soils. Overall, the results of this study emphasize the urgent need for greater understanding of bacterial community variations in response to human activities and climate change.

RevDate: 2019-05-19

Bajic P, Dornbier RA, Doshi CP, et al (2019)

Implications of the Genitourinary Microbiota in Prostatic Disease.

Current urology reports, 20(7):34 pii:10.1007/s11934-019-0904-6.

PURPOSE OF REVIEW: To summarize recent investigation into associations between the genitourinary microbiota and prostatic disease.

RECENT FINDINGS: The genitourinary tract is not sterile. There are microbial communities (microbiota) in each niche of the genitourinary tract including the bladder, prostate, and urethra, which have been the subject of increasing scientific interest. Investigators have utilized several unique methods to study them, resulting in a highly heterogeneous body of literature. To characterize these genitourinary microbiota, diverse clinical specimens have been analyzed, including urine obtained by various techniques, seminal fluid, expressed prostatic secretions, and prostatic tissue. Recent studies have attempted to associate the microbiota detected from these samples with urologic disease and have implicated the genitourinary microbiota in many common conditions, including benign prostatic hyperplasia (BPH), prostate cancer, and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). In this review, we summarize the recent literature pertaining to the genitourinary microbiota and its relationship to the pathophysiology and management of three common prostatic conditions: BPH, prostate cancer, and CP/CPPS.

RevDate: 2019-05-19

Mukhtar I, Anwar H, Hussain G, et al (2019)

Detection of Paracetamol as substrate of the gut microbiome.

Pakistan journal of pharmaceutical sciences, 32(2 (Supplementary)):751-757.

Gut microbiome, a new organ; represent targets to alter pharmacokinetics of orally administered drugs. Recently, in vitro trials endorsed the idea that orally administered drugs interact and some of their quantity may be taken up by normal microbiome during transit through gut. Such transport mechanisms in microbiome may compete for drug with the host itself. Currently, no data confirms specific transport system for paracetamol uptake by gut microbiome. In vivo trial was conducted in normal healthy male rats (n=36). Paracetamol was administered orally in a single dose of 75mg/kg to isolate microbial mass after transit of 2, 3, 4, 5 and 6 hours post drug administration. Paracetamol absorbance by microbiome was pursued by injecting extracted microbial lysate in RP-HPLC-UV with C18 column under isocratic conditions at 207nm using acetonitrile and water (25:75 v/v) pH 2.50 as mobile phase. Paracetamol absorbance (14.10±0.75μg/mg of microbial mass) and percent dose recovery (13.16±0.55%) seen at transit of 4 hours was significantly higher (P<0.05) compared to other groups. Study confirms the hypothesis of homology between membrane transporters of the gut microbiome and intestinal epithelium. Orally administered drugs can be absorbed by gut microbes competitively during transit in small intestine and it varies at various transit times.

RevDate: 2019-05-19

Veach AM, Morris R, Yip DZ, et al (2019)

Rhizosphere microbiomes diverge among Populus trichocarpa plant-host genotypes and chemotypes, but it depends on soil origin.

Microbiome, 7(1):76 pii:10.1186/s40168-019-0668-8.

BACKGROUND: Plants have developed defense strategies for phytopathogen and herbivore protection via coordinated metabolic mechanisms. Low-molecular weight metabolites produced within plant tissues, such as salicylic acid, represent one such mechanism which likely mediates plant - microbe interactions above and below ground. Salicylic acid is a ubiquitous phytohormone at low levels in most plants, yet are concentrated defense compounds in Populus, likely acting as a selective filter for rhizosphere microbiomes. We propagated twelve Populus trichocarpa genotypes which varied an order of magnitude in salicylic acid (SA)-related secondary metabolites, in contrasting soils from two different origins. After four months of growth, plant properties (leaf growth, chlorophyll content, and net photosynthetic rate) and plant root metabolomics specifically targeting SA metabolites were measured via GC-MS. In addition, rhizosphere microbiome composition was measured via Illumina MiSeq sequencing of 16S and ITS2 rRNA-genes.

RESULTS: Soil origin was the primary filter causing divergence in bacterial/archaeal and fungal communities with plant genotype secondarily influential. Both bacterial/archaeal and fungal evenness varied between soil origins and bacterial/archaeal diversity and evenness correlated with at least one SA metabolite (diversity: populin; evenness: total phenolics). The production of individual salicylic acid derivatives that varied by host genotype resulted in compositional differences for bacteria /archaea (tremuloidin) and fungi (salicylic acid) within one soil origin (Clatskanie) whereas soils from Corvallis did not illicit microbial compositional changes due to salicylic acid derivatives. Several dominant bacterial (e.g., Betaproteobacteria, Acidobacteria, Verrucomicrobia, Chloroflexi, Gemmatimonadete, Firmicutes) and one fungal phyla (Mortierellomycota) also correlated with specific SA secondary metabolites; bacterial phyla exhibited more negative interactions (declining abundance with increasing metabolite concentration) than positive interactions.

CONCLUSIONS: These results indicate microbial communities diverge most among soil origin. However, within a soil origin, bacterial/archaeal communities are responsive to plant SA production within greenhouse-based rhizosphere microbiomes. Fungal microbiomes are impacted by root SA-metabolites, but overall to a lesser degree within this experimental context. These results suggest plant defense strategies, such as SA and its secondary metabolites, may partially drive patterns of both bacterial/archaeal and fungal taxa-specific colonization and assembly.

RevDate: 2019-05-18

Birer C, ES Wright (2019)

Capturing the complex interplay between drugs and the intestinal microbiome.

Clinical pharmacology and therapeutics [Epub ahead of print].

Predicting drug interactions, disposition, and side effects is central to the practice of clinical pharmacology. Until recently, the human microbiome has been an underappreciated player in the dynamics of drug metabolism. It is now clear that humans are 'superorganisms' with about tenfold more microbial cells than human cells and harboring an immense diversity of microbial enzymes. Owing to the advent of new technologies, we are beginning to understand the human microbiome's impact on clinical pharmacology. This article is protected by copyright. All rights reserved.

RevDate: 2019-05-18

Pathirana E, McPherson A, Whittington R, et al (2019)

The Role of Tissue Type, Sampling and Nucleic Acid Purification Methodology on the Inferred Composition of Pacific Oyster (Crassostrea gigas) Microbiome.

Journal of applied microbiology [Epub ahead of print].

AIMS: This study evaluated methods to sample and extract nucleic acids from Pacific oysters to accurately determine the microbiome associated with different tissues.

METHODS AND RESULTS: Samples were collected from haemolymph, gill, gut and adductor-muscle, using swabs and homogenates of solid tissues. Nucleic acids were extracted from fresh and frozen samples using three different commercial kits. The bacterial DNA yield varied between methods (P < 0.05) and each tissue harboured a unique microbiota, except for gill and muscle. Higher bacterial DNA yields were obtained by swabbing compared to tissue homogenates and from fresh tissues compared to frozen tissues, without impacting the bacterial community composition estimated by 16S rRNA gene (V1-V3 region) sequencing. Despite the higher bacterial DNA yields with QIAamp® DNA microbiome kit, the E.Z.N.A.® Mollusc DNA kit identified twice as many operational taxonomic units (OTUs) and eliminated PCR inhibition from gut tissues.

CONCLUSIONS: Sampling and nucleic acid purification substantially affected the quantity and diversity of bacteria identified in Pacific oyster microbiome studies and a fit-for-purpose strategy is recommended.

Accurate identification of Pacific oyster microbial diversity is instrumental for understanding the polymicrobial aetiology of Pacific oyster mortality diseases which greatly impact oyster production. This article is protected by copyright. All rights reserved.

RevDate: 2019-05-18

Yu XL, Chan Y, Zhuang L, et al (2019)

Intra-oral single site comparisons of periodontal and peri-implant microbiota in health and disease.

Clinical oral implants research [Epub ahead of print].

OBJECTIVE: Periodontitis and peri-implantitis are oral infectious-inflammatory diseases that share similarities in their pathology and etiology. Our objective was to characterize the single-site subgingival and submucosal microbiomes of implant-rehabilitated, partially dentate Chinese subjects (n=18) presenting with both periodontitis and peri-implantitis.

MATERIALS AND METHODS: Subgingival/submucosal plaque samples were collected from four clinically-distinct sites in each subject: peri-implantitis submucosa (DI), periodontal pocket (DT), clinically-healthy (unaffected) peri-implant submucosa (HI), and clinically-healthy (unaffected) subgingival sulcus (HT). The bacterial microbiota present was analysed using Illumina MiSeq sequencing.

RESULTS: 26 phyla and 5,726 Operational Taxonomic Units (OTUs, 97% sequence similarity cut-off) were identified. Firmicutes, Proteobacteria, Fusobacteria, Bacteroidetes, Actinobacteria, Synergistetes, TM7 and Spirochaetes comprised 99.6% of the total reads detected. Bacterial communities within the DI, DT, HI and HT sites shared high levels of taxonomic similarity. 31 'core species' were present in >90% sites; with Streptococcus infantis/mitis/oralis (HMT-070/HMT-071/HMT-638/HMT-677) and Fusobacterium sp. HMT-203/HMT-698 being particularly prevalent and abundant. Beta-diversity analyses (Permanova-test, weighted-UniFrac) revealed the largest variance in the microbiota was at the subject level (46%), followed by periodontal health status (4%). Differing sets of OTUs were associated with periodontitis and peri-implantitis sites, respectively. This included putative 'periodontopathogens, such as Prevotella, Porphyromonas, Tannerella, Bacteroidetes [G-5] and Treponema spp. Interaction network analysis identified several putative patterns underlying dysbiosis in periodontitis/peri-implantitis sites.

CONCLUSIONS: Species (OTU) composition of the periodontal and peri-implant microbiota varied widely between subjects. The inter-subject variations in subgingival/submucosal microbiome composition outweighed differences observed between implant versus tooth sites, or between diseased versus healthy (unaffected) peri-implant/periodontal sites. This article is protected by copyright. All rights reserved.

RevDate: 2019-05-18

Eble H, Joswig M, Lamberti L, et al (2019)

Cluster partitions and fitness landscapes of the Drosophila fly microbiome.

Journal of mathematical biology pii:10.1007/s00285-019-01381-0 [Epub ahead of print].

The concept of genetic epistasis defines an interaction between two genetic loci as the degree of non-additivity in their phenotypes. A fitness landscape describes the phenotypes over many genetic loci, and the shape of this landscape can be used to predict evolutionary trajectories. Epistasis in a fitness landscape makes prediction of evolutionary trajectories more complex because the interactions between loci can produce local fitness peaks or troughs, which changes the likelihood of different paths. While various mathematical frameworks have been proposed to investigate properties of fitness landscapes, Beerenwinkel et al. (Stat Sin 17(4):1317-1342, 2007a) suggested studying regular subdivisions of convex polytopes. In this sense, each locus provides one dimension, so that the genotypes form a cube with the number of dimensions equal to the number of genetic loci considered. The fitness landscape is a height function on the coordinates of the cube. Here, we propose cluster partitions and cluster filtrations of fitness landscapes as a new mathematical tool, which provides a concise combinatorial way of processing metric information from epistatic interactions. Furthermore, we extend the calculation of genetic interactions to consider interactions between microbial taxa in the gut microbiome of Drosophila fruit flies. We demonstrate similarities with and differences to the previous approach. As one outcome we locate interesting epistatic information on the fitness landscape where the previous approach is less conclusive.

RevDate: 2019-05-18

DiLegge MJ, Manter DK, JM Vivanco (2019)

A novel approach to determine generalist nematophagous microbes reveals Mortierella globalpina as a new biocontrol agent against Meloidogyne spp. nematodes.

Scientific reports, 9(1):7521 pii:10.1038/s41598-019-44010-y.

Root-knot nematodes (RKN) such as Meloidogyne spp. are among the most detrimental pests in agriculture affecting several crops. New methodologies to manage RKN are needed such as efficient discovery of nematophagous microbes. In this study, we developed an in vitro high-throughput method relying on the free-living nematode Caenorhabditis elegans and the infection of those nematodes with a soil slurry containing a microbiome likely to house nematophagous microbes. Nematodes were monitored for presence of infection and sub-cultured repeatedly for the purpose of isolating pure cultures of the microbe responsible for conferring the nematicidal activity. Once soil microbes were confirmed to be antagonistic to C. elegans, they were tested for pathogenicity against Meloidogyne chitwoodi. Using this methodology, the fungal isolate Mortierella globalpina was confirmed to be pathogenic in vitro against M. chitwoodi by nematode trapping via hyphal adhesion to the cuticle layer, penetration of the cuticle layer, and subsequently digestion of its cellular contents. M. globalpina was also observed to reduce disease symptomology of RKNs in vivo via significant reduction of root-galls on tomato (Solanum lycopersicum var. Rutgers).

RevDate: 2019-05-18

Cho EJ, Leem S, Kim SA, et al (2019)

Circulating Microbiota-Based Metagenomic Signature for Detection of Hepatocellular Carcinoma.

Scientific reports, 9(1):7536 pii:10.1038/s41598-019-44012-w.

Circulating microbial dysbiosis is associated with chronic liver disease including nonalcoholic steatohepatitis and alcoholic liver disease. In this study, we evaluated whether disease-specific alterations of circulating microbiome are present in patients with cirrhosis and hepatocellular carcinoma (HCC), and their potential as diagnostic biomarkers for HCC. We performed cross-sectional metagenomic analyses of serum samples from 79 patients with HCC, 83 with cirrhosis, and 201 matching healthy controls, and validated the results in the same number of subjects. Serum bacterial DNA was analyzed using high-throughput pyrosequencing after amplification of the V3-V4 hypervariable regions of 16S rDNA. Blood microbial diversity was significantly reduced in HCC, compared with cirrhosis and control. There were significant differences in the relative abundances of several bacterial taxa that correlate with the presence of HCC, thus defining a specific blood microbiome-derived metagenomic signature of HCC. We identified 5 microbial gene markers-based model which distinguished HCC from controls with an area under the receiver-operating curve (AUC) of 0.879 and a balanced accuracy of 81.6%. In the validation, this model accurately distinguished HCC with an AUC of 0.875 and an accuracy of 79.8%. In conclusion, circulating microbiome-based signatures may be potential biomarkers for the detection HCC.

RevDate: 2019-05-18

Marie Booth J, Fusi M, Marasco R, et al (2019)

The role of fungi in heterogeneous sediment microbial networks.

Scientific reports, 9(1):7537 pii:10.1038/s41598-019-43980-3.

While prokaryote community diversity and function have been extensively studied in soils and sediments, the functional role of fungi, despite their huge diversity, is widely unexplored. Several studies have, nonetheless, revealed the importance of fungi in provisioning services to prokaryote communities. Here, we hypothesise that the fungal community plays a key role in coordinating entire microbial communities by controlling the structure of functional networks in sediment. We selected a sediment environment with high niche diversity due to prevalent macrofaunal bioturbation, namely intertidal mangrove sediment, and explored the assembly of bacteria, archaea and fungi in different sediment niches, which we characterised by biogeochemical analysis, around the burrow of a herbivorous crab. We detected a high level of heterogeneity in sediment biogeochemical conditions, and diverse niches harboured distinct communities of bacteria, fungi and archaea. Saprotrophic fungi were a pivotal component of microbial networks throughout and we invariably found fungi to act as keystone species in all the examined niches and possibly acting synergistically with other environmental variables to determine the overall microbial community structure. In consideration of the importance of microbial-based nutrient cycling on overall sediment ecosystem functioning, we underline that the fungal microbiome and its role in the functional interactome cannot be overlooked.

RevDate: 2019-05-18

Van der Helm JJ, Schim van der Loeff MF, de Vries E, et al (2019)

Vaginal herb use and Chlamydia trachomatis infection: cross-sectional study among women of various ethnic groups in Suriname.

BMJ open, 9(5):e025417 pii:bmjopen-2018-025417.

OBJECTIVE: Vaginal steam baths with herb leaves (herb use) is practised by some Surinamese women. We assessed herb use among women from the five most prevalent ethnic groups, and if herb use is associated with Chlamydia trachomatis infection.

SETTING: Participants were recruited at a sexually transmitted infection (STI) clinic and a family planning clinic (FP) in Paramaribo, Suriname.

PARTICIPANTS: 1040 women were included subsequently, comprising the following ethnic groups: Creole (26.7%), Hindustani (24.6%), Javanese (15.7%), Maroon (13.3%) and mixed descent (19.7%).

METHODS: Nurses collected a questionnaire and vaginal swabs for nucleic acid amplification C. trachomatis testing.

PRIMARY OUTCOMES: Determinants of vaginal herb use and C. trachomatis infection via univariable and multivariable logistic regression.

RESULTS: Herb use was most common among Maroon (68.8%) and Creole women (25.2%). In multivariable analysis including only Maroon and Creole women, determinants significantly associated with vaginal herb use were (OR; 95% CI): Maroon ethnic descent (5.33; 3.26 to 8.71 vs Creole), recruitment at the STI clinic (2.04; 1.24 to 3.36 vs FP), lower education levels (3.80; 1.68 to 8.57 lower vs higher, and 2.02; 0.90 to 4.51 middle vs higher). Lower age and recruitment at the STI clinic were associated with C. trachomatis infection, but not vaginal herb use.

CONCLUSION: In Suriname, vaginal herb use is common among Maroon and Creole women. Education, ethnic group and recruitment site were determinants for herb use. Vaginal herb use was not a determinant of C. trachomatis infection. Future research should focus on the effect of herb use on the vaginal microbiome and mucosal barrier.

RevDate: 2019-05-18

Frimodt-Møller N (2019)

The urine microbiome - Contamination or a novel paradigm?.

EBioMedicine pii:S2352-3964(19)30317-2 [Epub ahead of print].

RevDate: 2019-05-18

Hagihara M, Yamashita R, Matsumoto A, et al (2019)

The impact of probiotic Clostridium butyricum MIYAIRI 588 on murine gut metabolic alterations.

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy pii:S1341-321X(19)30039-X [Epub ahead of print].

INTRODUCTION: Clostridium butyricum MIYAIRI 588 (CBM 588) is a probiotic bacterium used in antidiarrheal medicine in Japan. A few studies analyzed the changes in gut microbiome in patients treated with antimicrobials based on metagenomics sequencing. However, the impact of CBM 588 on gut metabolic alterations has not been fully elucidated. This study was to reveal the impact of CBM 588 on gut metabolic alterations.

MATERIAL AND METHODS: In this in vivo study, mice were divided into four groups and CBM 588, clindamycin (CLDM), and normal saline (control) was orally administered (1. CLDM, 2. CBM 588, 3. CBM 588 + CLDM, 4. water) for 4 days. Fecal samples were collected to extract DNA for metagenomics analysis. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to obtain relative Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway abundance information derived from metagenomics data.

RESULTS: CLDM treatment resulted in a dramatic increase in Firmicutes phylum compared to non-CLDM-treated groups (control and CBM 588-treated group). Then, the CBM 588 + CLDM-treated group showed a trend similar in many metabolic pathways to the CLDM-treated group. On the other hand, the CBM 588 + CLDM-treated group showed higher relative abundance compared to the CLDM-treated group especially in starch and sucrose metabolism.

DISCUSSION: We concluded that CBM 588 caused a gut microbiome functional shift toward increased carbohydrate metabolism. These results support the hypothesis that CBM 588 treatment modulates gut microbiome under dysbiosis conditions due to antimicrobials.

RevDate: 2019-05-18

Harris TA, Gattu S, Propheter DC, et al (2019)

Resistin-like Molecule α Provides Vitamin-A-Dependent Antimicrobial Protection in the Skin.

Cell host & microbe pii:S1931-3128(19)30207-0 [Epub ahead of print].

Vitamin A deficiency increases susceptibility to skin infection. However, the mechanisms by which vitamin A regulates skin immunity remain unclear. Here, we show that resistin-like molecule α (RELMα), a small secreted cysteine-rich protein, is expressed by epidermal keratinocytes and sebocytes and serves as an antimicrobial protein that is required for vitamin-A-dependent resistance to skin infection. RELMα was induced by microbiota colonization of the murine skin, was bactericidal in vitro, and was protected against bacterial infection of the skin in vivo. RELMα expression required dietary vitamin A and was induced by the therapeutic vitamin A analog isotretinoin, which protected against skin infection in a RELMα-dependent manner. The RELM family member Resistin was expressed in human skin, was induced by vitamin A analogs, and killed skin bacteria, indicating a conserved function for RELM proteins in skin innate immunity. Our findings provide insight into how vitamin A promotes resistance to skin infection.

RevDate: 2019-05-18

Goel N, Nadler A, Reddy S, et al (2019)

Biliary microbiome in pancreatic cancer: alterations with neoadjuvant therapy.

HPB : the official journal of the International Hepato Pancreato Biliary Association pii:S1365-182X(19)30522-2 [Epub ahead of print].

BACKGROUND: Neoadjuvant therapy for pancreatic cancer is being employed more commonly. Most of these patients undergo biliary stenting which results in bacterial colonization and more surgical site infections (SSIs). However, the influence of neoadjuvant therapy on the biliary microbiome has not been studied.

METHODS: From 2007 to 2017, patients at our institution who underwent pancreatoduodenectomy (PD) and had operative bile cultures were studied. Patient demographics, stent placement, bile cultures, bacterial sensitivities, SSIs and clinically-relevant postoperative pancreatic fistulas (CR-POPF) were analyzed. Patients who underwent neoadjuvant therapy were compared to those who went directly to surgery. Standard statistical analyses were performed.

RESULTS: Eighty-three patients received neoadjuvant therapy while 89 underwent surgery alone. Patients who received neoadjuvant therapy were more likely to have enterococci (45 vs 22%, p < 0.01), and Klebsiella (37 vs 19%, p < 0.01) in their bile. Resistance to cephalosporins was more common in those who received neoadjuvant therapy (76 vs 60%, p < 0.05). Neoadjuvant therapy did not affect the incidence of SSIs or CR-POPFs.

CONCLUSION: The biliary microbiome is altered in patients undergoing pancreatoduodenectomy (PD) after neoadjuvant therapy. Most patients undergoing PD with a biliary stent have microorganisms resistant to cephalosporins. Antibiotic prophylaxis in these patients should cover enterococci and gram-negative bacteria.

RevDate: 2019-05-18

Jeong Y, Kim JW, You HJ, et al (2019)

Gut Microbial Composition and Function Are Altered in Patients with Early Rheumatoid Arthritis.

Journal of clinical medicine, 8(5): pii:jcm8050693.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation of the joints and extra-articular manifestations. Recent studies have shown that microorganisms affect RA pathogenesis. However, few studies have examined the microbial distribution of early RA patients, particularly female patients. In the present study, we investigated the gut microbiome profile and microbial functions in early RA female patients, including preclinical and clinically apparent RA cases. Changes in microbiological diversity, composition, and function in each group were analyzed using quantitative insights into microbial ecology (QIIME) and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). The results revealed the dysbiosis due to decreased diversity in the early RA patients compared with healthy subjects. There were significant differences in the microbial distribution of various taxa from phylum to genus levels between healthy subjects and early RA patients. Phylum Bacteroidetes was enriched in early RA patients, while Actinobacteria, including the genus Collinsella, was enriched in healthy subjects. Functional analysis based on clusters of orthologous groups revealed that the genes related to the biosynthesis of menaquinone, known to be derived from gram-positive bacteria, were enriched in healthy subjects, while iron transport-related genes were enriched in early RA patients. Genes related to the biosynthesis of lipopolysaccharide, the gram-negative bacterial endotoxin, were enriched in clinically apparent RA patients. The obvious differences in microbial diversity, taxa, and associated functions of the gut microbiota between healthy subjects and early RA patients highlight the involvement of the gut microbiome in the early stages of RA.

RevDate: 2019-05-17

Zheng F, Zhu D, Giles M, et al (2019)

Mineral and organic fertilization alters the microbiome of a soil nematode Dorylaimus stagnalis and its resistome.

The Science of the total environment, 680:70-78 pii:S0048-9697(19)31929-1 [Epub ahead of print].

Although the effects of fertilization on the abundance and diversity of soil nematodes have been widely studied, the impact of fertilization on soil nematode microbiomes remains largely unknown. Here, we investigated how different fertilizers: no fertilizer, mineral fertilizer, clean slurry (pig manure with a reduced antibiotic burden) and dirty slurry (pig manure with antibiotics) affect the microbiome of a dominant soil nematode and its associated antibiotic resistance genes (ARGs). The results of 16S rRNA gene high throughput sequencing showed that the microbiome of the soil nematode Dorylaimus stagnalis is diverse (Shannon index: 9.95) and dominated by Proteobacteria (40.3%). Application of mineral fertilizers significantly reduced the diversity of the nematode microbiome (by 28.2%; P < 0.05) but increased the abundance of Proteobacteria (by 70.1%; P = 0.001). Microbial community analysis, using a null hypothesis model, indicated that microbiomes associated with the nematode are not neutrally assembled. Organic fertilizers also altered the diversity of the nematode microbiome, but had no impact on its composition as illustrated by principal coordinates analysis (PCoA). Interestingly, although no change of total ARGs was observed in the nematode microbiome and no significant relationship existed between nematode microbiome and resistome, the abundance of 48 out of a total of 75 ARGs was enriched in the organic fertilizer treatments. Thus, the data suggests that ARGs in the nematode microbiome still had a risk of horizontal gene transfer under fertilization and nematodes might be a potential refuge for ARGs.

RevDate: 2019-05-17

Awoyemi A, Trøseid M, Arnesen H, et al (2019)

Effects of dietary intervention and n-3 PUFA supplementation on markers of gut-related inflammation and their association with cardiovascular events in a high-risk population.

Atherosclerosis, 286:53-59 pii:S0021-9150(19)30409-5 [Epub ahead of print].

BACKGROUND & AIMS: Dysbiosis of the gut microbiota is associated with increased levels of circulating lipopolysaccharide (LPS) and subsequent activation of systemic inflammation. Diet is an important modulator of the gut microbiome. We aimed to investigate whether circulating markers of gut-related inflammation, LPS binding protein (LBP) and soluble CD14 (sCD14) can be modulated by n-3 PUFA supplementation and/or diet counselling, and whether these markers are related to cardiovascular (CV) outcome.

METHODS: 484 men aged 65-75 years, at high CV-risk, were included and randomized in a 2 × 2 factorial design to 36-month intervention with dietary counselling, n-3 PUFA supplementation, or both. N-3 PUFA supplementation was placebo-controlled. ELISAs were used for determination of the biomarkers measured at baseline and study-end. A composite endpoint was defined as new CV-events and CV-mortality after 36 months.

RESULTS: There were no significant differences in changes of either LBP or sCD14 in the intervention groups compared to their respective controls (n-3 PUFA vs. placebo: p = 0.58, p = 0.15, diet vs. no-diet: p = 0.53, p = 0.59, respectively). The group with LBP levels above median had about 2-fold unadjusted risk of suffering an endpoint compared to the group below (HR 2.22, 95% CI 1.25-3.96; p = 0.01). A similar tendency was seen for sCD14 (HR 1.72, 95% CI 0.97-3.03; p = 0.06). After adjusting for covariates, LBP remained significantly associated with a two-fold CV-risk, whereas sCD14 gained statistical significance, however, lost when hsCRP was added to the model.

CONCLUSIONS: In our population, markers of gut-related inflammation associated with 36-month CV outcome. However, neither n-3 PUFA nor diet intervention had an effect on these markers.

RevDate: 2019-05-17

Bautista-de Los Santos QM, Chavarria KA, KL Nelson (2019)

Understanding the impacts of intermittent supply on the drinking water microbiome.

Current opinion in biotechnology, 57:167-174 pii:S0958-1669(18)30165-4 [Epub ahead of print].

Increasing access to piped water in low-income and middle-income countries combined with the many factors that threaten our drinking water supply infrastructure mean that intermittent water supply (IWS) will remain a common practice around the world. Common features of IWS include water stagnation, pipe drainage, intrusion, backflow, first flush events, and household storage. IWS has been shown to cause degradation as measured by traditional microbial water quality indicators. In this review, we build on new insights into the microbial ecology of continuous water supply systems revealed by sequencing methods to speculate about how intermittent supply conditions may further influence the drinking water microbiome, and identify priorities for future research.

RevDate: 2019-05-17

Yu L, He J, Wang L, et al (2019)

Incidence, aetiology, and serotype spectrum analysis of adult HFMD patients: a retrospective observational cohort study in Northern Zhejiang, China.

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases pii:S1201-9712(19)30222-X [Epub ahead of print].

BACKGROUND: Hand, foot, and mouth disease (HFMD) was rare among adults, whereas its clinical significance was underestimated. This study tried to systematically elucidate the epidemiological characteristics of adult HFMD.

METHODS: 266 adult patients of HFMD were recruited, with 40 healthy subjects served as the control. Swap or serum samples were collected. Enterovirus strain was tested by RT-PCR, and the cytokine expression was examined by commercial kits. Social-demographic data was collected through follow-up phone calls. Daily meteorological data were obtained from the China Meteorological Data Sharing Service System. Social-economic data was collected from the statistical bureau.

RESULTS: This study found several unique spatiotemporal patterns of the adult HFMD. Having children diagnosed as HFMD recently was a risk factor of HFMD, whereas keeping pets was an HFMD protective factor. Results of the study implied the existence of subclinical carriers or misdiagnosed patients who might be the latent infectious source of HFMD. Further, our study also indicated adults may act as the main infectious source of trans-regional spread of HFMD.

CONCLUSION: This study revealed the potential hazards of adult HFMD and reminded us of the vital clinical significance of further research to adult HFMD.

RevDate: 2019-05-17

Forster CS, Hsieh MH, Pérez-Losada M, et al (2019)

A single intravesical instillation of Lactobacillus rhamnosus GG is safe in children and adults with neuropathic bladder: A phase Ia clinical trial.

The journal of spinal cord medicine [Epub ahead of print].

CONTEXT/OBJECTIVE: Manipulation of the microbiome is an emerging approach to promote health. We conducted a Phase Ia safety study of a single bladder instillation of probiotics in asymptomatic patients with neuropathic bladder to determine the tolerability and safety of a single Lactobacillus instillation.

DESIGN: Phase Ia safety study.

SETTING: Outpatient rehabilitation clinic at a rehabilitation hospital (adults) and urology clinic at a free-standing children's hospital (children).

PARTICIPANTS: Ten patients with neuropathic bladder were included: five children with spina bifida and five adults with spinal cord injury.

INTERVENTIONS: A single Lactobacillus rhamnosus GG (Culturelle, 20 billion live organisms) instillation.

OUTCOME MEASURES: After the instillation, participants self-monitored symptoms using the Urinary Symptoms Questionnaire for People with Neuropathic Bladder using Intermittent Catheterization daily for one week. Repeat urinalysis, urine culture, and 16S bacterial rRNA-based microbiome analyses were performed 7-10 days after instillation.

RESULTS: Probiotic instillation was well-tolerated. One child had upper respiratory tract symptoms during the trial, and two had transient cloudy urine. No adults reported any symptoms following instillation. Lactobacillus did not grow on culture post-instillation. There were differences in beta diversity of the urine microbiome in children vs. adults with neuropathic bladder (P < 0.0156). Lactobacillus was present in the pre-instillation urinary microbiomes all of the adults and 4 out of 5 of the pediatric subjects, and identified in 4 out of 5 of both the adult and pediatric subjects' post-instillation urinary microbiomes.

CONCLUSION: Intravesical instillation of Culturelle probiotic may be safe and well-tolerated in patients with neuropathic bladder.

RevDate: 2019-05-17

Ramadan M, Solyman S, Yones M, et al (2019)

Skin Microbiome Differences in Atopic Dermatitis and Healthy Controls in Egyptian Children and Adults, and Association with Serum Immunoglobulin E.

Omics : a journal of integrative biology, 23(5):247-260.

Atopic dermatitis (AD) is a complex, multifactorial, chronic pruritic inflammatory skin disease. We report the first microbiome study and new insights on the relationship between skin microbiota variation and AD susceptibility in a population sample from Egypt. We characterized the skin microbiome in 75 patients with AD and 20 healthy controls using Illumina MiSeq sequencing of 16S rRNA gene. Overall, bacterial diversity of skin microbiome in patients with AD was less than those of the healthy subjects. Genus level analysis revealed significant abundance variations by age, disease severity, locality, or immune response. Among these genera, Streptococcus, Cutibacterium, and Corynebacterium appeared to be specific signatures for AD in children, adolescents, and adults, respectively, while Staphylococcus was noted as a potential biomarker candidate for AD. Additionally, functional potential of metagenomes shifted the overall metabolic pathways to participate in the exacerbation of disease. Total immunoglobulin E (IgE) levels were positively correlated with relative enrichment of certain Staphylococcus aureus subspecies. Finally, AD-related differences in skin bacterial diversity appeared to be in part linked to the serum IgE level. These new observations attest to the promise of microbiome science and metagenomic analysis in AD specifically, and clinical dermatology broadly.

RevDate: 2019-05-17

Aruoma OI, Hausman-Cohen S, Pizano J, et al (2019)

Personalized Nutrition: Translating the Science of NutriGenomics Into Practice: Proceedings From the 2018 American College of Nutrition Meeting.

Journal of the American College of Nutrition, 38(4):287-301.

Adverse reactions to foods and adverse drug reactions are inherent in product defects, medication errors, and differences in individual drug exposure. Pharmacogenetics is the study of genetic causes of individual variations in drug response and pharmacogenomics more broadly involves genome-wide analysis of the genetic determinants of drug efficacy and toxicity. The similarity of nutritional genomics and pharmacogenomics stems from the innate goal to identify genetic variants associated with metabolism and disease. Thus, nutrigenomics can be thought of as encompassing gene-diet interactions involving diverse compounds that are present in even the simplest foods. The advances in the knowledge base of the complex interactions among genotype, diet, lifestyle, and environment is the cornerstone that continues to elicit changes in current medical practice to ultimately yield personalized nutrition recommendations for health and risk assessment. This information could be used to understand how foods and dietary supplements uniquely affect the health of individuals and, hence, wellness. The individual's gut microbiota is not only paramount but pivotal in embracing the multiple-functional relationships with complex metabolic mechanisms involved in maintaining cellular homeostasis. The genetic revolution has ushered in an exciting era, one in which many new opportunities are expected for nutrition professionals with expertise in nutritional genomics. The American College of Nutrition's conference focused on "Personalized Nutrition: Translating the Science of NutriGenomics Into Practice" was designed to help to provide the education needed for the professional engagement of providers in the personalized medicine era.

RevDate: 2019-05-17

Amato KR, Maurice CF, Guillemin K, et al (2019)

Multidisciplinarity in Microbiome Research: A Challenge and Opportunity to Rethink Causation, Variability, and Scale.

BioEssays : news and reviews in molecular, cellular and developmental biology [Epub ahead of print].

This essay, written by a biologist, a microbial ecologist, a biological anthropologist, and an anthropologist-historian, examines tensions and translations in microbiome research on animals in the laboratory and field. The authors trace how research questions and findings in the laboratory are extrapolated into the field and vice versa, and the shifting evidentiary standards that these research settings require. Showing how complexities of microbiomes challenge traditional standards of causation, the authors contend that these challenges require new approaches to inferences used in ecology, anthropology, and history. As social scientists incorporate investigations of microbial life into their human studies, microbiome researchers venture into field settings to develop mechanistic understandings about the functions of complex microbial communities. These efforts generate new possibilities for cross-fertilizations and inference frameworks to interpret microbiome findings. Microbiome research should integrate multiple scales, levels of variability, and other disciplinary approaches to tackle questions spanning conditions from the laboratory to the field.

RevDate: 2019-05-17

Bosch TCG, Guillemin K, M McFall-Ngai (2019)

Evolutionary "Experiments" in Symbiosis: The Study of Model Animals Provides Insights into the Mechanisms Underlying the Diversity of Host-Microbe Interactions.

BioEssays : news and reviews in molecular, cellular and developmental biology [Epub ahead of print].

Current work in experimental biology revolves around a handful of animal species. Studying only a few organisms limits science to the answers that those organisms can provide. Nature has given us an overwhelming diversity of animals to study, and recent technological advances have greatly accelerated the ability to generate genetic and genomic tools to develop model organisms for research on host-microbe interactions. With the help of such models the authors therefore hope to construct a more complete picture of the mechanisms that underlie crucial interactions in a given metaorganism (entity consisting of a eukaryotic host with all its associated microbial partners). As reviewed here, new knowledge of the diversity of host-microbe interactions found across the animal kingdom will provide new insights into how animals develop, evolve, and succumb to the disease.

RevDate: 2019-05-17

Bauer KC, Rees T, BB Finlay (2019)

The Gut Microbiota-Brain Axis Expands Neurologic Function: A Nervous Rapport.

BioEssays : news and reviews in molecular, cellular and developmental biology [Epub ahead of print].

Does exploration of the gut microbiota-brain axis expand our understanding of what it means to be human? Recognition and conceptualization of a gut microbiota-brain axis challenges our study of the nervous system. Here, integrating gut microbiota-brain research into the metaorganism model is proposed. The metaorganism-an expanded, dynamic unit comprising the host and commensal organisms-asserts a radical blurring between man and microbe. The metaorganism nervous system interacts with the exterior world through microbial-colored lenses. Ongoing studies have reported that gut microbes contribute to brain function and pathologies, even shaping higher neurological functions. How will continued collaborative efforts (e.g., between neurobiology and microbiology), including partnerships with the arts (e.g., philosophy), contribute to the knowledge of microbe-to-mind interactions? While this is not a systemic review, this nascent field is briefly described, highlighting ongoing challenges and recommendations for emerging gut microbiota-brain research.

RevDate: 2019-05-17

Zuo K, Li J, Xu Q, et al (2019)

Dysbiotic gut microbes may contribute to hypertension by limiting vitamin D production.

Clinical cardiology [Epub ahead of print].

BACKGROUND: Accumulating studies have suggested that gut microbiota (GM) dysbiosis and vitamin D3 deficiency each play an important role during the progression of hypertension (HTN). However, few studies have characterized the underlying interaction between gut microbiota shift and vitamin D3 deficiency in HTN patients.

HYPOTHESIS: This study aimed to evaluate the possible crosstalk between GM dysbiosis and vitamin D deficiency in the pathogenesis of HTN METHODS: In a cohort of 34 HTN patients and 15 healthy controls, we analyzed the fecal microbiota products, GM composition, and the interaction between GM and vitamin D3.

RESULTS: Vitamin D3 was significantly decreased in feces of HTN patients (p=0.006, vs. controls) and was correlated with altered GM, including decreased Shannon index (R2 =0.1296, p=0.0111) and Pielou evenness (R2 =0.1509, p=0.0058). Moreover, vitamin D3 positively correlated with HTN-reduced bacterial genera, including Subdoligranulum (R2 =0.181, p=0.0023), Ruminiclostridium (R2 =0.1217, p=0.014), Intestinimonas (R2 =0.2036, p=0.0011), Pseudoflavonifractor (R2 =0.1014, p=0.0257), Paenibacillus (R2 =0.089, p=0.0373) and Marvinbryantia (R2 =0.08173, p=0.0464). Partial least squares structural equation modeling showed that 27.7% of the total effect of gut microbiome on HTN was mediated by limiting vitamin D production. Finally, receiver operating characteristic curve analysis revealed the predictive capacity of differential gut microbiome signatures and decreased vitamin D3 to distinguish HTN patients (AUC=0.749, p=0.006).

CONCLUSIONS: Our findings suggest that the GM dysbiosis contributing to the development of HTN might be partially mediated by vitamin D3 deficiency. Future studies involving the underlying mechanism and intervention strategies targeting microbiome composition and vitamin D3 to counteract the progression of HTN are warranted.

RevDate: 2019-05-17

Sato Y, Hori T, Koike H, et al (2019)

Transcriptome analysis of activated sludge microbiomes reveals an unexpected role of minority nitrifiers in carbon metabolism.

Communications biology, 2:179 pii:418.

Although metagenomics researches have illuminated microbial diversity in numerous biospheres, understanding individual microbial functions is yet difficult due to the complexity of ecosystems. To address this issue, we applied a metagenome-independent, de novo assembly-based metatranscriptomics to a complex microbiome, activated sludge, which has been used for wastewater treatment for over a century. Even though two bioreactors were operated under the same conditions, their performances differed from each other with unknown causes. Metatranscriptome profiles in high- and low-performance reactors demonstrated that denitrifiers contributed to the anaerobic degradation of heavy oil; however, no marked difference in the gene expression was found. Instead, gene expression-based nitrification activities that fueled the denitrifiers by providing the respiratory substrate were notably high in the high-performance reactor only. Nitrifiers-small minorities with relative abundances of <0.25%-governed the heavy-oil degradation performances of the reactors, unveiling an unexpected linkage of carbon- and nitrogen-metabolisms of the complex microbiome.

RevDate: 2019-05-17

Armour CR, Nayfach S, Pollard KS, et al (2019)

A Metagenomic Meta-analysis Reveals Functional Signatures of Health and Disease in the Human Gut Microbiome.

mSystems, 4(4): pii:mSystems00332-18.

While recent research indicates that human health is affected by the gut microbiome, the functional mechanisms that underlie host-microbiome interactions remain poorly resolved. Metagenomic clinical studies can address this problem by revealing specific microbial functions that stratify healthy and diseased individuals. To improve our understanding of the relationship between the gut microbiome and health, we conducted the first integrative functional analysis of nearly 2,000 publicly available fecal metagenomic samples obtained from eight clinical studies. We identified characteristics of the gut microbiome that associate generally with disease, including functional alpha-diversity, beta-diversity, and beta-dispersion. Using regression modeling, we identified specific microbial functions that robustly stratify diseased individuals from healthy controls. Many of these functions overlapped multiple diseases, suggesting a general role in host health, while others were specific to a single disease and may indicate disease-specific etiologies. Our results clarify potential microbiome-mediated mechanisms of disease and reveal features of the microbiome that may be useful for the development of microbiome-based diagnostics. IMPORTANCE The composition of the gut microbiome associates with a wide range of human diseases, but the mechanisms underpinning these associations are not well understood. To shift toward a mechanistic understanding, we integrated distinct metagenomic data sets to identify functions encoded in the gut microbiome that associate with multiple diseases, which may be important to human health. Additionally, we identified functions that associate with specific diseases, which may elucidate disease-specific etiologies. We demonstrated that the functions encoded in the microbiome can be used to classify disease status, but the inclusion of additional patient covariates may be necessary to obtain sufficient accuracy. Ultimately, this analysis advances our understanding of the gut microbiome functions that constitute a healthy microbiome and identifies potential targets for microbiome-based diagnostics and therapeutics.

RevDate: 2019-05-17

Werbner M, Barsheshet Y, Werbner N, et al (2019)

Social-Stress-Responsive Microbiota Induces Stimulation of Self-Reactive Effector T Helper Cells.

mSystems, 4(4): pii:mSystems00292-18.

Stressful life events are considered a risk factor for autoimmune disorders, though the mechanisms are unclear. Here we demonstrate that chronic social stress induces virulence-associated transcriptional patterns in the murine gut microbiota. The stress-influenced microbiota increased the presence of effector T helper cells in the mesenteric lymph nodes, including myelin-autoreactive cells. Inhibition of the bacterial quorum sensor QseC, which is also responsive to norepinephrine, diminished the presence of effector T helper cells and bacteria such as Acinetobacter in the mesenteric lymph nodes, without remarkably affecting the gut microbial composition. Together, our results delineate a model in which the immune reaction to stress-responsive microbiota may compromise tolerance to self and therefore may increase the risk for autoimmune diseases in susceptible individuals. IMPORTANCE How do stressful life events increase the risk for autoimmune disorders? Here we show that chronic social stress in mice promotes the expression of virulent genes in the gut microbiota and alters the microbial translocation into the mesenteric lymph nodes. Our results also suggest that the consequent immune response to the stress-affected microbiota may endanger the tolerance for self. The presence of specific translocated bacteria and the immune response in the mesenteric lymph nodes can be diminished using an inhibitor of the bacterial communication system without drastically affecting the gut microbial composition as antibiotics do.

RevDate: 2019-05-17

de la Cuesta-Zuluaga J, Kelley ST, Chen Y, et al (2019)

Age- and Sex-Dependent Patterns of Gut Microbial Diversity in Human Adults.

mSystems, 4(4): pii:mSystems00261-19.

Gut microbial diversity changes throughout the human life span and is known to be associated with host sex. We investigated the association of age, sex, and gut bacterial alpha diversity in three large cohorts of adults from four geographical regions: subjects from the United States and United Kingdom in the American Gut Project (AGP) citizen-science initiative and two independent cohorts of Colombians and Chinese. In three of the four cohorts, we observed a strong positive association between age and alpha diversity in young adults that plateaued after age 40 years. We also found sex-dependent differences that were more pronounced in younger adults than in middle-aged adults, with women having higher alpha diversity than men. In contrast to the other three cohorts, no association of alpha diversity with age or sex was observed in the Chinese cohort. The association of alpha diversity with age and sex remained after adjusting for cardiometabolic parameters in the Colombian cohort and antibiotic usage in the AGP cohort. We further attempted to predict the microbiota age in individuals using a machine-learning approach for the men and women in each cohort. Consistent with our alpha-diversity-based findings, U.S. and U.K. women had a significantly higher predicted microbiota age than men, with a reduced difference being seen above age 40 years. This difference was not observed in the Colombian cohort and was observed only in middle-aged Chinese adults. Together, our results provide new insights into the influence of age and sex on the biodiversity of the human gut microbiota during adulthood while highlighting similarities and differences across diverse cohorts. IMPORTANCE Microorganisms in the human gut play a role in health and disease, and in adults higher gut biodiversity has been linked to better health. Since gut microorganisms may be pivotal in the development of microbial therapies, understanding the factors that shape gut biodiversity is of utmost interest. We performed large-scale analyses of the relationship of age and sex to gut bacterial diversity in adult cohorts from four geographic regions: the United States, the United Kingdom, Colombia, and China. In the U.S., U.K., and Colombian cohorts, bacterial biodiversity correlated positively with age in young adults but plateaued at about age 40 years, with no positive association being found in middle-aged adults. Young, but not middle-aged, adult women had higher gut bacterial diversity than men, a pattern confirmed via supervised machine learning. Interestingly, in the Chinese cohort, minimal associations were observed between gut biodiversity and age or sex. Our results highlight the patterns of adult gut biodiversity and provide a framework for future research.

RevDate: 2019-05-17

Lutz HL, Ramírez-Puebla ST, Abbo L, et al (2019)

A Simple Microbiome in the European Common Cuttlefish, Sepia officinalis.

mSystems, 4(4): pii:mSystems00177-19.

The European common cuttlefish, Sepia officinalis, is used extensively in biological and biomedical research, yet its microbiome remains poorly characterized. We analyzed the microbiota of the digestive tract, gills, and skin in mariculture-raised S. officinalis using a combination of 16S rRNA amplicon sequencing, quantitative PCR (qPCR), and fluorescence spectral imaging. Sequencing revealed a highly simplified microbiota consisting largely of two single bacterial amplicon sequence variants (ASVs) of Vibrionaceae and Piscirickettsiaceae. The esophagus was dominated by a single ASV of the genus Vibrio. Imaging revealed bacteria in the family Vibrionaceae distributed in a discrete layer that lines the esophagus. This Vibrio was also the primary ASV found in the microbiota of the stomach, cecum, and intestine, but occurred at lower abundance, as determined by qPCR, and was found only scattered in the lumen rather than in a discrete layer via imaging analysis. Treatment of animals with the commonly used antibiotic enrofloxacin led to a nearly 80% reduction of the dominant Vibrio ASV in the esophagus but did not significantly alter the relative abundance of bacteria overall between treated versus control animals. Data from the gills were dominated by a single ASV in the family Piscirickettsiaceae, which imaging visualized as small clusters of cells. We conclude that bacteria belonging to the Gammaproteobacteria are the major symbionts of the cuttlefish Sepia officinalis cultured from eggs in captivity and that the esophagus and gills are major colonization sites. IMPORTANCE Microbes can play critical roles in the physiology of their animal hosts, as evidenced in cephalopods by the role of Vibrio (Aliivibrio) fischeri in the light organ of the bobtail squid and the role of Alpha- and Gammaproteobacteria in the reproductive system and egg defense in a variety of cephalopods. We sampled the cuttlefish microbiome throughout the digestive tract, gills, and skin and found dense colonization of an unexpected site, the esophagus, by a microbe of the genus Vibrio, as well as colonization of gills by Piscirickettsiaceae. This finding expands the range of organisms and body sites known to be associated with Vibrio and is of potential significance for understanding host-symbiont associations, as well as for understanding and maintaining the health of cephalopods in mariculture.

RevDate: 2019-05-17

Zegeye EK, Brislawn CJ, Farris Y, et al (2019)

Selection, Succession, and Stabilization of Soil Microbial Consortia.

mSystems, 4(4): pii:mSystems00055-19.

Soil microorganisms play fundamental roles in cycling of soil carbon, nitrogen, and other nutrients, yet we have a poor understanding of how soil microbiomes are shaped by their nutritional and physical environment. In this study, we investigated the successional dynamics of a soil microbiome during 21 weeks of enrichment on chitin and its monomer, N-acetylglucosamine. We examined succession of the soil communities in a physically heterogeneous soil matrix as well as a homogeneous liquid medium. The guiding hypothesis was that the initial species richness would influence the tendency for the selected consortia to stabilize and maintain a relatively constant community structure over time. We also hypothesized that long-term, substrate-driven growth would result in consortia with reduced species richness compared to the parent microbiome and that this process would be deterministic with relatively little variation between replicates. We found that the initial species richness does influence the long-term community stability in both liquid media and soil and that lower initial richness results in a more rapid convergence to stability. Despite use of the same soil inoculum and access to the same major substrate, the resulting community composition differed greatly in soil from that in liquid medium. Hence, distinct selective pressures in soils relative to homogenous liquid media exist and can control community succession dynamics. This difference is likely related to the fact that soil microbiomes are more likely to thrive, with fewer compositional changes, in a soil matrix than in liquid environments. IMPORTANCE The soil microbiome carries out important ecosystem functions, but interactions between soil microbial communities have been difficult to study due to the high microbial diversity and complexity of the soil habitat. In this study, we successfully obtained stable consortia with reduced complexity that contained species found in the original source soil. These consortia and the methods used to obtain them can be a valuable resource for exploration of specific mechanisms underlying soil microbial community ecology. The results of this study also provide new experimental context to better inform how soil microbial communities are shaped by new environments and how a combination of initial taxonomic structure and physical environment influences stability.

RevDate: 2019-05-17

Cai TT, Li H, Ma J, et al (2019)

Differential Markov random field analysis with an application to detecting differential microbial community networks.

Biometrika, 106(2):401-416.

Micro-organisms such as bacteria form complex ecological community networks that can be greatly influenced by diet and other environmental factors. Differential analysis of microbial community structures aims to elucidate systematic changes during an adaptive response to changes in environment. In this paper, we propose a flexible Markov random field model for microbial network structure and introduce a hypothesis testing framework for detecting differences between networks, also known as differential network analysis. Our global test for differential networks is particularly powerful against sparse alternatives. In addition, we develop a multiple testing procedure with false discovery rate control to identify the structure of the differential network. The proposed method is applied to data from a gut microbiome study on U.K. twins to evaluate how age affects the microbial community network.

RevDate: 2019-05-17

Youngblut ND, Reischer GH, Walters W, et al (2019)

Host diet and evolutionary history explain different aspects of gut microbiome diversity among vertebrate clades.

Nature communications, 10(1):2200 pii:10.1038/s41467-019-10191-3.

Multiple factors modulate microbial community assembly in the vertebrate gut, though studies disagree as to their relative contribution. One cause may be a reliance on captive animals, which can have very different gut microbiomes compared to their wild counterparts. To resolve this disagreement, we analyze a new, large, and highly diverse animal distal gut 16 S rRNA microbiome dataset, which comprises 80% wild animals and includes members of Mammalia, Aves, Reptilia, Amphibia, and Actinopterygii. We decouple the effects of host evolutionary history and diet on gut microbiome diversity and show that each factor modulates different aspects of diversity. Moreover, we resolve particular microbial taxa associated with host phylogeny or diet and show that Mammalia have a stronger signal of cophylogeny. Finally, we find that environmental filtering and microbe-microbe interactions differ among host clades. These findings provide a robust assessment of the processes driving microbial community assembly in the vertebrate intestine.

RevDate: 2019-05-17

Sherchand SP, A Aiyar (2019)

Ammonia generation by tryptophan synthase drives a key genetic difference between genital and ocular Chlamydia trachomatis isolates.

Proceedings of the National Academy of Sciences of the United States of America pii:1821652116 [Epub ahead of print].

A striking difference between genital and ocular clinical isolates of Chlamydia trachomatis is that only the former express a functional tryptophan synthase and therefore can synthesize tryptophan by indole salvage. Ocular isolates uniformly cannot use indole due to inactivating mutations within tryptophan synthase, indicating a selection against maintaining this enzyme in the ocular environment. Here, we demonstrate that this selection occurs in two steps. First, specific indole derivatives, produced by the human gut microbiome and present in serum, rapidly induce expression of C. trachomatis tryptophan synthase, even under conditions of tryptophan sufficiency. We demonstrate that these indole derivatives function by acting as de-repressors of C. trachomatis TrpR. Second, trp operon de-repression is profoundly deleterious when infected cells are in an indole-deficient environment, because in the absence of indole, tryptophan synthase deaminates serine to pyruvate and ammonia. We have used biochemical and genetic approaches to demonstrate that expression of wild-type tryptophan synthase is required for the bactericidal production of ammonia. Pertinently, although these indole derivatives de-repress the trpRBA operon of C. trachomatis strains with trpA or trpB mutations, no ammonia is produced, and no deleterious effects are observed. Our studies demonstrate that tryptophan synthase can catalyze the ammonia-generating β-elimination reaction within any live bacterium. Our results also likely explain previous observations demonstrating that the same indole derivatives inhibit the growth of other pathogenic bacterial species, and why high serum levels of these indole derivatives are favorable for the prognosis of diseased conditions associated with bacterial dysbiosis.

RevDate: 2019-05-17

Dodiya HB, Kuntz T, Shaik SM, et al (2019)

Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes.

The Journal of experimental medicine pii:jem.20182386 [Epub ahead of print].

We demonstrated that an antibiotic cocktail (ABX)-perturbed gut microbiome is associated with reduced amyloid-β (Aβ) plaque pathology and astrogliosis in the male amyloid precursor protein (APP)SWE /presenilin 1 (PS1)ΔE9 transgenic model of Aβ amyloidosis. We now show that in an independent, aggressive APPSWE/PS1L166P (APPPS1-21) mouse model of Aβ amyloidosis, an ABX-perturbed gut microbiome is associated with a reduction in Aβ pathology and alterations in microglial morphology, thus establishing the generality of the phenomenon. Most importantly, these latter alterations occur only in brains of male mice, not in the brains of female mice. Furthermore, ABX treatment lead to alterations in levels of selected microglial expressed transcripts indicative of the "M0" homeostatic state in male but not in female mice. Finally, we found that transplants of fecal microbiota from age-matched APPPS1-21 male mice into ABX-treated APPPS1-21 male restores the gut microbiome and partially restores Aβ pathology and microglial morphology, thus demonstrating a causal role of the microbiome in the modulation of Aβ amyloidosis and microglial physiology in mouse models of Aβ amyloidosis.

RevDate: 2019-05-17

Zhang J, Lacroix C, Wortmann E, et al (2019)

Gut microbial beta-glucuronidase and glycerol/diol dehydratase activity contribute to dietary heterocyclic amine biotransformation.

BMC microbiology, 19(1):99 pii:10.1186/s12866-019-1483-x.

BACKGROUND: Consuming red and processed meat has been associated with an increased risk of colorectal cancer (CRC), which is partly attributed to exposure to carcinogens such as heterocyclic amines (HCA) formed during cooking and preservation processes. The interaction of gut microbes and HCA can result in altered bioactivities and it has been shown previously that human gut microbiota can transform mutagenic HCA to a glycerol conjugate with reduced mutagenic potential. However, the major form of HCA in the colon are glucuronides (HCA-G) and it is not known whether these metabolites, via stepwise microbial hydrolysis and acrolein conjugation, are viable precursors for glycerol conjugated metabolites. We hypothesized that such a process could be concurrently catalyzed by bacterial beta-glucuronidase (B-GUS) and glycerol/diol dehydratase (GDH) activity. We therefore investigated how the HCA-G PhIP-N2-β-D-glucuronide (PhIP-G), a representative liver metabolite of PhIP (2-Amino-1-methyl-6-phenylimidazo [4,5-b] pyridine), which is the most abundant carcinogenic HCA in well-cooked meat, is transformed by enzymatic activity of human gut microbial representatives of the phyla Firmicutes, Bacteroidetes, and Proteobacteria.

RESULTS: We employed a combination of growth and enzymatic assays, and a bioanalysis approach combined with metagenomics. B-GUS of Faecalibacterium prausnitzii converted PhIP-G to PhIP and GDH of Flavonifractor plautii, Blautia obeum, Eubacterium hallii, and Lactobacillus reuteri converted PhIP to PhIP-M1 in the presence of glycerol. In addition, B-GUS- and GDH-positive bacteria cooperatively converted PhIP-G to PhIP-M1. A screen of genes encoding B-GUS and GDH was performed for fecal microbiome data from healthy individuals (n = 103) and from CRC patients (n = 53), which revealed a decrease in abundance of taxa with confirmed GDH and HCA transformation activity in CRC patients.

CONCLUSIONS: This study for the first time demonstrates that gut microbes mediate the stepwise transformation of PhIP-G to PhIP-M1 via the intermediate production of PhIP. Findings from this study suggest that targeted manipulation with gut microbes bearing specific functions, or dietary glycerol supplementation might modify gut microbial activity to reduce HCA-induced CRC risk.

RevDate: 2019-05-17

Basic M, A Bleich (2019)

Gnotobiotics: Past, present and future.

Laboratory animals, 53(3):232-243.

Gnotobiotics or gnotobiology is a research field exploring organisms with a known microbiological state. In animal research, the development of gnotobiotics started in the late 19th century with the rederivation of germ-free guinea pigs. Cutting-edge achievements were accomplished by scientists in the Laboratories of Bacteriology at the University of Notre Dame (LOBUND). The primary goals of gnotobiotics were not only the development of the equipment required for long-term husbandry but also phenotypic characterization of germ-free animals. The first isolators were designed by Reynolds and Gustafsson as rigid-wall stainless steel autoclave-like chambers, which were subsequently replaced by Trexler's flexible-film polyvinyl plastic isolators. Flexible-film or semi-rigid isolators are commonly used today. The long-term maintenance of gnotobiotic rodents is performed in positive-pressure isolators. However, to facilitate gnotobiotic experimental procedures, short-term husbandry systems have been developed. Gnotobiotic animal husbandry is laborious and requires experienced staff. Germ-free animals can be rederived from existing rodent colonies by hysterectomy or embryo transfer. The physiology and anatomy of germ-free rodents are different from those of specified pathogen-free (SPF) rodents. Furthermore, to guarantee gnotobiotic status, the colonies need to be regularly microbiologically monitored. Today, gnotobiotics provides a powerful tool to analyse functional effects of host-microbe interactions, especially in complex disease models. Gnotobiotic models combined with 'omics' approaches will be indispensable for future advances in microbiome research. Furthermore, these approaches will contribute to the development of novel therapeutic targets. In addition, regional or national gnotobiotic core facilities should be established in the future to support further applications of gnotobiotic models.

RevDate: 2019-05-17

Pannkuk EL, Laiakis EC, Girgis M, et al (2019)

Temporal Effects on Radiation Responses in Nonhuman Primates: Identification of Biofluid Small Molecule Signatures by Gas Chromatography⁻Mass Spectrometry Metabolomics.

Metabolites, 9(5): pii:metabo9050098.

Whole body exposure to ionizing radiation damages tissues leading to physical symptoms which contribute to acute radiation syndrome. Radiation biodosimetry aims to determine characteristic early biomarkers indicative of radiation exposure and is necessary for effective triage after an unanticipated radiological incident. Radiation metabolomics can address this aim by assessing metabolic perturbations following exposure. Gas chromatography-mass spectrometry (GC-MS) is a standardized platform ideal for compound identification. We performed GC time-of-flight MS for the global profiling of nonhuman primate urine and serum samples up to 60 d after a single 4 Gy γ-ray total body exposure. Multivariate statistical analysis showed higher group separation in urine vs. serum. We identified biofluid markers involved in amino acid, lipid, purine, and serotonin metabolism, some of which may indicate host microbiome dysbiosis. Sex differences were observed for amino acid fold changes in serum samples. Additionally, we explored mitochondrial dysfunction by tricarboxylic acid intermediate analysis in the first week with a GC tandem quadrupole MS platform. By adding this temporal component to our previous work exploring dose effects at 7 d, we observed the highest fold changes occurring at 3 d, returning closer to basal levels by 7 d. These results emphasize the utility of both MS-based metabolomics for biodosimetry and complementary analytical platforms for increased metabolome coverage.

RevDate: 2019-05-17

Estrada JA, I Contreras (2019)

Nutritional Modulation of Immune and Central Nervous System Homeostasis: The Role of Diet in Development of Neuroinflammation and Neurological Disease.

Nutrients, 11(5): pii:nu11051076.

The gut-microbiome-brain axis is now recognized as an essential part in the regulation of systemic metabolism and homeostasis. Accumulating evidence has demonstrated that dietary patterns can influence the development of metabolic alterations and inflammation through the effects of nutrients on a multitude of variables, including microbiome composition, release of microbial products, gastrointestinal signaling molecules, and neurotransmitters. These signaling molecules are, in turn, implicated in the regulation of the immune system, either promoting or inhibiting the production of pro-inflammatory cytokines and the expansion of specific leukocyte subpopulations, such as Th17 and Treg cells, which are relevant in the development of neuroinflammatory and neurodegenerative conditions. Metabolic diseases, like obesity and type 2 diabetes mellitus, are related to inadequate dietary patterns and promote variations in the aforementioned signaling pathways in patients with these conditions, which have been linked to alterations in neurological functions and mental health. Thus, maintenance of adequate dietary patterns should be an essential component of any strategy aiming to prevent neurological pathologies derived from systemic metabolic alterations. The present review summarizes current knowledge on the role of nutrition in the modulation of the immune system and its impact in the development of neuroinflammation and neurological disease.

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ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

ESP Usage

Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

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Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

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Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin (and even a collection of poetry — Chicago Poems by Carl Sandburg).

Timelines

ESP now offers a much improved and expanded collection of timelines, designed to give the user choice over subject matter and dates.

Biographies

Biographical information about many key scientists.

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are now being automatically maintained and generated on the ESP site.

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