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18 Aug 2019 at 01:34
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Bibliography on: Human Microbiome


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RJR: Recommended Bibliography 18 Aug 2019 at 01:34 Created: 

Human Microbiome

The human microbiome is the set of all microbes that live on or in humans. Together, a human body and its associated microbiomes constitute a human holobiont. Although a human holobiont is mostly mammal by weight, by cell count it is mostly microbial. The number of microbial genes in the associated microbiomes far outnumber the number of human genes in the human genome. Just as humans (and other multicellular eukaryotes) evolved in the constant presence of gravity, so they also evolved in the constant presence of microbes. Consequently, nearly every aspect of human biology has evolved to deal with, and to take advantage of, the existence of associated microbiota. In some cases, the absence of a "normal microbiome" can cause disease, which can be treated by the transplant of a correct microbiome from a healthy donor. For example, fecal transplants are an effective treatment for chronic diarrhea from over abundant Clostridium difficile bacteria in the gut.

Created with PubMed® Query: "human microbiome" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

RevDate: 2019-08-16

Conteville LC, Oliveira-Ferreira J, ACP Vicente (2019)

Gut Microbiome Biomarkers and Functional Diversity Within an Amazonian Semi-Nomadic Hunter-Gatherer Group.

Frontiers in microbiology, 10:1743.

Human groups that still maintain traditional modes of subsistence (hunter-gatherers and rural agriculturalists) represent human groups non-impacted by urban-industrialized lifestyles, and therefore their gut microbiome provides the basis for understanding the human microbiome evolution and its association with human health and disease. The Yanomami is the largest semi-nomadic hunter-gatherer group of the Americas, exploring different niches of the Amazon rainforest in Brazil and Venezuela. Here, based on shotgun metagenomic data, we characterized the gut microbiome of the Yanomami from Brazil and compared taxonomically and functionally with the Yanomami from Venezuela, with other traditional groups from the Amazon and an urban-industrialized group. Taxonomic biomarkers were identified to each South American traditional group studied, including each Yanomami group. Broader levels of functional categories poorly discriminated the traditional and urban-industrialized groups, but the stratification of these categories revealed clear segregation of these groups. The Yanomami/Brazil gut microbiome presented unique functional features, such as a higher abundance of gene families involved in regulation/cell signaling, motility/chemotaxis, and virulence, contrasting with the gut microbiomes from the Yanomami/Venezuela and the other groups. Our study revealed biomarkers, and taxonomic and functional features that distinguished the gut microbiome of Yanomami/Brazil and Yanomami/Venezuela individuals, despite their shared lifestyle, culture, and genetic background. These differences may be a reflection of the environmental and seasonal diversity of the niches they explore. Overall, their microbiome profiles are shared with South American and African traditional groups, probably due to their lifestyle. The unique features identified within the Yanomami highlight the bias imposed by underrepresented sampling, and factors such as variations over space and time (seasonality) that impact, mainly, the hunter-gatherers.

RevDate: 2019-08-16

Sudo N (2019)

Biogenic Amines: Signals Between Commensal Microbiota and Gut Physiology.

Frontiers in endocrinology, 10:504.

There is increasing interest in the interactions among the gut microbiota, gut, and brain, which is often referred to as the "microbiota-gut-brain" axis. Biogenic amines including dopamine, norepinephrine, serotonin, and histamines are all generated by commensal gut microorganisms and are suggested to play roles as signaling molecules mediating the function of the "microbiota-gut-brain" axis. In addition, such amines generated in the gut have attracted attention in terms of possible clues into the etiologies of depression, anxiety, and even psychosis. This review covers the latest research related to the potential role of microbe-derived amines such as catecholamine, serotonin, histamine, as well as other trace amines, in modulating not only gut physiology but also brain function of the host. Further attention in this field can offer not only insight into expanding the fundamental roles and impacts of the human microbiome, but also further offer new therapeutic strategies for psychological disorders based on regulating the balance of resident bacteria.

RevDate: 2019-08-16

Lacorte E, Gervasi G, Bacigalupo I, et al (2019)

A Systematic Review of the Microbiome in Children With Neurodevelopmental Disorders.

Frontiers in neurology, 10:727.

Background and Purpose: A relationship between gut microbiome and central nervous system (CNS), have been suggested. The human microbiome may have an influence on brain's development, thus implying that dysbiosis may contribute in the etiology and progression of some neurological/neuropsychiatric disorders. The objective of this systematic review was to identify evidence on the characterization and potential distinctive traits of the microbiome of children with neurodevelopmental disorders, as compared to healthy children. Methods: The review was performed following the methodology described in the Cochrane handbook for systematic reviews, and was reported based on the PRISMA statement for reporting systematic reviews and meta-analyses. All literature published up to April 2019 was retrieved searching the databases PubMed, ISI Web of Science and the Cochrane Database of Systematic Reviews. Only observational studies, published in English and reporting data on the characterization of the microbiome in humans aged 0-18 years with a neurodevelopmental disorder were included. Neurodevelopmental disorders were categorized according to the definition included in the Diagnostic and Statistical Manual of Mental Disorders, version 5 (DSM-5). Results: Bibliographic searches yielded 9,237 records. One study was identified through other data sources. A total of 16 studies were selected based on their relevance and pertinence to the topic of the review, and were then applied the predefined inclusion and exclusion criteria. A total of 10 case-control studies met the inclusion criteria, and were thus included in the qualitative analysis and applied the NOS score. Two studies reported data on the gut microbiome of children with ADHD, while 8 reported data on either the gut (n = 6) or the oral microbiome (n = 2) of children with ASD. Conclusions: All the 10 studies included in this review showed a high heterogeneity in terms of sample size, gender, clinical issues, and type of controls. This high heterogeneity, along with the small sample size of the included studies, strongly limited the external validity of results. The quality assessment performed using the NOS score showed an overall low to moderate methodological quality of the included studies. To better clarify the potential role of microbiome in patients with neurodevelopmental disorders, further high-quality observational (specifically cohort) studies are needed.

RevDate: 2019-08-15

Tierney BT, Yang Z, Luber JM, et al (2019)

The Landscape of Genetic Content in the Gut and Oral Human Microbiome.

Cell host & microbe, 26(2):283-295.e8.

Despite substantial interest in the species diversity of the human microbiome and its role in disease, the scale of its genetic diversity, which is fundamental to deciphering human-microbe interactions, has not been quantified. Here, we conducted a cross-study meta-analysis of metagenomes from two human body niches, the mouth and gut, covering 3,655 samples from 13 studies. We found staggering genetic heterogeneity in the dataset, identifying a total of 45,666,334 non-redundant genes (23,961,508 oral and 22,254,436 gut) at the 95% identity level. Fifty percent of all genes were "singletons," or unique to a single metagenomic sample. Singletons were enriched for different functions (compared with non-singletons) and arose from sub-population-specific microbial strains. Overall, these results provide potential bases for the unexplained heterogeneity observed in microbiome-derived human phenotypes. One the basis of these data, we built a resource, which can be accessed at https://microbial-genes.bio.

RevDate: 2019-08-14

Zhang F, Wang M, Yang J, et al (2019)

Response of gut microbiota in type 2 diabetes to hypoglycemic agents.

Endocrine pii:10.1007/s12020-019-02041-5 [Epub ahead of print].

PURPOSE: Accumulated evidence has indicated that the gut microbiome affected the pharmacology of anti-diabetic agents, and their metabolic products induced by the agents transformed the structure of gastrointestinal microbiota in return. However, the studies around heredity, ethnicity, or living condition, referring to human microbiome were mostly represented by an occidental pattern partial and rare studies that focused on the effect of several first-line hypoglycemic agents on the gut flora in a single medical center. Therefore, we aimed to explore the interaction between gut microbiome and type 2 diabetes (T2D) or hypoglycemics in Chinese population.

METHODS: A total of 130 T2D patients with a specific hypoglycemic treatment and 50 healthy volunteers were enrolled in this study. Gut microbiome compositons were analyzed by 16S ribosomal RNA gene-based sequencing protocol.

RESULTS: Hypoglycemic agents contributed to the alteration of specific species in gut bacteria rather than its total diversity. Metformin increased the abundance of Spirochaete, Turicibacter, and Fusobacterium. Insulin also increased Fusobacterium, and α-glucosidase inhibitors (α-GIs) contributed to the plentitude of Bifidobacterium and Lactobacillus. Both metformin and insulin improved taurine and hypotaurine metabolism, and α-GI promoted several amino acid pathways. Although the community of gut microbiota with metformin and insulin showed similarity, significant differences were available in each diabetic group with hypoglycemia.

CONCLUSIONS: Gut microbiota is significantly associated with anti-diabetic agents. The gut microbiome and metabolism have shown respective characteristics in different T2D groups, which were also significantly different from the healthy group. This study provides some new insights for identification and exploration of the pathogenesis of T2D.

RevDate: 2019-08-14

Pereira EM, de Mattos CS, Dos Santos OC, et al (2019)

Staphylococcus hominis subspecies can be identified by SDS-PAGE or MALDI-TOF MS profiles.

Scientific reports, 9(1):11736 pii:10.1038/s41598-019-48248-4.

Staphylococcus hominis is part of the normal human microbiome. Two subspecies, S. hominis hominis (Shh) and S. hominis novobiosepticus (Shn), have clinical significance. Forty-nine S. hominis isolates were analyzed by the MicroScan automated system, SDS-PAGE and MALDI-TOF methods, followed by partial sequencing of the 16S rDNA gene. The trehalose fermentation test, disk diffusion and broth microdilution tests were used to identify (novobiocin test) and access the susceptibility to oxacillin and vancomycin of isolates. The SCCmec elements and genomic diversity were evaluated by PCR and PFGE methods, respectively. Profiles of 28 (57%; 8 Shh and 20 Shn) isolates corroborated with the results found in all the applied methods of identification. The remaining 21 (43%) isolates were phenotypically identified as Shh by MicroScan; however, they were identified as Shn by SDS-PAGE and mass spectral, and confirmed by 16S rDNA sequencing. Among 41 isolates identified as Shn by the molecular and mass spectrometry methods, 19 (41%) were novobiocin-sensitive, and the trehalose test indicated 11 positive isolates, which are considered atypical phenotypic results for this subspecies. In addition, 92.7% of the isolates identified as Shn by these methods carried mecA gene, while only 12.5% of the Shh isolates were positive. Together, the results highlighted the SDS-PAGE and MALDI-TOF MS methods as promising tools for discriminating S. hominis subspecies.

RevDate: 2019-08-13

Anonymous (2019)

Vast pool of new proteins is found, thanks to the human microbiome.

Nature, 572(7769):287.

RevDate: 2019-08-12

Gargiullo L, Del Chierico F, D'Argenio P, et al (2019)

Gut Microbiota Modulation for Multidrug-Resistant Organism Decolonization: Present and Future Perspectives.

Frontiers in microbiology, 10:1704.

The emergence of antimicrobial resistance (AMR) is of great concern to global public health. Treatment of multi-drug resistant (MDR) infections is a major clinical challenge: the increase in antibiotic resistance leads to a greater risk of therapeutic failure, relapses, longer hospitalizations, and worse clinical outcomes. Currently, there are no validated treatments for many MDR or pandrug-resistant (PDR) infections, and preventing the spread of these pathogens through hospital infection control procedures and antimicrobial stewardship programs is often the only tool available to healthcare providers. Therefore, new solutions to control the colonization of MDR pathogens are urgently needed. In this narrative review, we discuss current knowledge of microbiota-mediated mechanisms of AMR and strategies for MDR colonization control. We focus particularly on fecal microbiota transplantation for MDR intestinal decolonization and report updated literature on its current clinical use.

RevDate: 2019-08-12

Mora D, Filardi R, Arioli S, et al (2019)

Development of omics-based protocols for the microbiological characterization of multi-strain formulations marketed as probiotics: the case of VSL#3.

Microbial biotechnology [Epub ahead of print].

The growing commercial interest in multi-strain formulations marketed as probiotics has not been accompanied by an equal increase in the evaluation of quality levels of these biotechnological products. The multi-strain product VSL#3 was used as a model to setup a microbiological characterization that could be extended to other formulations with high complexity. Shotgun metagenomics by deep Illumina sequencing was applied to DNA isolated from the commercial VSL#3 product to confirm strains identity safety and composition. Single-cell analysis was used to evaluate the cell viability, and β-galactosidase and urease activity have been used as marker to monitor the reproducibility of the production process. Similarly, these lots were characterized in detail by a metaproteomics approach for which a robust protein extraction protocol was combined with advanced mass spectrometry. The results identified over 1600 protein groups belonging to all strains present in the VSL#3 formulation. Of interest, only 3.2 % proteins showed significant differences mainly related to small variations in strain abundance. The protocols developed in this study addressed several quality criteria that are relevant for marketed multi-strain products and these represent the first efforts to define the quality of complex probiotic formulations such as VSL#3.

RevDate: 2019-08-12

Sberro H, Fremin BJ, Zlitni S, et al (2019)

Large-Scale Analyses of Human Microbiomes Reveal Thousands of Small, Novel Genes.

Cell pii:S0092-8674(19)30781-0 [Epub ahead of print].

Small proteins are traditionally overlooked due to computational and experimental difficulties in detecting them. To systematically identify small proteins, we carried out a comparative genomics study on 1,773 human-associated metagenomes from four different body sites. We describe >4,000 conserved protein families, the majority of which are novel; ∼30% of these protein families are predicted to be secreted or transmembrane. Over 90% of the small protein families have no known domain and almost half are not represented in reference genomes. We identify putative housekeeping, mammalian-specific, defense-related, and protein families that are likely to be horizontally transferred. We provide evidence of transcription and translation for a subset of these families. Our study suggests that small proteins are highly abundant and those of the human microbiome, in particular, may perform diverse functions that have not been previously reported.

RevDate: 2019-08-09

Hietala V, Horsma-Heikkinen J, Carron A, et al (2019)

The Removal of Endo- and Enterotoxins From Bacteriophage Preparations.

Frontiers in microbiology, 10:1674.

The production of phages for therapeutic purposes demands fast, efficient and scalable purification procedures. Phage lysates have a wide range of impurities, of which endotoxins of gram-negative bacteria and protein toxins produced by many pathogenic bacterial species are harmful to humans. The highest allowed endotoxin concentration for parenterally applied medicines is 5 EU/kg/h. The aim of this study was to evaluate the feasibility of different purification methods in endotoxin and protein toxin removal in the production of phage preparations for clinical use. In the purification assays, we utilized three phages: Escherichia phage vB_EcoM_fHoEco02, Acinetobacter phage vB_ApiM_fHyAci03, and Staphylococcus phage vB_SauM_fRuSau02. The purification methods tested in the study were precipitation with polyethylene glycol, ultracentrifugation, ultrafiltration, anion exchange chromatography, octanol extraction, two different endotoxin removal columns, and different combinations thereof. The efficiency of the applied purification protocols was evaluated by measuring phage titer and either endotoxins or staphylococcal enterotoxins A and C (SEA and SEC, respectively) from samples taken from different purification steps. The most efficient procedure in endotoxin removal was the combination of ultrafiltration and EndoTrap HD affinity column, which was able to reduce the endotoxin-to-phage ratio of vB_EcoM_fHoEco02 lysate from 3.5 × 104 Endotoxin Units (EU)/109 plaque forming units (PFU) to 0.09 EU/109 PFU. The combination of ultrafiltration and anion exchange chromatography resulted in ratio 96 EU/109 PFU, and the addition of octanol extraction step into this procedure still reduced this ratio threefold. The other methods tested either resulted to less efficient endotoxin removal or required the use of harmful chemicals that should be avoided when producing phage preparations for medical use. Ultrafiltration with 100,000 MWCO efficiently removed enterotoxins from vB_SauM_fRuSau02 lysate (from 1.3 to 0.06 ng SEA/109 PFU), and anion exchange chromatography reduced the enterotoxin concentration below 0.25 ng/ml, the detection limit of the assay.

RevDate: 2019-08-07

Stoyancheva G (2019)

Study of helveticin gene in Lactobacillus crispatus strains and evaluation of its use as a phylogenetic marker.

Archives of microbiology pii:10.1007/s00203-019-01711-2 [Epub ahead of print].

Lactobacilli are a part of the human microbiome in healthy humans. Studies of their physiological and genetic characteristics are the basis for their use in probiotic preparations. This report is a brief description of the helveticin gene found in two Lactobacillus crispatus strains, which are a part of the human microbiome. Our analysis showed that the two variants of the gene are not solely characteristic of strains isolated from humans. In the phylogenetic analysis, we found that the studied sequence (this gene) showed a significant difference between the species of the genus Lactobacillus and could be used as a phylogenetic marker.

RevDate: 2019-08-07

Roura E, Depoortere I, M Navarro (2019)

Review: Chemosensing of nutrients and non-nutrients in the human and porcine gastrointestinal tract.

Animal : an international journal of animal bioscience pii:S1751731119001794 [Epub ahead of print].

The gastrointestinal tract (GIT) is an interface between the external and internal milieus that requires continuous monitoring for nutrients or pathogens and toxic chemicals. The study of the physiological/molecular mechanisms, mediating the responses to the monitoring of the GIT contents, has been referred to as chemosensory science. While most of the progress in this area of research has been obtained in laboratory rodents and humans, significant steps forward have also been reported in pigs. The objective of this review was to update the current knowledge on nutrient chemosensing in pigs in light of recent advances in humans and laboratory rodents. A second objective relates to informing the existence of nutrient sensors with their functionality, particularly linked to the gut peptides relevant to the onset/offset of appetite. Several cell types of the intestinal epithelium such as Paneth, goblet, tuft and enteroendocrine cells (EECs) contain subsets of chemosensory receptors also found on the tongue as part of the taste system. In particular, EECs show specific co-expression patterns between nutrient sensors and/or transceptors (transport proteins with sensing functions) and anorexigenic hormones such as cholecystokinin (CCK), peptide tyrosine tyrosine (PYY) or glucagon-like peptide-1 (GLP-1), amongst others. In addition, the administration of bitter compounds has an inhibitory effect on GIT motility and on appetite through GLP-1-, CCK-, ghrelin- and PYY-labelled EECs in the human small intestine and colon. Furthermore, the mammalian chemosensory system is the target of some bacterial metabolites. Recent studies on the human microbiome have discovered that commensal bacteria have developed strategies to stimulate chemosensory receptors and trigger host cellular functions. Finally, the study of gene polymorphisms related to nutrient sensors explains differences in food choices, food intake and appetite between individuals.

RevDate: 2019-08-06

Chu DM, Valentine GC, Seferovic MD, et al (2019)

The Development of the Human Microbiome: Why Moms Matter.

Gastroenterology clinics of North America, 48(3):357-375.

The human body is cohabitated with trillions of commensal bacteria that are essential for our health. However, certain bacteria can also cause diseases in the human host. Before the microbiome can be attributed to disease risk and pathogenesis, normal acquisition and development of the microbiome must be understood. Here, we explore the evidence surrounding in utero microbial exposures and the significant of this exposure in the proper development of the fetal and neonatal microbiome. We further explore the development of the fetal and neonatal microbiome and its relationship to preterm birth, feeding practices, and mode of delivery, and maternal diet.

RevDate: 2019-08-05

Lo Presti A, Zorzi F, Del Chierico F, et al (2019)

Fecal and Mucosal Microbiota Profiling in Irritable Bowel Syndrome and Inflammatory Bowel Disease.

Frontiers in microbiology, 10:1655.

An imbalance in the bacterial species resulting in the loss of intestinal homeostasis has been described in inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). In this prospective study, we investigated whether IBD and IBS patients exhibit specific changes in richness and distribution of fecal and mucosal-associated microbiota. Additionally, we assessed potential 16S rRNA gene amplicons biomarkers for IBD, IBS, and controls (CTRLs) by comparison of taxonomic composition. The relative abundance of bacteria, at phylum and genus/species levels, and the bacterial diversity were determined through 16S rRNA sequence-based fecal and mucosal microbiota analysis. Linear discriminant analysis effect size (LEfSe) was used for biomarker discovery associated to IBD and IBS as compared to CTRLs. In fecal and mucosal samples, the microbiota richness was characterized by a microbial diversity reduction, going from CTRLs to IBS to IBD. β-diversity analysis showed a clear separation between IBD and CTRLs and between IBD and IBS with no significant separation between IBS and CTRLs. β-diversity showed a clear separation between mucosa and stool samples in all the groups. In IBD, there was no difference between inflamed and not inflamed mucosa. Based upon the LEfSe data, the Anaerostipes and Ruminococcaceae were identified as the most differentially abundant bacterial taxa in CTRLs. Erysipelotrichi was identified as potential biomarker for IBS, while Gammaproteobacteria, Enterococcus, and Enterococcaceae for IBD. This study provides an overview of the alterations of microbiota and may aid in identifying potential 16S rRNA gene amplicons mucosal biomarkers for IBD and IBS.

RevDate: 2019-08-05

Colosimo DA, Kohn JA, Luo PM, et al (2019)

Mapping Interactions of Microbial Metabolites with Human G-Protein-Coupled Receptors.

Cell host & microbe pii:S1931-3128(19)30346-4 [Epub ahead of print].

Despite evidence linking the human microbiome to health and disease, how the microbiota affects human physiology remains largely unknown. Microbiota-encoded metabolites are expected to play an integral role in human health. Therefore, assigning function to these metabolites is critical to understanding these complex interactions and developing microbiota-inspired therapies. Here, we use large-scale functional screening of molecules produced by individual members of a simplified human microbiota to identify bacterial metabolites that agonize G-protein-coupled receptors (GPCRs). Multiple metabolites, including phenylpropanoic acid, cadaverine, 9-10-methylenehexadecanoic acid, and 12-methyltetradecanoic acid, were found to interact with GPCRs associated with diverse functions within the nervous and immune systems, among others. Collectively, these metabolite-receptor pairs indicate that diverse aspects of human health are potentially modulated by structurally simple metabolites arising from primary bacterial metabolism.

RevDate: 2019-08-02

Vitetta L, Llewellyn H, D Oldfield (2019)

Gut Dysbiosis and the Intestinal Microbiome: Streptococcus thermophilus a Key Probiotic for Reducing Uremia.

Microorganisms, 7(8): pii:microorganisms7080228.

In the intestines, probiotics can produce antagonistic effects such as antibiotic-like compounds, bactericidal proteins such as bacteriocins, and encourage the production of metabolic end products that may assist in preventing infections from various pathobionts (capable of pathogenic activity) microbes. Metabolites produced by intestinal bacteria and the adoptions of molecular methods to cross-examine and describe the human microbiome have refreshed interest in the discipline of nephology. As such, the adjunctive administration of probiotics for the treatment of chronic kidney disease (CKD) posits that certain probiotic bacteria can reduce the intestinal burden of uremic toxins. Uremic toxins eventuate from the over manifestation of glucotoxicity and lipotoxicity, increased activity of the hexosamine and polyol biochemical and synthetic pathways. The accumulation of advanced glycation end products that have been regularly associated with a dysbiotic colonic microbiome drives the overproduction of uremic toxins in the colon and the consequent local pro-inflammatory processes. Intestinal dysbiosis associated with significant shifts in abundance and diversity of intestinal bacteria with a resultant and maintained uremia promoting an uncontrolled mucosal pro-inflammatory state. In this narrative review we further address the efficacy of probiotics and highlighted in part the probiotic bacterium Streptococcus thermophilus as an important modulator of uremic toxins in the gut of patients diagnosed with chronic kidney disease. In conjunction with prudent nutritional practices it may be possible to prevent the progression of CKD and significantly downregulate mucosal pro-inflammatory activity with the administration of probiotics that contain S. thermophilus.

RevDate: 2019-08-01

Fall NS, Lo CI, Fournier PE, et al (2019)

Arcanobacterium ihumii sp. nov., Varibaculum vaginae sp. nov. and Tessaracoccus timonensis sp. nov., isolated from vaginal swabs from healthy Senegalese women.

New microbes and new infections, 31:100585 pii:100585.

Culturomics studies the microbial variety of the human microbiome by combining diversified culture conditions, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA gene identification. This study identifies three putative new bacterial species: Arcanobacterium ihumii sp. nov. strain Marseille-P5647T, Varibaculum vaginae sp. nov. strain Marseille-P5644T and Tessaracoccus timonensis sp. nov. strain Marseille-P5995T, which we describe according to the concept of taxonogenomics.

RevDate: 2019-07-29

Yin G, Y Xia (2019)

Assessing the Hybrid Effects of Neutral and Niche Processes on Gut Microbiome Influenced by HIV Infection.

Frontiers in microbiology, 10:1467.

That both stochastic neutral and deterministic niche forces are in effect in shaping the community assembly and diversity maintenance is becoming an increasingly important consensus. However, assessing the effects of disease on the balance between the two forces in the human microbiome has not been explored to the best of our knowledge. In this article, we applied a hybrid model to address this issue by analyzing the potential effect of HIV infection on the human gut microbiome and adopted a further step of multimodality testing to improve the interpretation of their model. Our study revealed that although niche process is the dominant force in shaping human gut microbial communities, niche process- and neutral process-driven taxa could coexist in the same microbiome, confirming the notion of their joint responsibility. However, we failed to detect the effect of HIV infection in changing the balance. This suggests that the rule governing community assembly and diversity maintenance may be changed by the disturbance from HIV infection-caused dysbiosis. Although we admit that the general question of disease effect on community assembly and diversity maintenance may still be an open question, our study presents the first piece of evidence to reject the significant influence of diseases.

RevDate: 2019-07-24

Pietilä JP, Meri T, Siikamäki H, et al (2019)

Dientamoeba fragilis - the most common intestinal protozoan in the Helsinki Metropolitan Area, Finland, 2007 to 2017.

Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin, 24(29):.

BackgroundDespite the global distribution of the intestinal protozoan Dientamoeba fragilis, its clinical picture remains unclear. This results from underdiagnosis: microscopic screening methods either lack sensitivity (wet preparation) or fail to reveal Dientamoeba (formalin-fixed sample).AimIn a retrospective study setting, we characterised the clinical picture of dientamoebiasis and compared it with giardiasis. In addition, we evaluated an improved approach to formalin-fixed samples for suitability in Dientamoeba diagnostics.MethodsThis study comprised four parts: (i) a descriptive part scrutinising rates of Dientamoeba findings; (ii) a methodological part analysing an approach to detect Dientamoeba-like structures in formalin samples; (iii) a clinical part comparing demographics and symptoms between patients with dientamoebiasis (n = 352) and giardiasis (n = 272), and (iv) a therapeutic part (n = 89 patients) investigating correlation between faecal eradication and clinical improvement.ResultsThe rate of Dientamoeba findings increased 20-fold after introducing criteria for Dientamoeba-like structures in formalin-fixed samples (88.9% sensitivity and 83.3% specificity). A further increase was seen after implementing faecal PCR. Compared with patients with giardiasis, the symptoms in the Dientamoeba group lasted longer and more often included abdominal pain, cramping, faecal urgency and loose rather than watery stools. Resolved symptoms correlated with successful faecal eradication (p < 0.001).ConclusionsPreviously underdiagnosed, Dientamoeba has become the most frequently recorded pathogenic enteroparasite in Finland. This presumably results from improved diagnostics with either PCR or detection of Dientamoeba-like structures in formalin-fixed samples, an approach applicable also in resource-poor settings. Symptoms of dientamoebiasis differ slightly from those of giardiasis; patients with distressing symptoms require treatment.

RevDate: 2019-07-24

Dong Z, Chen B, Pan H, et al (2019)

Detection of Microbial 16S rRNA Gene in the Serum of Patients With Gastric Cancer.

Frontiers in oncology, 9:608.

Aberrance in the blood bacterial microbiome has been identified and validated in several non-infectious diseases, including cancer. The occurrence and progression of gastric cancer has been found to be associated with alterations in the microbiome composition. However, the composition of the blood microbiome in patients with gastric cancer is not well-characterized. To test this hypothesis, we conducted a case-control study to investigate the microbiota compositions in the serum of patients with gastric cancer. The serum microbiome was investigated in patients with gastric cancer, atypical hyperplasia, chronic gastritis, and in healthy controls using 16S rRNA gene sequencing targeting the V1-V2 region. Our results revealed that the structure of the serum microbiome in gastric cancer was significantly different from all other groups, and alpha diversity decreased from the healthy control to patients with gastric cancer. The serum microbiome correlated significantly with tumor-node-metastasis (TNM) stage, lymphatic metastasis, tumor diameter, and invasion depth in gastric cancer. Three genera or species, namely, Acinetobacter, Bacteroides, Haemophilus parainfluenzae, were enriched in patients with gastric cancer, whereas Sphingomonas, Comamonas, and Pseudomonas stutzeri were enriched in the healthy control. Furthermore, the structure of serum microbiota differed between gastric cancer lymphatic metastasis and non-lymphatic metastasis. As a pilot investigation to characterizing the serum microbiome in gastric cancer, our study provided a foundation for improving our understanding of the role of microbiota in the pathogenesis of gastric cancer.

RevDate: 2019-07-24

Kumar M, Ji B, Zengler K, et al (2019)

Modelling approaches for studying the microbiome.

Nature microbiology, 4(8):1253-1267.

Advances in metagenome sequencing of the human microbiome have provided a plethora of new insights and revealed a close association of this complex ecosystem with a range of human diseases. However, there is little knowledge about how the different members of the microbial community interact with each other and with the host, and we lack basic mechanistic understanding of these interactions related to health and disease. Mathematical modelling has been demonstrated to be highly advantageous for gaining insights into the dynamics and interactions of complex systems and in recent years, several modelling approaches have been proposed to enhance our understanding of the microbiome. Here, we review the latest developments and current approaches, and highlight how different modelling strategies have been applied to unravel the highly dynamic nature of the human microbiome. Furthermore, we discuss present limitations of different modelling strategies and provide a perspective of how modelling can advance understanding and offer new treatment routes to impact human health.

RevDate: 2019-07-24

Scribano D, Marzano V, Levi Mortera S, et al (2019)

Insights into the Periplasmic Proteins of Acinetobacter baumannii AB5075 and the Impact of Imipenem Exposure: A Proteomic Approach.

International journal of molecular sciences, 20(14): pii:ijms20143451.

Carbapenem-resistant Acinetobacter baumannii strains cause life-threatening infections due to the lack of therapeutic options. Although the main mechanisms underlying antibiotic-resistance have been extensively studied, the general response to maintain bacterial viability under antibiotic exposure deserves to be fully investigated. Since the periplasmic space contains several proteins with crucial cellular functions, besides carbapenemases, we decided to study the periplasmic proteome of the multidrug-resistant (MDR) A. baumannii AB5075 strain, grown in the absence and presence of imipenem (IMP). Through the proteomic approach, 65 unique periplasmic proteins common in both growth conditions were identified: eight proteins involved in protein fate, response to oxidative stress, energy metabolism, antibiotic-resistance, were differentially expressed. Among them, ABUW_1746 and ABUW_2363 gene products presented the tetratricopeptide repeat motif, mediating protein-protein interactions. The expression switch of these proteins might determine specific protein interactions to better adapt to changing environmental conditions. ABUW_2868, encoding a heat shock protein likely involved in protection against oxidative stress, was upregulated in IMP-exposed bacteria. Accordingly, the addition of periplasmic proteins from A. baumannii cultured with IMP increased bacterial viability in an antioxidant activity assay. Overall, this study provides the first insights about the composition of the periplasmic proteins of a MDR A. baumannii strain, its biological response to IMP and suggests possible new targets to develop alternative antibiotic drugs.

RevDate: 2019-07-24

Wakabayashi R, Nakahama Y, Nguyen V, et al (2019)

The Host-Microbe Interplay in Human Papillomavirus-Induced Carcinogenesis.

Microorganisms, 7(7): pii:microorganisms7070199.

Every year nearly half a million new cases of cervix cancer are diagnosed worldwide, making this malignancy the fourth commonest cancer in women. In 2018, more than 270,000 women died of cervix cancer globally with 85% of them being from developing countries. The majority of these cancers are caused by the infection with carcinogenic strains of human papillomavirus (HPV), which is also causally implicated in the development of other malignancies, including cancer of the anus, penis cancer and head and neck cancer. HPV is by far the most common sexually transmitted infection worldwide, however, most infected people do not develop cancer and do not even have a persistent infection. The development of highly effective HPV vaccines against most common high-risk HPV strains is a great medical achievement of the 21st century that could prevent up to 90% of cervix cancers. In this article, we review the current understanding of the balanced virus-host interaction that can lead to either virus elimination or the establishment of persistent infection and ultimately malignant transformation. We also highlight the influence of certain factors inherent to the host, including the immune status, genetic variants and the coexistence of other microbe infections and microbiome composition in the dynamic of HPV infection induced carcinogenesis.

RevDate: 2019-07-24

Hamidi B, Wallace K, AV Alekseyenko (2019)

MODIMA, a Method for Multivariate Omnibus Distance Mediation Analysis, Allows for Integration of Multivariate Exposure-Mediator-Response Relationships.

Genes, 10(7): pii:genes10070524.

Many important exposure-response relationships, such as diet and weight, can be influenced by intermediates, such as the gut microbiome. Understanding the role of these intermediates, the mediators, is important in refining cause-effect theories and discovering additional medical interventions (e.g., probiotics, prebiotics). Mediation analysis has been at the heart of behavioral health research, rapidly gaining popularity with the biomedical sciences in the last decade. A specific analytic challenge is being able to incorporate an entire 'omics assay as a mediator. To address this challenge, we propose a hypothesis testing framework for multivariate omnibus distance mediation analysis (MODIMA). We use the power of energy statistics, such as partial distance correlation, to allow for analysis of multivariate exposure-mediator-response triples. Our simulation results demonstrate the favorable statistical properties of our approach relative to the available alternatives. Finally, we demonstrate the application of the proposed methods in two previously published microbiome datasets. Our framework adds a new tool to the toolbox of approaches to the integration of 'omics big data.

RevDate: 2019-07-22

PeBenito AM, Liu M, Nazzal L, et al (2019)

Development of a humanized murine model for the study of Oxalobacter formigenes intestinal colonization.

The Journal of infectious diseases pii:5536758 [Epub ahead of print].

BACKGROUND: Oxalobacter formigenes are bacteria that colonize the human gut and degrade oxalate, a component of most kidney stones. Clinical and epidemiological studies suggest that O. formigenes colonization reduces the risk for kidney stones. We sought to develop murine models to allow investigating O. formigenes in the context of its native human microbiome.For humanization, we transplanted pooled feces from healthy, non-colonized human donors supplemented with a human O. formigenes strain into recipient mice. We compared transplanting microbiota into mice that were either treated with broad-spectrum antibiotics to suppress their native microbiome, or were germ-free, or received humanization without pre-treatment or received a sham gavage (controls).

RESULTS: All humanized mice were stably colonized with O. formigenes through 8 weeks post-gavage, whereas mice receiving sham gavage remained uncolonized (p<0.001). Humanization significantly changed the murine intestinal microbial community structure (p<0.001) with humanized germ-free and antibiotic-treated groups overlapping in β-diversity. Both the germ-free and antibiotic-treated mice had significantly increased numbers of human species compared to sham-gavaged mice (p<0.001).

CONCLUSIONS: Transplanting mice with human feces and O. formigenes introduced new microbial populations resembling the human microbiome, with stable O. formigenes colonization; such models can define optimal O. formigenes strains to facilitate clinical trials.

RevDate: 2019-07-22

O'Gorman DB, Pena-Diaz AM, Drosdowech D, et al (2019)

Response to Long et al regarding: "Cutibacterium acnes and the shoulder microbiome".

Journal of shoulder and elbow surgery, 28(8):e277-e278.

RevDate: 2019-07-20

Santiago-Rodriguez TM, EB Hollister (2019)

Human Virome and Disease: High-Throughput Sequencing for Virus Discovery, Identification of Phage-Bacteria Dysbiosis and Development of Therapeutic Approaches with Emphasis on the Human Gut.

Viruses, 11(7): pii:v11070656.

The virome is comprised of endogenous retroviruses, eukaryotic viruses, and bacteriophages and is increasingly being recognized as an essential part of the human microbiome. The human virome is associated with Type-1 diabetes (T1D), Type-2 diabetes (T2D), Inflammatory Bowel Disease (IBD), Human Immunodeficiency Virus (HIV) infection, and cancer. Increasing evidence also supports trans-kingdom interactions of viruses with bacteria, small eukaryotes and host in disease progression. The present review focuses on virus ecology and biology and how this translates mostly to human gut virome research. Current challenges in the field and how the development of bioinformatic tools and controls are aiding to overcome some of these challenges are also discussed. Finally, the present review also focuses on how human gut virome research could result in translational and clinical studies that may facilitate the development of therapeutic approaches.

RevDate: 2019-07-19

Huddleston JP, Thoden JB, Dopkins BJ, et al (2019)

Structural and Functional Characterization of YdjI, an Aldolase of Unknown Specificity in Escherichia coli K12.

Biochemistry [Epub ahead of print].

The ydj gene cluster is found in 80% of sequenced Escherichia coli genomes and other closely related species found in the human microbiome. Based on the annotations of the enzymes located in this cluster, it is expected that together they catalyze the catabolism of an unknown carbohydrate. The focus of this investigation is on YdjI, which is found in the ydj gene cluster of E. coli K-12. It is predicted to be a class II aldolase of unknown function. Here we describe a structural and functional characterization of this enzyme. YdjI catalyzes the hydrogen/deuterium exchange of the proS hydrogen at C3 of dihydroxyacetone or DHAP. In the presence of DHAP, YdjI catalyzes an aldol condensation with a variety of aldo-sugars. YdjI shows strong preference toward higher-order (seven-, eight- and nine-carbon) monosaccharides with specific hydroxyl stereochemistries and a negatively charged terminus (carboxylate or phosphate). The best substrate is L-arabinuronic acid with an apparent kcat = 3.0 s-1. The product, L-glycero-L-galacto-octuluronate-1-phosphate, has a value of kcat/Km of 2.1 × 103 M-1 s-1 in the retro-aldol reaction with YdjI. This is the first recorded synthesis of L-glycero-L-galacto-octuluronate-1-phosphate and six similar carbohydrates. The crystal structure of YdjI, determined to a nominal resolution of 1.75 Å (PDB code: 6OFU), reveals unusual positions for two arginine residues located near the active site. Computational docking was utilized to distinguish preferable binding orientations for L-glycero-L-galacto-octuluronate-1-phosphate. These results indicate a possible alternative binding orientation for L-glycero-L-galacto-octuluronate-1-phosphate than observed in other class II aldolases, which utilize shorter carbohydrate molecules.

RevDate: 2019-07-18

Novotný M, Klimova B, M Valis (2019)

Microbiome and Cognitive Impairment: Can Any Diets Influence Learning Processes in a Positive Way?.

Frontiers in aging neuroscience, 11:170.

The aim of this review is to summarize the effect of human intestinal microbiome on cognitive impairments and to focus primarily on the impact of diet and eating habits on learning processes. Better understanding of the microbiome could revolutionize the possibilities of therapy for many diseases. The authors performed a literature review of available studies on the research topic describing the influence of human microbiome and diet on cognitive impairment or learning processes found in the world's acknowledged databases Web of Science, PubMed, Springer, and Scopus. The digestive tube is populated by billions of living microorganisms including viruses, bacteria, protozoa, helminths, and microscopic fungi. In adulthood, under physiological conditions, the intestinal microbiome appears to be relatively steady. However, it is not true that it would not be influenced, both in the positive sense of the word and in the negative one. The basic pillars that maintain a steady microbiome are genetics, lifestyle, diet and eating habits, geography, and age. It is reported that the gastrointestinal tract and the brain communicate with each other through several pathways and one can speak about gut-brain axis. New evidence is published every year about the association of intestinal dysbiosis and neurological/psychiatric diseases. On the other hand, specific diets and eating habits can have a positive effect on a balanced microbiota composition and thus contribute to the enhancement of cognitive functions, which are important for any learning process.

RevDate: 2019-07-18

Zhou H, Suo J, J Zhu (2019)

[Therapeutic Relevance of Human Microbiota and Lung Cancer].

Zhongguo fei ai za zhi = Chinese journal of lung cancer, 22(7):464-469.

The human microbiome is closely related to human health status. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways, associated with approximately 20% of malignancies. The incidence and mortality of lung cancer (LC) in men in China are the highest among all malignancies, which is a serious threat to human health. Emerging evidence has suggested that the human microbiota may be closely related to lung cancer at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. At the same time, the human microbiota affects the efficacy of lung cancer on chemoradiotherapy, gene therapy, immunotherapy and other treatments. Immunotherapy is a promising method for the treatment of malignancies such as lung cancer, but the efficacy of immune checkpoint inhibitors in patients is heterogeneous. Preclinical studies based on lung cancer cell lines suggest that the intestinal microbiota can modulate responses to anti--PD-1 therapy through interactions with the host immune system. But for lung cancer patients, whether the intestinal flora can still regulate immunotherapy remains controversial. In this mini-review, we summarize current research findings describing therapeutic relevance of human microbiota and lung cancer. A better knowledge of the interplay between the human microbiome and lung cancer may promote the development of innovative strategies for prevention and personalized treatment in lung cancer.

RevDate: 2019-07-17

Gallon P, Parekh M, Ferrari S, et al (2019)

Metagenomics in ophthalmology: Hypothesis or real prospective?.

Biotechnology reports (Amsterdam, Netherlands), 23:e00355 pii:e00355.

Metagenomic analysis was originally associated with the studies of genetic material from environmental samples. But, with the advent of the Human Microbiome Project, it has now been applied in clinical practices. The ocular surface (OS) is the most exposed part of the eye, colonized by several microbial communities (both, OS and environmental) that contribute to the maintenance of the physiological state. Limited knowledge has been acquired on these microbes due to the limitations of conventional diagnostic methods. Emerging fields of research are focusing on Next Generation Sequencing (NGS) technologies to obtain reliable information on the OS microbiome. Currently only pre-specified pathogens can be detected by conventional culture-based techniques or Polymerase Chain Reaction (PCR), but there are conditions to state whether metagenomics could revolutionize the diagnosis of ocular diseases. The aim of this review is to provide an updated overview of the studies involving NGS technology for OS microbiome.

RevDate: 2019-07-16

Huang C, G Shi (2019)

Smoking and microbiome in oral, airway, gut and some systemic diseases.

Journal of translational medicine, 17(1):225 pii:10.1186/s12967-019-1971-7.

The human microbiome harbors a diverse array of microbes which establishes a mutually beneficial relation with the host in healthy conditions, however, the dynamic homeostasis is influenced by both host and environmental factors. Smoking contributes to modifications of the oral, lung and gut microbiome, leading to various diseases, such as periodontitis, asthma, chronic obstructive pulmonary disease, Crohn's disease, ulcerative colitis and cancers. However, the exact causal relationship between smoking and microbiome alteration remains to be further explored.

RevDate: 2019-07-13

Li JKM, Chiu PKF, CF Ng (2019)

The impact of microbiome in urological diseases: a systematic review.

International urology and nephrology pii:10.1007/s11255-019-02225-y [Epub ahead of print].

OBJECTIVE: The term microbiome is used to signify the ecological community of commensal, symbiotic, and pathogenic microorganisms that share our body space, in which there were increasing evidences to suggest that they might have potential roles in various medical conditions. While the study of microbiome in the urinary system is not as robust as the systems included in the Human Microbiome Project, there are still evidences in the literature showing that microbiome may have a role in urological diseases. Therefore, we would like to perform a systematic review on the topic and summarize the available evidence on the impact of microbiome on urological diseases.

METHODOLOGY: This review was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. After screening 589 abstracts and including additional studies (such as references from review papers), 76 studies were included for review and discussion.

RESULTS: Studies had suggested that there were correlations of microbiome of different body cavities (e.g., fecal, urinary and seminal fluid) with urological diseases. Also, different diseases would have different microbiome profile in different body cavities. Unfortunately, the studies on the association of microbiome and urological diseases were still either weak or inconsistent.

CONCLUSION: Studies suggested that there might be some relationship between microbiome and various urological diseases. However, further large-scale studies with control of confounding factors should be performed under a standardized methodology in order to have better understanding of the relationship. Also, more standardized reporting protocol for microbiome studies should be considered for better communications in future studies.

RevDate: 2019-07-12

Zhang Z, Yang J, Feng Q, et al (2019)

Compositional and Functional Analysis of the Microbiome in Tissue and Saliva of Oral Squamous Cell Carcinoma.

Frontiers in microbiology, 10:1439.

Oral squamous cell carcinoma (OSCC) is affected by the interaction between oral pathogen and holobionts, or the combination of the host and its microbial communities. Studies have indicated the structure and feature of the microbiome in OSCC tissue and saliva, the relationships between microbiota and OSCC sites, stages remain unclear. In the present study, OSCC tissue (T), saliva (S) and mouthwash (W) samples were collected from the same subjects and carried out the microbiome study by 16S sequencing. The results showed the T group was significantly different from the S and W groups with the character of lower richness and diversity. Proteobacteria were most enriched in the T group at the phylum level, while Firmicutes were predominant in groups S and W. At the genus level, the predominant taxa of group T were Acinetobacter and Fusobacterium, and for group S and W, the predominant taxa were Streptococcus and Prevotella. The genera related to late stage tumors were Acinetobacter and Fusobacterium, suggesting microbiota may be implicated in OSCC developing. Both compositional and functional analyses indicated that microbes in tumor tissue were potential indicator for the initiation and development of OSCC.

RevDate: 2019-07-11

Lam KN, Alexander M, PJ Turnbaugh (2019)

Precision Medicine Goes Microscopic: Engineering the Microbiome to Improve Drug Outcomes.

Cell host & microbe, 26(1):22-34.

Despite the recognition, nearly a century ago, that the human microbiome plays a clinically relevant role in drug disposition, mechanistic insights, and translational applications are still limited. Here, we highlight the recent re-emergence of "pharmacomicrobiomics," which seeks to understand how inter-individual variations in the microbiome shape drug efficacy and side effect profiles. Multiple bacterial species, genes, and enzymes have already been implicated in the direct biotransformation of drugs, both from targeted case studies and from systematic computational and experimental analyses. Indirect mechanisms are also at play; for example, microbial interactions with the host immune system can have broad effects on immunomodulatory drugs. Finally, we discuss multiple emerging strategies for the precise manipulation of complex microbial communities to improve treatment outcomes. In the coming years, we anticipate a shift toward a more comprehensive view of precision medicine that encompasses our human and microbial genomes and their combined metabolic activities.

RevDate: 2019-07-11

Mike LA (2019)

mSphere of Influence: Systematically Decoding Microbial Chemical Communication.

mSphere, 4(4): pii:4/4/e00319-19.

Laura A. Mike works in the field of bacterial pathogenesis. In this mSphere of Influence article, she reflects on how "Insights into Secondary Metabolism from a Global Analysis of Prokaryotic Biosynthetic Gene Clusters" by P. Cimermancic et al. (Cell 158:412-421, 2014, https://doi.org/10.1016/j.cell.2014.06.034) and "A Systematic Analysis of Biosynthetic Gene Clusters in the Human Microbiome Reveals a Common Family of Antibiotics" by M. S. Donia et al. (Cell 158:1402-1414, 2014, https://doi.org/10.1016/j.cell.2014.08.032) made an impact on her by systematically identifying microbiome-associated biosynthetic gene clusters predicted to synthesize secondary metabolites, which may facilitate interspecies interactions.

RevDate: 2019-07-09

Wree A, Geisler LJ, F Tacke (2019)

[Microbiome & NASH - partners in crime driving progression of fatty liver disease].

Zeitschrift fur Gastroenterologie, 57(7):871-882.

Along with the increasing prevalence of obesity, metabolic syndrome and type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) is rapidly increasing and poses a major challenge for gastroenterologists. Many studies have demonstrated that the microbiome is closely associated with the progression of nutrition-related diseases, especially of fatty liver disease. Changes in the quantity and quality of the intestinal flora, commonly referred to as dysbiosis, result in altered food metabolism, increased permeability of the intestinal barrier ("leaky gut") and consecutive inflammatory processes in the liver. This favors both the progression of obesity and metabolic disorders as well as NAFLD towards non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Important molecular mechanisms include microbial metabolites, microbial and endogenous signaling substances (so-called PAMPs/DAMPs) as well as bile acids. Essential cellular mechanisms include immune cells in the gut and liver, especially macrophages and Kupffer cells, as well as intestinal epithelial cells and hepatocytes as central regulators of metabolism. In this review article, we briefly summarize the relevant species of the human microbiome, describe the microbial analytics, explain the most important molecular relationships between microbiome and NAFLD/NASH, and finally the opportunities and challenges of microbiome-modulating therapy for the treatment of fatty liver disease.

RevDate: 2019-07-09

Jackson BR, Chow N, Forsberg K, et al (2019)

On the Origins of a Species: What Might Explain the Rise of Candida auris?.

Journal of fungi (Basel, Switzerland), 5(3): pii:jof5030058.

Candida auris is an emerging multidrug-resistant yeast first described in 2009 that has since caused healthcare-associated outbreaks of severe human infections around the world. In some hospitals, it has become a leading cause of invasive candidiasis. C. auris is markedly different from most other pathogenic Candida species in its genetics, antifungal resistance, and ability to spread between patients. The reasons why this fungus began spreading widely in the last decade remain a mystery. We examine available data on C. auris and related species, including genomic epidemiology, phenotypic characteristics, and sites of detection, to put forth hypotheses on its possible origins. C. auris has not been detected in the natural environment; related species have been detected in in plants, insects, and aquatic environments, as well as from human body sites. It can tolerate hypersaline environments and higher temperatures than most Candida species. We explore hypotheses about the pre-emergence niche of C. auris, whether in the environmental or human microbiome, and speculate on factors that might have led to its spread, including the possible roles of healthcare, antifungal use, and environmental changes, including human activities that might have expanded its presence in the environment or caused increased human contact.

RevDate: 2019-07-08

Amsterdam D, BE Ostrov (2018)

The Impact of the Microbiome on Immunosenescence.

Immunological investigations, 47(8):801-811.

Human microbiome investigations now provide evidence that changes in the microbiome over time and their interaction with the immune, endocrine, and nervous systems are associated with a wide array of disorders. Human immunological studies typically absent a microbiome consideration in their investigations. An area of recent exploration is the role of the microbiome as a critical partner in the development and function of the human immune system in aging. It is well known that immunologic maturation is influenced by a lifetime of interactions of the host with its companion microbiome. It is generally not well recognized that intestinal microbes play an essential role in the development and expansion of gut mucosal and systemic immune function. Gut microbial communities of elderly people have different composition and behavior compared to healthy younger adults. Comorbidities associated with microbial pathogens and an aberrant immune system tend to increase with aging. This review underscores the impact of the human-microbiome interface on the development and function of the immune system and on immunosenescence. These changes have important implications regarding health and health system utilization in the elderly population.

RevDate: 2019-07-07

Velsko IM, Fellows Yates JA, Aron F, et al (2019)

Microbial differences between dental plaque and historic dental calculus are related to oral biofilm maturation stage.

Microbiome, 7(1):102 pii:10.1186/s40168-019-0717-3.

BACKGROUND: Dental calculus, calcified oral plaque biofilm, contains microbial and host biomolecules that can be used to study historic microbiome communities and host responses. Dental calculus does not typically accumulate as much today as historically, and clinical oral microbiome research studies focus primarily on living dental plaque biofilm. However, plaque and calculus reflect different conditions of the oral biofilm, and the differences in microbial characteristics between the sample types have not yet been systematically explored. Here, we compare the microbial profiles of modern dental plaque, modern dental calculus, and historic dental calculus to establish expected differences between these substrates.

RESULTS: Metagenomic data was generated from modern and historic calculus samples, and dental plaque metagenomic data was downloaded from the Human Microbiome Project. Microbial composition and functional profile were assessed. Metaproteomic data was obtained from a subset of historic calculus samples. Comparisons between microbial, protein, and metabolomic profiles revealed distinct taxonomic and metabolic functional profiles between plaque, modern calculus, and historic calculus, but not between calculus collected from healthy teeth and periodontal disease-affected teeth. Species co-exclusion was related to biofilm environment. Proteomic profiling revealed that healthy tooth samples contain low levels of bacterial virulence proteins and a robust innate immune response. Correlations between proteomic and metabolomic profiles suggest co-preservation of bacterial lipid membranes and membrane-associated proteins.

CONCLUSIONS: Overall, we find that there are systematic microbial differences between plaque and calculus related to biofilm physiology, and recognizing these differences is important for accurate data interpretation in studies comparing dental plaque and calculus.

RevDate: 2019-07-06

Soligo M, Albini M, Bertoli FL, et al (2019)

Different responses of PC12 cells to different pro-nerve growth factor protein variants.

Neurochemistry international pii:S0197-0186(19)30150-0 [Epub ahead of print].

The present work aimed to explore the innovative hypothesis that different transcript/protein variants of a pro-neurotrophin may generate different biological outcomes in a cellular system. Nerve growth factor (NGF) is important in the development and progression of neurodegenerative and cancer conditions. Mature NGF (mNGF) originates from a precursor, proNGF, produced in mouse in two major variants, proNGF-A and proNGF-B. Different receptors bind mNGF and proNGF, generating neurotrophic or neurotoxic outcomes. It is known that dysregulation in the proNGF/mNGF ratio and in NGF-receptors expression affects brain homeostasis. To date, however, the specific roles of the two major proNGF variants remain unexplored. Here we attempted a first characterization of the possible differential effects of proNGF-A and proNGF-B on viability, differentiation and endogenous ngf gene expression in the PC12 cell line. We also investigated the differential involvement of NGF receptors in the actions of proNGF. We found that native mouse mNGF, proNGF-A and proNGF-B elicited different effects on PC12 cell survival and differentiation. Only mNGF and proNGF-A promoted neurotrophic responses when all NGF receptors are exposed at the cell surface. Tropomyosine receptor kinase A (TrkA) blockade inhibited cell differentiation, regardless of which NGF was added to culture media. Only proNGF-A exerted a pro-survival effect when TrkA was inhibited. Conversely, proNGF-B exerted differentiative effects when the p75 neurotrophin receptor (p75NTR) was antagonized. Stimulation with NGF variants differentially regulated the autocrine production of distinct proNgf mRNA. Overall, our findings suggest that mNGF and proNGF-A may elicit similar neurotrophic effects, not necessarily linked to activation of the same NGF-receptor, while the action of proNGF-B may be determined by the NGF-receptors balance. Thus, the proposed involvement of proNGF/NGF on the development and progression of neurodegenerative and tumor conditions may depend on the NGF-receptors balance, on specific NGF trancript expression and on the proNGF protein variant ratio.

RevDate: 2019-07-06

Ilves M, Kinaret PAS, Ndika J, et al (2019)

Surface PEGylation suppresses pulmonary effects of CuO in allergen-induced lung inflammation.

Particle and fibre toxicology, 16(1):28 pii:10.1186/s12989-019-0309-1.

BACKGROUND: Copper oxide (CuO) nanomaterials are used in a wide range of industrial and commercial applications. These materials can be hazardous, especially if they are inhaled. As a result, the pulmonary effects of CuO nanomaterials have been studied in healthy subjects but limited knowledge exists today about their effects on lungs with allergic airway inflammation (AAI). The objective of this study was to investigate how pristine CuO modulates allergic lung inflammation and whether surface modifications can influence its reactivity. CuO and its carboxylated (CuO COOH), methylaminated (CuO NH3) and PEGylated (CuO PEG) derivatives were administered here on four consecutive days via oropharyngeal aspiration in a mouse model of AAI. Standard genome-wide gene expression profiling as well as conventional histopathological and immunological methods were used to investigate the modulatory effects of the nanomaterials on both healthy and compromised immune system.

RESULTS: Our data demonstrates that although CuO materials did not considerably influence hallmarks of allergic airway inflammation, the materials exacerbated the existing lung inflammation by eliciting dramatic pulmonary neutrophilia. Transcriptomic analysis showed that CuO, CuO COOH and CuO NH3 commonly enriched neutrophil-related biological processes, especially in healthy mice. In sharp contrast, CuO PEG had a significantly lower potential in triggering changes in lungs of healthy and allergic mice revealing that surface PEGylation suppresses the effects triggered by the pristine material.

CONCLUSIONS: CuO as well as its functionalized forms worsen allergic airway inflammation by causing neutrophilia in the lungs, however, our results also show that surface PEGylation can be a promising approach for inhibiting the effects of pristine CuO. Our study provides information for health and safety assessment of modified CuO materials, and it can be useful in the development of nanomedical applications.

RevDate: 2019-07-05

Rodionov DA, Arzamasov AA, Khoroshkin MS, et al (2019)

Micronutrient Requirements and Sharing Capabilities of the Human Gut Microbiome.

Frontiers in microbiology, 10:1316.

The human gut microbiome harbors a diverse array of metabolic pathways contributing to its development and homeostasis via a complex web of diet-dependent metabolic interactions within the microbial community and host. Genomics-based reconstruction and predictive modeling of these interactions would provide a framework for diagnostics and treatment of dysbiosis-related syndromes via rational selection of therapeutic prebiotics and dietary nutrients. Of particular interest are micronutrients, such as B-group vitamins, precursors of indispensable metabolic cofactors, that are produced de novo by some gut bacteria (prototrophs) but must be provided exogenously in the diet for many other bacterial species (auxotrophs) as well as for the mammalian host. Cross-feeding of B vitamins between prototrophic and auxotrophic species is expected to strongly contribute to the homeostasis of microbial communities in the distal gut given the efficient absorption of dietary vitamins in the upper gastrointestinal tract. To confidently estimate the balance of microbiome micronutrient biosynthetic capabilities and requirements using available genomic data, we have performed a subsystems-based reconstruction of biogenesis, salvage and uptake for eight B vitamins (B1, B2, B3, B5, B6, B7, B9, and B12) and queuosine (essential factor in tRNA modification) over a reference set of 2,228 bacterial genomes representing 690 cultured species of the human gastrointestinal microbiota. This allowed us to classify the studied organisms with respect to their pathway variants and infer their prototrophic vs. auxotrophic phenotypes. In addition to canonical vitamin pathways, several conserved partial pathways were identified pointing to alternative routes of syntrophic metabolism and expanding a microbial vitamin "menu" by several pathway intermediates (vitamers) such as thiazole, quinolinate, dethiobiotin, pantoate. A cross-species comparison was applied to assess the extent of conservation of vitamin phenotypes at distinct taxonomic levels (from strains to families). The obtained reference collection combined with 16S rRNA gene-based phylogenetic profiles was used to deduce phenotype profiles of the human gut microbiota across in two large cohorts. This analysis provided the first estimate of B-vitamin requirements, production and sharing capabilities in the human gut microbiome establishing predictive phenotype profiling as a new approach to classification of microbiome samples. Future expansion of our reference genomic collection of metabolic phenotypes will allow further improvement in coverage and accuracy of predictive phenotype profiling of the human microbiome.

RevDate: 2019-07-01

Valentine G, Prince A, KM Aagaard (2019)

The Neonatal Microbiome and Metagenomics: What Do We Know and What Is the Future?.

NeoReviews, 20(5):e258-e271.

The human microbiota includes the trillions of microorganisms living in the human body whereas the human microbiome includes the genes and gene products of this microbiota. Bacteria were historically largely considered to be pathogens that inevitably led to human disease. However, because of advances in both cultivation-based methods and the advent of metagenomics, bacteria are now recognized to be largely beneficial commensal organisms and thus, key to normal and healthy human development. This relatively new area of medical research has elucidated insights into diseases such as inflammatory bowel disease and obesity, as well as metabolic and atopic disorders. However, much remains unknown about the complexity of microbe-microbe and microbe-host interactions. Future efforts aimed at answering key questions pertaining to the early establishment of the microbiome, alongside what defines its dysbiosis, will likely lead to long-term health and mitigation of disease. Here, we review the relevant literature pertaining to modulations in the perinatal and neonatal microbiome, the impact of environmental and maternal factors in shaping the neonatal microbiome, and future questions and directions in the exciting emerging arena of metagenomic medicine.

RevDate: 2019-07-02

Claassens NJ, Finger-Bou M, Scholten B, et al (2019)

Bicistronic Design-Based Continuous and High-Level Membrane Protein Production in Escherichia coli.

ACS synthetic biology [Epub ahead of print].

Escherichia coli has been widely used as a platform microorganism for both membrane protein production and cell factory engineering. The current methods to produce membrane proteins in this organism require the induction of target gene expression and often result in unstable, low yields. Here, we present a method combining a constitutive promoter with a library of bicistronic design (BCD) elements, which enables inducer-free, tuned translation initiation for optimal protein production. Our system mediates stable, constitutive production of bacterial membrane proteins at yields that outperform those obtained with E. coli Lemo21(DE3), the current gold standard for bacterial membrane protein production. We envisage that the continuous, fine-tunable, and high-level production of membrane proteins by our method will greatly facilitate their study and their utilization in engineering cell factories.

RevDate: 2019-07-02

Katsnelson A (2019)

Standards Seekers Put the Human Microbiome in Their Sights.

ACS central science, 5(6):929-932.

RevDate: 2019-07-02

Depommier C, Everard A, Druart C, et al (2019)

Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study.

Nature medicine pii:10.1038/s41591-019-0495-2 [Epub ahead of print].

Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well as type 2 diabetes mellitus1. The gut microbiota is a new key contributor involved in the onset of obesity-related disorders2. In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated type 2 diabetes mellitus or hypertension3-8. Since the administration of A. muciniphila has never been investigated in humans, we conducted a randomized, double-blind, placebo-controlled pilot study in overweight/obese insulin-resistant volunteers; 40 were enrolled and 32 completed the trial. The primary end points were safety, tolerability and metabolic parameters (that is, insulin resistance, circulating lipids, visceral adiposity and body mass). Secondary outcomes were gut barrier function (that is, plasma lipopolysaccharides) and gut microbiota composition. In this single-center study, we demonstrated that daily oral supplementation of 1010 A. muciniphila bacteria either live or pasteurized for three months was safe and well tolerated. Compared to placebo, pasteurized A. muciniphila improved insulin sensitivity (+28.62 ± 7.02%, P = 0.002), and reduced insulinemia (-34.08 ± 7.12%, P = 0.006) and plasma total cholesterol (-8.68 ± 2.38%, P = 0.02). Pasteurized A. muciniphila supplementation slightly decreased body weight (-2.27 ± 0.92 kg, P = 0.091) compared to the placebo group, and fat mass (-1.37 ± 0.82 kg, P = 0.092) and hip circumference (-2.63 ± 1.14 cm, P = 0.091) compared to baseline. After three months of supplementation, A. muciniphila reduced the levels of the relevant blood markers for liver dysfunction and inflammation while the overall gut microbiome structure was unaffected. In conclusion, this proof-of-concept study (clinical trial no. NCT02637115) shows that the intervention was safe and well tolerated and that supplementation with A. muciniphila improves several metabolic parameters.

RevDate: 2019-07-02

Tavakoli A, JL Flanagan (2019)

The Case for a More Holistic Approach to Dry Eye Disease: Is It Time to Move beyond Antibiotics?.

Antibiotics (Basel, Switzerland), 8(3): pii:antibiotics8030088.

Dry eye disease (DED) is one of the most frequent presentations to optometrists with over 16 million US adults (6.8% of adult population) diagnosed as having this disorder. The majority of associated marketed products offer relief from symptomatology but do not address aetiology. DED harbours many distinguishing features of a chronic inflammatory disorder. The recent explosion in human microbiome research has sparked interest in the ocular microbiome and its role in the preservation and extension of ocular surface health and in the contribution of the gut microbiome to chronic systemic inflammation and associated "Western life-style" diseases. With a significant lack of success for many patients using currently available DED treatments, in this era of the microbiome, we are interested in exploring potential novel therapies that aim to reconstitute healthy bacterial communities both locally and distally (in the gut) as a treatment for DED. Although this direction of investigation is in its infancy, burgeoning interest makes such a review timely. This paper considers a number of studies into the use functional foods and associated products to ameliorate dry eye.

RevDate: 2019-06-29

Korpela K, Dikareva E, Hanski E, et al (2019)

Cohort profile: Finnish Health and Early Life Microbiota (HELMi) longitudinal birth cohort.

BMJ open, 9(6):e028500 pii:bmjopen-2018-028500.

PURPOSE: HELMi (Health and Early Life Microbiota) is a longitudinal, prospective general population birth cohort, set up to identify environmental, lifestyle and genetic factors that modify the intestinal microbiota development in the first years of life and their relation to child health and well-being.

PARTICIPANTS: The HELMi cohort consists of 1055 healthy term infants born in 2016-2018 mainly at the capital region of Finland and their parents. The intestinal microbiota development of the infants is characterised based on nine, strategically selected, faecal samples and connected to extensive online questionnaire-collected metadata at weekly to monthly intervals focusing on the diet, other exposures and family's lifestyle as well as the health and growth of the child. Motor and cognitive developmental screening takes place at 18 months. Infant's DNA sample, mother's breast milk sample and both parent's spot faecal samples have been collected.

FINDINGS TO DATE: The mean age of the mothers was 32.8 (SD 4.1) and fathers/coparents 34.8 (5.3) years at the time of enrolment. Seventeen percentage (n=180) of the infants were born by caesarean section. Just under half (49%) were firstborns; 50.7% were males. At 3 months of age, 86% of the babies were exclusively breastfed and 2% exclusively formula-fed.

FUTURE PLANS: The current follow-up from pregnancy to first 24 months will be completed in March 2020, totalling to over 10 000 biological samples and over 50 000 questionnaire entries. The results are expected to identify environmental and host factors that affect early gut microbiota development and health, and hence give indications of how to prevent or reverse microbiota perturbations in infancy. This prospective cohort will be followed up further to identify how the early microbiota relates to later health outcomes, especially weight gain, infections and allergic and other chronic diseases.


RevDate: 2019-06-29

Lokugamage AU, SDC Pathberiya (2019)

The microbiome seeding debate - let's frame it around women-centred care.

Reproductive health, 16(1):91 pii:10.1186/s12978-019-0747-0.

In a global culture that is increasingly interested in ecological interventions, probiotics, 'friendly bacteria', microbiome preservation/restoration and long-term health, there is growing awareness of the idea of seeding the vaginal microbiome in the new born after caesarean section. It is postulated as a way of restoring helpful missing microbes and preventing long term non-communicable diseases of babies delivered by caesarean section. Currently, there is a deluge of evidence being published on the human microbiome, which can be challenging to digest and absorb by scientists, clinicians and patients. The specific evidence base around this technique is at its early stages. This commentary discusses what advice is currently available from a feminist and a person-centred care perspective.

ABSTRAKT: Det er en voksende interesse internasjonalt for økologiske intervensjoner, probiotika, 'snille bakterier', bevaring/gjenoppretting av. mikrobiomet og helse i et langtidsperspektiv. I denne sammenhengen er det en økende interesse for tanken om å så det vaginale mikrobiomet (vaginal seeding) på den nyfødte etter et keisersnitt. Dette er postulert som en måte å gjenopprette manglende normalflora/mikrobiom og forebygge langvarige ikke-smittsomme sykdommer hos barn født med keisersnitt. For tiden publiseres det mye forskning om menneskets mikrobiom, noe som kan være utfordrende å fordøye og ta til seg for forskere, klinikere og pasienter. Forskningen på denne spesifikke metoden er i sin begynnelse. Denne kommentaren drøfter hvilke råd som for øyeblikket er tilgjengelige, fra et feministisk og personsentrert omsorgsperspektiv. POPULARISERT SAMMENDRAG På NORSK: Det menneskelige mikrobiomet er summen av alle bakteriene som dekker den menneskelige kroppen og det hjelper kroppen i å fungere optimalt. Når mikrobiomet forstyrres, vil kroppen kunne få betennelsesreaksjoner og allergier. I fødsel finnes de «gode» bakteriene i kvinnens vagina. (det vaginale mikrobiomet) som man tror vil være fordelaktig for babyens evne til å utvikle et sunt immunsystem. Babyer som er født med keisersnitt vil ikke bli eksponert for disse «gode» bakteriene og det kan påvirke barnets immunforsvar negativt og potensielt øke sjansen for allergier og betennelsesreaksjoner i kroppen på lang sikt. Vaginal seeding (et forsøk på å gjenopprette balansen og noen av de gode bakterier i spedbarnet gjennom å tilføre mors vaginale bakterier via en kompress som strykes over spedbarnets ansikt) Vaginal seeding er en metode som noen forskere sier muligens delvis gjenoppretter de manglende «gode» bakteriene etter et keisersnitt. Forskningen er på et tidlig stadium. Det har vært avisartikler og en film om emnet og mødre har funnet ut om vaginal seeding som en måte å gjenopprette denne delen av babyens mikrobiom. Foreldre ønsker å diskutere vaginal seeding, men på nåværende tidspunkt er helsevesenet avventende og helsepersonell er ikke godt nok informert. Denne artikkelen vil se på den pågående diskusjonen. RéSUMé: Dans une culture mondiale qui s'intéresse de plus en plus aux interventions écologiques, aux probiotiques, aux «bactéries amicales», à la préservation / restauration du microbiome et à la santé à long terme, on commence à prendre conscience de l'idée d'ensemencer le microbiome vaginal chez le nouveau-né après une césarienne. Il est postulé comme un moyen de restaurer les microbes manquants et d'aider à prévenir les maladies non transmissibles à long terme des bébés mis au monde par césarienne. Il existe actuellement un déluge de preuves sur le microbiome humain, qui peuvent être difficiles à digérer et à absorber par les scientifiques, les cliniciens et les patients. La base de preuves spécifique autour de cette technique en est à ses débuts. Ce commentaire discute des conseils actuellement disponibles dans une perspective de soins féministe et centrée sur la personne. RéSUMé SIMPLIFIé: Le microbiome humain est constitué de tous les microbes qui recouvrent le corps humain et qui aident le corps à bien fonctionner. Lorsque le microbiome est perturbé, le corps devient plus inflammatoire et est sujet aux allergies. Lors de l'accouchement, le vagin d'une mère (le microbiome vaginal) contient des "bactéries amicales" qui pourraient être bénéfiques pour l'enfant et aider le bébé à développer un système immunitaire en bonne santé. Les bébés nés par césarienne ne sont généralement pas exposés à ces «bactéries bénéfiques», ce qui pourrait affecter négativement le système immunitaire du bébé et potentiellement augmenter le risque d'allergies et d'inflammation à long terme. Selon certains scientifiques, l'ensemencement vaginal pourrait partiellement restaurer les «bactéries amies» manquantes après la césarienne. La recherche en est à ses débuts. Il y a eu des articles de journaux et un film à ce sujet, et les mères ont découvert l'existence d'un ensemencement vaginal (où une compresse placée dans le vagin de la mère pourrait être appliquée sur l'enfant après la césarienne) afin de restaurer une partie du microbiome du bébé. Les parents souhaitent discuter de l'ensemencement vaginal, mais à l'heure actuelle, les organisations médicales sont prudentes et les praticiens ne sont pas suffisamment informés. Cet article examine le débat en cours.

RESUMO: Numa cultura global que está cada vez mais interessada em intervenções ecológicas, probióticos, "bactérias amigáveis", preservação/restauração do microbioma e saúde a longo prazo, há uma crescente consciência sobre a ideia de semear o microbioma vaginal no recém-nascido após uma cirurgia cesariana. Isso está sendo postulado como uma forma de restaurar micróbios úteis que lhe faltariam e prevenir doenças não transmissíveis em longo prazo para bebês que nasceram pela via cirúrgica. Atualmente, há um aumento massivo de evidências sendo publicadas sobre o microbioma humano cuja absorção e digestão pode ser desafiadora para cientistas, clínicos e pacientes. A base específica da evidência que cerca essa técnica ainda está em estágios preliminares. Este comentário discute o aconselhamento atualmente disponível numa perspectiva feminista e centrada na pessoa. SíNTESE SIMPLIFICADA: O microbioma humano está composto por todos os micróbios que cobrem o corpo humano e que ajudam o corpo a funcionar bem. Quando o microbioma é perturbado, o corpo tem mais inflamações e maior propensão a desenvolver alergias. Ao nascimento, há "bactérias amigáveis" na vagina materna (o microbioma vaginal) que podem ser benéficas à criança e ajudar o bebê a desenvolver um sistema imunológico saudável. Bebês que nascem por cesariana usualmente não são expostos a essas "bactérias amigáveis" e isso poderá afetar negativamente o sistema imunológico do bebê, aumentando potencialmente a probabilidade de alegrias e inflamações no longo prazo. A semeadura de bactéria vaginais é um método que alguns cientistas afirmam que poderá restaurar parcialmente as "bactérias amigáveis" faltantes depois de uma cesariana. Essa pesquisa está em fase preliminar. Houve alguns artigos em jornais e um filme sobre isso, e as mães descobriram a possibilidade da semeadura vaginal (quando é feito um swab da vagina materna que é esfregado no bebê após a cesárea) para restaurar parte do microbioma do bebê. Pais desejam discutir a semeadura vaginal, mas, no momento, as organizações médicas têm sido cautelosas e os profissionais não estão adequadamente informados. Este artigo aborda o debate em andamento.

RESUMEN: En una cultura global que está cada vez más interesada en las intervenciones ecológicas, los probióticos, las "bacterias amigables", la conservación/restauración de microbiomas y la salud a largo plazo, hay una creciente conciencia de la idea de sembrar el microbioma vaginal en el recién nacido después de la cesárea. Se postula como una forma de restaurar los microbios útiles faltantes y prevenir las enfermedades no transmisibles a largo plazo de los bebés nacidos por cesárea. Actualmente, se está publicando una gran cantidad de pruebas sobre el microbioma humano, que pueden ser difíciles de digerir y absorber por parte de científicos, clínicos y pacientes. La base de la evidencia específica en torno a esta técnica se encuentra en sus primeras etapas. Este artículo analiza qué consejos están disponibles actualmente desde una perspectiva feminista y de atención centrada en la persona.

RESUMEN EN LENGUAJE SENCILLO: El microbioma humano está hecho de todos las bacterias que cubren el cuerpo humano y que ayudan al cuerpo a funcionar bien. Cuando se altera el microbioma, el cuerpo se inflama más y es propenso a las alergias. En el parto, hay "bacterias amigables" en la vagina de la madre (el microbioma vaginal) que podrían ser beneficiosas para el niño y ayudar al bebé a desarrollar un sistema inmunológico saludable. Los bebés que nacen por cesárea generalmente no se exponen a estas "bacterias amigables" y esto podría afectar negativamente el sistema inmunológico del bebé, lo que podría aumentar la probabilidad de alergias e inflamación a largo plazo. La siembra vaginal es un método que algunos científicos dicen que podría restaurar parcialmente las "bacterias amigables" que faltan después de la cesárea. La investigación se encuentra en sus primeras etapas. Han habido artículos periodísticos y una película sobre esto, y las madres se han enterado de la siembra vaginal (donde se puede frotar el niño con una torunda de la vagina de la madre después de la cesárea) para restaurar la parte del microbioma del bebé. Los padres quieren hablar sobre la siembra vaginal, pero en la actualidad las organizaciones médicas son cautelosas y los profesionales no están informados adecuadamente. Este artículo analiza el debate en curso.

RevDate: 2019-06-28

Kooter I, Ilves M, Gröllers-Mulderij M, et al (2019)

Molecular Signature of Asthma-Enhanced Sensitivity to CuO Nanoparticle Aerosols from 3D Cell Model.

ACS nano, 13(6):6932-6946.

More than 5% of any population suffers from asthma, and there are indications that these individuals are more sensitive to nanoparticle aerosols than the healthy population. We used an air-liquid interface model of inhalation exposure to investigate global transcriptomic responses in reconstituted three-dimensional airway epithelia of healthy and asthmatic subjects exposed to pristine (nCuO) and carboxylated (nCuOCOOH) copper oxide nanoparticle aerosols. A dose-dependent increase in cytotoxicity (highest in asthmatic donor cells) and pro-inflammatory signaling within 24 h confirmed the reliability and sensitivity of the system to detect acute inhalation toxicity. Gene expression changes between nanoparticle-exposed versus air-exposed cells were investigated. Hierarchical clustering based on the expression profiles of all differentially expressed genes (DEGs), cell-death-associated DEGs (567 genes), or a subset of 48 highly overlapping DEGs categorized all samples according to "exposure severity", wherein nanoparticle surface chemistry and asthma are incorporated into the dose-response axis. For example, asthmatics exposed to low and medium dose nCuO clustered with healthy donor cells exposed to medium and high dose nCuO, respectively. Of note, a set of genes with high relevance to mucociliary clearance were observed to distinctly differentiate asthmatic and healthy donor cells. These genes also responded differently to nCuO and nCuOCOOH nanoparticles. Additionally, because response to transition-metal nanoparticles was a highly enriched Gene Ontology term (FDR 8 × 10-13) from the subset of 48 highly overlapping DEGs, these genes may represent biomarkers to a potentially large variety of metal/metal oxide nanoparticles.

RevDate: 2019-06-27

Gumkowski JD, Martinie RJ, Corrigan P, et al (2019)

Analysis of RNA methylation by phylogenetically diverse Cfr radical SAM enzymes reveals an iron-binding accessory domain in a clostridial enzyme.

Biochemistry [Epub ahead of print].

Cfr is a radical S-adenosylmethionine (SAM) RNA methylase linked to multi-drug antibiotic resistance in bacterial pathogens. It catalyzes a chemically challenging C-C-bond forming reaction to methylate C8 of A2503 [ Escherichia coli (Ec) numbering) of 23 S ribosomal RNA during ribosome assembly. The cfr gene has been identified as a mobile genetic element in diverse bacteria and in the genome of select Bacillales and Clostridiales species. Despite the importance of Cfr, few representatives have been purified and characterized in vitro. Here we show that Cfr homologs from Bacillus amyloliquefaciens, Enterococcus faecalis, Paenibacillus lautus, and Clostridioides difficile act as C8 adenine RNA methylases in biochemical assays. C. difficile Cfr contains an additional Cys-rich C-terminal domain that binds a mononuclear Fe2+ ion in a rubredoxin-type Cys4 motif. The C-terminal domain can be truncated with minimal impact on C. difficile Cfr activity, but turnover is diminished upon disruption of the Fe2+ binding site by Zn2+ substitution or ligand mutation. These findings indicate an important purpose for the observed C-terminal iron in the native fusion protein. Bioinformatic analysis of the C. difficile Cfr Cys-rich domain shows that it is widespread (~1000 homologs) as a stand-alone gene in pathogenic or commensal bacilli and clostridia, with >10% encoded adjacent to a predicted radical-SAM RNA methylase. Although the domain is not essential for in vitro C. difficile Cfr activity, genomic co-occurrence and high abundance in the human microbiome suggests a possible functional role for a specialized rubredoxin in certain radical-SAM RNA methylases with relevance to human health.

RevDate: 2019-06-24

Savijoki K, Nyman TA, Kainulainen V, et al (2019)

Growth Mode and Carbon Source Impact the Surfaceome Dynamics of Lactobacillus rhamnosus GG.

Frontiers in microbiology, 10:1272.

Bacterial biofilms have clear implications in disease and in food applications involving probiotics. Here, we show that switching the carbohydrate source from glucose to fructose increased the biofilm formation and the total surface-antigenicity of a well-known probiotic, Lactobacillus rhamnosus GG. Surfaceomes (all cell surface-associated proteins) of GG cells grown with glucose and fructose in planktonic and biofilm cultures were identified and compared, which indicated carbohydrate source-dependent variations, especially during biofilm growth. The most distinctive differences under these conditions were detected with several surface adhesins (e.g., MBF, SpaC pilus protein and penicillin-binding proteins), enzymes (glycoside hydrolases, PrsA, PrtP, PrtR, and HtrA) and moonlighting proteins (glycolytic, transcription/translation and stress-associated proteins, r-proteins, tRNA synthetases, Clp family proteins, PepC, PepN, and PepA). The abundance of several known adhesins and candidate moonlighters, including enzymes acting on casein-derived peptides (ClpP, PepC, and PepN), increased in the biofilm cells grown on fructose, from which the surface-associated aminopeptidase activity mediated by PepC and PepN was further confirmed by an enzymatic assay. The mucus binding factor (MBF) was found most abundant in fructose grown biofilm cells whereas SpaC adhesin was identified specifically from planktonic cells growing on fructose. An additional indirect ELISA indicated both growth mode- and carbohydrate-dependent differences in abundance of SpaC, whereas the overall adherence of GG assessed with porcine mucus indicated that the carbon source and the growth mode affected mucus adhesion. The adherence of GG cells to mucus was almost completely inhibited by anti-SpaC antibodies regardless of growth mode and/or carbohydrate source, indicating the key role of the SpaCBA pilus in adherence under the tested conditions. Altogether, our results suggest that carbon source and growth mode coordinate mechanisms shaping the proteinaceous composition of GG cell surface, which potentially contributes to resistance, nutrient acquisition and cell-cell interactions under different conditions. In conclusion, the present study shows that different growth regimes and conditions can have a profound impact on the adherent and antigenic features of GG, thereby providing new information on how to gain additional benefits from this probiotic.

RevDate: 2019-06-24

Stinson LF, Boyce MC, Payne MS, et al (2019)

The Not-so-Sterile Womb: Evidence That the Human Fetus Is Exposed to Bacteria Prior to Birth.

Frontiers in microbiology, 10:1124.

The human microbiome includes trillions of bacteria, many of which play a vital role in host physiology. Numerous studies have now detected bacterial DNA in first-pass meconium and amniotic fluid samples, suggesting that the human microbiome may commence in utero. However, these data have remained contentious due to underlying contamination issues. Here, we have used a previously described method for reducing contamination in microbiome workflows to determine if there is a fetal bacterial microbiome beyond the level of background contamination. We recruited 50 women undergoing non-emergency cesarean section deliveries with no evidence of intra-uterine infection and collected first-pass meconium and amniotic fluid samples. Full-length 16S rRNA gene sequencing was performed using PacBio SMRT cell technology, to allow high resolution profiling of the fetal gut and amniotic fluid bacterial microbiomes. Levels of inflammatory cytokines were measured in amniotic fluid, and levels of immunomodulatory short chain fatty acids (SCFAs) were quantified in meconium. All meconium samples and most amniotic fluid samples (36/43) contained bacterial DNA. The meconium microbiome was dominated by reads that mapped to Pelomonas puraquae. Aside from this species, the meconium microbiome was remarkably heterogeneous between patients. The amniotic fluid microbiome was more diverse and contained mainly reads that mapped to typical skin commensals, including Propionibacterium acnes and Staphylococcus spp. All meconium samples contained acetate and propionate, at ratios similar to those previously reported in infants. P. puraquae reads were inversely correlated with meconium propionate levels. Amniotic fluid cytokine levels were associated with the amniotic fluid microbiome. Our results demonstrate that bacterial DNA and SCFAs are present in utero, and have the potential to influence the developing fetal immune system.

RevDate: 2019-06-21

Lemas D, Wright L, Francois M, et al (2019)

Recruitment and Retention of Pregnant and Breastfeeding Mothers for Longitudinal Clinical Microbiome Studies (OR30-08-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz048.OR30-08-19.

Objectives: Accumulating data suggest the health benefits of breastfeeding are, in part, mediated through interactions with the human microbiome. Despite these observations, recruitment of pregnant mothers in longitudinal clinical microbiome studies remains a significant challenge. The goal of this study is to develop data-driven strategies for recruitment and retention of breastfeeding mothers' into longitudinal clinical microbiome studies.

Methods: We recruited a total of 40 mothers (20 pregnant and 20 breastfeeding) to complete in-depth semi-structured interviews at the UF Clinical and Translational Science Institute. Additionally, mothers were asked to use self-administered microbiome collection kits and complete questionnaires related to health history, infant feeding practices, and physical activity. Informative interviews were designed to identify women's understanding, motivations and barriers surrounding longitudinal clinical research participation and their preferences for providing non-invasive biological samples.

Results: Our preliminary analysis indicates that 1) barriersfor participating in research include convenience, confidentiality and child protection; 2) factors motivating participation in research include general interest in breastfeeding, schedule, and perceived research relevance; 3) participant recruitment should consider social media and 4) biological sample collection should include adequate instructions and drop-off convenience.

Conclusions: The results of this study provide valuable theoretical and practical insights on how to effectively recruit and retain pregnant and breastfeeding women into longitudinal microbiome studies.

Funding Sources: 1K01DK115632-01A1.

RevDate: 2019-06-21

Faramarzi S, K Krishnan (2019)

The Spectacular Role of the Human Microbiome in Preventing Post-prandial or Metabolic Endotoxemia (OR23-02-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.OR23-02-19.

Objectives: To determine if 30-d of oral spore-based probiotic supplementation could reduce dietary endotoxemia.

Methods: Apparently healthy men and women (n = 75) were screened for post-prandial dietary endotoxemia. Subjects whose serum endotoxin concentration increased by at least 5-fold from pre-meal levels at 5-h post-prandial were considered "responders" and were randomized to receive either placebo (rice flour) or a commercial spore-based probiotic supplement [Bacillus indicus (HU36), Bacillus subtilis (HU58), Bacillus coagulans, and Bacillus licheniformis, and Bacillus clausii] for 30-d. The dietary endotoxemia test was repeated at the conclusion of the supplementation period. Dietary endotoxin (LAL) and triglycerides (enzymatic) were measured using an automated chemistry analyzer. Serum disease risk biomarkers were measured using bead-based multiplex assays (Luminex and Milliplex) as secondary, exploratory measures.

Results: Data were statistically analyzed using repeated measures ANOVA and a P < 0.05. We found that spore-based probiotic supplementation was associated with a 42% reduction in endotoxin (12.9 ± 3.5 vs 6.1 ± 2.6, P = 0.011) and 24% reduction in triglyceride (212 ± 28 vs 138 ± 12, P = 0.004) in the post-prandial period Placebo subjects presented with a 36% increase in endotoxin (10.3 ± 3.4 vs 15.4 ± 4.1, P = 0.011) and 5% decrease in triglycerides (191 ± 24 vs 186 ± 28, P = 0.004) over the same post-prandial period. We also found that spore-based probiotic supplementation was associated with significant post-prandial reductions in IL-12p70 (24.3 ± 2.2 vs 21.5 ± 1.7, P = 0.017) and IL-1β (1.9 ± 0.2 vs 1.6 ± 0.1, P = 0.020). Compared to placebo post supplementation, probiotic subject had less ghrelin (6.8 ± 0.4 vs 8.3 ± 1.1, P = 0.017) compared to placebo subjects.

Conclusions: 30 days of supplementation with spore-based probiotics showed a 60% reduction in biomarkers of leaky gut when compared to the placebo group. These findings suggest that probiotics may play an integral role in reducing chronic low-grade inflammation that leads to chronic disease and autoimmunity.

Funding Sources: The present study was funded in part by a competitive research grant from Microbiome Labs, LLC (Glenview, IL) to the University of North Texas.

RevDate: 2019-06-21

Koontz JM, Dancy BCR, Horton CL, et al (2019)

The Role of the Human Microbiome in Chemical Toxicity.

International journal of toxicology [Epub ahead of print].

There is overwhelming evidence that the microbiome must be considered when evaluating the toxicity of chemicals. Disruption of the normal microbial flora is a known effect of toxic exposure, and these disruptions may lead to human health effects. In addition, the biotransformation of numerous compounds has been shown to be dependent on microbial enzymes, with the potential for different host health outcomes resulting from variations in the microbiome. Evidence suggests that such metabolism of environmental chemicals by enzymes from the host's microbiota can affect the toxicity of that chemical to the host. Chemical-microbial interactions can be categorized into two classes: Microbiome Modulation of Toxicity (MMT) and Toxicant Modulation of the Microbiome (TMM). MMT refers to transformation of a chemical by microbial enzymes or metabolites to modify the chemical in a way that makes it more or less toxic. TMM is a change in the microbiota that results from a chemical exposure. These changes span a large magnitude of effects and may vary from microbial gene regulation, to inhibition of a specific enzyme, to the death of the microbes. Certain microbiomes or microbiota may become associated with different health outcomes, such as resistance or susceptibility to exposure to certain toxic chemicals, the ability to recover following a chemical-induced injury, the presence of disease-associated phenotypes, and the effectiveness of immune responses. Future work in toxicology will require an understanding of how the microbiome interacts with toxicants to fully elucidate how a compound will affect a diverse, real-world population.

RevDate: 2019-06-20

Zhang YJ, Hu HW, Chen QL, et al (2019)

Transfer of antibiotic resistance from manure-amended soils to vegetable microbiomes.

Environment international, 130:104912 pii:S0160-4120(19)31273-5 [Epub ahead of print].

The increasing antimicrobial resistance in manure-amended soil can potentially enter food chain, representing an important vehicle for antibiotic resistance genes (ARGs) transmission into human microbiome. However, the pathways for transmission of ARGs from soil to plant remain unclear. Here, we explored the impacts of poultry and cattle manure application on the patterns of resistome in soil and lettuce microbiome including rhizosphere, root endosphere, leaf endosphere and phyllosphere, to identify the potential transmission routes of ARGs in the soil-plant system. After 90 days of cultivation, a total of 144 ARGs were detected in all samples using high-throughput quantitative PCR. Rhizosphere soil samples harbored the most diverse ARGs compared with other components of lettuce. Cattle manure application increased the abundance of ARGs in root endophyte, while poultry manure application increased ARGs in rhizosphere, root endophyte and phyllosphere, suggesting that poultry manure may have a stronger impact on lettuce resistomes. The ARG profiles were significantly correlated with the bacterial community, and the enrichment of soil and plant resistomes was strongly affected by the bacterial taxa including Solibacteres, Chloroflexi, Acidobacteria, Gemm-1 and Gemmatimonadetes, as revealed by the network analyses. Moreover, the overlaps of ARGs between lettuce tissues and soil were identified, which indicated that plant and environmental resistomes are interconnected. Our findings provide insights into the transmission routes of ARGs from manured soil to vegetables, and highlight the potential risks of plant resistome migration to the human food chain.

RevDate: 2019-06-20

Shen X, Yao YF, Li JY, et al (2019)

[Human mycobiome and diseases].

Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology, 37(3):314-319.

The proportion of mycobiome is less than 1% of human microbiome. However, fungal community plays a key role in human health and diseases. With high-throughput sequencing applications, the structure and composition of mycobiome in the mouth, lung, gut, vagina, and skin have been analyzed, and the role of microbiome in diseases has been investigated. Mycobiome also influences the composition of bacteriome and includes key species that maintain the structure and function of microbial communities. Fungi also influence host immune responses. In this review, we summarized the mycobiome com-position at various sites and different diseases and the interactions between fungi-bacteria and fungi-host.

RevDate: 2019-06-15

Picardo SL, Coburn B, AR Hansen (2019)

The microbiome and cancer for clinicians.

Critical reviews in oncology/hematology, 141:1-12 pii:S1040-8428(19)30112-X [Epub ahead of print].

The human microbiome is an emerging target in cancer development and therapeutics. It may be directly oncogenic, through promotion of mucosal inflammation or systemic dysregulation, or may alter anti-cancer immunity/therapy. Microorganisms within, adjacent to and distant from tumors may affect cancer progression, and interactions and differences between these populations can influence the course of disease. Here we review the microbiome as it pertains to cancer for clinicians. The microbiota of cancers including colorectal, pancreas, breast and prostate are discussed. We examine "omics" technologies, microbiota associated with tumor tissue and tumor-site fluids such as feces and urine, as well as indirect effects of the gut microbiome. We describe roles of the microbiome in immunotherapy, and how it can be modulated to improve cancer therapeutics. While research is still at an early stage, there is potential to exploit the microbiome, as modulation may increase efficacy of treatments, reduce toxicities and prevent carcinogenesis.

RevDate: 2019-06-15

Szafrański SP, Kilian M, Yang I, et al (2019)

Diversity patterns of bacteriophages infecting Aggregatibacter and Haemophilus species across clades and niches.

The ISME journal pii:10.1038/s41396-019-0450-8 [Epub ahead of print].

Aggregatibacter and Haemophilus species are relevant human commensals and opportunistic pathogens. Consequently, their bacteriophages may have significant impact on human microbial ecology and pathologies. Our aim was to reveal the prevalence and diversity of bacteriophages infecting Aggregatibacter and Haemophilus species that colonize the human body. Genome mining with comparative genomics, screening of clinical isolates, and profiling of metagenomes allowed characterization of 346 phages grouped in 52 clusters and 18 superclusters. Less than 10% of the identified phage clusters were represented by previously characterized phages. Prophage diversity patterns varied significantly for different phage types, host clades, and environmental niches. A more diverse phage community lysogenizes Haemophilus influenzae and Haemophilus parainfluenzae strains than Aggregatibacter actinomycetemcomitans and "Haemophilus ducreyi". Co-infections occurred more often in "H. ducreyi". Phages from Aggregatibacter actinomycetemcomitans preferably lysogenized strains of specific serotype. Prophage patterns shared by subspecies clades of different bacterial species suggest similar ecoevolutionary drivers. Changes in frequencies of DNA uptake signal sequences and guanine-cytosine content reflect phage-host long-term coevolution. Aggregatibacter and Haemophilus phages were prevalent at multiple oral sites. Together, these findings should help exploring the ecoevolutionary forces shaping virus-host interactions in the human microbiome. Putative lytic phages, especially phiKZ-like, may provide new therapeutic options.

RevDate: 2019-06-12

Nichols RG, Peters JM, AD Patterson (2019)

Interplay Between the Host, the Human Microbiome, and Drug Metabolism.

Human genomics, 13(1):27 pii:10.1186/s40246-019-0211-9.

The human microbiome is composed of four major areas including intestinal, skin, vaginal, and oral microbiomes, with each area containing unique species and unique functionalities. The human microbiome may be modulated with prebiotics, probiotics, and postbiotics to potentially aid in the treatment of diseases like irritable bowel syndrome, bacterial vaginosis, atopic dermatitis, gingivitis, obesity, or cancer. There is also potential for many of the inhabitants of the human microbiome to directly modulate host gene expression and modulate host detoxifying enzyme activity like cytochrome P450s (CYPs), dehydrogenases, and carboxylesterases. Therefore, the microbiome may be important to consider during drug discovery, risk assessment, and dosing regimens for various diseases given that the human microbiome has been shown to impact host detoxification processes.

RevDate: 2019-06-11

Zhao L, Xu J, Shang X, et al (2019)

Synaptic memory devices from CoO/Nb:SrTiO3 junction.

Royal Society open science, 6(4):181098 pii:rsos181098.

Non-volatile memristors are promising for future hardware-based neurocomputation application because they are capable of emulating biological synaptic functions. Various material strategies have been studied to pursue better device performance, such as lower energy cost, better biological plausibility, etc. In this work, we show a novel design for non-volatile memristor based on CoO/Nb:SrTiO3 heterojunction. We found the memristor intrinsically exhibited resistivity switching behaviours, which can be ascribed to the migration of oxygen vacancies and charge trapping and detrapping at the heterojunction interface. The carrier trapping/detrapping level can be finely adjusted by regulating voltage amplitudes. Gradual conductance modulation can therefore be realized by using proper voltage pulse stimulations. And the spike-timing-dependent plasticity, an important Hebbian learning rule, has been implemented in the device. Our results indicate the possibility of achieving artificial synapses with CoO/Nb:SrTiO3 heterojunction. Compared with filamentary type of the synaptic device, our device has the potential to reduce energy consumption, realize large-scale neuromorphic system and work more reliably, since no structural distortion occurs.

RevDate: 2019-06-06

Wijeyesekera A, Wagner J, De Goffau M, et al (2019)

Multi-Compartment Profiling of Bacterial and Host Metabolites Identifies Intestinal Dysbiosis and Its Functional Consequences in the Critically Ill Child.

Critical care medicine [Epub ahead of print].

OBJECTIVES: Adverse physiology and antibiotic exposure devastate the intestinal microbiome in critical illness. Time and cost implications limit the immediate clinical potential of microbial sequencing to identify or treat intestinal dysbiosis. Here, we examined whether metabolic profiling is a feasible method of monitoring intestinal dysbiosis in critically ill children.

DESIGN: Prospective multicenter cohort study.

SETTING: Three U.K.-based PICUs.

PATIENTS: Mechanically ventilated critically ill (n = 60) and age-matched healthy children (n = 55).

INTERVENTIONS: Collection of urine and fecal samples in children admitted to the PICU. A single fecal and urine sample was collected in healthy controls.

MEASUREMENTS AND MAIN RESULTS: Untargeted and targeted metabolic profiling using 1H-nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry or urine and fecal samples. This was integrated with analysis of fecal bacterial 16S ribosomal RNA profiles and clinical disease severity indicators. We observed separation of global urinary and fecal metabolic profiles in critically ill compared with healthy children. Urinary excretion of mammalian-microbial co-metabolites hippurate, 4-cresol sulphate, and formate were reduced in critical illness compared with healthy children. Reduced fecal excretion of short-chain fatty acids (including butyrate, propionate, and acetate) were observed in the patient cohort, demonstrating that these metabolites also distinguished between critical illness and health. Dysregulation of intestinal bile metabolism was evidenced by increased primary and reduced secondary fecal bile acid excretion. Fecal butyrate correlated with days free of intensive care at 30 days (r = 0.38; p = 0.03), while urinary formate correlated inversely with vasopressor requirement (r = -0.2; p = 0.037).

CONCLUSIONS: Disruption to the functional activity of the intestinal microbiome may result in worsening organ failure in the critically ill child. Profiling of bacterial metabolites in fecal and urine samples may support identification and treatment of intestinal dysbiosis in critical illness.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: 2019-06-06

Hsu T, Gemmell MR, Franzosa EA, et al (2019)

Comparative genomics and genome biology of Campylobacter showae.

Emerging microbes & infections, 8(1):827-840.

Campylobacter showae a bacterium historically linked to gingivitis and periodontitis, has recently been associated with inflammatory bowel disease and colorectal cancer. Our aim was to generate genome sequences for new clinical C. showae strains and identify functional properties explaining their pathogenic potential. Eight C. showae genomes were assessed, four strains isolated from inflamed gut tissues from paediatric Crohn's disease patients, three strains from colonic adenomas, and one from a gastroenteritis patient stool. Genome assemblies were analyzed alongside the only 3 deposited C. showae genomes. The pangenome from these 11 strains consisted of 4686 unique protein families, and the core genome size was estimated at 1050 ± 15 genes with each new genome contributing an additional 206 ± 16 genes. Functional assays indicated that colonic strains segregated into 2 groups: adherent/invasive vs. non-adherent/non-invasive strains. The former possessed Type IV secretion machinery and S-layer proteins, while the latter contained Cas genes and other CRISPR associated proteins. Comparison of gene profiles with strains in Human Microbiome Project metagenomes showed that gut-derived isolates share genes specific to tongue dorsum and supragingival plaque counterparts. Our findings indicate that C. showae strains are phenotypically and genetically diverse and suggest that secretion systems may play an important role in virulence potential.

RevDate: 2019-06-06

Vress D, B Lim (2019)

Understanding the human microbiome: new icing on an old cake.

BJOG : an international journal of obstetrics and gynaecology [Epub ahead of print].

RevDate: 2019-06-10

LaPierre N, Mangul S, Alser M, et al (2019)

MiCoP: microbial community profiling method for detecting viral and fungal organisms in metagenomic samples.

BMC genomics, 20(Suppl 5):423 pii:10.1186/s12864-019-5699-9.

BACKGROUND: High throughput sequencing has spurred the development of metagenomics, which involves the direct analysis of microbial communities in various environments such as soil, ocean water, and the human body. Many existing methods based on marker genes or k-mers have limited sensitivity or are too computationally demanding for many users. Additionally, most work in metagenomics has focused on bacteria and archaea, neglecting to study other key microbes such as viruses and eukaryotes.

RESULTS: Here we present a method, MiCoP (Microbiome Community Profiling), that uses fast-mapping of reads to build a comprehensive reference database of full genomes from viruses and eukaryotes to achieve maximum read usage and enable the analysis of the virome and eukaryome in each sample. We demonstrate that mapping of metagenomic reads is feasible for the smaller viral and eukaryotic reference databases. We show that our method is accurate on simulated and mock community data and identifies many more viral and fungal species than previously-reported results on real data from the Human Microbiome Project.

CONCLUSIONS: MiCoP is a mapping-based method that proves more effective than existing methods at abundance profiling of viruses and eukaryotes in metagenomic samples. MiCoP can be used to detect the full diversity of these communities. The code, data, and documentation are publicly available on GitHub at: https://github.com/smangul1/MiCoP .

RevDate: 2019-06-10

Tang ZZ, Chen G, Hong Q, et al (2019)

Multi-Omic Analysis of the Microbiome and Metabolome in Healthy Subjects Reveals Microbiome-Dependent Relationships Between Diet and Metabolites.

Frontiers in genetics, 10:454.

The human microbiome has been associated with health status, and risk of disease development. While the etiology of microbiome-mediated disease remains to be fully elucidated, one mechanism may be through microbial metabolism. Metabolites produced by commensal organisms, including in response to host diet, may affect host metabolic processes, with potentially protective or pathogenic consequences. We conducted multi-omic phenotyping of healthy subjects (N = 136), in order to investigate the interaction between diet, the microbiome, and the metabolome in a cross-sectional sample. We analyzed the nutrient composition of self-reported diet (3-day food records and food frequency questionnaires). We profiled the gut and oral microbiome (16S rRNA) from stool and saliva, and applied metabolomic profiling to plasma and stool samples in a subset of individuals (N = 75). We analyzed these multi-omic data to investigate the relationship between diet, the microbiome, and the gut and circulating metabolome. On a global level, we observed significant relationships, particularly between long-term diet, the gut microbiome and the metabolome. Intake of plant-derived nutrients as well as consumption of artificial sweeteners were associated with significant differences in circulating metabolites, particularly bile acids, which were dependent on gut enterotype, indicating that microbiome composition mediates the effect of diet on host physiology. Our analysis identifies dietary compounds and phytochemicals that may modulate bacterial abundance within the gut and interact with microbiome composition to alter host metabolism.

RevDate: 2019-06-10

Belforte FS, Fernandez N, Tonín Monzón F, et al (2019)

Getting to Know the Gut Microbial Diversity of Metropolitan Buenos Aires Inhabitants.

Frontiers in microbiology, 10:965.

In recent years, the field of immunology has been revolutionized by the growing understanding of the fundamental role of microbiota in the immune system function. The immune system has evolved to maintain a symbiotic relationship with these microbes. The aim of our study was to know in depth the uncharacterized metagenome of the Buenos Aires (BA) city population and its metropolitan area, being the second most populated agglomeration in the southern hemisphere. For this purpose, we evaluated 30 individuals (age: 35.23 ± 8.26 years and BMI: 23.91 ± 3.4 kg/m2), from the general population of BA. The hypervariable regions V3-V4 of the bacterial 16S gene was sequenced by MiSeq-Illumina system, obtaining 47526 ± 4718 sequences/sample. The dominant phyla were Bacteroidetes, Firmicutes, Proteobacteria, Verrucomicrobia, and Actinobacteria. Additionally, we compared the microbiota of BA with other westernized populations (Santiago de Chile, Rosario-Argentina, United States-Human-microbiome-project, Bologna-Italy) and the Hadza population of hunter-gatherers. The unweighted UniFrac clustered together all westernized populations, leaving the hunter-gatherer population from Hadza out. In particular, Santiago de Chile's population turns out to be the closest to BA's, principally due to the presence of Verrucomicrobiales of the genus Akkermansia. These microorganisms have been proposed as a hallmark of a healthy gut. Finally, westernized populations showed more abundant metabolism related KEEG pathways than hunter-gatherers, including carbohydrate metabolism (amino sugar and nucleotide sugar metabolism), amino acid metabolism (alanine, aspartate and glutamate metabolism), lipid metabolism, biosynthesis of secondary metabolites, and sulfur metabolism. These findings contribute to promote research and comparison of the microbiome in different human populations, in order to develop more efficient therapeutic strategies for the restoration of a healthy dialogue between host and environment.

RevDate: 2019-06-04

Granato ET, Meiller-Legrand TA, KR Foster (2019)

The Evolution and Ecology of Bacterial Warfare.

Current biology : CB, 29(11):R521-R537.

Bacteria have evolved a wide range of mechanisms to harm and kill their competitors, including chemical, mechanical and biological weapons. Here we review the incredible diversity of bacterial weapon systems, which comprise antibiotics, toxic proteins, mechanical weapons that stab and pierce, viruses, and more. The evolution of bacterial weapons is shaped by many factors, including cell density and nutrient abundance, and how strains are arranged in space. Bacteria also employ a diverse range of combat behaviours, including pre-emptive attacks, suicidal attacks, and reciprocation (tit-for-tat). However, why bacteria carry so many weapons, and why they are so often used, remains poorly understood. By comparison with animals, we argue that the way that bacteria live - often in dense and genetically diverse communities - is likely to be key to their aggression as it encourages them to dig in and fight alongside their clonemates. The intensity of bacterial aggression is such that it can strongly affect communities, via complex coevolutionary and eco-evolutionary dynamics, which influence species over space and time. Bacterial warfare is a fascinating topic for ecology and evolution, as well as one of increasing relevance. Understanding how bacteria win wars is important for the goal of manipulating the human microbiome and other important microbial systems.

RevDate: 2019-06-03

Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, et al (2019)

Mapping human microbiome drug metabolism by gut bacteria and their genes.

Nature pii:10.1038/s41586-019-1291-3 [Epub ahead of print].

Individuals vary widely in drug responses, which can be dangerous and expensive due to treatment delays and adverse effects. Growing evidence implicates the gut microbiome in this variability, however the molecular mechanisms remain largely unknown. Here we measured the ability of 76 diverse human gut bacteria to metabolize 271 oral drugs and found that many of these drugs are chemically modified by microbes. We combined high-throughput genetics with mass spectrometry to systematically identify drug-metabolizing microbial gene products. These microbiome-encoded enzymes can directly and significantly impact intestinal and systemic drug metabolism in mice and can explain drug-metabolizing activities of human gut bacteria and communities based on their genomic contents. These causal links between microbiota gene content and metabolic activities connect interpersonal microbiome variability to interpersonal differences in drug metabolism, which has implications for medical therapy and drug development across multiple disease indications.

RevDate: 2019-06-04

Williams DW, G Gibson (2019)

Classification of individuals and the potential to detect sexual contact using the microbiome of the pubic region.

Forensic science international. Genetics, 41:177-187 pii:S1872-4973(19)30070-5 [Epub ahead of print].

In the absence of traditional DNA evidence, detection of sexual contact during intercourse is an important need for forensic analysis that might be addressed by studies of the pubic microbiome. Since 16S sequencing of various other body parts has shown that the microbiome may be individualizing, we reasoned that transfer of the assailant's microbiome to a victim might be detectable. Microbiome profiles were generated from pubic hairs and swabs taken from the pubic mound region of 12 couples and 19 singles, and evaluated for similarity over an average of four collection times with varying degrees of self-reported sexual activity. A model constructed using a Random Forest classifier was able to predict samples belonging to the same individual collected up to 6 months apart, demonstrating the stability of the pubic mound microbiome over this time frame. Couples were found to be significantly more similar to one another than to unrelated members of the opposite sex, in proportion to shared sexual activity. Further analyses using the Deblur method to assign operational taxonomic units (OTUs) establish that at least 10% of the victim's pubic microbiome must be derived from the attacker in order to detect transfer, but that single transfer events will not generally be discovered. Nevertheless, Bayesian SourceTracker software is shown to have potential to establish that sexual contact occurred when the assailant is known, or to exonerate suspects as contributors to a mixed microbiome. Our results establish limited potential of the pubic hair/pubic area microbiome as a tool for forensic associations.

RevDate: 2019-05-30

Anonymous (2019)

After the Integrative Human Microbiome Project, what's next for the microbiome community?.

Nature, 569(7758):599.

RevDate: 2019-05-30

Proctor L (2019)

Priorities for the next 10 years of human microbiome research.

Nature, 569(7758):623-625.

RevDate: 2019-05-30

Lloyd-Price J, Arze C, Ananthakrishnan AN, et al (2019)

Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.

Nature, 569(7758):655-662.

Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database (http://ibdmdb.org), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.

RevDate: 2019-05-30

Integrative HMP (iHMP) Research Network Consortium (2019)

The Integrative Human Microbiome Project.

Nature, 569(7758):641-648.

The NIH Human Microbiome Project (HMP) has been carried out over ten years and two phases to provide resources, methods, and discoveries that link interactions between humans and their microbiomes to health-related outcomes. The recently completed second phase, the Integrative Human Microbiome Project, comprised studies of dynamic changes in the microbiome and host under three conditions: pregnancy and preterm birth; inflammatory bowel diseases; and stressors that affect individuals with prediabetes. The associated research begins to elucidate mechanisms of host-microbiome interactions under these conditions, provides unique data resources (at the HMP Data Coordination Center), and represents a paradigm for future multi-omic studies of the human microbiome.

RevDate: 2019-05-30

Fettweis JM, Serrano MG, Brooks JP, et al (2019)

The vaginal microbiome and preterm birth.

Nature medicine pii:10.1038/s41591-019-0450-2 [Epub ahead of print].

The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes 'omics' data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.

RevDate: 2019-05-29

Varoni EM, Bavarian R, Robledo-Sierra J, et al (2019)

World Workshop on Oral Medicine VII: Targeting the microbiome for oral medicine specialists-Part 1. A methodological guide.

Oral diseases, 25 Suppl 1:12-27.

Advances in high-throughput sequencing technologies have allowed for a rapid increase in knowledge about the human microbiome in both healthy and diseased states, which is expected to increase our understanding of multifactorial diseases. The World Workshop on Oral Medicine VII chose the microbiome as one of its topics of focus. Part 1 of this review provides updated knowledge in the field of microbiome research, describes the advantages and disadvantages of currently available sequencing technologies, and proposes a seven-step "recipe" for designing and performing studies that is supported by contemporary evidence. Part 2 of this review in a companion paper discusses the results of high-throughput sequencing studies published to date on the microbiota associated with oral mucosal diseases. The goal of this collective enterprise is to encourage more oral medicine specialists to become engaged in multidisciplinary collaborations to investigate the role of the microbiome in relation to oral diseases, which could potentially lead to enhanced diagnosis, risk assessment and treatment of these patients.

RevDate: 2019-05-28

Gilbert JA, SV Lynch (2019)

Community ecology as a framework for human microbiome research.

Nature medicine pii:10.1038/s41591-019-0464-9 [Epub ahead of print].

The field of human microbiome research has revealed the intimate co-association of humans with diverse communities of microbes in various habitats in the human body, and the necessity of these microbes for the maintenance of human health. Microbial heterogeneity between humans and across spatial and temporal gradients requires multidimensional datasets and a unifying set of theories and statistical tools to analyze the human microbiome and fully realize the potential of this field. Here we consider the utility of community ecology as a framework for the interrogation and interpretation of the human microbiome.

RevDate: 2019-05-24

Pulkkinen E, Wicklund A, Oduor JMO, et al (2019)

Characterization of vB_ApiM_fHyAci03, a novel lytic bacteriophage that infects clinical Acinetobacter strains.

Archives of virology pii:10.1007/s00705-019-04284-z [Epub ahead of print].

We present here the isolation and characterization of Acinetobacter pittii phage vB_ApiM_fHyAci03 (fHyAci03), which belongs to the family Myoviridae. The fHyAci03 genome was found to be 165,975 bp in length and predicted to contain 255 genes. While the whole genome was 92.4% identical to Acinetobacter baumannii phage KARL-1, phylogenetic analysis based on phage long distal tail fiber amino acid sequences assigned fHyAci03 and KARL-1 to different subclusters, reflecting their different host species. Together with phylogenetic analysis, genome comparisons indicated that fHyAci03 is a novel member of the subfamily Tevenvirinae. Host range experiments revealed that fHyAci03 could infect two clinical strains of Acinetobacter nosocomialis and six clinical strains of A. pittii. Thus, fHyAci03 is a novel lytic phage that infects clinical Acinetobacter strains and represents a potential new candidate to be used in phage therapy.

RevDate: 2019-06-10

Virtanen S, Rantsi T, Virtanen A, et al (2019)

Vaginal Microbiota Composition Correlates Between Pap Smear Microscopy and Next Generation Sequencing and Associates to Socioeconomic Status.

Scientific reports, 9(1):7750 pii:10.1038/s41598-019-44157-8.

Recent research on vaginal microbiota relies on high throughput sequencing while microscopic methods have a long history in clinical use. We investigated the correspondence between microscopic findings of Pap smears and the vaginal microbiota composition determined by next generation sequencing among 50 asymptomatic women. Both methods produced coherent results regarding the distinction between Lactobacillus-dominant versus mixed microbiota, reassuring gynaecologists for the use of Pap smear or wet mount microscopy for rapid evaluation of vaginal bacteria as part of diagnosis. Cytologic findings identified women with bacterial vaginosis and revealed that cytolysis of vaginal epithelial cells is associated to Lactobacillus crispatus-dominated microbiota. Education and socio-economic status were associated to the vaginal microbiota variation. Our results highlight the importance of including socio-economic status as a co-factor in future vaginal microbiota studies.

RevDate: 2019-06-10

Ross AA, Rodrigues Hoffmann A, JD Neufeld (2019)

The skin microbiome of vertebrates.

Microbiome, 7(1):79 pii:10.1186/s40168-019-0694-6.

The skin constitutes the primary physical barrier between vertebrates and their external environment. Characterization of skin microorganisms is essential for understanding how a host evolves in association with its microbial symbionts, modeling immune system development, diagnosing illnesses, and exploring the origins of potential zoonoses that affect humans. Although many studies have characterized the human microbiome with culture-independent techniques, far less is known about the skin microbiome of other mammals, amphibians, birds, fish, and reptiles. The aim of this review is to summarize studies that have leveraged high-throughput sequencing to better understand the skin microorganisms that associate with members of classes within the subphylum Vertebrata. Specifically, links will be explored between the skin microbiome and vertebrate characteristics, including geographic location, biological sex, animal interactions, diet, captivity, maternal transfer, and disease. Recent literature on parallel patterns between host evolutionary history and their skin microbial communities, or phylosymbiosis, will also be analyzed. These factors must be considered when designing future microbiome studies to ensure that the conclusions drawn from basic research translate into useful applications, such as probiotics and successful conservation strategies for endangered and threatened animals.

RevDate: 2019-05-24

Biesiekierski JR, Jalanka J, HM Staudacher (2019)

Can Gut Microbiota Composition Predict Response to Dietary Treatments?.

Nutrients, 11(5): pii:nu11051134.

Dietary intervention is a challenge in clinical practice because of inter-individual variability in clinical response. Gut microbiota is mechanistically relevant for a number of disease states and consequently has been incorporated as a key variable in personalised nutrition models within the research context. This paper aims to review the evidence related to the predictive capacity of baseline microbiota for clinical response to dietary intervention in two specific health conditions, namely, obesity and irritable bowel syndrome (IBS). Clinical trials and larger predictive modelling studies were identified and critically evaluated. The findings reveal inconsistent evidence to support baseline microbiota as an accurate predictor of weight loss or glycaemic response in obesity, or as a predictor of symptom improvement in irritable bowel syndrome, in dietary intervention trials. Despite advancement in quantification methodologies, research in this area remains challenging and larger scale studies are needed until personalised nutrition is realistically achievable and can be translated to clinical practice.

RevDate: 2019-06-10

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

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: 2019-05-31

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.

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 timescale 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

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: 2019-06-01

Levi Mortera S, Soggiu A, Vernocchi P, et al (2019)

Metaproteomic investigation to assess gut microbiota shaping in newborn mice: A combined taxonomic, functional and quantitative approach.

Journal of proteomics, 203:103378 pii:S1874-3919(19)30150-2 [Epub ahead of print].

Breastfeeding is nowadays known to be one of the most critical factors contributing to the development of an efficient immune system. In the last decade, a consistent number of pieces of evidence demonstrated the relationship between a healthy organism and its gut microbiota. However, this link is still not fully understood and requires further investigation. We recently adopted a murine model to describe the impact of either maternal milk or parental genetic background, on the composition of the gut microbial population in the first weeks of life. A metaproteomic approach to such complex environments is a big challenge that requires a strong effort in both data production and analysis, including the set-up of dedicated multitasking bioinformatics pipelines. Herein we present an LC-MS/MS based investigation to monitor mouse gut microbiota in the early life, aiming at characterizing its functions and metabolic activities together with a taxonomic description in terms of operational taxonomic units. We provided a quantitative evaluation of bacterial metaproteins, taking into account differential expression results in relation to the functional and taxonomic classification, particularly with proteins from orthologues groups. This allowed the reduction of the bias arising from the presence of a high number of shared peptides, and proteins, among different bacterial species. We also focused on host mucosal proteome and its modulation, according to different microbiota composition. SIGNIFICANCE: This paper would represent a reference work for investigations on gut microbiota in early life, from both a microbiological and a functional proteomic point of view. We focused on the shaping of the mouse gut microbiota in dependence on the feeding modality, defining a reliable taxonomic description, highlighting some functional characteristics of the microbial community, and performing a first quantitative evaluation by data independent analysis in metaproteomics.

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: 2019-05-16

Oduor JMO, Kiljunen S, Kadija E, et al (2019)

Genomic characterization of four novel Staphylococcus myoviruses.

Archives of virology pii:10.1007/s00705-019-04267-0 [Epub ahead of print].

We report here the annotation of the complete genomes of four novel lytic Staphylococcus phages; Stab20, Stab21, Stab22 and Stab23. These phages have double-stranded DNA genomes ranging between 153,338 and 155,962 bp in size with terminal repeats of 10,814-12,304 bp. The genome analysis suggests that they represent new phage species within the genus Kayvirus in the subfamily Twortvirinae of the family Herelleviridae.

RevDate: 2019-05-23

Scott AJ, Alexander JL, Merrifield CA, et al (2019)

International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis.

Gut pii:gutjnl-2019-318556 [Epub ahead of print].

OBJECTIVE: In this consensus statement, an international panel of experts deliver their opinions on key questions regarding the contribution of the human microbiome to carcinogenesis.

DESIGN: International experts in oncology and/or microbiome research were approached by personal communication to form a panel. A structured, iterative, methodology based around a 1-day roundtable discussion was employed to derive expert consensus on key questions in microbiome-oncology research.

RESULTS: Some 18 experts convened for the roundtable discussion and five key questions were identified regarding: (1) the relevance of dysbiosis/an altered gut microbiome to carcinogenesis; (2) potential mechanisms of microbiota-induced carcinogenesis; (3) conceptual frameworks describing how the human microbiome may drive carcinogenesis; (4) causation versus association; and (5) future directions for research in the field.The panel considered that, despite mechanistic and supporting evidence from animal and human studies, there is currently no direct evidence that the human commensal microbiome is a key determinant in the aetiopathogenesis of cancer. The panel cited the lack of large longitudinal, cohort studies as a principal deciding factor and agreed that this should be a future research priority. However, while acknowledging gaps in the evidence, expert opinion was that the microbiome, alongside environmental factors and an epigenetically/genetically vulnerable host, represents one apex of a tripartite, multidirectional interactome that drives carcinogenesis.

CONCLUSION: Data from longitudinal cohort studies are needed to confirm the role of the human microbiome as a key driver in the aetiopathogenesis of cancer.

RevDate: 2019-06-10

Bui TPN, Troise AD, Fogliano V, et al (2019)

Anaerobic Degradation of N-ε-Carboxymethyllysine, a Major Glycation End-Product, by Human Intestinal Bacteria.

Journal of agricultural and food chemistry [Epub ahead of print].

Modifications of lysine contribute to the amount of dietary advanced glycation end-products reaching the colon. However, little is known about the ability of intestinal bacteria to metabolize dietary N-ε-carboxymethyllysine (CML). Successive transfers of fecal microbiota in growth media containing CML were used to identify and isolate species able to metabolize CML under anaerobic conditions. From our study, only donors exposed to processed foods degraded CML, and anaerobic bacteria enrichments from two of them used 77 and 100% of CML. Oscillibacter and Cloacibacillus evryensis increased in the two donors after the second transfer, highlighting that the bacteria from these taxa could be candidates for anaerobic CML degradation. A tentative identification of CML metabolites produced by a pure culture of Cloacibacillus evryensis was performed by mass spectrometry: carboxymethylated biogenic amines and carboxylic acids were identified as CML degradation products. The study confirmed the ability of intestinal bacteria to metabolize CML under anoxic conditions.

RevDate: 2019-05-15

Chernikova D, Yuan I, M Shaker (2019)

Prevention of allergy with diverse and healthy microbiota: an update.

Current opinion in pediatrics, 31(3):418-425.

PURPOSE OF REVIEW: Microbiota consist of symbiotic microscopic neighbors that interact on and within our bodies in diverse and incompletely understood ways throughout our lifetime. Though various associations with allergic disease have been described, clear effective therapeutic interventions to prevent allergy have been elusive.

RECENT FINDINGS: The human microbiome is influenced by multiple factors, including: mode of infant delivery (vaginal vs. cesarean section), breastfeeding, diet, presence of siblings and pets, exposure to antibiotics and other medications (particularly antacids), lifestyle, and developmental context. Microbial species promoting atopic responses and tolerance have been described. Specific microbiota likely act through distinct metabolic pathways to promote the health of their human hosts, optimally directing the developing immune system away from pro-allergic, Th2-dominated responses to more T-regulatory-influenced behaviors.

SUMMARY: Evidence suggests that specific healthy infant microbiome signatures may influence development of some components of the allergic march of childhood by decreasing atopic dermatitis, asthma, and food allergy. Further understanding of factors that influence healthy microbiota may lead to specific strategies tailored for early intervention and disease prevention.

RevDate: 2019-05-16

Ahmed B, Cox MJ, L Cuthbertson (2019)

Growing up with your airway microbiota: a risky business.

Thorax, 74(6):525-526.

RevDate: 2019-06-10

Beghini F, Renson A, Zolnik CP, et al (2019)

Tobacco exposure associated with oral microbiota oxygen utilization in the New York City Health and Nutrition Examination Study.

Annals of epidemiology, 34:18-25.e3.

PURPOSE: The effect of tobacco exposure on the oral microbiome has not been established.

METHODS: We performed amplicon sequencing of the 16S ribosomal RNA gene V4 variable region to estimate bacterial community characteristics in 259 oral rinse samples, selected based on self-reported smoking and serum cotinine levels, from the 2013-2014 New York City Health and Nutrition Examination Study. We identified differentially abundant operational taxonomic units (OTUs) by primary and secondhand tobacco exposure, and used "microbe set enrichment analysis" to assess shifts in microbial oxygen utilization.

RESULTS: Cigarette smoking was associated with depletion of aerobic OTUs (Enrichment Score test statistic ES = -0.75, P = .002) with a minority (29%) of aerobic OTUs enriched in current smokers compared with never smokers. Consistent shifts in the microbiota were observed for current cigarette smokers as for nonsmokers with secondhand exposure as measured by serum cotinine levels. Differential abundance findings were similar in crude and adjusted analyses.

CONCLUSIONS: Results support a plausible link between tobacco exposure and shifts in the oral microbiome at the population level through three lines of evidence: (1) a shift in microbiota oxygen utilization associated with primary tobacco smoke exposure; (2) consistency of abundance fold changes associated with current smoking and shifts along the gradient of secondhand smoke exposure among nonsmokers; and (3) consistency after adjusting for a priori hypothesized confounders.

RevDate: 2019-05-09

Rodricks J, Huang Y, Mantus E, et al (2019)

Do Interactions Between Environmental Chemicals and the Human Microbiome Need to Be Considered in Risk Assessments?.

Risk analysis : an official publication of the Society for Risk Analysis [Epub ahead of print].

One of the most dynamic and fruitful areas of current health-related research concerns the various roles of the human microbiome in disease. Evidence is accumulating that interactions between substances in the environment and the microbiome can affect risks of disease, in both beneficial and adverse ways. Although most of the research has concerned the roles of diet and certain pharmaceutical agents, there is increasing interest in the possible roles of environmental chemicals. Chemical risk assessment has, to date, not included consideration of the influence of the microbiome. We suggest that failure to consider the possible roles of the microbiome could lead to significant error in risk assessment results. Our purpose in this commentary is to summarize some of the evidence supporting our hypothesis and to urge the risk assessment community to begin considering and influencing how results from microbiome-related research could be incorporated into chemical risk assessments. An additional emphasis in our commentary concerns the distinct possibility that research on chemical-microbiome interactions will also reduce some of the significant uncertainties that accompany current risk assessments. Of particular interest is evidence suggesting that the microbiome has an influence on variability in disease risk across populations and (of particular interest to chemical risk) in animal and human responses to chemical exposure. The possible explanatory power of the microbiome regarding sources of variability could reduce what might be the most significant source of uncertainty in chemical risk assessment.

RevDate: 2019-05-18

Zhu L, Zou Q, Cao X, et al (2019)

Enterococcus faecalis Encodes an Atypical Auxiliary Acyl Carrier Protein Required for Efficient Regulation of Fatty Acid Synthesis by Exogenous Fatty Acids.

mBio, 10(3): pii:mBio.00577-19.

Acyl carrier proteins (ACPs) play essential roles in the synthesis of fatty acids and transfer of long fatty acyl chains into complex lipids. The Enterococcus faecalis genome contains two annotated acp genes, called acpA and acpB AcpA is encoded within the fatty acid synthesis (fab) operon and appears essential. In contrast, AcpB is an atypical ACP, having only 30% residue identity with AcpA, and is not essential. Deletion of acpB has no effect on E. faecalis growth or de novo fatty acid synthesis in media lacking fatty acids. However, unlike the wild-type strain, where growth with oleic acid resulted in almost complete blockage of de novo fatty acid synthesis, the ΔacpB strain largely continued de novo fatty acid synthesis under these conditions. Blockage in the wild-type strain is due to repression of fab operon transcription, leading to levels of fatty acid synthetic proteins (including AcpA) that are insufficient to support de novo synthesis. Transcription of the fab operon is regulated by FabT, a repressor protein that binds DNA only when it is bound to an acyl-ACP ligand. Since AcpA is encoded in the fab operon, its synthesis is blocked when the operon is repressed and acpA thus cannot provide a stable supply of ACP for synthesis of the acyl-ACP ligand required for DNA binding by FabT. In contrast to AcpA, acpB transcription is unaffected by growth with exogenous fatty acids and thus provides a stable supply of ACP for conversion to the acyl-ACP ligand required for repression by FabT. Indeed, ΔacpB and ΔfabT strains have essentially the same de novo fatty acid synthesis phenotype in oleic acid-grown cultures, which argues that neither strain can form the FabT-acyl-ACP repression complex. Finally, acylated derivatives of both AcpB and AcpA were substrates for the E. faecalis enoyl-ACP reductases and for E. faecalis PlsX (acyl-ACP; phosphate acyltransferase).IMPORTANCE AcpB homologs are encoded by many, but not all, lactic acid bacteria (Lactobacillales), including many members of the human microbiome. The mechanisms regulating fatty acid synthesis by exogenous fatty acids play a key role in resistance of these bacteria to those antimicrobials targeted at fatty acid synthesis enzymes. Defective regulation can increase resistance to such inhibitors and also reduce pathogenesis.

RevDate: 2019-05-06

Jagodzinski A, Zielinska E, Laczmanski L, et al (2019)

The early years of life. Are they influenced by our microbiome?.

Ginekologia polska, 90(4):228-232.

Human microbiome contains the genetic pool of bacteria and other microbes such as Achaea, fungi and viruses inhabiting the human body. It holds an immense potential to affect both physiological and pathological processes. The microbiome's composition can be defined in detail by analyzing ribosomal 16S rRNA and metagenomic tests. Recent increases in cesar- ean sections, the use of antibiotics during pregnancy, the increasing amount of prematurely born children and changes in infant nutrition have an impact on the microbiome forming process. A correlation between the bowel microbiome's com- position and the occurrence of certain diseases, especially inflammatory bowel diseases (IBD), asthma and type 1 diabetes has been demonstrated. The influence on the development of cognitive functions and behaviour has also been displayed. This correlation justifies attempts to restore the beneficial the composition of the microbiome through the use of probiotics, vaginal microflora transfer in case of cesarean section and encouraging breastfeeding. Development of multiple studies on the topic of the human microbiome and its impact on the human body is necessary in order to reach final conclusions. The aim of this article is to summarize recent findings regarding the development of the human microbiome from the first days of life and the influence of changes in its composition on human health.

RevDate: 2019-05-08

Fiedorová K, Radvanský M, Němcová E, et al (2019)

The Impact of DNA Extraction Methods on Stool Bacterial and Fungal Microbiota Community Recovery.

Frontiers in microbiology, 10:821.

Our understanding of human gut microbiota in health and disease depends on accurate and reproducible microbial data acquisition. The critical step in this process is to apply an appropriate methodology to extract microbial DNA, since biases introduced during the DNA extraction process may result in inaccurate microbial representation. In this study, we attempted to find a DNA extraction protocol which could be effectively used to analyze both the bacterial and fungal community. We evaluated the effect of five DNA extraction methods (QIAamp DNA Stool Mini Kit, PureLinkTM Microbiome DNA Purification Kit, ZR Fecal DNA MiniPrepTM Kit, NucleoSpin® DNA Stool Kit, and IHMS protocol Q) on bacterial and fungal gut microbiome recovery using (i) a defined system of germ-free mice feces spiked with bacterial or fungal strains, and (ii) non-spiked human feces. In our experimental setup, we confirmed that the examined methods significantly differed in efficiency and quality, which affected the identified stool microbiome composition. In addition, our results indicated that fungal DNA extraction might be prone to be affected by reagent/kit contamination, and thus an appropriate blank control should be included in mycobiome research. Overall, standardized IHMS protocol Q, recommended by the International Human Microbiome Consortium, performed the best when considering all the parameters analyzed, and thus could be applied not only in bacterial, but also in fungal microbiome research.


RJR Experience and Expertise


Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.


Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.


Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.


Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.


While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.


Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.


Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.


Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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E-mail: RJR8222@gmail.com

Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

short personal version

Curriculum Vitae for R J Robbins

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RJR Picks from Around the Web (updated 11 MAY 2018 )