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Bibliography on: Human Microbiome

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ESP: PubMed Auto Bibliography 15 Sep 2019 at 01:40 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: 2019-09-14

Polkowska-Pruszyńska B, Gerkowicz A, D Krasowska (2019)

The gut microbiome alterations in allergic and inflammatory skin diseases - an update.

Journal of the European Academy of Dermatology and Venereology : JEADV [Epub ahead of print].

The human microbiome is a wide range of microorganisms residing in and on our body. The homeostasis between host immune system and the microbial environment allows mutual benefits and protection. Physiological bacterial colonization is essential for the establishment of organism immunity. The human microbiota ecosystem can be divided into several compartments, out of which intestinal flora strongly affects our health and plays a crucial role in the pathophysiology of many diseases. The gastrointestinal tract, being a major guardian of the immune system, maintains the homeostasis with the commensal microorganisms by tolerating the typical flora antigens. The dysbiosis may trigger an inflammatory response followed by tissue damage or autoimmune processes. The gut microbiome alterations are linked to the pathogenesis of the allergic, cardiovascular, gastrointestinal, metabolic, neurodevelopmental, psychiatric and neurodegenerative diseases and cancer. Moreover, there is increasing evidence connecting the skin condition with the gastrointestinal microbiome, which has been described as the skin-gut axis. The aim of this study was to review the literature regarding the role of the gut microbiome alterations in the pathogenesis of selected allergic and inflammatory skin diseases.

RevDate: 2019-09-14

Ndika J, Seemab U, Poon WL, et al (2019)

Silver, titanium dioxide, and zinc oxide nanoparticles trigger miRNA/isomiR expression changes in THP-1 cells that are proportional to their health hazard potential.

Nanotoxicology [Epub ahead of print].

After over a decade of nanosafety research, it is indisputable that the vast majority of nano-sized particles induce a plethora of adverse cellular responses - the severity of which is linked to the material's physicochemical properties. Differentiated THP-1 cells were previously exposed for 6 h and 24 h to silver, titanium dioxide, and zinc oxide nanoparticles at the maximum molar concentration at which no more than 15% cellular cytotoxicity was observed. All three nanoparticles differed in extent of induction of biological pathways corresponding to immune response signaling and metal ion homeostasis. In this study, we integrated gene and miRNA expression profiles from the same cells to propose miRNA biomarkers of adverse exposure to metal-based nanoparticles. We employed RNA sequencing together with a quantitative strategy that also enables analysis of the overlooked repertoire of length and sequence miRNA variants called isomiRs. Whilst only modest changes in expression were observed within the first 6 h of exposure, the miRNA/isomiR (miR) profiles of each nanoparticle were unique. Via canonical correlation and pathway enrichment analyses, we identified a co-regulated miR-mRNA cluster, predicted to be highly relevant for cellular response to metal ion homeostasis. These miRs were annotated to be canonical or variant isoforms of hsa-miR-142-5p, -342-3p, -5100, -6087, -6894-3p, and -7704. Hsa-miR-5100 was differentially expressed in response to each nanoparticle in both the 6 h and 24 h exposures. Taken together, this co-regulated miR-mRNA cluster could represent potential biomarkers of sub-toxic metal-based nanoparticle exposure.

RevDate: 2019-09-10

Forsberg KJ, Bhatt IV, Schmidtke DT, et al (2019)

Functional metagenomics-guided discovery of potent Cas9 inhibitors in the human microbiome.

eLife, 8: pii:46540.

CRISPR-Cas systems protect bacteria and archaea from phages and other mobile genetic elements, which use small anti-CRISPR (Acr) proteins to overcome CRISPR-Cas immunity. Because Acrs are challenging to identify, their natural diversity and impact on microbial ecosystems are underappreciated. To overcome this discovery bottleneck, we developed a high-throughput functional selection to isolate ten DNA fragments from human oral and fecal metagenomes that inhibit Streptococcus pyogenes Cas9 (SpyCas9) in Escherichia coli. The most potent Acr from this set, AcrIIA11, was recovered from a Lachnospiraceae phage. We found that AcrIIA11 inhibits SpyCas9 in bacteria and in human cells. AcrIIA11 homologs are distributed across diverse bacteria; many distantly-related homologs inhibit both SpyCas9 and a divergent Cas9 from Treponema denticola. We find that AcrIIA11 antagonizes SpyCas9 using a different mechanism than other previously characterized Type II-A Acrs. Our study highlights the power of functional selection to uncover widespread Cas9 inhibitors within diverse microbiomes.

RevDate: 2019-09-10

Kumar M, Singh P, Murugesan S, et al (2020)

Microbiome as an Immunological Modifier.

Methods in molecular biology (Clifton, N.J.), 2055:595-638.

Humans are living ecosystems composed of human cells and microbes. The microbiome is the collection of microbes (microbiota) and their genes. Recent breakthroughs in the high-throughput sequencing technologies have made it possible for us to understand the composition of the human microbiome. Launched by the National Institutes of Health in USA, the human microbiome project indicated that our bodies harbor a wide array of microbes, specific to each body site with interpersonal and intrapersonal variabilities. Numerous studies have indicated that several factors influence the development of the microbiome including genetics, diet, use of antibiotics, and lifestyle, among others. The microbiome and its mediators are in a continuous cross talk with the host immune system; hence, any imbalance on one side is reflected on the other. Dysbiosis (microbiota imbalance) was shown in many diseases and pathological conditions such as inflammatory bowel disease, celiac disease, multiple sclerosis, rheumatoid arthritis, asthma, diabetes, and cancer. The microbial composition mirrors inflammation variations in certain disease conditions, within various stages of the same disease; hence, it has the potential to be used as a biomarker.

RevDate: 2019-09-10

Mark Welch JL, Dewhirst FE, GG Borisy (2019)

Biogeography of the Oral Microbiome: The Site-Specialist Hypothesis.

Annual review of microbiology, 73:335-358.

Microbial communities are complex and dynamic, composed of hundreds of taxa interacting across multiple spatial scales. Advances in sequencing and imaging technology have led to great strides in understanding both the composition and the spatial organization of these complex communities. In the human mouth, sequencing results indicate that distinct sites host microbial communities that not only are distinguishable but to a meaningful degree are composed of entirely different microbes. Imaging suggests that the spatial organization of these communities is also distinct. Together, the literature supports the idea that most oral microbes are site specialists. A clear understanding of microbiota structure at different sites in the mouth enables mechanistic studies, informs the generation of hypotheses, and strengthens the position of oral microbiology as a model system for microbial ecology in general.

RevDate: 2019-09-08

Boto L, Pineda M, R Pineda (2019)

Potential impacts of horizontal gene transfer on human health and physiology and how anthropogenic activity can affect it.

The FEBS journal [Epub ahead of print].

Horizontal gene transfer is widespread among Prokaryotes driving their evolution. In this paper we review the potential impact in humans of the horizontal gene transfer between prokaryotes living in close association with humans in two scenarios: horizontal transfer in human microbiomes and transfer between microbes living in human managed environments. Although our vision is focused on the possible impact of these transfers in the propagation of antibiotic resistance genes or pathogenicity determinants, we also discuss possible human physiological adaptations via gene transfer between resident and occasional bacteria in the human microbiome. This article is protected by copyright. All rights reserved.

RevDate: 2019-09-07

Fielding RA, Reeves AR, Jasuja R, et al (2019)

Muscle strength is increased in mice that are colonized with microbiota from high-functioning older adults.

Experimental gerontology pii:S0531-5565(19)30477-2 [Epub ahead of print].

Evidence in support of a gut-muscle axis has been reported in rodents, but studies in older adult humans are limited. Accordingly, the primary goals of the present study were to compare gut microbiome composition in older adults that differed in terms of the percentage of whole body lean mass and physical functioning (high-functioning, HF, n = 18; low-functioning, LF, n = 11), and to evaluate the causative role of the gut microbiome on these variables by transferring fecal samples from older adults into germ-free mice. Family-level Prevotellaceae, genus-level Prevotella and Barnesiella, and the bacterial species Barnesiella intestinihominis were higher in HF older adults at the initial study visit, at a 1-month follow-up visit, in HF human fecal donors, and in HF-colonized mice, when compared with their LF counterparts. Grip strength was significantly increased by 6.4% in HF-, when compared with LF-colonized mice. In contrast, despite significant differences for the percentage of whole body lean mass and physical functioning when comparing the human fecal donors, the percentage of whole body lean mass and treadmill endurance capacity were not different when comparing human microbiome-containing mice. In sum, these data suggest a role for gut bacteria on the maintenance of muscle strength, but argue against a role for gut bacteria on the maintenance of the percentage of whole body lean mass or endurance capacity, findings that collectively add to elucidation of the gut-muscle axis in older adults.

RevDate: 2019-09-07

Wheeler KM, MA Liss (2019)

The Microbiome and Prostate Cancer Risk.

Current urology reports, 20(10):66 pii:10.1007/s11934-019-0922-4.

PURPOSE OF THE REVIEW: There is an abundance of evidence that the human microbiome plays an important and nuanced role in controlling human metabolism, immunity, and cancer. Herein we aim to review the most current research looking at prostate cancer and its link with the gut and genitourinary microbiome. There is now a host of evidence for a unique genitourinary (GU) microbiome. The prostate microbiota, to include viral, bacterial, fungal, and parasitic contributions, as assessed from formalin-fixed tissue is described nicely in the study by Banerjee et al. Further hierarchical analysis by this group found a unique microbiome signature for higher Gleason score cancers and validation PCR studies noted a marked number of viral genomic insertions into host DNA. Shretha et al. also recently established unique GU microbiomes in patients with prostate cancer or benign prostate pathology based on urine samples. The gut microbiome likely also has an indirect but significant role in prostate cancer development and treatment. Liss et al. and Golombos et al. found significant associations between specific gut microbiota and prostate cancer. Interestingly, the balance of inflammatory and anti-inflammatory bacterial lipopolysaccharides, production of bile salts, and metabolism of dietary fiber to short chain fatty acids all likely play important roles in creating systemic pro- or anti-carcinogenic states. In terms of prostate cancer treatment effects, Sfanos et al. noted a unique microbial signature in patients undergoing oral androgen deprivation therapy (ADT) as compared with prostate cancer patients not on ADT. Patients undergoing ADT also had enrichment of bacterial metabolic pathways promoting androgen synthesis. Together, these studies have identified a unique GU microbiome and linked both the GU microbiome and unique gut microbial signatures with prostate cancer and prostate cancer treatments. Whether this information can be used in cancer prevention, treatment, or diagnosis are areas of ongoing and active research.

RevDate: 2019-09-07

Soto-Perez P, Bisanz JE, Berry JD, et al (2019)

CRISPR-Cas System of a Prevalent Human Gut Bacterium Reveals Hyper-targeting against Phages in a Human Virome Catalog.

Cell host & microbe pii:S1931-3128(19)30417-2 [Epub ahead of print].

Bacteriophages are abundant within the human gastrointestinal tract, yet their interactions with gut bacteria remain poorly understood, particularly with respect to CRISPR-Cas immunity. Here, we show that the type I-C CRISPR-Cas system in the prevalent gut Actinobacterium Eggerthella lenta is transcribed and sufficient for specific targeting of foreign and chromosomal DNA. Comparative analyses of E. lenta CRISPR-Cas systems across (meta)genomes revealed 2 distinct clades according to cas sequence similarity and spacer content. We assembled a human virome database (HuVirDB), encompassing 1,831 samples enriched for viral DNA, to identify protospacers. This revealed matches for a majority of spacers, a marked increase over other databases, and uncovered "hyper-targeted" phage sequences containing multiple protospacers targeted by several E. lenta strains. Finally, we determined the positional mismatch tolerance of observed spacer-protospacer pairs. This work emphasizes the utility of merging computational and experimental approaches for determining the function and targets of CRISPR-Cas systems.

RevDate: 2019-09-07

Wang S, Ryan CA, Boyaval P, et al (2019)

Maternal Vertical Transmission Affecting Early-life Microbiota Development.

Trends in microbiology pii:S0966-842X(19)30208-2 [Epub ahead of print].

The association of the human microbiome with health outcomes has attracted much interest toward its therapeutic manipulation. The likelihood of modulating the human microbiome in early life is high and offers great potential to exert profound effects on human development since the early microbiota shows more flexibility compared to that of adults. The human microbiota, being similar to human genetics, can be transmitted from mother to infant, providing insights into early microbiota acquisition, subsequent development, and potential opportunities for intervention. Here, we review adaptations of the maternal microbiota during pregnancy, birth, and infancy, the acquisition and succession of early-life microbiota, and highlight recent efforts to elucidate mother-to-infant microbiota transmission. We further discuss how the mother-to-infant microbial transmission is shaped; and finally we address potential directions for future studies to promote our understanding within this field.

RevDate: 2019-09-08

Cammarota G, Putignani L, A Gasbarrini (2019)

Gut microbiome beats two to zero host genome.

Hepatobiliary surgery and nutrition, 8(4):378-380.

RevDate: 2019-09-06

Badal VD, Wright D, Katsis Y, et al (2019)

Challenges in the construction of knowledge bases for human microbiome-disease associations.

Microbiome, 7(1):129 pii:10.1186/s40168-019-0742-2.

The last few years have seen tremendous growth in human microbiome research, with a particular focus on the links to both mental and physical health and disease. Medical and experimental settings provide initial sources of information about these links, but individual studies produce disconnected pieces of knowledge bounded in context by the perspective of expert researchers reading full-text publications. Building a knowledge base (KB) consolidating these disconnected pieces is an essential first step to democratize and accelerate the process of accessing the collective discoveries of human disease connections to the human microbiome. In this article, we survey the existing tools and development efforts that have been produced to capture portions of the information needed to construct a KB of all known human microbiome-disease associations and highlight the need for additional innovations in natural language processing (NLP), text mining, taxonomic representations, and field-wide vocabulary standardization in human microbiome research. Addressing these challenges will enable the construction of KBs that help identify new insights amenable to experimental validation and potentially clinical decision support.

RevDate: 2019-09-04

Basu Thakur P, Long AR, Nelson BJ, et al (2019)

Complex Responses to Hydrogen Peroxide and Hypochlorous Acid by the Probiotic Bacterium Lactobacillus reuteri.

mSystems, 4(5): pii:4/5/e00453-19.

Inflammatory diseases of the gut are associated with increased intestinal oxygen concentrations and high levels of inflammatory oxidants, including hydrogen peroxide (H2O2) and hypochlorous acid (HOCl), which are antimicrobial compounds produced by the innate immune system. This contributes to dysbiotic changes in the gut microbiome, including increased populations of proinflammatory enterobacteria (Escherichia coli and related species) and decreased levels of health-associated anaerobic Firmicutes and Bacteroidetes The pathways for H2O2 and HOCl resistance in E. coli have been well studied, but little is known about how commensal and probiotic bacteria respond to inflammatory oxidants. In this work, we have characterized the transcriptomic response of the anti-inflammatory, gut-colonizing Gram-positive probiotic Lactobacillus reuteri to both H2O2 and HOCl. L. reuteri mounts distinct but overlapping responses to each of these stressors, and both gene expression and survival were strongly affected by the presence or absence of oxygen. Oxidative stress response in L. reuteri required several factors not found in enterobacteria, including the small heat shock protein Lo18, polyphosphate kinase 2, and RsiR, an L. reuteri-specific regulator of anti-inflammatory mechanisms.IMPORTANCE Reactive oxidants, including hydrogen peroxide and hypochlorous acid, are antimicrobial compounds produced by the immune system during inflammation. Little is known, however, about how many important types of bacteria present in the human microbiome respond to these oxidants, especially commensal and other health-associated species. We have now mapped the stress response to both H2O2 and HOCl in the intestinal lactic acid bacterium Lactobacillus reuteri.

RevDate: 2019-09-03

Abid MB, CJ Koh (2019)

Probiotics in health and disease: fooling Mother Nature?.

Infection pii:10.1007/s15010-019-01351-0 [Epub ahead of print].

Probiotics are ubiquitous, consumption by the general public is common, and the dogma remains that they are beneficial for general and gut health. However, evolving evidence suggests a potentially "harmful" impact of many commercially available probiotics. There is also significant variability in formulations that leads to a lack of a universally acceptable definition of probiotics. In this perspective, we review the flaws with definition, relevant observational and randomized studies that showed both positive and negative impacts on health and disease, unbiased interpretation of key trials, emerging evidence from microbiome and immuno-oncological studies, and impact on systemic immunity. We propose that caution be exercised prior to endorsements of their illness-directed consumption and rampant general usage. As a deeper understanding of the human microbiome accrues and our ability to manipulate this complex ecosystem improves, the probiotic of tomorrow might be the precision tool that deals with diseases on a broad front. Gut microbiome, akin to fingerprints, is indigenous to an individual and 'one size fits all' prescription strategy should be discouraged until a more universally acceptable 'favorable taxa' or a 'personalized probiotic,' to complement an individual's native microbiota, gets fashioned.

RevDate: 2019-09-05

Godoy-Vitorino F (2019)

Human microbial ecology and the rising new medicine.

Annals of translational medicine, 7(14):342.

The first life forms on earth were Prokaryotic, and the evolution of all Eukaryotic life occurred with the help of bacteria. Animal-associated microbiota also includes members of the archaea, fungi, protists, and viruses. The genomes of this host-associated microbial life are called the microbiome. Across the mammalian tree, microbiomes guarantee the development of immunity, physiology, and resistance to pathogens. In humans, all surfaces and cavities are colonized by a microbiome, maintained by a careful balance between the host response and its colonizers-thus humans are considered now supraorganisms. These microbiomes supply essential ecosystem services that benefit health through homeostasis, and the loss of the indigenous microbiota leads to dysbiosis, which can have significant consequences to disease. This educational review aims to describe the importance of human microbial ecology, explain the ecological terms applied to the study of the human microbiome, developments within the cutting-edge microbiome field, and implications to diagnostic and treatment.

RevDate: 2019-09-02

Derrien M, Alvarez AS, WM de Vos (2019)

The Gut Microbiota in the First Decade of Life.

Trends in microbiology pii:S0966-842X(19)30214-8 [Epub ahead of print].

Appreciation of the importance of the gut microbiome is growing, and it is becoming increasingly relevant to identify preventive or therapeutic solutions targeting it. The composition and function of the gut microbiota are relatively well described for infants (less than 3 years) and adults, but have been largely overlooked in pre-school (3-6 years) and primary school-age (6-12 years) children, as well as teenagers (12-18 years). Early reports suggested that the infant microbiota would attain an adult-like structure at the age of 3 years, but recent studies have suggested that microbiota development may take longer. This development time is of key importance because there is evidence to suggest that deviations in this development may have consequences in later life. In this review, we provide an overview of current knowledge concerning the gut microbiota, its evolution, variation, and response to dietary challenges during the first decade of life with a focus on healthy pre-school and primary school-age children (up to 12 years) from various populations around the globe. This knowledge should facilitate the identification of diet-based approaches targeting individuals of this age group, to promote the development of a healthy microbiota in later life.

RevDate: 2019-09-06

Yan ZZ, Chen QL, Zhang YJ, et al (2019)

Antibiotic resistance in urban green spaces mirrors the pattern of industrial distribution.

Environment international, 132:105106 pii:S0160-4120(19)32108-7 [Epub ahead of print].

Urban green spaces are closely related to the activities and health of urban residents. Turf grass and soil are two major interfaces between the environmental and human microbiome, which represent potential pathways for the spread of antibiotic resistance genes (ARGs) from environmental to human microbiome through skin-surface contact. However, the information regarding the prevalence of ARGs in urban green spaces and drivers in shaping their distribution patterns remain unclear. Here, we profiled a wide spectrum of ARGs in grass phyllosphere and soils from 40 urban parks across Greater Melbourne, Australia, using high throughput quantitative PCR. A total of 217 and 218 unique ARGs and MGEs were detected in grass phyllosphere and soils, respectively, conferring resistance to almost all major classes of antibiotics commonly used in human and animals. The plant microbiome contained a core resistome, which occupied >84% of the total abundance of ARGs. In contrast, no core resistome was identified in the soil microbiome. The difference between plant and soil resistome composition was attributed to the difference in bacterial community structure and intensity of environmental and anthropogenic influence. Most importantly, the abundance of ARGs in urban green spaces was significantly positively related to industrial factors including total number of business, number of manufacturing, and number of electricity, gas, water and waste services in the region. Structural equation models further revealed that industrial distribution was a major factor shaping the ARG profiles in urban green spaces after accounting for multiple drivers. These findings have important implications for mitigation of the potential risks posed by ARGs to urban residents.

RevDate: 2019-08-29

Putignani L, Gasbarrini A, B Dallapiccola (2019)

Potential of multiomics technology in precision medicine.

Current opinion in gastroenterology [Epub ahead of print].

PURPOSE OF REVIEW: The 'precision medicine' refers to the generation of identification and classification criteria for advanced taxonomy of patients, exploiting advanced models to infer optimized clinical decisions for each disease phenotype.

RECENT FINDINGS: The current article reviews new advances in the past 18 months on the microbiomics science intended as new discipline contributing to advanced 'precision medicine'. Recently published data highlight the importance of multidimensional data in the description of deep disease phenotypes, including microbiome and immune profiling, and support the efficacy of the systems medicine to better stratify patients, hence optimizing diagnostics, clinical management and response to treatments.

SUMMARY: The articles referenced in this review help inform the reader on new decision-support systems that can be based on multiomics patients' data including microbiome and immune profiling. These harmonized and integrated data can be elaborated by artificial intelligence to generate optimized diagnostic pipelines and clinical interventions.

RevDate: 2019-08-31

Herd P, Palloni A, Rey F, et al (2018)

Social and population health science approaches to understand the human microbiome.

Nature human behaviour, 2(11):808-815.

The microbiome is now considered our 'second genome' with potentially comparable importance to the genome in determining human health. There is, however, a relatively limited understanding of the broader environmental factors, particularly social conditions, that shape variation in human microbial communities. Fulfilling the promise of microbiome research - particularly the microbiome's potential for modification - will require collaboration between biologists and social and population scientists. For life scientists, the plasticity and adaptiveness of the microbiome calls for an agenda to understand the sensitivity of the microbiome to broader social environments already known to be powerful predictors of morbidity and mortality. For social and population scientists, attention to the microbiome may help answer nagging questions about the underlying biological mechanisms that link social conditions to health. We outline key substantive and methodological advances that can be made if collaborations between social and population health scientists and life scientists are strategically pursued.

RevDate: 2019-08-28

Chen J, Douglass J, Prasath V, et al (2019)

The microbiome and breast cancer: a review.

Breast cancer research and treatment pii:10.1007/s10549-019-05407-5 [Epub ahead of print].

The human microbiome plays an integral role in physiology, with most microbes considered benign or beneficial. However, some microbes are known to be detrimental to human health, including organisms linked to cancers and other diseases characterized by aberrant inflammation. Dysbiosis, a state of microbial imbalance with harmful bacteria species outcompeting benign bacteria, can lead to maladies including cancer. The microbial composition varies across body sites, with the gut, urogenital, and skin microbiomes particularly well characterized. However, the microbiome associated with normal breast tissue and breast diseases is poorly understood. Collectively, studies have shown that breast tissue has a distinct microbiome with particular species enriched in the breast tissue itself, as well as the nipple aspirate and gut bacteria of women with breast cancer. More importantly, the breast and associated microbiomes may modulate therapeutic response and serve as potential biomarkers for diagnosing and staging breast cancer.

RevDate: 2019-08-28

Creekmore BC, Gray JH, Walton WG, et al (2019)

Mouse Gut Microbiome-Encoded β-Glucuronidases Identified Using Metagenome Analysis Guided by Protein Structure.

mSystems, 4(4): pii:4/4/e00452-19.

Gut microbial β-glucuronidase (GUS) enzymes play important roles in drug efficacy and toxicity, intestinal carcinogenesis, and mammalian-microbial symbiosis. Recently, the first catalog of human gut GUS proteins was provided for the Human Microbiome Project stool sample database and revealed 279 unique GUS enzymes organized into six categories based on active-site structural features. Because mice represent a model biomedical research organism, here we provide an analogous catalog of mouse intestinal microbial GUS proteins-a mouse gut GUSome. Using metagenome analysis guided by protein structure, we examined 2.5 million unique proteins from a comprehensive mouse gut metagenome created from several mouse strains, providers, housing conditions, and diets. We identified 444 unique GUS proteins and organized them into six categories based on active-site features, similarly to the human GUSome analysis. GUS enzymes were encoded by the major gut microbial phyla, including Firmicutes (60%) and Bacteroidetes (21%), and there were nearly 20% for which taxonomy could not be assigned. No differences in gut microbial gus gene composition were observed for mice based on sex. However, mice exhibited gus differences based on active-site features associated with provider, location, strain, and diet. Furthermore, diet yielded the largest differences in gus composition. Biochemical analysis of two low-fat-associated GUS enzymes revealed that they are variable with respect to their efficacy of processing both sulfated and nonsulfated heparan nonasaccharides containing terminal glucuronides.IMPORTANCE Mice are commonly employed as model organisms of mammalian disease; as such, our understanding of the compositions of their gut microbiomes is critical to appreciating how the mouse and human gastrointestinal tracts mirror one another. GUS enzymes, with importance in normal physiology and disease, are an attractive set of proteins to use for such analyses. Here we show that while the specific GUS enzymes differ at the sequence level, a core GUSome functionality appears conserved between mouse and human gastrointestinal bacteria. Mouse strain, provider, housing location, and diet exhibit distinct GUSomes and gus gene compositions, but sex seems not to affect the GUSome. These data provide a basis for understanding the gut microbial GUS enzymes present in commonly used laboratory mice. Further, they demonstrate the utility of metagenome analysis guided by protein structure to provide specific sets of functionally related proteins from whole-genome metagenome sequencing data.

RevDate: 2019-08-30

Cao L, Shcherbin E, H Mohimani (2019)

A Metabolome- and Metagenome-Wide Association Network Reveals Microbial Natural Products and Microbial Biotransformation Products from the Human Microbiota.

mSystems, 4(4): pii:4/4/e00387-19.

The human microbiome consists of thousands of different microbial species, and tens of thousands of bioactive small molecules are associated with them. These associated molecules include the biosynthetic products of microbiota and the products of microbial transformation of host molecules, dietary components, and pharmaceuticals. The existing methods for characterization of these small molecules are currently time consuming and expensive, and they are limited to the cultivable bacteria. Here, we propose a method for detecting microbiota-associated small molecules based on the patterns of cooccurrence of molecular and microbial features across multiple microbiomes. We further map each molecule to the clade in a phylogenetic tree that is responsible for its production/transformation. We applied our proposed method to the tandem mass spectrometry and metagenomics data sets collected by the American Gut Project and to microbiome isolates from cystic fibrosis patients and discovered the genes in the human microbiome responsible for the production of corynomycolenic acid, which serves as a ligand for human T cells and induces a specific immune response against infection. Moreover, our method correctly associated pseudomonas quinolone signals, tyrvalin, and phevalin with their known biosynthetic gene clusters.IMPORTANCE Experimental advances have enabled the acquisition of tandem mass spectrometry and metagenomics sequencing data from tens of thousands of environmental/host-oriented microbial communities. Each of these communities contains hundreds of microbial features (corresponding to microbial species) and thousands of molecular features (corresponding to microbial natural products). However, with the current technology, it is very difficult to identify the microbial species responsible for the production/biotransformation of each molecular feature. Here, we develop association networks, a new approach for identifying the microbial producer/biotransformer of natural products through cooccurrence analysis of metagenomics and mass spectrometry data collected on multiple microbiomes.

RevDate: 2019-08-26

Brüssow H (2019)

Problems with the concept of gut microbiota dysbiosis.

Microbial biotechnology [Epub ahead of print].

The human microbiome research is with the notable exception of fecal transplantation still mostly in a descriptive phase. Part of the difficulty for translating research into medical interventions is due to the large compositional complexity of the microbiome resulting in datasets that need sophisticated statistical methods for their analysis and do not lend to industrial applications. Another part of the difficulty might be due to logical flaws in terminology particularly concerning 'dysbiosis' that avoids circular conclusions and is based on sound ecological and evolutionary reasoning. Many case-control studies are underpowered necessitating more meta-analyses that sort out consistent from spurious dysbiosis-disease associations. We also need for the microbiome a transition from statistical associations to causal relationships with diseases that fulfil a set of modified Koch's postulates for commensals. Disturbingly, the most sophisticated statistical analyses explain only a small percentage of the variance in the microbiome. Microbe-microbe interactions irrelevant to the host and stochastic processes might play a greater role than anticipated. To satisfy the concept of Karl Popper about conjectures and refutations in the scientific process, we should also conduct more experiments that try to refute the role of the commensal gut microbiota for human health and disease.

RevDate: 2019-08-24

Satokari R (2019)

Modulation of Gut Microbiota for Health by Current and Next-Generation Probiotics.

Nutrients, 11(8): pii:nu11081921.

The human gut microbiota is a complex ecosystem and has an essential role in maintaining intestinal and systemic health. Microbiota dysbiosis is associated with a number of intestinal and systemic conditions and its modulation for human health is of great interest. Gut microbiota is a source of novel health-promoting bacteria, often termed as next-generation probiotics in order to distinguish them from traditional probiotics. The previous lessons learned with traditional probiotics can help the development of next-generation probiotics that target specific health issues and needs.

RevDate: 2019-08-23

Mittelman K, D Burstein (2019)

Tiny Hidden Genes within Our Microbiome.

Cell, 178(5):1034-1035.

Exploration of tiny protein-coding sequences within the human microbiome reveals thousands of conserved gene families that have been overlooked by traditional analyses. These small proteins may play key roles in the crosstalk among bacteria within the microbiome and in interactions with their human hosts.

RevDate: 2019-08-25

Mu X, Zhao C, Yang J, et al (2019)

Group B Streptococcus colonization induces Prevotella and Megasphaera abundance-featured vaginal microbiome compositional change in non-pregnant women.

PeerJ, 7:e7474 pii:7474.

Background: Previous studies have indicated that variations in the vaginal microbiome result in symptomatic conditions. Group B Streptococcus (GBS) is a significant neonatal pathogen and maternal vaginal colonization has been recognized as an important risk factor for neonatal disease. Therefore, it is important to discover the relationship between the composition of the vaginal microbiome and GBS colonization. This study explores the potential relationship between the composition of the vaginal microbiome and GBS colonization in non-pregnant Chinese women.

Methods: A total of 22 GBS-positive, non-pregnant women and 44 matched GBS-negative women were recruited for the current study. The composition of the vaginal microbiome was profiled by sequencing the 16S rRNA genes. The microbiome diversity and variation were then evaluated.

Results: The vaginal microbiome of the 66 subjects enrolled in the current study were compared and the results showed that GBS-positive women exhibited significant vaginal microbial differences compared with the GBS-negative women based on the analysis of similarities (r = 0.306, p < 0.01). The relative abundance of the bacterial genus Lactobacillus (p < 0.01) was significantly lower in the GBS-positive group, while the abundances of the bacterial genera Prevotella (p < 0.01), Megasphaera (p < 0.01), and Streptococcus (p < 0.01) were significantly higher in the GBS-positive group.

Discussion: The current study addressed significant variations across the communities of the vaginal microbiome in GBS-positive and GBS-negative women in a Chinese cohort, which paves the way for a larger cohort-based clinical validation study and the development of therapeutic probiotics in the future.

RevDate: 2019-08-25

Guo J, Lv Q, Ariff A, et al (2019)

Western oropharyngeal and gut microbial profiles are associated with allergic conditions in Chinese immigrant children.

The World Allergy Organization journal, 12(8):100051 pii:100051.

Background: The allergy epidemic resulting from western environment/lifestyles is potentially due to modifications of the human microbiome. Therefore, it is of interest to study immigrants living in a western environment as well as their counterparts in the country of origin to understand differences in their microbiomes and health status.

Methods: We investigated 58 Australian Chinese (AC) children from Perth, Western Australia as well as 63 Chinese-born Chinese (CC) children from a city in China. Oropharyngeal (OP) and fecal samples were collected. To assess the microbiomes, 16s ribosomal RNA (rRNA) sequencing for variable regions V3 and V4 was used. Skin prick tests (SPT) were performed to measure the children's atopic status. Information on food allergy and wheezing were acquired from a questionnaire.

Results: AC children had more allergic conditions than CC children. The alpha diversity (mean species diversity) of both OP and gut microbiome was lower in AC children compared to CC children for richness estimate (Chao1), while diversity evenness (Shannon index) was higher. The beta diversity (community similarity) displayed a distinct separation of the OP and gut microbiota between AC and CC children. An apparent difference in microbial abundance was observed for many bacteria. In AC children, we sought to establish consistent trends in bacterial relative abundance that are either higher or lower in AC versus CC children and higher or lower in children with allergy versus those without allergy. The majority of OP taxa showed a consistent trend while the majority of fecal taxa showed a contrasting trend.

Conclusion: Distinct differences in microbiome compositions were found in both oropharyngeal and fecal samples of AC and CC children. The association of the OP microbiome with allergic condition is different from that of the gut microbiome in AC children. The microbiome profiles are changed by the western environment/lifestyle and are associated with allergies in Chinese immigrant children in Australia.

RevDate: 2019-09-05

Pendegraft AH, Guo B, N Yi (2019)

Bayesian hierarchical negative binomial models for multivariable analyses with applications to human microbiome count data.

PloS one, 14(8):e0220961 pii:PONE-D-18-33781.

The analyses of large volumes of metagenomic data extracted from aggregate populations of microscopic organisms residing on and in the human body are advancing contemporary understandings of the integrated participation of microbes in human health and disease. Next generation sequencing technology facilitates said analyses in terms of diversity, community composition, and differential abundance by filtering and binning microbial 16S rRNA genes extracted from human tissues into operational taxonomic units. However, current statistical tools restrict study designs to investigations of limited numbers of host characteristics mediated by limited numbers of samples potentially yielding a loss of relevant information. This paper presents a Bayesian hierarchical negative binomial model as an efficient technique capable of compensating for multivariable sets including tens or hundreds of host characteristics as covariates further expanding analyses of human microbiome count data. Simulation studies reveal that the Bayesian hierarchical negative binomial model provides a desirable strategy by often outperforming three competing negative binomial model in terms of type I error while simultaneously maintaining consistent power. An application of the Bayesian hierarchical negative binomial model using subsets of the open data published by the American Gut Project demonstrates an ability to identify operational taxonomic units significantly differentiable among persons diagnosed by a medical professional with either inflammatory bowel disease or irritable bowel syndrome that are consistent with contemporary gastrointestinal literature.

RevDate: 2019-08-21

Spencer SP, Fragiadakis GK, JL Sonnenburg (2019)

Pursuing Human-Relevant Gut Microbiota-Immune Interactions.

Immunity, 51(2):225-239.

The gut microbiota is a complex and plastic network of diverse organisms intricately connected with human physiology. Recent advances in profiling approaches of both the microbiota and the immune system now enable a deeper exploration of immunity-microbiota connections. An important next step is to elucidate a human-relevant "map" of microbial-immune wiring while focusing on animal studies to probe a prioritized subset of interactions. Here, we provide an overview of this field's current status and discuss two approaches for establishing priorities for detailed investigation: (1) longitudinal intervention studies in humans probing the dynamics of both the microbiota and the immune system and (2) the study of traditional populations to assess lost features of human microbial identity whose absence may be contributing to the rise of immunological disorders. These human-centered approaches offer a judicious path forward to understand the impact of the microbiota in immune development and function.

RevDate: 2019-08-19

Mougeot JC, Stevens CB, Morton DS, et al (2019)

Oral Microbiome and Cancer Therapy-Induced Oral Mucositis.

Journal of the National Cancer Institute. Monographs, 2019(53):.

Characterization of the role of oral microbiome in cancer therapy-induced oral mucositis (CTOM) is critical in preventing the clinically deleterious effects on patients' health that are associated with CTOM. Funding initiatives related to the National Institutes of Health human microbiome project have resulted in groundbreaking advancements in biology and medicine during the last decade. These advancements have shown that a human being is in fact a superorganism made of human cells and associated symbiotic or commensal microbiota. In this review, we describe the state of science as it relates to fundamental knowledge on oral microbiome and its role in CTOM. We also discuss how state-of-the-art technologies and systems biology tools may be used to help tackle the difficult challenges ahead to develop effective treatments or preventive therapies for oral mucositis. We make a clear distinction between disease processes pertaining to the oral microbiome, which includes opportunistic pathogens that may be defined as pathobionts, and those infectious disease processes initiated by exogenous pathogens. We also explored the extent to which knowledge from the gastrointestinal tract in disease and intestinal mucositis could help us better understand CTOM pathobiology. Finally, we propose a model in which the oral microbiome participates in the current five-step CTOM pathobiology model. With the advent of more sophisticated metagenomics technologies and methods of analysis, much hope lies ahead to implement an effective holistic approach to treat cancer patients affected by CTOM.

RevDate: 2019-08-18

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: 2019-08-18

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: 2019-08-18

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: 2019-09-01

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: 2019-08-30

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: 2019-08-20

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: 2019-08-15

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: 2019-08-23

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

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

Cell, 178(5):1245-1259.e14.

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: 2019-08-11

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: 2019-08-21

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: 2019-08-08

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: 2019-08-30

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

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

Cell host & microbe, 26(2):273-282.e7.

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: 2019-08-04

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: 2019-08-02

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: 2019-08-11

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: 2019-07-26

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: 2019-08-20

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: 2019-08-11

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: 2019-08-20

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: 2019-08-09

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: 2019-08-06

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, 58(31):3340-3353.

The ydj gene cluster is found in 80% of sequenced Escherichia coli genomes and other closely related species in the human microbiome. On the basis of 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 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 pro-S hydrogen at C3 of dihydroxyacetone phosphate (DHAP). In the presence of DHAP, YdjI catalyzes an aldol condensation with a variety of aldo sugars. YdjI shows a strong preference for 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 of 3.0 s-1. The product, l-glycero-l-galacto-octuluronate-1-phosphate, has a kcat/Km value 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 (Protein Data Bank entry 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 compared to that observed in other class II aldolases, which utilize shorter carbohydrate molecules.

RevDate: 2019-08-12

Peters DL, Wang W, Zhang X, et al (2019)

Metaproteomic and Metabolomic Approaches for Characterizing the Gut Microbiome.

Proteomics, 19(16):e1800363.

The gut microbiome has been shown to play a significant role in human healthy and diseased states. The dynamic signaling that occurs between the host and microbiome is critical for the maintenance of host homeostasis. Analyzing the human microbiome with metaproteomics, metabolomics, and integrative multi-omics analyses can provide significant information on markers for healthy and diseased states, allowing for the eventual creation of microbiome-targeted treatments for diseases associated with dysbiosis. Metaproteomics enables functional activity information to be gained from the microbiome samples, while metabolomics provides insight into the overall metabolic states affecting/representing the host-microbiome interactions. Combining these functional -omic platforms together with microbiome composition profiling allows for a holistic overview on the functional and metabolic state of the microbiome and its influence on human health. Here the benefits of metaproteomics, metabolomics, and the integrative multi-omic approaches to investigating the gut microbiome in the context of human health and diseases are reviewed.

RevDate: 2019-08-11

Ticinesi A, Nouvenne A, Cerundolo N, et al (2019)

Gut Microbiota, Muscle Mass and Function in Aging: A Focus on Physical Frailty and Sarcopenia.

Nutrients, 11(7): pii:nu11071633.

Human gut microbiota is able to influence the host physiology by regulating multiple processes, including nutrient absorption, inflammation, oxidative stress, immune function, and anabolic balance. Aging is associated with reduced microbiota biodiversity, increased inter-individual variability, and over-representation of pathobionts, and these phenomena may have great relevance for skeletal muscle mass and function. For this reason, the presence of a gut-muscle axis regulating the onset and progression of age-related physical frailty and sarcopenia has been recently hypothesized. In this narrative review, we summarize the studies supporting a possible association between gut microbiota-related parameters with measures of muscle mass, muscle function, and physical performance in animal models and humans. Reduced muscle mass has been associated with distinct microbiota composition and reduced fermentative capacity in mice, and the administration of probiotics or butyrate to mouse models of muscle wasting has been associated with improved muscle mass. However, no studies have targeted the human microbiome associated with sarcopenia. Limited evidence from human studies shows an association between microbiota composition, involving key taxa such as Faecalibacterium and Bifidobacterium, and grip strength. Similarly, few studies conducted on patients with parkinsonism showed a trend towards a different microbiota composition in those with reduced gait speed. No studies have assessed the association of fecal microbiota with other measures of physical performance. However, several studies, mainly with a cross-sectional design, suggest an association between microbiota composition and frailty, mostly assessed according to the deficit accumulation model. Namely, frailty was associated with reduced microbiota biodiversity, and lower representation of butyrate-producing bacteria. Therefore, we conclude that the causal link between microbiota and physical fitness is still uncertain due to the lack of targeted studies and the influence of a large number of covariates, including diet, exercise, multimorbidity, and polypharmacy, on both microbiota composition and physical function in older age. However, the relationship between gut microbiota and physical function remains a very promising area of research for the future.

RevDate: 2019-07-23

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: 2019-09-01

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: 2019-08-30

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: 2019-07-26

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: 2019-07-14

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: 2019-08-28

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: 2019-07-18

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: 2019-07-22

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: 2019-07-17

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: 2019-08-20

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

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

Neurochemistry international, 129:104498.

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: 2019-07-17

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: 2019-07-08

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: 2019-07-25

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, 8(7):1685-1690.

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: 2019-08-21

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, 25(7):1096-1103.

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: 2019-07-01

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: 2019-07-19

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.

TRIAL REGISTRATION NUMBER: NCT03996304; Pre-results.

RevDate: 2019-07-12

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: 2019-07-23

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

Analysis of RNA Methylation by Phylogenetically Diverse Cfr Radical S-Adenosylmethionine Enzymes Reveals an Iron-Binding Accessory Domain in a Clostridial Enzyme.

Biochemistry, 58(29):3169-3184.

Cfr is a radical S-adenosylmethionine (SAM) RNA methylase linked to multidrug antibiotic resistance in bacterial pathogens. It catalyzes a chemically challenging C-C bond-forming reaction to methylate C8 of A2503 (Escherichia coli numbering) of 23S rRNA 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 homologues 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 the rate of turnover is decreased 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 (∼1400 homologues) 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, the genomic co-occurrence and high abundance in the human microbiome suggest a possible functional role for a specialized rubredoxin in certain radical SAM RNA methylases that are relevant to human health.

RevDate: 2019-06-27

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: 2019-06-27

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: 2019-07-23

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

The Role of the Human Microbiome in Chemical Toxicity.

International journal of toxicology, 38(4):251-264.

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: 2019-08-04

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

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

Environment international, 130:104912.

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: 2019-09-04
CmpDate: 2019-09-04

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: 2019-07-23

Picardo SL, Coburn B, AR Hansen (2019)

The microbiome and cancer for clinicians.

Critical reviews in oncology/hematology, 141:1-12.

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: 2019-07-10

Bernstein DB, Dewhirst FE, D Segrè (2019)

Metabolic network percolation quantifies biosynthetic capabilities across the human oral microbiome.

eLife, 8: pii:39733.

The biosynthetic capabilities of microbes underlie their growth and interactions, playing a prominent role in microbial community structure. For large, diverse microbial communities, prediction of these capabilities is limited by uncertainty about metabolic functions and environmental conditions. To address this challenge, we propose a probabilistic method, inspired by percolation theory, to computationally quantify how robustly a genome-derived metabolic network produces a given set of metabolites under an ensemble of variable environments. We used this method to compile an atlas of predicted biosynthetic capabilities for 97 metabolites across 456 human oral microbes. This atlas captures taxonomically-related trends in biomass composition, and makes it possible to estimate inter-microbial metabolic distances that correlate with microbial co-occurrences. We also found a distinct cluster of fastidious/uncultivated taxa, including several Saccharibacteria (TM7) species, characterized by their abundant metabolic deficiencies. By embracing uncertainty, our approach can be broadly applied to understanding metabolic interactions in complex microbial ecosystems.

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: 2019-06-14

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: 2019-06-13

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: 2019-09-01

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, 47(9):e727-e734.

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.

RevDate: 2019-09-02
CmpDate: 2019-09-02

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: 2019-06-15

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: 2019-08-29

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.

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ESP Quick Facts

ESP Origins

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

ESP Support

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

ESP Rationale

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

ESP Goal

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

ESP Usage

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

ESP Content

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

ESP Help

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

ESP Plans

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

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Papers in Classical Genetics

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

Digital Books

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

Timelines

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

Biographies

Biographical information about many key scientists.

Selected Bibliographies

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

ESP Picks from Around the Web (updated 07 JUL 2018 )