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Bibliography on: Human Microbiome

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ESP: PubMed Auto Bibliography 23 May 2019 at 01:43 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: 2019-05-22

Amato KR (2019)

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

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

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

RevDate: 2019-05-20

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

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

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

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

RevDate: 2019-05-20

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

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

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

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

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

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

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

RevDate: 2019-05-18

Mortera SL, Soggiu A, Vernocchi P, et al (2019)

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

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

Breastfeeding is nowadays known to be one of the most critical factors contributing to the development of an efficient immune system. In the last decade, a consistent number of pieces of evidence demonstrated the relationship between a healthy organism and its gut microbiota. However, this link is still not fully understood and requires further investigation. We recently adopted a murine model to describe the impact of either maternal milk or parental genetic background, on the composition of the gut microbial population in the first weeks of life. A metaproteomic approach to such complex environments is a big challenge that requires a strong effort in both data production and analysis, including the set-up of dedicated multitasking bioinformatics pipelines. Herein we present an LC-MS/MS based investigation to monitor mouse gut microbiota in the early life, aiming at characterizing its functions and metabolic activities together with a taxonomic description in terms of operational taxonomic units. We provided a quantitative evaluation of bacterial metaproteins, taking into account differential expression results in relation to the functional and taxonomic classification, particularly with proteins from orthologues groups. This allowed the reduction of the bias arising from the presence of a high number of shared peptides, and proteins, among different bacterial species. We also focused on host mucosal proteome and its modulation, according to different microbiota composition. SIGNIFICANCE: This paper would represent a reference work for investigations on gut microbiota in early life, from both a microbiological and a functional proteomic point of view. We focused on the shaping of the mouse gut microbiota in dependence on the feeding modality, defining a reliable taxonomic description, highlighting some functional characteristics of the microbial community, and performing a first quantitative evaluation by data independent analysis in metaproteomics. Data are available via MassIVE with identifier MSV000082651.

RevDate: 2019-05-18

Birer C, ES Wright (2019)

Capturing the complex interplay between drugs and the intestinal microbiome.

Clinical pharmacology and therapeutics [Epub ahead of print].

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

RevDate: 2019-05-16

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

Genomic characterization of four novel Staphylococcus myoviruses.

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

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

RevDate: 2019-05-16

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

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

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

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

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

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

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

RevDate: 2019-05-15

Chernikova D, Yuan I, M Shaker (2019)

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

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

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

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

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

RevDate: 2019-05-11

Ahmed B, Cox MJ, L Cuthbertson (2019)

Growing up with your airway microbiota: a risky business.

RevDate: 2019-05-11

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

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

Annals of epidemiology pii:S1047-2797(18)30677-X [Epub ahead of print].

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

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

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

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

RevDate: 2019-05-09

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

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

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

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

RevDate: 2019-05-08

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

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

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

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

RevDate: 2019-05-06

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

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

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

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

RevDate: 2019-05-06

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

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

Frontiers in microbiology, 10:821.

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

RevDate: 2019-05-05

Seferovic MD, Pace RM, Caroll M, et al (2019)

Visualization of Microbes by 16S in situ Hybridization in Term and Preterm Placentae without Intraamniotic Infection.

American journal of obstetrics and gynecology pii:S0002-9378(19)30622-2 [Epub ahead of print].

BACKGROUND: Numerous reports have documented bacteria in the placental membranes and basal plate decidua in the absence of immunopathology using histological techniques. Similarly, independent metagenomic characterizations have identified an altered taxonomical makeup in association with spontaneous preterm birth (PTB). Here we sought to corroborate these findings by localizing presumptive intact bacteria using molecular histology within the placental microanatomy.

OBJECTIVES: Here we examined for microbes in term and preterm gestations using a signal amplified 16S universal in situ hybridization (ISH) probe set for bacterial rRNA, alongside traditional histologic methods of Warthin-Starry and Gram stains, as well as clinical culture methodologies. We further sought to differentiate accompanying 16S gene sequencing taxonomic profiles from germ free (gnotobiotic) mouse and extraction and amplicon contamination controls.

STUDY DESIGN: Placentae were collected from a total of n=53 subjects, comprised of term, labored (n 4) and unlabored Cesarean deliveries (n 22) and preterm vaginal (n 18) and Cesarean deliveries (n 8); a placenta from a single subject with clinical and histologic evident choriomanionitis was employed as a 'positive' control (n 1). The preterm cohort included spontaneous PTB with (n 6) and without (n 10) preterm premature rupture of membranes (PPROM), as well as medically indicated PTBs (n 10). Placental microbes were visualized using an in situ hybridization probe set designed against highly conserved regions of the bacterial 16S ribosome, which produces an amplified stable signal using branched DNA probes. Extracted bacterial nucleic acid from these same samples were subjected to 16S rRNA metagenomic sequencing (Illumina, V4) for course taxonomical analysis, alongside environmental and kit contaminant controls. A subset of unlabored, Cesarean delivered term pregnancies were also assessed with clinical culture for readily cultivatable pathogenic microbes.

RESULTS: Molecular ISH of bacterial rRNA enabled visualization and localization of low-abundance microbes after systematic high power scanning. Despite the absence of clinical or histological chorioamnionitis in 52 of 53 subjects, instances of 16S rRNA signal were confidently observed in 13 of 16 sPTB placentas, which was not significantly different from term unlabored Cesarean specimens (18 of 22; p>0.05). 16S rRNA signal was largely localized to the villus parenchyma and/or syncytiotrophoblast, and less commonly the chorion and the maternal intervillous space. In all term and unlabored Cesarean deliveries, visualization of evident placental microbes by ISH occurred in the absence of clinical or histological detection using conventional clinical cultivation, H&E, and Gram staining. In one subject, appreciable villous bacteria localized to an infarction, where 16S microbial detection was confirmed by Warthin-Starry stain. In all instances, parallel sample principle coordinate analysis using Bray-Cutis distances of 16S rRNA gene sequencing data demonstrated consistent taxonomical distinction from all negative or potential contamination controls (p=0.024, PERMANOVA). Classification from contaminant filtered data identified a distinct taxonomical makeup among term and preterm cohorts when compared to contaminant controls (FDR<0.05).

CONCLUSIONS: Presumptively intact placental microbes are visualized as low-abundance, low-biomass and sparse populations within the placenta regardless of gestational age and mode of delivery. Their taxonomic makeup is distinct from contamination controls. These findings further support several previously published findings, including our own, which have used metagenomics to characterize low-abundance and low-biomass microbial communities in the placenta.

RevDate: 2019-05-03

Chetwynd AJ, Ogilvie LA, Nzakizwanayo J, et al (2019)

The potential of nanoflow liquid chromatography-nano electrospray ionisation-mass spectrometry for global profiling the faecal metabolome.

Journal of chromatography. A pii:S0021-9673(19)30396-6 [Epub ahead of print].

Faeces are comprised of a wide array of metabolites arising from the circulatory system as well as the human microbiome. A global metabolite analysis (metabolomics) of faecal extracts offers the potential to uncover new compounds which may be indicative of the onset of bowel diseases such as colorectal cancer (CRC). To date, faecal metabolomics is still in its infancy and the compounds of low abundance present in faecal extracts poorly characterised. In this study, extracts of faeces from healthy subjects were profiled using a sensitive nanoflow-nanospray LC-MS platform which resulted in highly repeatable peak retention times (<2% CV) and intensities (<15% CV). Analysis of the extracts revealed wide coverage of the faecal metabolome including detection of low abundant signalling compounds such as sex steroids and eicosanoids, alongside highly abundant pharmaceuticals and tetrapyrrole metabolites. A small pilot study investigating differences in metabolomics profiles of faecal samples obtained from 7 CRC, 25 adenomatous polyp and 26 healthy groups revealed that secondary bile acids, conjugated androgens, eicosanoids, phospholipids and an unidentified haem metabolite were potential classes of metabolites that discriminated between the CRC and control sample groups. However, much larger follow up studies are needed to confirm which components of the faecal metabolome are associated with actual CRC disease rather than dietary influences. This study reveals the potential of nanospray-nanoflow LC-MS profiling of faecal samples from large scale cohort studies for uncovering the role of the faecal metabolome in colorectal disease formation.

RevDate: 2019-05-03

Sharma A, Richardson M, Cralle L, et al (2019)

Longitudinal homogenization of the microbiome between both occupants and the built environment in a cohort of United States Air Force Cadets.

Microbiome, 7(1):70 pii:10.1186/s40168-019-0686-6.

BACKGROUND: The microbiome of the built environment has important implications for human health and wellbeing; however, bidirectional exchange of microbes between occupants and surfaces can be confounded by lifestyle, architecture, and external environmental exposures. Here, we present a longitudinal study of United States Air Force Academy cadets (n = 34), which have substantial homogeneity in lifestyle, diet, and age, all factors that influence the human microbiome. We characterized bacterial communities associated with (1) skin and gut samples from roommate pairs, (2) four built environment sample locations inside the pairs' dormitory rooms, (3) four built environment sample locations within shared spaces in the dormitory, and (4) room-matched outdoor samples from the window ledge of their rooms.

RESULTS: We analyzed 2,170 samples, which generated 21,866 unique amplicon sequence variants. Linear convergence of microbial composition and structure was observed between an occupants' skin and the dormitory surfaces that were only used by that occupant (i.e., desk). Conversely, bacterial community beta diversity (weighted Unifrac) convergence between the skin of both roommates and the shared dormitory floor between the two cadet's beds was not seen across the entire study population. The sampling period included two semester breaks in which the occupants vacated their rooms; upon their return, the beta diversity similarity between their skin and the surfaces had significantly decreased compared to before the break (p < 0.05). There was no apparent convergence between the gut and building microbiota, with the exception of communal bathroom door-handles, which suggests that neither co-occupancy, diet, or lifestyle homogenization had a significant impact on gut microbiome similarity between these cadets over the observed time frame. As a result, predictive classifier models were able to identify an individual more accurately based on the gut microbiota (74%) compared to skin (51%).

CONCLUSIONS: To the best of our knowledge, this is the first study to show an increase in skin microbial similarity of two individuals who start living together for the first time and who are not genetically related or romantically involved. Cohabitation was significantly associated with increased skin microbiota similarity but did not significantly influence the gut microbiota. Following a departure from the occupied space of several weeks, the skin microbiota, but not the gut microbiota, showed a significant reduction in similarity relative to the building. Overall, longitudinal observation of these dynamics enables us to dissect the influence of occupation, diet, and lifestyle factors on occupant and built environment microbial ecology.

RevDate: 2019-05-01

Vangay P, Hillmann BM, D Knights (2019)

Microbiome Learning Repo (ML Repo): A public repository of microbiome regression and classification tasks.

GigaScience, 8(5):.

The use of machine learning in high-dimensional biological applications, such as the human microbiome, has grown exponentially in recent years, but algorithm developers often lack the domain expertise required for interpretation and curation of the heterogeneous microbiome datasets. We present Microbiome Learning Repo (ML Repo, available at, a public, web-based repository of 33 curated classification and regression tasks from 15 published human microbiome datasets. We highlight the use of ML Repo in several use cases to demonstrate its wide application, and we expect it to be an important resource for algorithm developers.

RevDate: 2019-04-27

Zhao S, Lieberman TD, Poyet M, et al (2019)

Adaptive Evolution within Gut Microbiomes of Healthy People.

Cell host & microbe pii:S1931-3128(19)30159-3 [Epub ahead of print].

Natural selection shapes bacterial evolution in all environments. However, the extent to which commensal bacteria diversify and adapt within the human gut remains unclear. Here, we combine culture-based population genomics and metagenomics to investigate the within-microbiome evolution of Bacteroides fragilis. We find that intra-individual B. fragilis populations contain substantial de novo nucleotide and mobile element diversity, preserving years of within-person history. This history reveals multiple signatures of within-person adaptation, including parallel evolution in sixteen genes. Many of these genes are implicated in cell-envelope biosynthesis and polysaccharide utilization. Tracking evolutionary trajectories using near-daily metagenomic sampling, we find evidence for years-long coexistence in one subject despite adaptive dynamics. We used public metagenomes to investigate one adaptive mutation common in our cohort and found that it emerges frequently in Western, but not Chinese, microbiomes. Collectively, these results demonstrate that B. fragilis adapts within individual microbiomes, pointing to factors that promote long-term gut colonization.

RevDate: 2019-04-28

Raju SC, Lagström S, Ellonen P, et al (2019)

Gender-Specific Associations Between Saliva Microbiota and Body Size.

Frontiers in microbiology, 10:767.

Objective: The human intestinal microbiota likely play an important role in the development of overweight and obesity. However, the associations between saliva microbiota and body mass index (BMI) have been sparsely studied. The aim of this study was to identify the associations between saliva microbiota and body size in Finnish children.

Methods: The saliva microbiota of 900 Finnish children, aged 11-14 years with measured height and weight, was characterized using 16S rRNA (V3-V4) sequencing.

Results: The core saliva microbiota consisted of 14 genera that were present in more than 95% of the Finnish children. The saliva microbiota profiles were gender-specific with higher alpha-diversity in boys than girls and significant differences between the genders in community composition and abundances. Alpha-diversity differed between normal weight and overweight girls and between normal weight and obese boys. The composition was dissimilar between normal weight and obese girls, but not in boys. The relative abundance profiles differed according to body size. Decrease in commensal saliva bacteria were observed in all the body sizes when compared to normal weight children. Notably, the relative abundance of bacteria related to, Veillonella, Prevotella, Selenomonas, and Streptococcus was reduced in obese children.

Conclusion: Saliva microbiota diversity and composition were significantly associated with body size and gender in Finnish children. Body size-specific saliva microbiota profiles open new avenues for studying the potential roles of microbiota in weight development and management.

RevDate: 2019-04-29

Wassan JT, Wang H, Browne F, et al (2019)

Phy-PMRFI: Phylogeny-aware Prediction of Metagenomic Functions using Random Forest Feature Importance.

IEEE transactions on nanobioscience [Epub ahead of print].

High-throughput sequencing techniques have accelerated functional metagenomics studies through the generation of large volumes of "omics" data. The integration of these data using computational approaches is potentially useful for predicting metagenomic functions. Machine learning (ML) models can be trained using microbial features which are then used to classify microbial data into different functional classes. For example, ML analyses over the human microbiome data have been linked to the prediction of important biological states. For analysing omics data, integrating abundance count of taxonomical features with their biological relationships is important. These relationships can potentially be uncovered from the phylogenetic tree of microbial taxa. In this paper, we propose a novel integrative framework Phy-PMRFI. This framework is driven by the phylogeny-based modeling of omics data to predict metagenomic functions using important features selected by a Random Forest Importance (RFI) strategy. The proposed framework integrates the underlying phylogenetic tree information with abundance measures of microbial species (features) by creating a novel phylogeny and abundance aware matrix structure (PAAM). Phy-PMRFI progresses by ranking the microbial features using an RFI measure. This is then used as input for microbiome classification. The resultant feature set enhances the performance of state-of-art methods such as Support Vector Machines. Our proposed integrative framework also outperforms the state-of-the-art pipeline of Phylogenetic Isometric Log-Ratio Transform (PhILR) and MetaPhyl. Prediction accuracy of 90 % is obtained with Phy-PMRFI over human throat microbiome in comparison to other approaches of PhILR with 53% and MetaPhyl with 71% Accuracy.

RevDate: 2019-04-26

Zhang X, D Figeys (2019)

Perspective and Guidelines for Metaproteomics in Microbiome Studies.

Journal of proteome research [Epub ahead of print].

The microbiome is emerging as a prominent factor affecting human health, and its dysbiosis is associated with various diseases. Compositional profiling of microbiome is increasingly being supplemented with functional characterization. Metaproteomics is intrinsically focused on functional changes and therefore will be an important tool in those studies of the human microbiome. In the past decade, development of new experimental and bioinformatic approaches for metaproteomics has enabled large-scale human metaproteomic studies. However, challenges still exist, and there remains a lack of standardizations and guidelines for properly performing metaproteomic studies on human microbiome. Herein, we provide a perspective of recent developments, the challenges faced, and the future directions of metaproteomics and its applications. In addition, we propose a set of guidelines/recommendations for performing and reporting the results from metaproteomic experiments for the study of human microbiomes. We anticipate that these guidelines will be optimized further as more metaproteomic questions are raised and addressed, and metaproteomic applications are published, so that they are eventually recognized and applied in the field.

RevDate: 2019-04-29

Holster S, Lindqvist CM, Repsilber D, et al (2019)

The Effect of Allogenic Versus Autologous Fecal Microbiota Transfer on Symptoms, Visceral Perception and Fecal and Mucosal Microbiota in Irritable Bowel Syndrome: A Randomized Controlled Study.

Clinical and translational gastroenterology, 10(4):e00034.

OBJECTIVES: Fecal microbiota transfer (FMT) is suggested as a potential treatment for patients with irritable bowel syndrome (IBS). We aimed to study the effect of allogenic and autologous FMT on IBS symptoms, visceral sensitivity, and compositional changes in fecal and mucosa-adherent microbiota.

METHODS: Seventeen patients with IBS were randomized either to receive fecal material from a healthy donor (allogenic) or to receive their own fecal material (autologous). The fecal material was administered into the cecum by whole colonoscopy after bowel cleansing.

RESULTS: No significant differences were found between the allogenic and the autologous FMT regarding symptom scores. However, symptom scores of patients receiving allogenic fecal material significantly decreased after FMT compared with baseline (P = 0.02), which was not the case in the autologous group (P = 0.16). Visceral sensitivity was not affected except for a small beneficial effect on urge scores in the autologous group (P < 0.05). While both fecal and mucosa-adherent microbiota of some patients shifted to their respective donor's fecal microbiota, some patients showed no relevant microbial changes after allogenic FMT. Large compositional shifts in fecal and mucosa-adherent microbiota also occurred in the autologous group.

CONCLUSIONS: This study showed that a single FMT by colonoscopy may have beneficial effects in IBS; however, the allogenic fecal material was not superior to the autologous fecal material. This suggests that bowel cleansing prior to the colonoscopy and/or processing of the fecal material as part of the FMT routine contribute to symptoms and gut microbiota composition changes in IBS.

RevDate: 2019-04-27

Hollister EB, Oezguen N, Chumpitazi BP, et al (2019)

Leveraging Human Microbiome Features to Diagnose and Stratify Children with Irritable Bowel Syndrome.

The Journal of molecular diagnostics : JMD, 21(3):449-461.

Accurate diagnosis and stratification of children with irritable bowel syndrome (IBS) remain challenging. Given the central role of recurrent abdominal pain in IBS, we evaluated the relationships of pediatric IBS and abdominal pain with intestinal microbes and fecal metabolites using a comprehensive clinical characterization and multiomics strategy. Using rigorous clinical phenotyping, we identified preadolescent children (aged 7 to 12 years) with Rome III IBS (n = 23) and healthy controls (n = 22) and characterized their fecal microbial communities using whole-genome shotgun metagenomics and global unbiased fecal metabolomic profiling. Correlation-based approaches and machine learning algorithms identified associations between microbes, metabolites, and abdominal pain. IBS cases differed from controls with respect to key bacterial taxa (eg, Flavonifractor plautii and Lachnospiraceae bacterium 7_1_58FAA), metagenomic functions (eg, carbohydrate metabolism and amino acid metabolism), and higher-order metabolites (eg, secondary bile acids, sterols, and steroid-like compounds). Significant associations between abdominal pain frequency and severity and intestinal microbial features were identified. A random forest classifier built on metagenomic and metabolic markers successfully distinguished IBS cases from controls (area under the curve, 0.93). Leveraging multiple lines of evidence, intestinal microbes, genes/pathways, and metabolites were associated with IBS, and these features were capable of distinguishing children with IBS from healthy children. These multi-omics features, and their links to childhood IBS coupled with nutritional interventions, may lead to new microbiome-guided diagnostic and therapeutic strategies.

RevDate: 2019-04-29

Díez López C, Vidaki A, Ralf A, et al (2019)

Novel taxonomy-independent deep learning microbiome approach allows for accurate classification of different forensically relevant human epithelial materials.

Forensic science international. Genetics, 41:72-82 pii:S1872-4973(19)30017-1 [Epub ahead of print].

Correct identification of different human epithelial materials such as from skin, saliva and vaginal origin is relevant in forensic casework as it provides crucial information for crime reconstruction. However, the overlap in human cell type composition between these three epithelial materials provides challenges for their differentiation and identification when using previously proposed human cell biomarkers, while their microbiota composition largely differs. By using validated 16S rRNA gene massively parallel sequencing data from the Human Microbiome Project of 1636 skin, oral and vaginal samples, 50 taxonomy-independent deep learning networks were trained to classify these three tissues. Validation testing was performed in de-novo generated high-throughput 16S rRNA gene sequencing data using the Ion Torrent™ Personal Genome Machine from 110 test samples: 56 hand skin, 31 saliva and 23 vaginal secretion specimens. Body-site classification accuracy of these test samples was very high as indicated by AUC values of 0.99 for skin, 0.99 for oral, and 1 for vaginal secretion. Misclassifications were limited to 3 (5%) skin samples. Additional forensic validation testing was performed in mock casework samples by de-novo high-throughput sequencing of 19 freshly-prepared samples and 22 samples aged for 1 up to 7.6 years. All of the 19 fresh and 20 (91%) of the 22 aged mock casework samples were correctly tissue-type classified. Moreover, comparing the microbiome results with outcomes from previous human mRNA-based tissue identification testing in the same 16 aged mock casework samples reveals that our microbiome approach performs better in 12 (75%), similarly in 2 (12.5%), and less good in 2 (12.5%) of the samples. Our results demonstrate that this new microbiome approach allows for accurate tissue-type classification of three human epithelial materials of skin, oral and vaginal origin, which is highly relevant for future forensic investigations.

RevDate: 2019-04-21

Inkpen SA (2019)

Health, ecology and the microbiome.

eLife, 8: pii:47626.

Advances in microbiomics have changed the way in which many researchers think about health and disease. These changes have also raised a number of philosophical questions around these topics, such as the types of living systems to which these concepts can be applied. Here, I discuss the human microbiome from two perspectives: the first treats the microbiome as part of a larger system that includes the human; the second treats the microbiome as an independent ecosystem that provides services to humans. Drawing on the philosophy of medicine and ecology, I explore two questions: i) how can we make sense of disease and dysfunction in these two perspectives? ii) are these two perspectives complimentary or do they compete with each other?

RevDate: 2019-04-17

Wang T, Yang C, H Zhao (2019)

Prediction analysis for microbiome sequencing data.

Biometrics [Epub ahead of print].

One goal of human microbiome studies is to relate host traits with human microbiome compositions. The analysis of microbial community sequencing data presents great statistical challenges, especially when the samples have different library sizes and the data are overdispersed with many zeros. To address these challenges, we introduce a new statistical framework, called predictive analysis in metagenomics via inverse regression (PAMIR), to analyze microbiome sequencing data. Within this framework, an inverse regression model is developed for overdispersed microbiota counts given the trait, and then a prediction rule is constructed by taking advantage of the dimension-reduction structure in the model. An efficient Monte Carlo expectation-maximization algorithm is proposed for maximum likelihood estimation. The method is further generalized to accommodate other types of covariates. We demonstrate the advantages of PAMIR through simulations and two real data examples.

RevDate: 2019-04-19

Garretto A, Hatzopoulos T, C Putonti (2019)

virMine: automated detection of viral sequences from complex metagenomic samples.

PeerJ, 7:e6695 pii:6695.

Metagenomics has enabled sequencing of viral communities from a myriad of different environments. Viral metagenomic studies routinely uncover sequences with no recognizable homology to known coding regions or genomes. Nevertheless, complete viral genomes have been constructed directly from complex community metagenomes, often through tedious manual curation. To address this, we developed the software tool virMine to identify viral genomes from raw reads representative of viral or mixed (viral and bacterial) communities. virMine automates sequence read quality control, assembly, and annotation. Researchers can easily refine their search for a specific study system and/or feature(s) of interest. In contrast to other viral genome detection tools that often rely on the recognition of viral signature sequences, virMine is not restricted by the insufficient representation of viral diversity in public data repositories. Rather, viral genomes are identified through an iterative approach, first omitting non-viral sequences. Thus, both relatives of previously characterized viruses and novel species can be detected, including both eukaryotic viruses and bacteriophages. Here we present virMine and its analysis of synthetic communities as well as metagenomic data sets from three distinctly different environments: the gut microbiota, the urinary microbiota, and freshwater viromes. Several new viral genomes were identified and annotated, thus contributing to our understanding of viral genetic diversity in these three environments.

RevDate: 2019-04-26

Aleti G, Baker JL, Tang X, et al (2019)

Identification of the Bacterial Biosynthetic Gene Clusters of the Oral Microbiome Illuminates the Unexplored Social Language of Bacteria during Health and Disease.

mBio, 10(2): pii:mBio.00321-19.

Small molecules are the primary communication media of the microbial world. Recent bioinformatic studies, exploring the biosynthetic gene clusters (BGCs) which produce many small molecules, have highlighted the incredible biochemical potential of the signaling molecules encoded by the human microbiome. Thus far, most research efforts have focused on understanding the social language of the gut microbiome, leaving crucial signaling molecules produced by oral bacteria and their connection to health versus disease in need of investigation. In this study, a total of 4,915 BGCs were identified across 461 genomes representing a broad taxonomic diversity of oral bacteria. Sequence similarity networking provided a putative product class for more than 100 unclassified novel BGCs. The newly identified BGCs were cross-referenced against 254 metagenomes and metatranscriptomes derived from individuals either with good oral health or with dental caries or periodontitis. This analysis revealed 2,473 BGCs, which were differentially represented across the oral microbiomes associated with health versus disease. Coabundance network analysis identified numerous inverse correlations between BGCs and specific oral taxa. These correlations were present in healthy individuals but greatly reduced in individuals with dental caries, which may suggest a defect in colonization resistance. Finally, corroborating mass spectrometry identified several compounds with homology to products of the predicted BGC classes. Together, these findings greatly expand the number of known biosynthetic pathways present in the oral microbiome and provide an atlas for experimental characterization of these abundant, yet poorly understood, molecules and socio-chemical relationships, which impact the development of caries and periodontitis, two of the world's most common chronic diseases.IMPORTANCE The healthy oral microbiome is symbiotic with the human host, importantly providing colonization resistance against potential pathogens. Dental caries and periodontitis are two of the world's most common and costly chronic infectious diseases and are caused by a localized dysbiosis of the oral microbiome. Bacterially produced small molecules, often encoded by BGCs, are the primary communication media of bacterial communities and play a crucial, yet largely unknown, role in the transition from health to dysbiosis. This study provides a comprehensive mapping of the BGC repertoire of the human oral microbiome and identifies major differences in health compared to disease. Furthermore, BGC representation and expression is linked to the abundance of particular oral bacterial taxa in health versus dental caries and periodontitis. Overall, this study provides a significant insight into the chemical communication network of the healthy oral microbiome and how it devolves in the case of two prominent diseases.

RevDate: 2019-04-16

Gonzalez E, Pitre FE, NJB Brereton (2019)

ANCHOR: A 16S rRNA gene amplicon pipeline for microbial analysis of multiple environmental samples.

Environmental microbiology [Epub ahead of print].

Analysis of 16S ribosomal RNA (rRNA) gene amplification data for microbial barcoding can be inaccurate across complex environmental samples. A method is presented, ANCHOR, designed for improved species level microbial identification using paired-end sequences directly, multiple high-complexity samples and multiple reference databases. An SOP is reported alongside benchmarking against artificial, single sample and replicated mock datasets. The method is then directly tested using a real-world dataset from surface swabs of the International Space Station (ISS). Simple mock community analysis identified 100% of the expected species and 99% of expected gene copy variants (100% identical). A replicated mock community revealed similar or better numbers of expected species compared to MetaAmp, DADA2, Mothur, and QIIME1. Analysis of the ISS microbiome identified 714 putative unique species/strains and differential abundance analysis distinguished significant differences between the Destiny module (US laboratory) and Harmony module (sleeping quarters). Harmony was remarkably dominated by human gastrointestinal tract bacteria, similar to enclosed environments on earth; however, Destiny module bacteria also derived from non-human microbiome carriers present on the ISS, the laboratory's research animals. ANCHOR can help substantially improve sequence resolution of 16S rRNA gene amplification data within biologically replicated environmental experiments and integrated multi-database annotation enhances interpretation of complex, non-reference microbiomes. This article is protected by copyright. All rights reserved.

RevDate: 2019-04-21

Parida S, D Sharma (2019)

The power of small changes: Comprehensive analyses of microbial dysbiosis in breast cancer.

Biochimica et biophysica acta. Reviews on cancer, 1871(2):392-405 pii:S0304-419X(19)30042-3 [Epub ahead of print].

Disparate occurrence of breast cancer remains an intriguing question since only a subset of women with known risk factors develop cancer. Recent studies suggest an active role of local and distant microbiota in breast cancer initiation, progression, and overall prognosis. A dysbiotic microbiota predisposes the body to develop cancer by inducing genetic instability, initiating DNA damage and proliferation of the damaged progeny, eliciting favorable immune response, metabolic dysregulation and altered response to therapy. In this review, we present our analyses of the existing datasets and discuss the local dysbiosis observed in breast cancer patients and different aspects of breast carcinogenesis that can be potentially influenced by local breast microbiota. Striking differences between microbial community compositions in breast of cancer patients compared to healthy individuals were noted. Differences in microbiome were also apparent between benign and malignant disease and between nipple aspirate fluid of healthy individuals and breast survivors. We also discuss the identification of distinct bacterial, fungal, viral as well as parasite signatures for breast cancer. These microbes are capable of producing numerous secondary metabolites that can act as signaling mediators effecting breast cancer progression. We review how microbes potentially alter response to therapy affecting drug metabolism, pharmacokinetics, anti-tumor effects and toxicity. In conclusion, breast harbors a community of microbes that can communicate with the host cells inducing downstream signaling pathways and modulating various aspects of breast cancer growth and metastatic progression and an improved understanding of microbial dysbiosis can potentially reduce breast cancer risk and improve outcomes of breast cancer patients. The human microbiome, now referred to as, the "forgotten organ" contains a metagenome that is 100-fold more diverse compared to the human genome, thereby, is critically associated with human health [1,2]. With the revelations of the human microbiome project and advent of deep sequencing techniques, a plethora of information has been acquired in recent years. Body sites like stomach, bladder and lungs, once thought to be sterile, are now known to harbor millions of indigenous microbial species. Approximately 80% of the healthy microbiome consists of Firmicutes and Bacteroidetes accompanied by Verrucomicrobia, Actinobacteria, Proteobacteria, Tenericutes and Cyanobacteria [2-7]. The role of microbiome in diabetes, obesity and even neurodegenerative diseases was greatly appreciated in the last decade [1,7-14] and now it has been established that microbiome significantly contributes to many organ specific cancers [1,15,16].

RevDate: 2019-04-13

Lerner A, Shoenfeld Y, T Matthias (2019)

Probiotics: If It Does Not Help It Does Not Do Any Harm. Really?.

Microorganisms, 7(4): pii:microorganisms7040104.

Probiotics per definition should have beneficial effects on human health, and their consumption has tremendously increased in the last decades. In parallel, the amount of published material and claims for their beneficial efficacy soared continuously. Recently, multiple systemic reviews, meta-analyses, and expert opinions expressed criticism on their claimed effects and safety. The present review describes the dark side of the probiotics, in terms of problematic research design, incomplete reporting, lack of transparency, and under-reported safety. Highlighted are the potential virulent factors and the mode of action in the intestinal lumen, risking the physiological microbiome equilibrium. Finally, regulatory topics are discussed to lighten the heterogeneous guidelines applied worldwide. The shift in the scientific world towards a better understanding of the human microbiome, before consumption of the probiotic cargo, is highly endorsed. It is hoped that better knowledge will extend the probiotic repertoire, re-confirm efficacy or safety, establish their efficacy and substantiate their beneficial effects.

RevDate: 2019-04-17

Jeong H, Arif B, Caetano-Anollés G, et al (2019)

Horizontal gene transfer in human-associated microorganisms inferred by phylogenetic reconstruction and reconciliation.

Scientific reports, 9(1):5953 pii:10.1038/s41598-019-42227-5.

Horizontal gene transfer (HGT) is widespread in the evolution of prokaryotes, especially those associated with the human body. Here, we implemented large-scale gene-species phylogenetic tree reconstructions and reconciliations to identify putative HGT-derived genes in the reference genomes of microbiota isolated from six major human body sites by the NIH Human Microbiome Project. Comparisons with a control group representing microbial genomes from diverse natural environments indicated that HGT activity increased significantly in the genomes of human microbiota, which is confirmatory of previous findings. Roughly, more than half of total genes in the genomes of human-associated microbiota were transferred (donated or received) by HGT. Up to 60% of the detected HGTs occurred either prior to the colonization of the human body or involved bacteria residing in different body sites. The latter could suggest 'genetic crosstalk' and movement of bacterial genes within the human body via hitherto poorly understood mechanisms. We also observed that HGT activity increased significantly among closely-related microorganisms and especially when they were united by physical proximity, suggesting that the 'phylogenetic effect' can significantly boost HGT activity. Finally, we identified several core and widespread genes least influenced by HGT that could become useful markers for building robust 'trees of life' and address several outstanding technical challenges to improve the phylogeny-based genome-wide HGT detection method for future applications.

RevDate: 2019-04-16

Shetty SA, Smidt H, WM de Vos (2019)

Reconstructing functional networks in the human intestinal tract using synthetic microbiomes.

Current opinion in biotechnology, 58:146-154 pii:S0958-1669(18)30230-1 [Epub ahead of print].

The human intestinal tract harbors one of the most densely populated and open microbial ecosystems. The application of multi-omics approaches has provided insight into a wide array of complex interactions between the various groups of mainly anaerobic colonic microbes as well as the host-microbe dialogue. Integration of multi-omics techniques in cultivation based experiments that vary in complexity from monocultures to synthetic microbial communities identified key metabolic players in the trophic interactions as well as their ecological dynamics. A synergy between these approaches will be of utmost importance to reconstruct the functional interaction networks at the ecosystem level within the human intestinal microbiome. The improved understanding of microbiome functioning at ecosystem level will further aid in developing better predictive models and design of effective microbiome modulation strategies for health benefits.

RevDate: 2019-04-08

Algazina T, Yermekbayeva B, Batpenova G, et al (2019)


Georgian medical news.

Psoriatic disease is a chronic inflammatory disease characterized by skin lesions. Psoriasis development has been associated both with genetic and environmental factors. Though skin and gut microbiota has been implicated in number of pathologies including atopic dermatitis, inflammatory bowel disease, Crohn's disease, allergy, and obesity, its role has been poorly studied in psoriatic disease, which incorporates both psoriasis and psoriatic arthritis. This literature review summarizes the most recent and major findings on microbiota features in psoriatic disease. Despite conflicting findings, psoriasis patients were frequently found to have distinct microbial composition in both skin and guts especially in the major bacterial phyla, Firmicutes, Bacteroidetes, and genus Akkermansia. Furthermore, bacterial DNA has been found in psoriatic patients both locally and systemically, and altogether suggesting a crucial role of bacteria in psoriatic disease and future studies in this field.

RevDate: 2019-04-18

Checinska Sielaff A, Urbaniak C, Mohan GBM, et al (2019)

Characterization of the total and viable bacterial and fungal communities associated with the International Space Station surfaces.

Microbiome, 7(1):50 pii:10.1186/s40168-019-0666-x.

BACKGROUND: The International Space Station (ISS) is a closed system inhabited by microorganisms originating from life support systems, cargo, and crew that are exposed to unique selective pressures such as microgravity. To date, mandatory microbial monitoring and observational studies of spacecraft and space stations have been conducted by traditional culture methods, although it is known that many microbes cannot be cultured with standard techniques. To fully appreciate the true number and diversity of microbes that survive in the ISS, molecular and culture-based methods were used to assess microbial communities on ISS surfaces. Samples were taken at eight pre-defined locations during three flight missions spanning 14 months and analyzed upon return to Earth.

RESULTS: The cultivable bacterial and fungal population ranged from 104 to 109 CFU/m2 depending on location and consisted of various bacterial (Actinobacteria, Firmicutes, and Proteobacteria) and fungal (Ascomycota and Basidiomycota) phyla. Amplicon sequencing detected more bacterial phyla when compared to the culture-based analyses, but both methods identified similar numbers of fungal phyla. Changes in bacterial and fungal load (by culture and qPCR) were observed over time but not across locations. Bacterial community composition changed over time, but not across locations, while fungal community remained the same between samplings and locations. There were no significant differences in community composition and richness after propidium monoazide sample treatment, suggesting that the analyzed DNA was extracted from intact/viable organisms. Moreover, approximately 46% of intact/viable bacteria and 40% of intact/viable fungi could be cultured.

CONCLUSIONS: The results reveal a diverse population of bacteria and fungi on ISS environmental surfaces that changed over time but remained similar between locations. The dominant organisms are associated with the human microbiome and may include opportunistic pathogens. This study provides the first comprehensive catalog of both total and intact/viable bacteria and fungi found on surfaces in closed space systems and can be used to help develop safety measures that meet NASA requirements for deep space human habitation. The results of this study can have significant impact on our understanding of other confined built environments on the Earth such as clean rooms used in the pharmaceutical and medical industries.

RevDate: 2019-04-04

Sessa L, Reddel S, Manno E, et al (2019)

Distinct gut microbiota profile in antiretroviral therapy-treated perinatally HIV-infected patients associated with cardiac and inflammatory biomarkers.

AIDS (London, England), 33(6):1001-1011.

OBJECTIVE: Persistent inflammation and higher risk to develop cardiovascular diseases still represent a major complication for HIV-infected patients despite effective antiretroviral therapy (ART). We investigated the correlation between the gut microbiota profile, markers of inflammation, vascular endothelial activation (VEA) and microbial translocation (MT) in perinatally HIV-infected patients (PHIV) under ART.

DESIGN: Cross-sectional study including 61 ART-treated PHIV (age range 3-30 years old) and 71 age-matched healthy controls. Blood and stool sample were collected at the same time and analyzed for gut microbiota composition and plasma biomarkers.

METHODS: Gut microbiota composition was determined by 16S rRNA targeted-metagenomics. Soluble markers of MT, inflammation and VEA were quantified by ELISA or Luminex assay. Markers of immune activation were analyzed by flow cytometry on CD4 and CD8T cells.

RESULTS: We identified two distinct gut microbiota profiles (groups A and B) among PHIV. No different clinical parameters (age, sex, ethnicity, clinical class), dietary and sexual habits were found between the groups. The group A showed a relative dominance of Akkermansia muciniphila, whereas gut microbiota of group B was characterized by a higher biodiversity. The analysis of soluble markers revealed a significantly higher level of soluble E-selectine (P = 0.0296), intercellular adhesion molecule-1 (P = 0.0028), vascular adhesion molecule-1 (P = 0.0230), IL-6 (P = 0.0247) and soluble CD14 (P = 0.0142) in group A compared with group B.

CONCLUSION: Distinctive gut microbiota profiles are differently associated with inflammation, microbial translocation and VEA. Future studies are needed to understand the role of A. muciniphila and risk to develop cardiovascular diseases in PHIV.

RevDate: 2019-04-10

Brown SM, Chen H, Hao Y, et al (2019)

MGS-Fast: Metagenomic shotgun data fast annotation using microbial gene catalogs.

GigaScience, 8(4):.

BACKGROUND: Current methods used for annotating metagenomics shotgun sequencing (MGS) data rely on a computationally intensive and low-stringency approach of mapping each read to a generic database of proteins or reference microbial genomes.

RESULTS: We developed MGS-Fast, an analysis approach for shotgun whole-genome metagenomic data utilizing Bowtie2 DNA-DNA alignment of reads that is an alternative to using the integrated catalog of reference genes database of well-annotated genes compiled from human microbiome data. This method is rapid and provides high-stringency matches (>90% DNA sequence identity) of the metagenomics reads to genes with annotated functions. We demonstrate the use of this method with data from a study of liver disease and synthetic reads, and Human Microbiome Project shotgun data, to detect differentially abundant Kyoto Encyclopedia of Genes and Genomes gene functions in these experiments. This rapid annotation method is freely available as a Galaxy workflow within a Docker image.

CONCLUSIONS: MGS-Fast can confidently transfer functional annotations from gene databases to metagenomic reads, with speed and accuracy.

RevDate: 2019-04-02

Chernikova D, Yuan I, M Shaker (2019)

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

Current opinion in pediatrics [Epub ahead of print].

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

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

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

RevDate: 2019-04-02

Sander MA, Sander MS, Isaac-Renton JL, et al (2019)

The Cutaneous Microbiome: Implications for Dermatology Practice.

Journal of cutaneous medicine and surgery [Epub ahead of print].

The human integument is inhabited by a vast array of microorganisms known collectively as the cutaneous microbiome. As a result of advances in laboratory science, our understanding of the diversity and complexity of the human microbiome is rapidly evolving. In particular, advances in the field of genomics have enabled the study of the cutaneous microbiome with a hitherto unimaginable level of detail, resulting in a maturation of our understanding of cutaneous health and disease. Herein, we review current microbiology concepts and highlight the key features of recent laboratory advances, particularly with respect to genomics. We provide a summary of new findings related to normal skin flora, interactions between host immunity and microbial communities, and microbial relationships with common skin disorders. Finally, we review the implications for dermatologists.

RevDate: 2019-04-02

Sharma A, Buschmann MM, JA Gilbert (2019)

Pharmacomicrobiomics: The holy grail to variability in drug response?.

Clinical pharmacology and therapeutics [Epub ahead of print].

The human body, with 3.0×1013 cells and more than 3.8×1013 microorganisms, has nearly a one-to-one ratio of resident microbes to human cells. Initiatives like the Human Microbiome Project, American Gut, and Flemish Gut have identified associations between microbial taxa and human health. The study of interactions between microbiome and pharmaceutical agents i.e. pharamacomicrobiomics has revealed an instrumental role of the microbiome in modulating drug response that alters the therapeutic outcomes. In this review, we present our current comprehension of the relationship of the microbiome, host biology, and pharmaceutical agents such as cardiovascular drugs, analgesics and chemotherapeutic-agents to human disease and treatment outcomes. We also discuss the significance of studying diet-gene-drug interactions and further address the key challenges associated with pharamacomicrobiomics. Finally, we examine proposed models employing systems biology for the application of pharmacomicrobiomics and other omics data, and provide approaches to elucidate microbiome-drug interactions to improve future translation to personalized medicine. This article is protected by copyright. All rights reserved.

RevDate: 2019-04-14

Hamidi B, Wallace K, Vasu C, et al (2019)

[Formula: see text]-test: robust distance-based multivariate analysis of variance.

Microbiome, 7(1):51 pii:10.1186/s40168-019-0659-9.

BACKGROUND: Community-wide analyses provide an essential means for evaluation of the effect of interventions or design variables on the composition of the microbiome. Applications of these analyses are omnipresent in microbiome literature, yet some of their statistical properties have not been tested for robustness towards common features of microbiome data. Recently, it has been reported that PERMANOVA can yield wrong results in the presence of heteroscedasticity and unbalanced sample sizes.

FINDINGS: We develop a method for multivariate analysis of variance, [Formula: see text], based on Welch MANOVA that is robust to heteroscedasticity in the data. We do so by extending a previously reported method that does the same for two-level independent factor variables. Our approach can accommodate multi-level factors, stratification, and multiple post hoc testing scenarios. An R language implementation of the method is available at .

CONCLUSION: Our method resolves potential for confounding of location and dispersion effects in multivariate analyses by explicitly accounting for the differences in multivariate dispersion in the data tested. The methods based on [Formula: see text] have general applicability in microbiome and other 'omics data analyses.

RevDate: 2019-04-02

Massari F, Mollica V, Di Nunno V, et al (2019)

The Human Microbiota and Prostate Cancer: Friend or Foe?.

Cancers, 11(4): pii:cancers11040459.

The human microbiome is gaining increasing attention in the medical community, as knowledge on its role not only in health but also in disease development and response to therapies is expanding. Furthermore, the connection between the microbiota and cancer, especially the link between the gut microbiota and gastrointestinal tumors, is becoming clearer. The interaction between the microbiota and the response to chemotherapies and, more recently, to immunotherapy has been widely studied, and a connection between a peculiar type of microbiota and a better response to these therapies and a different incidence in toxicities has been hypothesized. As knowledge on the gut microbiota increases, interest in the residing microbial population in other systems of our body is also increasing. Consequently, the urinary microbiota is under evaluation for its possible implications in genitourinary diseases, including cancer. Prostate cancer is the most common cancer in the male population; thus, research regarding its etiology and possible factors correlated to disease progression or the response to specific therapies is thriving. This review has the purpose to recollect the current knowledge on the relationship between the human microbiota and prostate cancer.

RevDate: 2019-04-02

Nava Lara RA, Aguilera-Mendoza L, Brizuela CA, et al (2019)

Heterologous Machine Learning for the Identification of Antimicrobial Activity in Human-Targeted Drugs.

Molecules (Basel, Switzerland), 24(7): pii:molecules24071258.

The emergence of microbes resistant to common antibiotics represent a current treat to human health. It has been recently recognized that non-antibiotic labeled drugs may promote antibiotic-resistance mechanisms in the human microbiome by presenting a secondary antibiotic activity; hence, the development of computer-assisted procedures to identify antibiotic activity in human-targeted compounds may assist in preventing the emergence of resistant microbes. In this regard, it is worth noting that while most antibiotics used to treat human infectious diseases are non-peptidic compounds, most known antimicrobials nowadays are peptides, therefore all computer-based models aimed to predict antimicrobials either use small datasets of non-peptidic compounds rendering predictions with poor reliability or they predict antimicrobial peptides that are not currently used in humans. Here we report a machine-learning-based approach trained to identify gut antimicrobial compounds; a unique aspect of our model is the use of heterologous training sets, in which peptide and non-peptide antimicrobial compounds were used to increase the size of the training data set. Our results show that combining peptide and non-peptide antimicrobial compounds rendered the best classification of gut antimicrobial compounds. Furthermore, this classification model was tested on the latest human-approved drugs expecting to identify antibiotics with broad-spectrum activity and our results show that the model rendered predictions consistent with current knowledge about broad-spectrum antibiotics. Therefore, heterologous machine learning rendered an efficient computational approach to classify antimicrobial compounds.

RevDate: 2019-04-06

Jaja-Chimedza A, Zhang L, Wolff K, et al (2018)

A dietary isothiocyanate-enriched moringa (Moringa oleifera) seed extract improves glucose tolerance in a high-fat-diet mouse model and modulates the gut microbiome.

Journal of functional foods, 47:376-385.

Moringa oleifera (moringa) has been traditionally used for the treatment of diabetes and in water purification. We previously showed that moringa seed extract (MSE), standardized to its primary bioactive isothiocyanate (MIC-1), modulated inflammatory and antioxidant signaling pathways in vitro. To understand the efficacy and mechanisms of action of MSE in vivo, we incorporated MSE into the diets of normal and obese C57Bl/6J male mice fed a standard low-fat diet or a very high-fat diet for 12 wk, respectively. MSE supplementation resulted in reduced body weight, decreased adiposity, improved glucose tolerance, reduced inflammatory gene expression, and increased antioxidant gene expression. 16S rRNA gene sequencing and quantitative PCR of fecal/cecal samples showed major modulation of the gut microbial community and a significantly reduced bacterial load, similar to an antibiotic response. This suggests that MSE improves metabolic health by its intracellular anti-inflammatory and antioxidant activities, and/or its antibiotic-like restructuring of the gut microbiota.

RevDate: 2019-04-03

Guo M, Xu E, D Ai (2019)

Inferring Bacterial Infiltration in Primary Colorectal Tumors From Host Whole Genome Sequencing Data.

Frontiers in genetics, 10:213.

Colorectal cancer is the third most common cancer worldwide with abysmal survival, thus requiring novel therapy strategies. Numerous studies have frequently observed infiltrating bacteria within the primary tumor tissues derived from patients. These studies have implicated the relative abundance of these bacteria as a contributing factor in tumor progression. Infiltrating bacteria are believed to be among the major drivers of tumorigenesis, progression, and metastasis and, hence, promising targets for new treatments. However, measuring their abundance directly remains challenging. One potential approach is to use the unmapped reads of host whole genome sequencing (hWGS) data, which previous studies have considered as contaminants and discarded. Here, we developed rigorous bioinformatics and statistical procedures to identify tumor-infiltrating bacteria associated with colorectal cancer from such whole genome sequencing data. Our approach used the reads of whole genome sequencing data of colon adenocarcinoma tissues not mapped to the human reference genome, including unmapped paired-end read pairs and single-end reads, the mates of which were mapped. We assembled the unmapped read pairs, remapped all those reads to the collection of human microbiome reference, and then computed their relative abundance of microbes by maximum likelihood (ML) estimation. We analyzed and compared the relative abundance and diversity of infiltrating bacteria between primary tumor tissues and associated normal blood samples. Our results showed that primary tumor tissues contained far more diverse total infiltrating bacteria than normal blood samples. The relative abundance of Bacteroides fragilis, Bacteroides dorei, and Fusobacterium nucleatum was significantly higher in primary colorectal tumors. These three bacteria were among the top ten microbes in the primary tumor tissues, yet were rarely found in normal blood samples. As a validation step, most of these bacteria were also closely associated with colorectal cancer in previous studies with alternative approaches. In summary, our approach provides a new analytic technique for investigating the infiltrating bacterial community within tumor tissues. Our novel cloud-based bioinformatics and statistical pipelines to analyze the infiltrating bacteria in colorectal tumors using the unmapped reads of whole genome sequences can be freely accessed from GitHub at

RevDate: 2019-04-03

Reid G, Gadir AA, R Dhir (2019)

Probiotics: Reiterating What They Are and What They Are Not.

Frontiers in microbiology, 10:424.

It has been over seventeen years since the scientific definition of probiotics was crafted, along with guidelines ensuring the appropriate use of the term. This definition is now used globally, yet on a consistent basis scientists, media and industry misrepresent probiotics or make generalized statements that illustrate a misunderstanding of their utility and limitations. The rate of discovery of novel organisms with potentially therapeutic benefit for both human and environmental health is progressing at an unprecedented rate. However, the term "probiotic" is often misapplied to describe any microbe with plausible therapeutic utility in the human host. It is argued that strict compliance to the scientific definition of the term "probiotic" and avoidance of generalizations to the whole field of probiotics based upon studies of one product, will help advance the development and validation of microbial therapies, and applications to improve human health.

RevDate: 2019-04-12

van der Veer C, Hertzberger RY, Bruisten SM, et al (2019)

Comparative genomics of human Lactobacillus crispatus isolates reveals genes for glycosylation and glycogen degradation: implications for in vivo dominance of the vaginal microbiota.

Microbiome, 7(1):49 pii:10.1186/s40168-019-0667-9.

BACKGROUND: A vaginal microbiota dominated by lactobacilli (particularly Lactobacillus crispatus) is associated with vaginal health, whereas a vaginal microbiota not dominated by lactobacilli is considered dysbiotic. Here we investigated whether L. crispatus strains isolated from the vaginal tract of women with Lactobacillus-dominated vaginal microbiota (LVM) are pheno- or genotypically distinct from L. crispatus strains isolated from vaginal samples with dysbiotic vaginal microbiota (DVM).

RESULTS: We studied 33 L. crispatus strains (n = 16 from LVM; n = 17 from DVM). Comparison of these two groups of strains showed that, although strain differences existed, both groups degraded various carbohydrates, produced similar amounts of organic acids, inhibited Neisseria gonorrhoeae growth, and did not produce biofilms. Comparative genomics analyses of 28 strains (n = 12 LVM; n = 16 DVM) revealed a novel, 3-fragmented glycosyltransferase gene that was more prevalent among strains isolated from DVM. Most L. crispatus strains showed growth on glycogen-supplemented growth media. Strains that showed less-efficient (n = 6) or no (n = 1) growth on glycogen all carried N-terminal deletions (respectively, 29 and 37 amino acid deletions) in a putative pullulanase type I protein.

DISCUSSION: L. crispatus strains isolated from LVM were not phenotypically distinct from L. crispatus strains isolated from DVM; however, the finding that the latter were more likely to carry a 3-fragmented glycosyltransferase gene may indicate a role for cell surface glycoconjugates, which may shape vaginal microbiota-host interactions. Furthermore, the observation that variation in the pullulanase type I gene is associated with growth on glycogen discourages previous claims that L. crispatus cannot directly utilize glycogen.

RevDate: 2019-04-02

Li Z, Lee K, Karagas MR, et al (2018)

Conditional Regression Based on a Multivariate Zero-Inflated Logistic-Normal Model for Microbiome Relative Abundance Data.

Statistics in biosciences, 10(3):587-608.

The human microbiome plays critical roles in human health and has been linked to many diseases. While advanced sequencing technologies can characterize the composition of the microbiome in unprecedented detail, it remains challenging to disentangle the complex interplay between human microbiome and disease risk factors due to the complicated nature of microbiome data. Excessive numbers e f zero values, high dimensionality, the hierarchical phylogenetic tree and compositional structure are compounded and consequently make existing methods inadequate to appropriately address these issues. We propose a multivariate two-part zero-inflated logistic normal (MZILN) model to analyze the association of disease risk factors with individual microbial taxa and overall microbial community composition. This approach can naturally handle excessive numbers e f zeros and the compositional data structure with the discrete part and the logistic-normal part e f the model. For parameter estimation, an estimating equations approach is employed that enables us to address the complex inter-taxa correlation structure induced by the hierarchical phylogenetic tree structure and the compositional data structure. This model is able to incorporate standard regularization approaches to deal with high dimensionality. Simulation shews that our model outperforms existing methods. Our approach is also compared to ethers using the analysis of real microbiome data.

RevDate: 2019-03-28

Ames NJ, Barb JJ, Ranucci A, et al (2019)

The oral microbiome of patients undergoing treatment for severe aplastic anemia: a pilot study.

Annals of hematology pii:10.1007/s00277-019-03599-w [Epub ahead of print].

The microbiome, an intriguing component of the human body, composed of trillions of microorganisms, has prompted scientific exploration to identify and understand its function and role in health and disease. As associations between microbiome composition, disease, and symptoms accumulate, the future of medicine hinges upon a comprehensive knowledge of these microorganisms for patient care. The oral microbiome may provide valuable and efficient insight for predicting future changes in disease status, infection, or treatment course. The main aim of this pilot study was to characterize the oral microbiome in patients with severe aplastic anemia (SAA) during their therapeutic course. SAA is a hematologic disease characterized by bone marrow failure which if untreated is fatal. Treatment includes either hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). In this study, we examined the oral microbiome composition of 24 patients admitted to the National Institutes of Health (NIH) Clinical Center for experimental SAA treatment. Tongue brushings were collected to assess the effects of treatment on the oral microbiome. Twenty patients received standard IST (equine antithymocyte globulin and cyclosporine) plus eltrombopag. Four patients underwent HSCT. Oral specimens were obtained at three time points during treatment and clinical follow-up. Using a novel approach to 16S rRNA gene sequence analysis encompassing seven hypervariable regions, results demonstrated a predictable decrease in microbial diversity over time among the transplant patients. Linear discriminant analysis or LefSe reported a total of 14 statistically significant taxa (p < 0.05) across time points in the HSCT patients. One-way plots of relative abundance for two bacterial species (Haemophilus parainfluenzae and Rothia mucilaginosa) in the HSCT group, show the differences in abundance between time points. Only one bacterial species (Prevotella histicola) was noted in the IST group with a p value of 0.065. The patients receiving immunosuppressive therapy did not exhibit a clear change in diversity over time; however, patient-specific changes were noted. In addition, we compared our findings to tongue dorsum samples from healthy participants in the Human Microbiome Project (HMP) database and found among HSCT patients, approximately 35% of bacterial identifiers (N = 229) were unique to this study population and were not present in tongue dorsum specimens obtained from the HMP. Among IST-treated patients, 45% (N = 351) were unique to these patients and not identified by the HMP. Although antibiotic use may have likely influenced bacterial composition and diversity, some literature suggests a decreased impact of antimicrobials on the oral microbiome as compared to their effect on the gut microbiome. Future studies with larger sample sizes that focus on the oral microbiome and the effects of antibiotics in an immunosuppressed patient population may help establish these potential associations.

RevDate: 2019-03-28

Shannon MB, Limeira R, Johansen D, et al (2019)

Bladder urinary oxygen tension is correlated with urinary microbiota composition.

International urogynecology journal pii:10.1007/s00192-019-03931-y [Epub ahead of print].

INTRODUCTION AND HYPOTHESIS: Presence of microbial communities (microbiota) in an organ system depends on environmental factors, such as oxygen availability. We describe a novel technique to measure bladder urine oxygen tension (BUOT) in ambulatory women and use that technique to compare BUOT values to female urinary microbiota and participant urinary signs and symptoms.

METHODS: Ambulatory female urogynecology patients presenting for clinical care who were willing to undergo transurethral catheterization underwent BUOT determination with a non-invasive flow-through oxygen sensor. To detect urinary microbiota in the bladder, 16S rRNA gene sequencing was performed on catheterized urine. Multivariate statistical analyses were performed to examine potential correlations among BUOT, urinary microbiota compositions and clinical variables.

RESULTS: Significant variation in BUOT existed between individuals (range: 0.47-51.5 mmHg; median: 23.1 ± 13.5). Microbiota compositions were associated with BUOT (p = 0.03). BUOT was significantly lower in urines that were nitrite negative on dipstick analysis (p = 0.0001) and in participants who answered yes to having urinary leakage on the validated Urinary Distress Inventory (p = 0.01).

CONCLUSIONS: BUOTs can be measured in ambulatory women. For urogynecology patients, a wide range of values exist. BUOT may be associated with the presence of urinary microbiota and resultant signs and symptoms.

RevDate: 2019-03-28

George A (2019)

Antimicrobial Resistance (AMR) in the Food Chain: Trade, One Health and Codex.

Tropical medicine and infectious disease, 4(1): pii:tropicalmed4010054.

Strategies that take on a One Health approach to addressing antimicrobial resistance (AMR) focused on reducing human use of antimicrobials, but policy-makers now have to grapple with a different set of political, economic, and highly sensitive trade interests less amenable to government direction, to tackle AMR in the food chain. Understanding the importance and influence of the intergovernmental Codex negotiations underway on AMR in the Food Chain is very weak but essential for AMR public policy experts. National and global food producing industries are already under pressure as consumers learn about the use of antimicrobials in food production and more so when the full impact of AMR microorganisms in the food chain and on the human microbiome is better understood. Governments will be expected to respond. Trade-related negotiations on access and use made of antimicrobials is political: the relevance of AMR 'evidence' is already contested and not all food producers or users of antimicrobials in the food chain are prepared to, or capable of, moving at the same pace. In trade negotiations governments defend their interpretation of national interest. Given AMR in the global food chain threatens national interest, both AMR One Health and zoonotic disease experts should understand and participate in all trade-related AMR negotiations to protect One Health priorities. To help facilitate this an overview and analysis of Codex negotiations is provided.

RevDate: 2019-03-29

El-Awady A, de Sousa Rabelo M, Meghil MM, et al (2019)

Polymicrobial synergy within oral biofilm promotes invasion of dendritic cells and survival of consortia members.

NPJ biofilms and microbiomes, 5:11 pii:84.

Years of human microbiome research have confirmed that microbes rarely live or function alone, favoring diverse communities. Yet most experimental host-pathogen studies employ single species models of infection. Here, the influence of three-species oral microbial consortium on growth, virulence, invasion and persistence in dendritic cells (DCs) was examined experimentally in human monocyte-derived dendritic cells (DCs) and in patients with periodontitis (PD). Cooperative biofilm formation by Streptococcus gordonii, Fusobacterium nucleatum and Porphyromonas gingivalis was documented in vitro using growth models and scanning electron microscopy. Analysis of growth rates by species-specific 16s rRNA probes revealed distinct, early advantages to consortium growth for S. gordonii and F. nucleatum with P. gingivalis, while P. gingivalis upregulated its short mfa1 fimbriae, leading to increased invasion of DCs. F. nucleatum was only taken up by DCs when in consortium with P. gingivalis. Mature consortium regressed DC maturation upon uptake, as determined by flow cytometry. Analysis of dental plaques of PD and healthy subjects by 16s rRNA confirmed oral colonization with consortium members, but DC hematogenous spread was limited to P. gingivalis and F. nucleatum. Expression of P. gingivalis mfa1 fimbriae was increased in dental plaques and hematogenous DCs of PD patients. P. gingivalis in the consortium correlated with an adverse clinical response in the gingiva of PD subjects. In conclusion, we have identified polymicrobial synergy in a three-species oral consortium that may have negative consequences for the host, including microbial dissemination and adverse peripheral inflammatory responses.

RevDate: 2019-03-26

Brito IL, Gurry T, Zhao S, et al (2019)

Transmission of human-associated microbiota along family and social networks.

Nature microbiology pii:10.1038/s41564-019-0409-6 [Epub ahead of print].

The human microbiome, described as an accessory organ because of the crucial functions it provides, is composed of species that are uniquely found in humans1,2. Yet, surprisingly little is known about the impact of routine interpersonal contacts in shaping microbiome composition. In a relatively 'closed' cohort of 287 people from the Fiji Islands, where common barriers to bacterial transmission are absent, we examine putative bacterial transmission in individuals' gut and oral microbiomes using strain-level data from both core single-nucleotide polymorphisms and flexible genomic regions. We find a weak signal of transmission, defined by the inferred sharing of genotypes, across many organisms that, in aggregate, reveals strong transmission patterns, most notably within households and between spouses. We were unable to determine the directionality of transmission nor whether it was direct. We further find that women harbour strains more closely related to those harboured by their familial and social contacts than men, and that transmission patterns of oral-associated and gut-associated microbiota need not be the same. Using strain-level data alone, we are able to confidently predict a subset of spouses, highlighting the role of shared susceptibilities, behaviours or social interactions that distinguish specific links in the social network.

RevDate: 2019-04-21

Leynaert B, Le Moual N, Neukirch C, et al (2019)

[Environmental risk factors for asthma developement].

Presse medicale (Paris, France : 1983), 48(3 Pt 1):262-273.

The prevalence of asthma has increased rapidly since the early 1970s, and only changes in exposure to environmental factors; which go together with changes in lifestyle, are likely to explain such a rapid increase. Exposure to allergens is a risk factor for allergic sensitization, and allergic sensitization is a risk factor for allergic asthma. However, apart from indoor mold exposure as a risk factor for childhood asthma, there is insufficient evidence to conclude that the associations between allergen exposure and asthma development are causal. A new challenge for research is to analyze the huge amount of data derived from the metagenomic characterization of the environmental and human microbiome, to understand the role of interactions between viruses, bacteria and allergens in the development of asthma. It is recognized that prenatal and postnatal exposure to air pollution and maternal smoking increase the risk of developing asthma in children. In adults, the data are scarce and the results remain controversial as regards these exposures and asthma incidence. Further research is needed to appraise the effect of exposure to phenols, phthalates and perfluorinated compounds, which are widespread in the environment and may be associated with asthma, especially in children. Frequent use of chemicals for home cleaning especially in the form of sprays - which is a common practice at the population level - is a risk factor for the development of adult asthma. The domestic use of cleaning products might also be a risk factor for asthma in children exposed at home. The chemicals involved in these relationships are still to be identified. Occupational asthma is a major phenotype of adult asthma. A significant part of these asthma cases might relate to occupational exposure to cleaning products. While there is evidence of associations between diet during pregnancy or during childhood and the risk of developing asthma in children, the data in adults are insufficient. Beyond genetic factors, body composition is influenced by dietary choices and physical activity. Further research is needed to clarify the complex interplay between these nutritional factors and asthma development. The new challenge for research is to decipher the role of all the environmental factors to which the individual is exposed since conception ("exposome") in the development of asthma, using a holistic approach.

RevDate: 2019-03-25

Ahern GJ, Hennessy AA, Ryan CA, et al (2019)

Advances in Infant Formula Science.

Annual review of food science and technology, 10:75-102.

Human milk contains a plethora of nutrients and bioactive components to help nourish the developing neonate and is considered the "gold standard" for early life nutrition-as befits the only food "designed" by evolution to feed human infants. Over the past decade, there is considerable evidence that highlights the "intelligence" contained in milk components that contribute to infant health beyond basic nutrition-in areas such as programming the developing microbiome and immune system and protecting against infection. Such discoveries have led to new opportunities for infant milk formula (IMF) manufacturers to refine nutritional content in order to simulate the functionality of breast milk. These include the addition of specialized protein fractions as well as fatty acid and complex carbohydrate components-all of which have mechanistic supporting evidence in terms of improving the health and nutrition of the infant. Moreover, IMF is the single most important dietary intervention whereby the human microbiome can be influenced at a crucial early stage of development. In this respect, it is expected that the complexity of IMF will continue to increase as we get a greater understanding of how it can modulate microbiota development (including the development of probiotics, prebiotics, and synbiotics) and influence long-term health. This review provides a scientific evaluation of key features of importance to infant nutrition, including differences in milk composition and emerging "humanized" ingredients.

RevDate: 2019-03-29

Reddel S, Del Chierico F, Quagliariello A, et al (2019)

Gut microbiota profile in children affected by atopic dermatitis and evaluation of intestinal persistence of a probiotic mixture.

Scientific reports, 9(1):4996 pii:10.1038/s41598-019-41149-6.

Atopic dermatitis (AD) has been hypothesised to be associated with gut microbiota (GM) composition. We performed a comparative study of the GM profile of 19 AD children and 18 healthy individuals aimed at identifying bacterial biomarkers associated with the disease. The effect of probiotic intake (Bifidobacterium breve plus Lactobacillus salivarius) on the modulation of GM and the probiotic persistence in the GM were also evaluated. Faecal samples were analysed by real-time PCR and 16S rRNA targeted metagenomics. Although the probiotics, chosen for this study, did not shape the entire GM profile, we observed the ability of these species to pass through the gastrointestinal tract and to persist (only B. breve) in the GM. Moreover, the GM of patients compared to CTRLs showed a dysbiotic status characterised by an increase of Faecalibacterium, Oscillospira, Bacteroides, Parabacteroides and Sutterella and a reduction of short-chain fatty acid (SCFA)-producing bacteria (i.e., Bifidobacterium, Blautia, Coprococcus, Eubacterium and Propionibacterium). Taken togheter these results show an alteration in AD microbiota composition with the depletion or absence of some species, opening the way to future probiotic intervention studies.

RevDate: 2019-03-21

Nguyen VD, Nguyen TT, Pham TT, et al (2019)

Molecular screening and genetic diversity analysis of anticancer Azurin-encoding and Azurin-like genes in human gut microbiome deduced through cultivation-dependent and cultivation-independent studies.

International microbiology : the official journal of the Spanish Society for Microbiology pii:10.1007/s10123-019-00070-8 [Epub ahead of print].

Azurin, a bacteriocin produced by a human gut bacterium Pseudomonas aeruginosa, can reveal selectively cytotoxic and induce apoptosis in cancer cells. After overcoming two phase I trials, a functional region of Azurin called p28 has been approved as a drug for the treatment of brain tumor glioma by FDA. The present study aims to improve a screening procedure and assess genetic diversity of Azurin genes in P. aeruginosa and Azurin-like genes in the gut microbiome of a specific population in Vietnam and global populations. Firstly, both cultivation-dependent and cultivation-independent techniques based on genomic and metagenomic DNAs extracted from fecal samples of the healthy specific population were performed and optimized to detect Azurin genes. Secondly, the Azurin gene sequences were analyzed and compared with global populations by using bioinformatics tools. Finally, the screening procedure improved from the first step was applied for screening Azurin-like genes, followed by the protein synthesis and NCI in vitro screening for anticancer activity. As a result, this study has successfully optimized the annealing temperatures to amplify DNAs for screening Azurin genes and applying to Azurin-like genes from human gut microbiota. The novelty of this study is the first of its kind to classify Azurin genes into five different genotypes at a global scale and confirm the potential anticancer activity of three Azurin-like synthetic proteins (Cnazu1, Dlazu11, and Ruazu12). The results contribute to the procedure development applied for screening anticancer proteins from human microbiome and a comprehensive understanding of their therapeutic response at a genetic level.

RevDate: 2019-03-29

Brown EEF, Cooper A, Carrillo C, et al (2019)

Selection of Multidrug-Resistant Bacteria in Medicated Animal Feeds.

Frontiers in microbiology, 10:456.

Exposure to antimicrobial resistant (AMR) bacteria is a major public health issue which may, in part, have roots in food production practices that are conducive to the selection of AMR bacteria ultimately impacting the human microbiome through food consumption. Of particular concern is the prophylactic use of antibiotics in animal husbandry, such as the medication of feeds with sulfonamides and other antibiotics not considered clinically relevant, but which may nonetheless co-select for multi-drug resistant (MDR) bacteria harboring resistance to medically important antibiotics. Using a MDR Klebsiella pneumoniae strain exhibiting resistance to sulfonamides and beta-lactams (including carbapenem) as a model, we examined the ability of non-medicated and commercially medicated (sulfonamide) animal feeds to select for the model strain when inoculated at low levels by measuring its recovery along with key AMR markers, sul1(sulfonamide) and blaKPC-3 (meropenem), under different incubation conditions. When non-medicated feeds were supplemented with defined amounts of sulfadiazine the model strain was significantly enriched after incubation in Mueller Hinton Broth at 37°C overnight, or in same at room temperature for a week, with consistent detection of both the sul1 and blaKPC-3 markers as determined by polymerase chain reaction (PCR) techniques to screen colony isolates recovered on plating media. Significant recoveries of the inoculated strain and the sul1 and blaKPC-3 markers were observed with one of three commercially medicated (sulfamethazine) feeds tested under various incubation conditions. These results demonstrate that under certain conditions the prophylactic use of so-called non-priority antibiotics in feeds can potentially lead to co-selection of environmental AMR bacteria with resistance to medically important antibiotics, which may have far-reaching implications for human health.

RevDate: 2019-03-21

Ma ZS, Li L, NJ Gotelli (2019)

Diversity-disease relationships and shared species analyses for human microbiome-associated diseases.

The ISME journal pii:10.1038/s41396-019-0395-y [Epub ahead of print].

Diversity indices have been routinely computed in the study of human microbiome-associated diseases (MADs). However, it is still unclear whether there is a consistent diversity-disease relationship (DDR) for the human MADs, and whether there are consistent differences in the taxonomic composition of microbiomes sampled from healthy versus diseased individuals. Here we reanalyzed raw data and used a meta-analysis to compare the microbiome diversity and composition of healthy versus diseased individuals in 41 comparisons extracted from 27 previously published studies of human MADs. In the DDR analysis, the average effect size across studies did not differ from zero for a comparison of healthy versus diseased individuals. In 30 of 41 comparisons (73%) there was no significant difference in microbiome diversity of healthy versus diseased individuals, or of different disease classes. For the species composition analysis (shared species analysis), the effect sizes were significantly different from zero. In 33 of 41 comparisons (80%), there were fewer OTUs (operational taxonomic units) shared between healthy and diseased individuals than expected by chance, but with 49% (20 of 41 comparisons) statistically significant. These results imply that the taxonomic composition of disease-associated microbiomes is often distinct from that of healthy individuals. Because species composition changes with disease state, some microbiome OTUs may serve as potential diagnostic indicators of disease. However, the overall species diversity of human microbiomes is not a reliable indicator of disease.

RevDate: 2019-03-20

Chen QL, Cui HL, Su JQ, et al (2019)

Antibiotic Resistomes in Plant Microbiomes.

Trends in plant science pii:S1360-1385(19)30052-4 [Epub ahead of print].

Microorganisms associated with plants may alter the traits of the human microbiome important for human health, but this alteration has largely been overlooked. The plant microbiome is an interface between plants and the environment, and provides many ecosystem functions such as improving nutrient uptake and protecting against biotic and abiotic stress. The plant microbiome also represents a major pathway by which humans are exposed to microbes and genes consumed with food, such as pathogenic bacteria, antibiotic-resistant bacteria, and antibiotic-resistance genes. In this review we highlight the main findings on the composition and function of the plant microbiome, and underline the potential of plant microbiomes in the dissemination of antibiotic resistance via food consumption or direct contact.

RevDate: 2019-04-27

Tovaglieri A, Sontheimer-Phelps A, Geirnaert A, et al (2019)

Species-specific enhancement of enterohemorrhagic E. coli pathogenesis mediated by microbiome metabolites.

Microbiome, 7(1):43 pii:10.1186/s40168-019-0650-5.

BACKGROUND: Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans to enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice are relatively resistant to this pathogen. This intrinsic species-specific difference in EHEC infection limits the translation of murine research to human. Furthermore, studying the mechanisms underlying this differential susceptibility is a difficult problem due to complex in vivo interactions between the host, pathogen, and disparate commensal microbial communities.

RESULTS: We utilize organ-on-a-chip (Organ Chip) microfluidic culture technology to model damage of the human colonic epithelium induced by EHEC infection, and show that epithelial injury is greater when exposed to metabolites derived from the human gut microbiome compared to mouse. Using a multi-omics approach, we discovered four human microbiome metabolites-4-methyl benzoic acid, 3,4-dimethylbenzoic acid, hexanoic acid, and heptanoic acid-that are sufficient to mediate this effect. The active human microbiome metabolites preferentially induce expression of flagellin, a bacterial protein associated with motility of EHEC and increased epithelial injury. Thus, the decreased tolerance to infection observed in humans versus other species may be due in part to the presence of compounds produced by the human intestinal microbiome that actively promote bacterial pathogenicity.

CONCLUSION: Organ-on-chip technology allowed the identification of specific human microbiome metabolites modulating EHEC pathogenesis. These identified metabolites are sufficient to increase susceptibility to EHEC in our human Colon Chip model and they contribute to species-specific tolerance. This work suggests that higher concentrations of these metabolites could be the reason for higher susceptibility to EHEC infection in certain human populations, such as children. Furthermore, this research lays the foundation for therapeutic-modulation of microbe products in order to prevent and treat human bacterial infection.

RevDate: 2019-04-06

LaPierre N, Ju CJ, Zhou G, et al (2019)

MetaPheno: A critical evaluation of deep learning and machine learning in metagenome-based disease prediction.

Methods (San Diego, Calif.) pii:S1046-2023(18)30362-1 [Epub ahead of print].

The human microbiome plays a number of critical roles, impacting almost every aspect of human health and well-being. Conditions in the microbiome have been linked to a number of significant diseases. Additionally, revolutions in sequencing technology have led to a rapid increase in publicly-available sequencing data. Consequently, there have been growing efforts to predict disease status from metagenomic sequencing data, with a proliferation of new approaches in the last few years. Some of these efforts have explored utilizing a powerful form of machine learning called deep learning, which has been applied successfully in several biological domains. Here, we review some of these methods and the algorithms that they are based on, with a particular focus on deep learning methods. We also perform a deeper analysis of Type 2 Diabetes and obesity datasets that have eluded improved results, using a variety of machine learning and feature extraction methods. We conclude by offering perspectives on study design considerations that may impact results and future directions the field can take to improve results and offer more valuable conclusions. The scripts and extracted features for the analyses conducted in this paper are available via GitHub:

RevDate: 2019-04-20

Cohen LJ, Cho JH, Gevers D, et al (2019)

Genetic Factors and the Intestinal Microbiome Guide Development of Microbe-Based Therapies for Inflammatory Bowel Diseases.

Gastroenterology pii:S0016-5085(19)33559-0 [Epub ahead of print].

The intestinal microbiota is a dynamic community of bacteria, fungi, and viruses that mediates mucosal homeostasis and physiology. Imbalances in the microbiome and aberrant immune responses to gut bacteria can disrupt homeostasis and are associated with inflammatory bowel diseases (IBDs) in humans and colitis in mice. We review genetic variants associated with IBD and their effects on the intestinal microbiome, the immune response, and disease pathogenesis. The intestinal microbiome, which includes microbial antigens, adjuvants, and metabolic products, affects the development and function of the intestinal mucosa and inflammatory responses in the gut. Therefore, strategies to manipulate the microbiome might be used in treatment of IBD. We review microbe-based therapies for IBD and the potential to engineer patients' intestinal microbiota. We discuss how studies of patients with IBD and mouse models have advanced our understanding of the interactions between genetic factors and the gut microbiome and challenges to the development of microbe-based therapies for IBD.

RevDate: 2019-03-16

Shaw LP, Bassam H, Barnes CP, et al (2019)

Modelling microbiome recovery after antibiotics using a stability landscape framework.

The ISME journal pii:10.1038/s41396-019-0392-1 [Epub ahead of print].

Treatment with antibiotics is one of the most extreme perturbations to the human microbiome. Even standard courses of antibiotics dramatically reduce the microbiome's diversity and can cause transitions to dysbiotic states. Conceptually, this is often described as a 'stability landscape': the microbiome sits in a landscape with multiple stable equilibria, and sufficiently strong perturbations can shift the microbiome from its normal equilibrium to another state. However, this picture is only qualitative and has not been incorporated in previous mathematical models of the effects of antibiotics. Here, we outline a simple quantitative model based on the stability landscape concept and demonstrate its success on real data. Our analytical impulse-response model has minimal assumptions with three parameters. We fit this model in a Bayesian framework to data from a previous study of the year-long effects of short courses of four common antibiotics on the gut and oral microbiomes, allowing us to compare parameters between antibiotics and microbiomes, and further validate our model using data from another study looking at the impact of a combination of last-resort antibiotics on the gut microbiome. Using Bayesian model selection we find support for a long-term transition to an alternative microbiome state after courses of certain antibiotics in both the gut and oral microbiomes. Quantitative stability landscape frameworks are an exciting avenue for future microbiome modelling.

RevDate: 2019-03-27

Douillard FP, WM de Vos (2019)

Biotechnology of health-promoting bacteria.

Biotechnology advances pii:S0734-9750(19)30044-8 [Epub ahead of print].

Over the last decade, there has been an increasing scientific and public interest in bacteria that may positively contribute to human gut health and well-being. This interest is reflected by the ever-increasing number of developed functional food products containing health-promoting bacteria and reaching the market place as well as by the growing revenue and profits of notably bacterial supplements worldwide. Traditionally, the origin of probiotic-marketed bacteria was limited to a rather small number of bacterial species that mostly belong to lactic acid bacteria and bifidobacteria. Intensifying research efforts on the human gut microbiome offered novel insights into the role of human gut microbiota in health and disease, while also providing a deep and increasingly comprehensive understanding of the bacterial communities present in this complex ecosystem and their interactions with the gut-liver-brain axis. This resulted in rational and systematic approaches to select novel health-promoting bacteria or to engineer existing bacteria with enhanced probiotic properties. In parallel, the field of gut microbiomics developed into a fertile framework for the identification, isolation and characterization of a phylogenetically diverse array of health-promoting bacterial species, also called next-generation therapeutic bacteria. The present review will address these developments with specific attention for the selection and improvement of a selected number of health-promoting bacterial species and strains that are extensively studied or hold promise for future food or pharma product development.

RevDate: 2019-04-12

Minot SS (2019)

De novo Assembly Vastly Expands the Known Microbial Universe.

Trends in microbiology, 27(5):385-386.

The study of the human microbiome relies heavily on the genomes of bacterial isolates that can be grown in culture. A recent study (Pasolli et al. Cell 2019;176:649-662) of stool microbiome samples generated over 150 000 microbial genomes without any culture, vastly expanding our knowledge of the biases in existing reference databases.

RevDate: 2019-03-29

Perz AI, Giles CB, Brown CA, et al (2019)

MNEMONIC: MetageNomic Experiment Mining to create an OTU Network of Inhabitant Correlations.

BMC bioinformatics, 20(Suppl 2):96 pii:10.1186/s12859-019-2623-x.

BACKGROUND: The number of publicly available metagenomic experiments in various environments has been rapidly growing, empowering the potential to identify similar shifts in species abundance between different experiments. This could be a potentially powerful way to interpret new experiments, by identifying common themes and causes behind changes in species abundance.

RESULTS: We propose a novel framework for comparing microbial shifts between conditions. Using data from one of the largest human metagenome projects to date, the American Gut Project (AGP), we obtain differential abundance vectors for microbes using experimental condition information provided with the AGP metadata, such as patient age, dietary habits, or health status. We show it can be used to identify similar and opposing shifts in microbial species, and infer putative interactions between microbes. Our results show that groups of shifts with similar effects on microbiome can be identified and that similar dietary interventions display similar microbial abundance shifts.

CONCLUSIONS: Without comparison to prior data, it is difficult for experimentalists to know if their observed changes in species abundance have been observed by others, both in their conditions and in others they would never consider comparable. Yet, this can be a very important contextual factor in interpreting the significance of a shift. We've proposed and tested an algorithmic solution to this problem, which also allows for comparing the metagenomic signature shifts between conditions in the existing body of data.

RevDate: 2019-04-02

Burcham ZM, Schmidt CJ, Pechal JL, et al (2019)

Detection of critical antibiotic resistance genes through routine microbiome surveillance.

PloS one, 14(3):e0213280 pii:PONE-D-18-26200.

Population-based public health data on antibiotic resistance gene carriage is poorly surveyed. Research of the human microbiome as an antibiotic resistance reservoir has primarily focused on gut associated microbial communities, but data have shown more widespread microbial colonization across organs than originally believed, with organs previously considered as sterile being colonized. Our study demonstrates the utility of postmortem microbiome sampling during routine autopsy as a method to survey antibiotic resistance carriage in a general population. Postmortem microbial sampling detected pathogens of public health concern including genes for multidrug efflux pumps, carbapenem, methicillin, vancomycin, and polymixin resistances. Results suggest that postmortem assessments of host-associated microbial communities are useful in acquiring community specific data while reducing selective-participant biases.

RevDate: 2019-04-15
CmpDate: 2019-04-15

Elzinga J, van der Oost J, de Vos WM, et al (2019)

The Use of Defined Microbial Communities To Model Host-Microbe Interactions in the Human Gut.

Microbiology and molecular biology reviews : MMBR, 83(2): pii:83/2/e00054-18.

The human intestinal ecosystem is characterized by a complex interplay between different microorganisms and the host. The high variation within the human population further complicates the quest toward an adequate understanding of this complex system that is so relevant to human health and well-being. To study host-microbe interactions, defined synthetic bacterial communities have been introduced in gnotobiotic animals or in sophisticated in vitro cell models. This review reinforces that our limited understanding has often hampered the appropriate design of defined communities that represent the human gut microbiota. On top of this, some communities have been applied to in vivo models that differ appreciably from the human host. In this review, the advantages and disadvantages of using defined microbial communities are outlined, and suggestions for future improvement of host-microbe interaction models are provided. With respect to the host, technological advances, such as the development of a gut-on-a-chip system and intestinal organoids, may contribute to more-accurate in vitro models of the human host. With respect to the microbiota, due to the increasing availability of representative cultured isolates and their genomic sequences, our understanding and controllability of the human gut "core microbiota" are likely to increase. Taken together, these advancements could further unravel the molecular mechanisms underlying the human gut microbiota superorganism. Such a gain of insight would provide a solid basis for the improvement of pre-, pro-, and synbiotics as well as the development of new therapeutic microbes.

RevDate: 2019-04-03

Plantinga AM, Chen J, Jenq RR, et al (2019)

pldist: ecological dissimilarities for paired and longitudinal microbiome association analysis.

Bioinformatics (Oxford, England) pii:5341424 [Epub ahead of print].

MOTIVATION: The human microbiome is notoriously variable across individuals, with a wide range of 'healthy' microbiomes. Paired and longitudinal studies of the microbiome have become increasingly popular as a way to reduce unmeasured confounding and to increase statistical power by reducing large inter-subject variability. Statistical methods for analyzing such datasets are scarce.

RESULTS: We introduce a paired UniFrac dissimilarity that summarizes within-individual (or within-pair) shifts in microbiome composition and then compares these compositional shifts across individuals (or pairs). This dissimilarity depends on a novel transformation of relative abundances, which we then extend to more than two time points and incorporate into several phylogenetic and non-phylogenetic dissimilarities. The data transformation and resulting dissimilarities may be used in a wide variety of downstream analyses, including ordination analysis and distance-based hypothesis testing. Simulations demonstrate that tests based on these dissimilarities retain appropriate type 1 error and high power. We apply the method in two real datasets.

The R package pldist is available on GitHub at

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RevDate: 2019-03-07

Salvucci E (2019)

The human-microbiome superorganism and its modulation to restore health.

International journal of food sciences and nutrition [Epub ahead of print].

Microbiome is the community of microorganism that co-live with a host. The human being is the result of the integration of its genome and the coexistence with millions of microorganisms throughout its evolutionary history. Human-microbiome association can be considered a step of integration in evolution, constituting a superorganism. Many emergent diseases are related to the loss of part of this microbiome and its restoration can be achieved by different strategies. Gut microbiome imbalance is particularly associated with numerous inflammatory, immune and nervous system-related diseases by a communication pathway called microbiome-brain axis. Modulation of microbiome by administering prebiotics, like arabinoxylans, and synbiotics is a plausible treatment for dysbiosis, the regulation of neurotransmitters and alleviation of neurological manifestations.

RevDate: 2019-04-11

Rego S, Dagan-Rosenfeld O, Bivona SA, et al (2019)

Much ado about nothing: A qualitative study of the experiences of an average-risk population receiving results of exome sequencing.

Journal of genetic counseling, 28(2):428-437.

The increasing availability of exome sequencing to the general ("healthy") population raises questions about the implications of genomic testing for individuals without suspected Mendelian diseases. Little is known about this population's motivations for undergoing exome sequencing, their expectations, reactions, and perceptions of utility. In order to address these questions, we conducted in-depth semi-structured interviews with 12 participants recruited from a longitudinal multi-omics profiling study that included exome sequencing. Participants were interviewed after receiving exome results, which included Mendelian disease-associated pathogenic and likely pathogenic variants, pharmacogenetic variants, and risk assessments for multifactorial diseases such as type 2 diabetes. The primary motivation driving participation in exome sequencing was personal curiosity. While they reported feeling validation and relief, participants were frequently underwhelmed by the results and described having expected more from exome sequencing. All participants reported discussing the results with at least some family, friends, and healthcare providers. Participants' recollection of the results returned to them was sometimes incorrect or incomplete, in many cases aligning with their perceptions of their health risks when entering the study. These results underscore the need for different genetic counseling approaches for generally healthy patients undergoing exome sequencing, in particular the need to provide anticipatory guidance to moderate participants' expectations. They also provide a preview of potential challenges clinicians may face as genomic sequencing continues to scale-up in the general population despite a lack of full understanding of its impact.

RevDate: 2019-04-05

Haahtela T (2019)

A biodiversity hypothesis.

Allergy [Epub ahead of print].

Biodiversity hypothesis states that contact with natural environments enriches the human microbiome, promotes immune balance and protects from allergy and inflammatory disorders. We are protected by two nested layers of biodiversity, microbiota of the outer layer (soil, natural waters, plants, animals) and inner layer (gut, skin, airways). The latter inhabits our body and is colonized from the outer layer. Explosion of human populations along with cultural evolution is profoundly changing our environment and lifestyle. Adaptive immunoregulatory circuits and dynamic homeostasis are at stake in the newly emerged urban surroundings. In allergy, and chronic inflammatory disorders in general, exploring the determinants of immunotolerance is the key for prevention and more effective treatment. Loss of immunoprotective factors, derived from nature, is a new kind of health risk poorly acknowledged until recently. The paradigm change has been implemented in the Finnish allergy programme (2008-2018), which emphasized tolerance instead of avoidance. The first results are promising, as allergy burden has started to reduce. The rapidly urbanizing world is facing serious biodiversity loss with global warming, which are interconnected. Biodiversity hypothesis of health and disease has societal impact, for example, on city planning, food and energy production and nature conservation. It has also a message for individuals for health and well-being: take nature close, to touch, eat, breathe, experience and enjoy. Biodiverse natural environments are dependent on planetary health, which should be a priority also among health professionals.

RevDate: 2019-03-05

Wallace DJ, Sayre NL, Patterson TT, et al (2019)

Spinal cord injury and the human microbiome: beyond the brain-gut axis.

Neurosurgical focus, 46(3):E11.

In addition to standard management for the treatment of the acute phase of spinal cord injury (SCI), implementation of novel neuroprotective interventions offers the potential for significant reductions in morbidity and long-term health costs. A better understanding of the systemic changes after SCI could provide insight into mechanisms that lead to secondary injury. An emerging area of research involves the complex interplay of the gut microbiome and the CNS, i.e., a brain-gut axis, or perhaps more appropriately, a CNS-gut axis. This review summarizes the relevant literature relating to the gut microbiome and SCI. Experimental models in stroke and traumatic brain injury demonstrate the bidirectional communication of the CNS to the gut with postinjury dysbiosis, gastrointestinal-associated lymphoid tissue-mediated neuroinflammatory responses, and bacterial-metabolite neurotransmission. Similar findings are being elucidated in SCI as well. Experimental interventions in these areas have shown promise in improving functional outcomes in animal models. This commensal relationship between the human body and its microbiome, particularly the gut microbiome, represents an exciting frontier in experimental medicine.

RevDate: 2019-03-29
CmpDate: 2019-03-21

Meyer F, Bremges A, Belmann P, et al (2019)

Assessing taxonomic metagenome profilers with OPAL.

Genome biology, 20(1):51 pii:10.1186/s13059-019-1646-y.

The explosive growth in taxonomic metagenome profiling methods over the past years has created a need for systematic comparisons using relevant performance criteria. The Open-community Profiling Assessment tooL (OPAL) implements commonly used performance metrics, including those of the first challenge of the initiative for the Critical Assessment of Metagenome Interpretation (CAMI), together with convenient visualizations. In addition, we perform in-depth performance comparisons with seven profilers on datasets of CAMI and the Human Microbiome Project. OPAL is freely available at .

RevDate: 2019-03-08

Piersigilli F, Lam TT, Vernocchi P, et al (2019)

Identification of new biomarkers of bronchopulmonary dysplasia using metabolomics.

Metabolomics : Official journal of the Metabolomic Society, 15(2):20 pii:10.1007/s11306-019-1482-9.

OBJECTIVE: To identify new biomarkers of bronchopulmonary dysplasia (BPD) in preterm neonates.

STUDY DESIGN: Metabolomic study of prospectively collected tracheal aspirate (TA) samples from preterm neonates admitted in 2 neonatal intensive care units measured by a mass spectroscopy-based assay and analysed using partial least squares-discriminant analysis.

RESULTS: We evaluated 160 TA samples from 68 neonates, 44 with BPD and 24 without BPD in the first week of life. A cluster of 53 metabolites was identified as characteristic of BPD, with 18 select metabolites being highly significant in the separation of BPD versus No BPD. To control for the gestational age (GA) differences, we did a sub-group analyses, and noted that the amino acids histidine, glutamic acid, citrulline, glycine and isoleucine levels were higher in neonates with BPD. In addition, acylcarnitines C16-OH and C18:1-OH were also higher in neonates who developed BPD, but especially in the most preterm infants (neonates with GA < 27 weeks).

CONCLUSION: Metabolomics is a promising approach to identify novel specific biomarkers for BPD.

RevDate: 2019-03-06

Reid G (2019)

Disentangling What We Know About Microbes and Mental Health.

Frontiers in endocrinology, 10:81.

Much has been written in recent years about the gut-brain axis. Exciting pilot studies suggest probiotic applications to the gut can reduce anxiety and depression via the vagus nerve. But not to diminish such findings, much still needs to be considered, including the fact that the vagus nerve links to many other body sites that also host a microbiome. Questions remain that touch the core of being human: (i) Do our microbes influence happiness and to what extent? (ii) What components of the gut microbiota and their function, including as it relates to mental health, are critical and how do they differ between agile, fit hunter gatherers and obese westerners or Danes described as the happiest people on the planet? (iii) What role do environmental pollutants play in this microbes-host ecosystem? While approaching life from a reductionist perspective has a long history in science, we need to try to interrogate these health and disease issues from a wider perspective. For verification of a link between the gut microbiota and brain, and to test new therapies, human studies are needed, and are long overdue.

RevDate: 2019-03-03

Song Z, Wang X, Zhou X, et al (2019)

Taxonomic Distribution of FosB in Human-Microbiota and Activity Comparison of Fosfomycin Resistance.

Frontiers in microbiology, 10:200.

FosB, a Mg2+ dependent thioltransferase, confers antibiotic resistance to fosfomycin through enzymatic drug inactivation. Among all antibiotic resistant proteins in the Antibiotic Resistance Genes Database and the Comprehensive Antibiotic Resistance Database, FosB is within 5% of the most number of ARPs identified in Human Microbiome Project reference database but mainly distributed in limited genera, i.e., 122 of total 133 FosB homologues are found from Bacillus and Staphylococcus. Furthermore, these FosB sequences could be divided into three clusters based on their phylogenetic relationship, i.e., two groups of FosB were mainly from Bacillus, and another was mainly from Staphylococcus. Finally, we confirmed that FosB from the group of Staphylococcus presented the highest resistance ability to fosfomycin by in silico and in vitro comparisons. In summary, this study elaborates the specific taxonomic characteristics and resistant abilities of FosB in human microbiota, which might help in developing more promising fosfomycin-like antibiotics.

RevDate: 2019-02-27

Shan Y, Wu W, Fan W, et al (2019)

House dust microbiome and human health risks.

International microbiology : the official journal of the Spanish Society for Microbiology pii:10.1007/s10123-019-00057-5 [Epub ahead of print].

People spend a lot of time indoors and the indoor microbiome is a major part of the environment that we are exposed to. However, awareness of the exposure to the indoor microbiome and its health effects remains poor. Outdoor environment (soil and air), indoor sources (ventilation, dampness and building materials), human occupants, and pets compose the indoor microbial community. It has been estimated that up to 500-1000 different species can be present in house dust. House dust is a major source and reservoir of indoor microbiome, which influences human microbiome and determines health and disease. Herein, we review the origins and the components of the fungal and bacterial communities in house dust and their possible effect on human health, in particular on allergic disorders, intestinal microbiome, and immune responses. We expect to lay a solid foundation for the further study on the mechanisms of how the house dust microbes interact with the host microbiome and the human immune system.

RevDate: 2019-03-14

Falony G, Vandeputte D, Caenepeel C, et al (2019)

The human microbiome in health and disease: hype or hope.

Acta clinica Belgica, 74(2):53-64.

OBJECTIVES: The prognostic, diagnostic, and therapeutic potential of the human gut microbiota is widely recognised. However, translation of microbiome findings to clinical practice is challenging. Here, we discuss current knowledge and applications in the field.

METHODS: We revisit some recent advances in the field of faecal microbiome analyses with a focus on covariate analyses and ecological interpretation.

RESULTS: Population-level characterization of gut microbiota variation among healthy volunteers has allowed identifying microbiome covariates required for clinical studies. Currently, microbiome research is moving from relative to quantitative approaches that will shed a new light on microbiota-host interactions in health and disease.

CONCLUSIONS: Covariate characterization and technical advances increase reproducibility of microbiome research. Targeted in vitro/in vivo intervention studies will accelerate clinical implementation of microbiota findings.

RevDate: 2019-04-18

NIH Human Microbiome Portfolio Analysis Team (2019)

A review of 10 years of human microbiome research activities at the US National Institutes of Health, Fiscal Years 2007-2016.

Microbiome, 7(1):31 pii:10.1186/s40168-019-0620-y.

The National Institutes of Health (NIH) is the primary federal government agency for biomedical research in the USA. NIH provides extensive support for human microbiome research with 21 of 27 NIH Institutes and Centers (ICs) currently funding this area through their extramural research programs. This analysis of the NIH extramural portfolio in human microbiome research briefly reviews the early history of this field at NIH, summarizes the program objectives and the resources developed in the recently completed 10-year (fiscal years 2007-2016) $215 M Human Microbiome Project (HMP) program, evaluates the scope and range of the $728 M NIH investment in extramural human microbiome research activities outside of the HMP over fiscal years 2012-2016, and highlights some specific areas of research which emerged from this investment. This analysis closes with a few comments on the technical needs and knowledge gaps which remain for this field to be able to advance over the next decade and for the outcomes of this research to be able to progress to microbiome-based interventions for treating disease and supporting health.

RevDate: 2019-04-18

2017 NIH-wide microbiome workshop writing team (2019)

2017 NIH-wide workshop report on "The Human Microbiome: Emerging Themes at the Horizon of the 21st Century".

Microbiome, 7(1):32 pii:10.1186/s40168-019-0627-4.

The National Institutes of Health (NIH) organized a three-day human microbiome research workshop, August 16-18, 2017, to highlight the accomplishments of the 10-year Human Microbiome Project program, the outcomes of the investments made by the 21 NIH Institutes and Centers which now fund this area, and the technical challenges and knowledge gaps which will need to be addressed in order for this field to advance over the next 10 years. This report summarizes the key points in the talks, round table discussions, and Joint Agency Panel from this workshop.

RevDate: 2019-02-27

Ma Z, L Li (2018)

Semen Microbiome Biogeography: An Analysis Based on a Chinese Population Study.

Frontiers in microbiology, 9:3333.

Investigating inter-subject heterogeneity (or spatial distribution) of human semen microbiome diversity is of important significance. Theoretically, the spatial distribution of biodiversity constitutes the core of microbiome biogeography. Practically, the inter-subject heterogeneity is crucial for understanding the normal (healthy) flora of semen microbiotas as well as their possible changes associated with abnormal fertility. In this article, we analyze the scaling (changes) of semen microbiome diversity across individuals with DAR (diversity-area relationship) analysis, a recent extension to classic SAR (species-area relationship) law in biogeography and ecology. Specifically, the unit of "area" is individual subject, and the microbial diversity in seminal fluid of an individual (area) is assessed via metagenomic DNA sequencing technique and measured in the Hill numbers. The DAR models were then fitted to the accrued diversity across different number of individuals (area size). We further tested the difference in DAR parameters among the healthy, subnormal, and abnormal microbiome samples in terms of their fertility status based on a cross-sectional study of a Chinese cohort. Given that no statistically significant differences in the DAR parameters were detected among the three groups, we built unified DAR models for semen microbiome by combining the healthy, subnormal, and abnormal groups. The model parameters were used to (i) estimate the microbiome diversity scaling in a population (cohort), and construct the so-termed DAR profile; (ii) predict/construct the maximal accrual diversity (MAD) profile in a population; (iii) estimate the pair-wise diversity overlap (PDO) between two individuals and construct the PDO profile; (iv) assess the ratio of individual diversity to population (RIP) accrual diversity. The last item (RIP) is a new concept we propose in this study, which is essentially a ratio of local diversity to regional or global diversity (LRD/LGD), applicable to general biodiversity investigation beyond human microbiome.

RevDate: 2019-03-29

McSkimming DI, Banack HR, Genco R, et al (2019)


American journal of epidemiology, 188(4):807-808.

RevDate: 2019-03-14

De Filippis F, Pasolli E, Tett A, et al (2019)

Distinct Genetic and Functional Traits of Human Intestinal Prevotella copri Strains Are Associated with Different Habitual Diets.

Cell host & microbe, 25(3):444-453.e3.

The role of intestinal Prevotella species in human health is controversial, with both positive and negative associations. Strain-level diversity may contribute to discrepancies in genus and species associations with health and disease. We dissected the gut metagenomes of Italians with varying dietary habits, investigating the presence of distinct Prevotella copri strains. Fiber-rich diets were linked to P. copri types with enhanced potential for carbohydrate catabolism. P. copri strains associated with an omnivore diet had a higher prevalence of the leuB gene-involved in branched-chain amino acid biosynthesis-a risk factor for glucose intolerance and type 2 diabetes. These P. copri pangenomes were compared to existing cohorts, providing evidence of distinct gene repertoires characterizing different P. copri populations, with drug metabolism and complex carbohydrate degradation significantly associated with Western and non-Western individuals, respectively. Strain-level P. copri diversity in gut microbiomes is affected by diet and should be considered when examining host-microbe associations.

RevDate: 2019-04-18
CmpDate: 2019-04-18

Rogers GB, Ward J, Brown A, et al (2019)

Inclusivity and equity in human microbiome research.

Lancet (London, England), 393(10173):728-729.

RevDate: 2019-02-19

Araos R, EMC D'Agata (2019)

The human microbiota and infection prevention.

Infection control and hospital epidemiology pii:S0899823X1900028X [Epub ahead of print].

The human microbiome participates in numerous aspects of human physiology and disease states. Recently, studies have begun to explore the role of the microbiome in colonization, infection and transmission of pathogens. This review provides a summary of the methodological principles used in microbiome studies and the published evidence of the impact of microbiome dysbiosis in infection prevention.

RevDate: 2019-04-08
CmpDate: 2019-04-08

Li H, Zhou XY, Yang XR, et al (2019)

Spatial and seasonal variation of the airborne microbiome in a rapidly developing city of China.

The Science of the total environment, 665:61-68.

Exposure to airborne microbes (AM) can affect the human microbiome and has various consequences for human health. Investigating the profiles of AM and the potential bacterial pathogens within, along with the factors influencing their community, is pivotal for understanding the impact of AM on human health. In this study, we collected AM during spring and summer from 11 sites with various levels of urbanization in the city of Xiamen, China. Bacterial community compositions of the AM were determined based on 16S rRNA gene amplicon sequencing. Firmicutes and Proteobacteria were the predominating phyla in the airborne bacterial communities, and a higher (P < 0.05) diversity of AM was found during the summer as compared to the spring. Significant differences in the community structure of the AM and the potential bacterial pathogens within airborne microbes were observed among the seasons and the sites with different levels of urbanization. Increases and/or decreases in the abundance of Bacillus and Acinetobacter could explain a major part of the variations in the AM community compositions. The proportion of potential bacterial pathogens during the summer was significantly higher (P < 0.01) than in the spring, and the relative abundance of several bacterial pathogens (i.e. Burkholderia multivoran, Enterococcus faecium and Streptococcus thermophilus) related to human diseases (39.8% of total pathogens on average) increased with increasing urbanization levels, suggesting that urbanization can increase the AM-associated human health risk.

RevDate: 2019-02-21

Bai J, Jhaney I, Daniel G, et al (2019)

Pilot Study of Vaginal Microbiome Using QIIME 2™ in Women With Gynecologic Cancer Before and After Radiation Therapy.

Oncology nursing forum, 46(2):E48-E59.

OBJECTIVES: To characterize the vaginal microbiome using QIIME 2™ (Quantitative Insights Into Microbial Ecology 2) in women with gynecologic cancer.

SAMPLE &AMP; SETTING: 19 women with gynecologic cancer before and after radiation therapy at a comprehensive cancer center in Atlanta, Georgia.

METHODS &AMP; VARIABLES: This pilot study analyzed vaginal microbiome communities using a microbiome analysis pipeline, beginning with 16S rRNA gene sequencing and processing through use of a bioinformatics pipeline to downstream microbial statistical analysis.

RESULTS: The findings showed the methods to be robust, and most women with gynecologic cancer showed depletion of Lactobacillus. Compared to those pre-radiation therapy, women post-radiation therapy showed higher abundances of Mobiluncus, Atopobium, and Prevotella but lower abundances of Lactobacillus, Gardnerella, and Peptostreptococcus, which are associated with bacterial vaginosis.

IMPLICATIONS FOR NURSING: This study presents the fundamentals of human microbiome data collection and analysis methods to inform nursing science. Assessing the vaginal microbiome provides a potential pathway to develop interventions to ameliorate dysbiosis of the vaginal microbiome.

RevDate: 2019-04-18

Luo Z, Li M, Wu Y, et al (2019)

Systemic translocation of Staphylococcus drives autoantibody production in HIV disease.

Microbiome, 7(1):25 pii:10.1186/s40168-019-0646-1.

BACKGROUND: Increased autoreactive antibodies have been reported in HIV disease; however, the mechanism accounting for autoantibody induction in HIV remains unknown.

RESULTS: Herein, we show that seasonal influenza vaccination induces autoantibody production (e.g., IgG anti-nuclear antibody (ANA) and anti-double-stranded DNA antibody (anti-dsDNA)) in some viral-suppressed antiretroviral therapy (ART)-treated HIV+ subjects, but not in healthy controls. These autoantibodies were not derived from antigen-specific B cells but from activated "bystander" B cells analyzed by single-cell assay and by study of purified polyclonal ANAs from plasma. To explore the mechanism of autoantibody generation in HIV+ subjects, plasma level of microbial products, gene expression profile of B cells, and B cell receptor (BCR) repertoires were analyzed. We found that autoantibody production was associated with increased plasma level of microbial translocation; the patients with high autoantibodies had skewed B cell repertoires and upregulation of genes related to innate immune activation in response to microbial translocation. By analyzing circulating microbial 16S rDNA in plasma, the relative abundance of Staphylococcus was found to be associated with autoantibody production in HIV+ subjects. Finally, we found that injection of heat-killed Staphylococcus aureus promoted germinal center B cell responses and autoantibody production in mice, consistent with the notion that autoantibody production in HIV+ patients is triggered by microbial products.

CONCLUSIONS: Our results showed that translocation of Staphylococcus can promote B cell activation through enhancing germinal center response and induces autoantibody production. It uncovers a potential mechanism linking microbial translocation and autoimmunity in HIV+ disease and provides a strong rationale for targeting Staphylococcus to prevent autoantibody production.

RevDate: 2019-02-14

Shkoporov AN, C Hill (2019)

Bacteriophages of the Human Gut: The "Known Unknown" of the Microbiome.

Cell host & microbe, 25(2):195-209.

The human gut microbiome is a dense and taxonomically diverse consortium of microorganisms. While the bacterial components of the microbiome have received considerable attention, comparatively little is known about the composition and physiological significance of human gut-associated bacteriophage populations (phageome). By extrapolating our knowledge of phage-host interactions from other environments, one could expect that >1012 viruses reside in the human gut, and we can predict that they play important roles in regulating the complex microbial networks operating in this habitat. Before delving into their function, we need to first overcome the challenges associated with studying and characterizing the phageome. In this Review, we summarize the available methods and main findings regarding taxonomic composition, community structure, and population dynamics in the human gut phageome. We also discuss the main challenges in the field and identify promising avenues for future research.

RevDate: 2019-04-22
CmpDate: 2019-04-22

Reddel S, Putignani L, F Del Chierico (2019)

The Impact of Low-FODMAPs, Gluten-Free, and Ketogenic Diets on Gut Microbiota Modulation in Pathological Conditions.

Nutrients, 11(2): pii:nu11020373.

The gut microbiota performs several essential protective, structural, and metabolic functions for host health. The maintenance of a beneficial microbiota requires a homeostatic equilibrium within microbial communities, and between the microorganisms and the host. The gut microbiota composition may be affected by external factors, among them diet habits may be considered most important. In some pathological conditions such as irritable bowel syndrome (IBS), celiac disease (CD), or neurological disorders (ND), specific dietary regimens as low-fermentable, oligo-, di-, mono-saccharides and polyols (FODMAPs), ketogenic (KD), and gluten-free (GFD) diets are considered therapeutic. These kinds of diets are characterized by a reduction or exclusion of a specific nutrient from the entire dietary pattern. Despite these alimentary regimens showing beneficial effects on disease symptoms, they can affect microbiota composition, especially if they are protracted for a long time. To date, only a few studies have reported the effects of these diets on gut microbiota. In this review, we discuss the effects of low-FODMAPs, KD, and GFD on gut microbiota modulation in pathological conditions, advancing the possibility of depicting a balanced diet and developing personalized dietary intervention protocols.

RevDate: 2019-04-05

Blakeley-Ruiz JA, Erickson AR, Cantarel BL, et al (2019)

Metaproteomics reveals persistent and phylum-redundant metabolic functional stability in adult human gut microbiomes of Crohn's remission patients despite temporal variations in microbial taxa, genomes, and proteomes.

Microbiome, 7(1):18 pii:10.1186/s40168-019-0631-8.

BACKGROUND: The gut microbiome plays a fundamental role in the human host's overall health by contributing key biological functions such as expanded metabolism and pathogen defense/immune control. In a healthy individual, the gut microbiome co-exists within the human host in a symbiotic, non-inflammatory relationship that enables mutual benefits, such as microbial degradation of indigestible food products into small molecules that the host can utilize, and enhanced pathogen defense. In abnormal conditions, such as Crohn's disease, this favorable metabolic relationship breaks down and a variety of undesirable activities result, including chronic inflammation and other health-related issues. It has been difficult, however, to elucidate the overall functional characteristics of this relationship because the microbiota can vary substantially in composition for healthy humans and possibly even more in individuals with gut disease conditions such as Crohn's disease. Overall, this suggests that microbial membership composition may not be the best way to characterize a phenotype. Alternatively, it seems to be more informative to examine and characterize the functional composition of a gut microbiome. Towards that end, this study examines 25 metaproteomes measured in several Crohn's disease patients' post-resection surgery across the course of 1 year, in order to examine persistence of microbial taxa, genes, proteins, and metabolic functional distributions across time in individuals whose microbiome might be more variable due to the gut disease condition.

RESULTS: The measured metaproteomes were highly personalized, with all the temporally-related metaproteomes clustering most closely by individual. In general, the metaproteomes were remarkably distinct between individuals and to a lesser extent within individuals. This prompted a need to characterize the metaproteome at a higher functional level, which was achieved by annotating identified protein groups with KEGG orthologous groups to infer metabolic modules. At this level, similar and redundant metabolic functions across multiple phyla were observed across time and between individuals. Tracking through these various metabolic modules revealed a clear path from carbohydrate, lipid, and amino acid degradation to central metabolism and finally the production of fermentation products.

CONCLUSIONS: The human gut metaproteome can vary quite substantially across time and individuals. However, despite substantial intra-individual variation in the metaproteomes, there is a clear persistence of conserved metabolic functions across time and individuals. Additionally, the persistence of these core functions is redundant across multiple phyla but is not always observable in the same sample. Finally, the gut microbiome's metabolism is not driven by a set of discrete linear pathways but a web of interconnected reactions facilitated by a network of enzymes that connect multiple molecules across multiple pathways.

RevDate: 2019-02-08

Healy CM, GP Moran (2019)

The microbiome and oral cancer: More questions than answers.

Oral oncology, 89:30-33.

Recent advances in DNA sequencing technology have facilitated rapid advances in the analysis of the human microbiome and its role in human disease. Several studies have now shown that OSCC and some oral premalignant conditions are associated with alterations in the oral microbiome. These studies raise questions regarding the role of the oral microbiome in the progression of oral malignancies and whether microbiome change is a significant risk factor in the development of oral cancer. This short review summarises current knowledge in the field and highlights questions that require further investigation.

RevDate: 2019-03-17

Bekker V, Zwittink RD, Knetsch CW, et al (2019)

Dynamics of the Gut Microbiota in Children Receiving Selective or Total Gut Decontamination Treatment during Hematopoietic Stem Cell Transplantation.

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation pii:S1083-8791(19)30095-3 [Epub ahead of print].

Bloodstream infections and graft-versus-host disease are common complications after hematopoietic stem cell transplantation (HSCT) procedures, associated with the gut microbiota that acts as a reservoir for opportunistic pathogens. Selective gut decontamination (SGD) and total gut decontamination (TGD) during HSCT have been associated with a decreased risk of developing these complications after transplantation. However, because studies have shown conflicting results, the use of these treatments remains subject of debate. In addition, their impact on the gut microbiota is not well studied. The aim of this study was to elucidate the dynamics of the microbiota during and after TGD and to compare these with the dynamics of SGD. In this prospective, observational, single-center study fecal samples were longitudinally collected from 19 children eligible for allogenic HSCT (TGD, n=12; SGD, n=7), weekly during hospital admission and monthly after discharge. In addition, fecal samples were collected from 3 family stem cell donors. Fecal microbiota structure of patients and donors was determined by 16S rRNA gene amplicon sequencing. Microbiota richness and diversity markedly decreased during SGD and TGD and gradually increased after cessation of decontamination treatment. During SGD, gut microbiota composition was relatively stable and dominated by Bacteroides, whereas it showed high inter- and intraindividual variation and low Bacteroides abundance during TGD. In some children TGD allowed the genera Enterococcus and Streptococcus to thrive during treatment. A gut microbiota dominated by Bacteroides was associated with increased predicted activity of several metabolic processes. Comparing the microbiota of recipients and their donors indicated that receiving an SCT did not alter the patient's microbiota to become more similar to that of its donor. Overall, our findings indicate that SGD and TGD affect gut microbiota structure in a treatment-specific manner. Whether these treatments affect clinical outcomes via interference with the gut microbiota needs to be further elucidated.

RevDate: 2019-02-10

Lu H, Ren Z, Li A, et al (2019)

Tongue coating microbiome data distinguish patients with pancreatic head cancer from healthy controls.

Journal of oral microbiology, 11(1):1563409 pii:1563409.

Background: The microbiota plays a critical role in the process of human carcinogenesis. Pancreatic head carcinoma (PHC)-associated tongue coating microbiome dysbiosis has not yet been clearly defined.Objective: Our aim is to reveal the bacterial composition shifts in the microbiota of the tongue coat of PHC patients.Design: The tongue coating microbiota was analyzed in 30 PHC patients and 25 healthy controls using 16S rRNA gene sequencing technology.Results: The microbiome diversity of the tongue coat in PHC patients was significantly increased, as shown by the Shannon, Simpson, inverse Simpson, Obs and incidence-based coverage estimators. Principal component analysis revealed that PHC patients were colonized by remarkably different tongue coating microbiota than healthy controls and liver cancer patients. Linear discriminant analysis effect size revealed that Leptotrichia, Fusobacterium,Rothia, Actinomyces, Corynebacterium, Atopobium, Peptostreptococcus, Catonella, Oribacterium, Filifactor, Campylobacter, Moraxella and Tannerella were overrepresented in the tongue coating of PHC patients, and Haemophilus, Porphyromonas and Paraprevotella were enriched in the tongue coating microbiota of healthy controls. Strikingly, Haemophilus, Porphyromonas, Leptotrichia and Fusobacterium could distinguish PHC patients from healthy subjects, and Streptococcus and SR1 could distinguish PHC patients from liver cancer patients. Conclusions: These findings identified the microbiota dysbiosis of the tongue coat in PHC patients, and provide insight into the association between the human microbiome and pancreatic cancer.

RevDate: 2019-03-13

Morales E, Chen J, KL Greathouse (2019)

Compositional Analysis of the Human Microbiome in Cancer Research.

Methods in molecular biology (Clifton, N.J.), 1928:299-335.

Gut microbial composition has shown to be associated with obesity, diabetes mellitus, inflammatory bowel disease, colitis, autoimmune disorders, and cancer, among other diseases. Microbiome research has significantly evolved through the years and continues to advance as we develop new and better strategies to more accurately measure its composition and function. Careful selection of study design, inclusion and exclusion criteria of participants, and methodology are paramount to accurately analyze microbial structure. Here we present the most up-to-date available information on methods for gut microbial collection and analysis.

RevDate: 2019-04-12
CmpDate: 2019-04-12

Forster SC, Kumar N, Anonye BO, et al (2019)

A human gut bacterial genome and culture collection for improved metagenomic analyses.

Nature biotechnology, 37(2):186-192.

Understanding gut microbiome functions requires cultivated bacteria for experimental validation and reference bacterial genome sequences to interpret metagenome datasets and guide functional analyses. We present the Human Gastrointestinal Bacteria Culture Collection (HBC), a comprehensive set of 737 whole-genome-sequenced bacterial isolates, representing 273 species (105 novel species) from 31 families found in the human gastrointestinal microbiota. The HBC increases the number of bacterial genomes derived from human gastrointestinal microbiota by 37%. The resulting global Human Gastrointestinal Bacteria Genome Collection (HGG) classifies 83% of genera by abundance across 13,490 shotgun-sequenced metagenomic samples, improves taxonomic classification by 61% compared to the Human Microbiome Project (HMP) genome collection and achieves subspecies-level classification for almost 50% of sequences. The improved resource of gastrointestinal bacterial reference sequences circumvents dependence on de novo assembly of metagenomes and enables accurate and cost-effective shotgun metagenomic analyses of human gastrointestinal microbiota.

RevDate: 2019-02-14

Du Toit A (2019)

Expanding diversity of the human microbiome.

Nature reviews. Microbiology, 17(3):126.


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.

Electronic Scholarly Publishing
21454 NE 143rd Street
Woodinville, WA 98077

E-mail: RJR8222 @

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).


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


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 )