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Bibliography on: Microbiome

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ESP: PubMed Auto Bibliography 25 Sep 2018 at 01:38 Created: 


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

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

Citations The Papers (from PubMed®)

RevDate: 2018-09-24

Liu Y, Tran DQ, JM Rhoads (2018)

Probiotics in Disease Prevention and Treatment.

Journal of clinical pharmacology, 58 Suppl 10:S164-S179.

Few treatments for human diseases have received as much investigation in the past 20 years as probiotics. In 2017, English-language meta-analyses totaling 52 studies determined the effect of probiotics on conditions ranging from necrotizing enterocolitis and colic in infants to constipation, irritable bowel syndrome, and hepatic encephalopathy in adults. The strongest evidence in favor of probiotics lies in the prevention or treatment of 5 disorders: necrotizing enterocolitis, acute infectious diarrhea, acute respiratory tract infections, antibiotic-associated diarrhea, and infant colic. Probiotic mechanisms of action include the inhibition of bacterial adhesion; enhanced mucosal barrier function; modulation of the innate and adaptive immune systems (including induction of tolerogenic dendritic cells and regulatory T cells); secretion of bioactive metabolites; and regulation of the enteric and central nervous systems. Future research is needed to identify the optimal probiotic and dose for specific diseases, to address whether the addition of prebiotics (to form synbiotics) would enhance activity, and to determine if defined microbial communities would provide benefit exceeding that of single-species probiotics.

RevDate: 2018-09-24

Li J, Tang M, Y Xue (2018)

Review of the effects of silver nanoparticle exposure on gut bacteria.

Journal of applied toxicology : JAT [Epub ahead of print].

Gut bacteria are involved in regulating several important physiological functions in the host, and intestinal dysbacteriosis plays an important role in several human diseases, including intestinal, metabolic and autoimmune disorders. Although silver nanoparticles (AgNPs) are increasingly being incorporated into medical and consumer products due to their unique physicochemical properties, studies have indicated their potential to affect adversely the gut bacteria. In this review, we focus on the biotoxicological effects of AgNPs entering the gastrointestinal tract and the relationship of these effects with important nanoscale properties. We discuss in detail the mechanisms underlying the bactericidal toxicity effects of AgNPs and explore the relationships between AgNPs, gut bacteria and disease. Finally, we highlight the need to focus on the negative effects of AgNPs usage to facilitate appropriate development of these particles.

RevDate: 2018-09-24

Simona C, Stefania V, Franco T, et al (2018)

Microbiome profiling in extremely acidic soils affected by hydrothermal fluids: the case of Solfatara Crater (Campi Flegrei, southern Italy).

FEMS microbiology ecology pii:5105751 [Epub ahead of print].

An integrated geochemical and microbiological investigation of soils from the Solfatara Crater (Campi Flegrei, southern Italy) demonstrated that interstitial soil gases dominated by CO2 and other typical hydrothermal gaseous species (e.g. H2S, CH4, ethane, benzene, alkenes and S-bearing organic compounds) influenced the composition of microbial communities. The relatively high concentrations of hydrothermal fluids permeating the soil produced acidic conditions and whitish deposits that characterize the Solfatara Crater floor. Archaea and Bacteria showed almost equal cell abundance (up to 3.2 x 107 and 4.2 x 107 cell/g, respectively) with relatively low levels of biodiversity and equitability in sites characterized by elevated temperatures (up to 70°C), very low pH values (up to 2.2) and reducing conditions. In these sites, high-throughput sequencing showed the marked selection of microorganisms, mainly affiliated with the genera Thermoplasma, Ferroplasma and Acidithiobacillus. A relatively high biodiversity and concomitant distinctive structure of the microbial community were observed in soils poorly affected by fumarolic emissions that were oxic and rich in organic matter.

RevDate: 2018-09-24

Miklavcic JJ, Badger TM, Bowlin AK, et al (2018)

Human Breast-Milk Feeding Enhances the Humoral and Cell-Mediated Immune Response in Neonatal Piglets.

The Journal of nutrition pii:5105885 [Epub ahead of print].

Background: The benefits of breastfeeding infants are well characterized, including those on the immune system. However, determining the mechanism by which human breast milk (HBM) elicits effects on immune response requires investigation in an appropriate animal model.

Objective: The primary aim of this study was to develop a novel porcine model and to determine the differential effects of feeding HBM and a commercial milk formula (MF) on immune response and gastrointestinal microbial colonization in a controlled environment.

Methods: Male piglets were fed HBM (n = 26) or MF (n = 26) from day 2 through day 21. Piglets were vaccinated (n = 9/diet group) with cholera toxin and cholera toxin subunit B (CTB) and tetanus toxoid at 21 d or were fed placebo (n = 6/diet group) and then weaned to a standard solid diet at the age of 21 d. Humoral and cell-mediated immune responses were assessed from blood on days 35 and 48. Immune response was further examined from tissues, including mesenteric lymph nodes (MLNs), Peyer's patches (PPs), and spleen. The colonization of gut microbiota was characterized from feces on days 16 and 49.

Results: Serum antibody titers in piglets fed HBM were 4-fold higher (P < 0.05) to CTB and 3-fold higher (P < 0.05) to tetanus toxoid compared with piglets fed MF on day 48. Compared with MF, the numbers of immunoglobulin A antibody-producing cells to CTB were 13-fold higher (P < 0.05) in MLNs and 11-fold higher (P < 0.05) in PPs in the HBM diet group on day 51. In addition, significantly increased T cell proliferation was observed in the HBM group relative to the MF group. Furthermore, microbial diversity in the HBM group was lower (P < 0.05) than in the MF group.

Conclusions: This porcine model appears to be valid for studying the effects of early postnatal diet on immune responses and the gastrointestinal microbiome. Our results lay the groundwork for future studies defining the role of infant diet on microbiota and immune function.

RevDate: 2018-09-24

Rubio LA (2018)

Possibilities of early life programming in broiler chickens via intestinal microbiota modulation.

Poultry science pii:5106131 [Epub ahead of print].

The strong selection in search for a higher growth rate in broilers has resulted in adverse effects such as metabolic disorders, low responsiveness of the immune system, and decreased resistance to pathogens. On the other hand, newly hatched chicks rely mostly on innate immune responses until their gut gets colonized with microbiota. In consequence, early access to active substances or bacteria (pre- and post-hatch) is particularly relevant here because in broilers much of the immune system development occurs early in life. Therefore, early stimulation of beneficial microflora is critical, as it affects, to a great extent, the entire life-span of an individual, and also because the nutritional manipulations of the gastrointestinal tract (GIT) microbiome to enhance productivity and health are rather limited by the resilience of the ecosystem once established in the chicken´s gut. Early life or developmental programming is based on the assumption that the development of diseases later in life can be modulated by perturbations or environmental exposures during critical pre- or early post-natal life. Substances such as plant derivatives, Na butyrate, pre- and probiotics, and β-glucans have been shown to induce beneficial microbiological and immunological changes within the GIT, and therefore are potential candidates to be used as tools to manipulate GIT functionality in the young chicken. Accordingly, substances as these might represent promising candidates to study intestinal microbiota/immune system modulation in broilers´ early stages of breeding. In ovo-delivered prebiotics and synbiotics have been shown to have no adverse effect on the development of the immune system in exposed chickens, while being able to affect lymphoid-organs' morphology in chickens. In ovo procedures have also been proposed as means of promoting a healthy microflora in embryonic guts and stimulating maturation of the cellular and humoral immune responses in central and peripheral immune organs, including those in the GIT. The purpose of this presentation is to discuss the potential usefulness of the instruments currently available to induce early life programming in broilers.

RevDate: 2018-09-24

Azad MB, Robertson B, Atakora F, et al (2018)

Human Milk Oligosaccharide Concentrations Are Associated with Multiple Fixed and Modifiable Maternal Characteristics, Environmental Factors, and Feeding Practices.

The Journal of nutrition pii:5105883 [Epub ahead of print].

Background: Human milk oligosaccharides (HMOs) shape the developing gut microbiome and influence immune function. Aside from genetic Secretor status, the factors influencing HMO synthesis and secretion are largely unknown.

Objective: We aimed to identify modifiable and nonmodifiable factors associated with HMO concentrations.

Methods: This prospective observational study included a representative subset of 427 mothers participating in the CHILD birth cohort (mean age: 33 y, 73% Caucasian). Breast milk was collected at 3-4 mo postpartum. Concentrations of 19 predominant HMOs were measured by rapid high-throughput HPLC. Secretor status was defined by the presence of 2'-fucosylactose. Associations with maternal, infant, and environmental factors were explored using multivariable regression. Breastfeeding duration was explored as a secondary outcome.

Results: Overall, 72% of mothers were Secretors and the mean ± SD duration of any breastfeeding was 12.8 ± 5.7 mo. HMO profiles were highly variable; total HMO concentrations varied 3.7-fold and individual HMOs varied 20- to >100-fold. Secretor mothers had higher total HMO concentrations than did non-Secretors (mean: 15.91 ± 2.80 compared with 8.94 ± 1.51 μmol/mL, P < 0.001) and all individual HMOs differed by Secretor status, except for disialyllacto-N-tetraose (DSLNT). Most HMO concentrations were lower in milk collected later in lactation, although some were higher including DSLNT and 3'-sialyllactose. Independent of Secretor status and lactation stage, seasonal and geographic variation was observed for several HMOs. Parity, ethnicity, and breastfeeding exclusivity also emerged as independent factors associated with some HMOs, whereas diet quality and mode of delivery did not. Together, these factors explained between 14% (for 6'-sialyllactose) and 92% (for 2'-fucosyllactose) of the observed variation in HMO concentrations. Lower concentrations of lacto-N-hexaose or fucodisialyllacto-N-hexaose were associated with earlier breastfeeding cessation.

Conclusions: HMO concentrations vary widely between mothers and are associated with multiple characteristics beyond genetic Secretor status, as well as feeding practices and environmental factors. Further research is warranted to determine how these associations affect infant health. This study was registered at as NCT03225534.

RevDate: 2018-09-24

Palmer-Young EC, Raffel TR, QS McFrederick (2018)

pH-mediated inhibition of a bumble bee parasite by an intestinal symbiont.

Parasitology pii:S0031182018001555 [Epub ahead of print].

Gut symbionts can augment resistance to pathogens by stimulating host-immune responses, competing for space and nutrients, or producing antimicrobial metabolites. Gut microbiota of social bees, which pollinate many crops and wildflowers, protect hosts against diverse infections and might counteract pathogen-related bee declines. Bumble bee gut microbiota, and specifically abundance of Lactobacillus 'Firm-5' bacteria, can enhance resistance to the trypanosomatid parasite Crithidia bombi. However, the mechanism underlying this effect remains unknown. We hypothesized that the Firm-5 bacterium Lactobacillus bombicola, which produces lactic acid, inhibits C. bombi via pH-mediated effects. Consistent with our hypothesis, L. bombicola spent medium inhibited C. bombi growth via reduction in pH that was both necessary and sufficient for inhibition. Inhibition of all parasite strains occurred within the pH range documented in honey bees, though sensitivity to acidity varied among strains. Spent medium was slightly more potent than HCl, d- and l-lactic acids for a given pH, suggesting that other metabolites also contribute to inhibition. Results implicate symbiont-mediated reduction in gut pH as a key determinant of trypanosomatid infection in bees. Future investigation into in vivo effects of gut microbiota on pH and infection intensity would test the relevance of these findings for bees threatened by trypanosomatids.

RevDate: 2018-09-24

Murakami T, Segawa T, Takeuchi N, et al (2018)

Metagenomic analyses highlight the symbiotic association between the glacier stonefly Andiperla willinki and its bacterial gut community.

Environmental microbiology [Epub ahead of print].

The glacier stonefly Andiperla willinki is the largest metazoan inhabiting the Patagonian glaciers. In this study, we analysed the gut microbiome of the aquatic nymphs by 16S rRNA gene amplicon and metagenomic sequencing. The bacterial gut community was consistently dominated by taxa typical of animal digestive tracts, such as Dysgonomonadaceae and Lachnospiraceae, as well as those generally indigenous to glacier environments, such as Polaromonas. Interestingly, the dominant Polaromonas phylotypes detected in the stonefly gut were almost never detected in the glacier surface habitat. Fluorescence in situ hybridization analysis revealed that the bacterial lineages typical of animal guts colonized the gut wall in a co-aggregated form, while Polaromonas cells were not included in the aggregates. Draft genomes of several dominant bacterial lineages were reconstructed from metagenomic datasets and indicated that the predominant Dysgonomonadaceae bacterium is capable of degrading various polysaccharides derived from host-ingested food, such as algae, and that other dominant bacterial lineages ferment saccharides liberated by the polysaccharide degradation. Our results suggest that the gut bacteria-host association in the glacier stonefly contributes to host nutrition as well as material cycles in the glacier environment. This article is protected by copyright. All rights reserved.

RevDate: 2018-09-24

Gӧrӧcs Z, Tamamitsu M, Bianco V, et al (2018)

A deep learning-enabled portable imaging flow cytometer for cost-effective, high-throughput, and label-free analysis of natural water samples.

Light, science & applications, 7:66 pii:67.

We report a deep learning-enabled field-portable and cost-effective imaging flow cytometer that automatically captures phase-contrast color images of the contents of a continuously flowing water sample at a throughput of 100 mL/h. The device is based on partially coherent lens-free holographic microscopy and acquires the diffraction patterns of flowing micro-objects inside a microfluidic channel. These holographic diffraction patterns are reconstructed in real time using a deep learning-based phase-recovery and image-reconstruction method to produce a color image of each micro-object without the use of external labeling. Motion blur is eliminated by simultaneously illuminating the sample with red, green, and blue light-emitting diodes that are pulsed. Operated by a laptop computer, this portable device measures 15.5 cm × 15 cm × 12.5 cm, weighs 1 kg, and compared to standard imaging flow cytometers, it provides extreme reductions of cost, size and weight while also providing a high volumetric throughput over a large object size range. We demonstrated the capabilities of this device by measuring ocean samples at the Los Angeles coastline and obtaining images of its micro- and nanoplankton composition. Furthermore, we measured the concentration of a potentially toxic alga (Pseudo-nitzschia) in six public beaches in Los Angeles and achieved good agreement with measurements conducted by the California Department of Public Health. The cost-effectiveness, compactness, and simplicity of this computational platform might lead to the creation of a network of imaging flow cytometers for large-scale and continuous monitoring of the ocean microbiome, including its plankton composition.

RevDate: 2018-09-24

Hernandez-Agreda A, Leggat W, TD Ainsworth (2018)

A Comparative Analysis of Microbial DNA Preparation Methods for Use With Massive and Branching Coral Growth Forms.

Frontiers in microbiology, 9:2146.

In the last two decades, over 100 studies have investigated the structure of the coral microbiome. However, as yet there are no standardized methods applied to sample preservation and preparation, with different studies using distinct methods. There have also been several comparisons made of microbiome data generated across different studies, which have not addressed the influence of the methodology employed over each of the microbiome datasets. Here, we assess three different preservation methods; salt saturated dimethyl sulfoxide (DMSO) - EDTA, snap freezing with liquid nitrogen and 4% paraformaldehyde solution, and two different preparation methodologies; bead beating and crushing, that have been applied to study the coral microbiome. We compare the resultant bacterial assemblage data for two coral growth forms, the massive coral Goniastrea edwardsi and the branching coral Isopora palifera. We show that microbiome datasets generated from differing preservation and processing protocols are comparable in composition (presence/absence). Significant discrepancies between preservation and homogenization methods are observed in structure (relative abundance), and in the occurrence and dominance of taxa, with rare (low abundance and low occurrence) phylotypes being the most variable fraction of the microbial community. Finally, we provide evidence to support chemical preservation with DMSO as effective as snap freezing samples for generating reliable and robust microbiome datasets. In conclusion, we recommend where possible a standardized preservation and extraction method be taken up by the field to provide the best possible practices for detailed assessments of symbiotic and conserved bacterial associations.

RevDate: 2018-09-24

Brandt J, M Albertsen (2018)

Investigation of Detection Limits and the Influence of DNA Extraction and Primer Choice on the Observed Microbial Communities in Drinking Water Samples Using 16S rRNA Gene Amplicon Sequencing.

Frontiers in microbiology, 9:2140.

In recent years, 16S rRNA gene amplicon sequencing has been widely adopted for analyzing the microbial communities in drinking water (DW). However, no comprehensive attempts have been made to illuminate the inherent method biases specifically relating to DW communities. In this study, we investigated the impact of DNA extraction and primer choice on the observed microbial community, and furthermore estimated the detection limit of the 16S rRNA gene amplicon sequencing in these experimental settings. Of the two DNA extraction kits investigated, the PowerWater DNA Isolation Kit resulted in higher yield, better reproducibility and more OTUs identified compared to the FastDNA SPIN Kit for Soil, which is also commonly used within DW microbiome research. The use of three separate primer-sets targeting the V1-3, V3-4, and V4 region of the 16S rRNA gene revealed large differences in OTU abundances, with some of the primers unable to detect entire phyla. Estimations of the detection limit were based on bacteria-free water samples (1 L) spiked with Escherichia coli cells in different concentrations [101-106 cells/ml]. E.coli could be detected in all samples, however, samples with ∼101 cells/ml had several contaminating OTUs constituting approximately 8% of the read abundances. Based on our findings, we recommend using the PowerWater DNA Isolation Kit for DNA extraction in combination with PCR amplification of the V3-4 or V4 region for DW samples if a broad overview of the microbial community is to be obtained.

RevDate: 2018-09-23

Liu Y, Baba Y, Ishimoto T, et al (2018)

Progress in characterizing the linkage between Fusobacterium nucleatum and gastrointestinal cancer.

Journal of gastroenterology pii:10.1007/s00535-018-1512-9 [Epub ahead of print].

Microbiome research is a rapidly advancing field in human cancers. Fusobacterium nucleatum is an oral bacterium, indigenous to the human oral cavity, that plays a role in periodontal disease. Recent studies have found that F. nucleatum can promote gastrointestinal tumor progression and affect the prognosis of the disease. In addition, F. nucleatum may contribute to the chemo-resistance of gastrointestinal cancers. This review summarizes recent progress in the pathogenesis of F. nucleatum and its impact on gastrointestinal cancer.

RevDate: 2018-09-23

Andreassen M, Rudi K, Angell IL, et al (2018)

Allergen Immunization Induces Major Changes in Microbiota Composition and Short-Chain Fatty Acid Production in Different Gut Segments in a Mouse Model of Lupine Food Allergy.

International archives of allergy and immunology pii:000492006 [Epub ahead of print].

BACKGROUND: The incidence of food allergies in western countries has increased in recent decades.

OBJECTIVES: To study the association between gut bacterial microbiota composition, short-chain fatty acids (SCFAs) and food allergy in a mouse model.

METHODS: After oral immunizations with the human food allergen lupine with the adjuvant cholera toxin (CT) (or buffer in controls), sensitization and anaphylactic responses were determined. Gastrointestinal content was collected from the distal ileum, cecum, colon, and fecal pellets, and the bacterial diversity and composition was determined by deep sequencing of the 16S rRNA gene. SCFAs in gastrointestinal content supernatants were determined by gas chromatography.

RESULTS: The microbiota signatures were profoundly affected by allergen immunization. Ten operational taxonomic units (OTUs) were significantly different between immunized and control animals for at least one of the intestinal segments; eight of these OTUs belonged to the Clostridia class. Although consistent across all four gut segments, the colon showed the highest number of OTUs significantly associated with allergic immunization. SCFA levels in the cecum were also altered by immunization.

CONCLUSIONS: Allergen immunization with CT in the present food allergy model induced profound changes in the microbiome composition and SCFA production. The result suggests that the colon may be the most sensitive gut segment for investigating changes in the gut microbiome.

RevDate: 2018-09-23

Wang N, Zhu F, Chen L, et al (2018)

Proteomics, metabolomics and metagenomics for type 2 diabetes and its complications.

Life sciences pii:S0024-3205(18)30587-3 [Epub ahead of print].

Type 2 diabetes mellitus (T2DM) is one of the most common diseases of endocrine and metabolic disorders, whose mechanism is still largely unknown. Fortunately, various "omics" tools have been employed to better understand the progression pathologies of T2DM and its complications. More specifically, proteomics, metabolomics and metagenomics have played crucial roles in advancing deeper understanding of the physiological processes and regulatory mechanisms of T2DM, such as regulation of signaling pathways perturbed by glucose levels, intestinal microorganism, and inflammation and so on. By analyzing the dynamic change and modification of proteins, proteomics has become an important tool in biology and medicine. Metabolomic analysis can amplify and quantify metabolites in living organisms to reveal the relative relationship between metabolites and physiological and pathological changes. There are also increasing evidences that the human microbiome, specifically the gastrointestinal microbiome have a potential role in the etiology and pathological outcomes of T2DM and its complications. This article summarized and discussed the recent applications of these "omics" tools in finding biomarkers for T2DM and its complications. We also reviewed employing multiple "omics" to further advance our understanding of this pathology. This review will benefit deeper understanding in new therapeutic and/or diagnostic biological target for the discovery of T2DM and its complications.

RevDate: 2018-09-23

Wagner M, Tubre DJ, JA Asensio (2018)

Evolution and Current Trends in the Management of Acute Appendicitis.

The Surgical clinics of North America, 98(5):1005-1023.

The treatment of appendicitis has evolved since the first appendectomy in the eighteenth century. It seems to have come full circle with nonoperative management in the era before frequent surgical interventions, to open surgical interventions, minimally invasive interventions, and now back to a renewed interest in nonoperative management of acute appendicitis. Scoring systems to help refine the diagnosis of acute appendicitis and advances in medical imaging have also changed the management of this condition. Scientific investigations into the effects the microbiome of the appendix plays in this disease process are also being considered.

RevDate: 2018-09-22

Kennedy AD, Wittmann BM, Evans AM, et al (2018)

Metabolomics in the Clinic: A Review of the Shared and Unique Features of Untargeted Metabolomics for Clinical Research and Clinical Testing.

Journal of mass spectrometry : JMS [Epub ahead of print].

Metabolomics is the untargeted measurement of the metabolome, which is comprised of the complement of small molecules detected in a biological sample. As such, metabolomic analysis produces a global biochemical phenotype. It is a technology that has been utilized in the research setting for over a decade. The metabolome is directly linked to and is influenced by genetics, epigenetics, environmental factors and the microbiome - all of which affect health. Metabolomics can be applied to human clinical diagnostics and to other fields such as veterinary medicine, nutrition, exercise, physiology, agriculture/plant biochemistry, and toxicology. Applications of metabolomics in clinical testing are emerging, but several aspects of its use as a clinical test differ from applications focused on research or biomarker discovery and need to be considered for metabolomics clinical test data to have optimum impact, be meaningful, and be used responsibly. In this review, we deconstruct aspects and challenges of metabolomics for clinical testing by illustrating the significance of test design, accurate and precise data acquisition, quality control, data processing, n-of-1 comparison to a reference population, and biochemical pathway analysis. We describe how metabolomics technology is integral to defining individual biochemical phenotypes, elaborates on human health and disease, and fits within the precision medicine landscape. Finally, we conclude by outlining some future steps needed to bring metabolomics into the clinical space and to be recognized by the broader medical and regulatory fields.

RevDate: 2018-09-22

Lee JJ, Kim SH, Lee MJ, et al (2018)

Different Upper Airway Microbiome and Their Functional Genes Associated with Asthma in Young Adults and Elderly Individuals.

Allergy [Epub ahead of print].

BACKGROUND: Microbes in the airway has been shown to be associated with the pathogenesis of asthma. The upper airway microbiome influences the dysbiosis of the lower airway microbiome. However, to date, the influence of upper airway microbiome for adult and elderly asthma has not been fully elucidated. Here, the metagenome of upper airway microbiome of young adults and elderly was analyzed to identify their association with adult asthma.

METHODS: Nasopharyngeal swabs were collected from young-adult and elderly asthma patients and non-asthmatic subjects. The compositions and functional genes of airway microbiome were analyzed by high-throughput sequencing.

RESULTS: The composition of microbiota differed between young-adult and elderly, and it was different between asthmatics and non-asthmatics in each age group. Different bacteria were related to FEV1% predicted in each age group. Genes related to lysine degradation, N-glycan biosynthesis, caprolactam degradation, and PPAR signaling pathway, which could be related to the reduction of inflammation and degradation of air pollutants, were higher in non-asthmatics. Genes related to pentose phosphate pathway, lipopolysaccharide biosynthesis, flagella assembly, and bacterial chemotaxis - which may all be related to increased inflammation and colonization of pathogenic bacteria - were higher in young-adult asthmatic patients. However, the functional genes of airway microbiome in elderly patients were not significantly different according to asthma morbidity.

CONCLUSIONS: These results suggest that the composition and function of upper airway microbiome could influence asthma pathogenesis, and the microbiome could play various roles depending on the age group. This article is protected by copyright. All rights reserved.

RevDate: 2018-09-22

Sindberg GM, Callen SE, Banerjee S, et al (2018)

Morphine Potentiates Dysbiotic Microbial and Metabolic Shifts in Acute SIV Infection.

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology pii:10.1007/s11481-018-9805-6 [Epub ahead of print].

Human Immunodeficiency Virus (HIV) pathogenesis has been closely linked with microbial translocation, which is believed to drive inflammation and HIV replication. Opioid drugs have been shown to worsen this symptom, leading to a faster progression of HIV infection to Acquired Immunodeficiency Syndrome (AIDS). The interaction of HIV and opioid drugs has not been studied at early stages of HIV, particularly in the gut microbiome where changes may precede translocation events. This study modeled early HIV infection by examining Simian Immunodeficiency Virus (SIV)-infected primates at 21 days or less both independently and in the context of opioid use. Fecal samples were analyzed both for 16S analysis of microbial populations as well as metabolite profiles via mass spectrometry. Our results indicate that changes are minor in SIV treated animals in the time points examined, however animals treated with morphine and SIV had significant changes in their microbial communities and metabolic profiles. This occurred in a time-independent fashion with morphine regardless of how long the animal had morphine in its system. Globally, the observed changes support that microbial dysbiosis is occurring in these animals at an early time, which likely contributes to the translocation events observed later in SIV/HIV pathogenesis. Additionally, metabolic changes were predictive of specific treatment groups, which could be further developed as a diagnostic tool or future intervention target to overcome and slow the progression of HIV infection to AIDS.

RevDate: 2018-09-22

Gudra D, Shoaie S, Fridmanis D, et al (2018)

A widely used sampling device in colorectal cancer screening programmes allows for large-scale microbiome studies.

Gut pii:gutjnl-2018-316225 [Epub ahead of print].

RevDate: 2018-09-22

Underwood MA (2018)

Probiotics and the prevention of necrotizing enterocolitis.

Journal of pediatric surgery pii:S0022-3468(18)30563-3 [Epub ahead of print].

BACKGROUND: Immaturity of the host immune system and alterations in the intestinal microbiome appear to be key factors in the pathogenesis of necrotizing enterocolitis (NEC). The aim of this paper is to weigh the evidence for the use of probiotics to prevent NEC in premature infants.

METHODS: Animal studies, randomized controlled trials, observational cohort studies and meta-analyses involving administration of probiotic products for the prevention of NEC were reviewed. This review of the evidence summarizes the available preclinical and clinical data.

RESULTS: In animal models probiotic microbes alter the intestinal microbiome, decrease inflammation and intestinal permeability and decrease the incidence and severity of experimental NEC. In randomized, placebo-controlled trials and cohort studies of premature infants, probiotic microbes decrease the risk of NEC, death and sepsis.

CONCLUSION: Evidence is strong for the prevention of NEC with the use of combination probiotics in premature infants who receive breast milk. The potential risks and benefits of probiotic administration to premature infants should be carefully reviewed with parents.

TYPE OF STUDY: Therapeutic.


RevDate: 2018-09-22

Michelini S, Balakrishnan B, Parolo S, et al (2018)

A reverse metabolic approach to weaning: in silico identification of immune-beneficial infant gut bacteria, mining their metabolism for prebiotic feeds and sourcing these feeds in the natural product space.

Microbiome, 6(1):171 pii:10.1186/s40168-018-0545-x.

BACKGROUND: Weaning is a period of marked physiological change. The introduction of solid foods and the changes in milk consumption are accompanied by significant gastrointestinal, immune, developmental, and microbial adaptations. Defining a reduced number of infections as the desired health benefit for infants around weaning, we identified in silico (i.e., by advanced public domain mining) infant gut microbes as potential deliverers of this benefit. We then investigated the requirements of these bacteria for exogenous metabolites as potential prebiotic feeds that were subsequently searched for in the natural product space.

RESULTS: Using public domain literature mining and an in silico reverse metabolic approach, we constructed probiotic-prebiotic-food associations, which can guide targeted feeding of immune health-beneficial microbes by weaning food; analyzed competition and synergy for (prebiotic) nutrients between selected microbes; and translated this information into designing an experimental complementary feed for infants enrolled in a pilot clinical trial (

CONCLUSIONS: In this study, we applied a benefit-oriented microbiome research strategy for enhanced early-life immune health. We extended from "classical" to molecular nutrition aiming to identify nutrients, bacteria, and mechanisms that point towards targeted feeding to improve immune health in infants around weaning. Here, we present the systems biology-based approach we used to inform us on the most promising prebiotic combinations known to support growth of beneficial gut bacteria ("probiotics") in the infant gut, thereby favorably promoting development of the immune system.

RevDate: 2018-09-22

Turner A, Veysey M, Keely S, et al (2018)

Interactions between Bitter Taste, Diet and Dysbiosis: Consequences for Appetite and Obesity.

Nutrients, 10(10): pii:nu10101336.

The type 2 family of taste receptors (T2Rs) detect and respond to bitter tastants. These receptors are expressed throughout the gastrointestinal (GI) tract, with location dependant roles. In the oral cavity, T2Rs are involved in the conscious perception of bitter tastants, while in the lower GI tract they have roles in chemoreception and regulation of GI function. Through these diverse roles, these receptors may be involved in modulating appetite and diet, with consequences for weight regulation and obesity. Interestingly, the concentration of T2Rs in the GI tract is greatest in the large intestine, the organ with the densest colonisation of bacteria. The gut microbiome has been the subject of intense research, as a plethora of roles linking microbiota to human health continue to be uncovered. Of particular interest is the microbial signature associated with obesity. Obesity is a leading health concern, and advances in our understanding of this disease are needed. Diet is a known modifiable factor in the development of obesity. However, diet only partially explains disease risk. Changes in microbial energy harvesting by the microbiota plays a role in obesity, and the composition of these energy harvesting populations may be controlled by taste receptors. This review explores T2Rs as a potential link between obesity and the human GI microbiome.

RevDate: 2018-09-21

Guss JD, Ziemian SN, Luna M, et al (2018)

The effects of metabolic syndrome, obesity, and the gut microbiome on load-induced osteoarthritis.

Osteoarthritis and cartilage pii:S1063-4584(18)31461-4 [Epub ahead of print].

OBJECTIVE: Metabolic syndrome is characterized by obesity, hyperglycemia, hypertension, insulin resistance, and dyslipidemia. Metabolic syndrome is associated with osteoarthritis (OA), but it is unclear if the association is attributable to increased mechanical loading on joints caused by obesity or other aspects of metabolic syndrome. Here we examined the effects of metabolic syndrome, obesity, and the gut microbiome on load-induced OA.

DESIGN: Cartilage damage was induced through cyclic compressive loading in four groups of adult male mice: Toll-like receptor-5 deficient (TLR5KO) mice that develop metabolic syndrome due to alterations in the gut microbiome, TLR5KO mice submitted to chronic antibiotics to prevent metabolic syndrome (TLR5KOΔMicrobiota), C57BL/6J mice fed a high fat diet to cause obesity (HFD), and untreated C57BL/6J mice (WT). Loading was applied for 2 weeks (n=10-11/group) or 6 weeks (n=10-11/group).

RESULTS: After 2 weeks of loading, cartilage damage (OARSI score) was not different among groups. After 6 weeks of loading, HFD mice had increased load-induced cartilage damage, while TLR5KO mice had cartilage damage comparable to WT mice. TLR5KOΔMicrobiota mice had less cartilage damage than other groups. HFD mice had elevated serum inflammatory markers. Each group had a distinct gut microbiome composition.

CONCLUSIONS: Severe obesity increased load-induced cartilage damage, while milder changes in adiposity/metabolic syndrome seen in TLR5KO mice did not. Furthermore, the effects of systemic inflammation/obesity on cartilage damage depend on the duration of mechanical loading. Lastly, reduced cartilage damage in the TLR5KOΔMicrobiota mice suggests that the gut microbiome may influence cartilage pathology.

RevDate: 2018-09-21

Allaband C, McDonald D, Vázquez-Baeza Y, et al (2018)

Microbiome 101: Studying, Analyzing, and Interpreting Gut Microbiome Data for Clinicians.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association pii:S1542-3565(18)31008-5 [Epub ahead of print].

Advances in technical capabilities for reading out complex human microbiomes are leading to an explosion of microbiome research, leading in turn to intense interest among clinicians in applying these techniques to their patients. In this review, we discuss the content of the human microbiome, including inter- and intra-subject variability, considerations of study design including important confounding factors, and different methods in the laboratory and on the computer to read out the microbiome and its resulting gene products and metabolites. We highlight several common pitfalls for clinicians, including the expectation that an individual's microbiome will be stable, that diet can induce rapid changes that are large compared to the differences among subjects, that everyone has essentially the same core stool microbiome, and that different laboratory and computational methods will yield essentially the same results. We also highlight the current limitations and future promise of these techniques, with the expectation that an understanding of these considerations will help accelerate the path towards routine clinical application of these techniques developed in research settings.

RevDate: 2018-09-21

Keebaugh ES, Yamada R, Obadia B, et al (2018)

Microbial Quantity Impacts Drosophila Nutrition, Development, and Lifespan.

iScience, 4:247-259.

In Drosophila, microbial association can promote development or extend life. We tested the impact of microbial association during malnutrition and show that microbial quantity is a predictor of fly longevity. Although all tested microbes, when abundantly provided, can rescue lifespan on low-protein diet, the effect of a single inoculation seems linked to the ability of that microbial strain to thrive under experimental conditions. Microbes, dead or alive, phenocopy dietary protein, and the calculated dependence on microbial protein content is similar to the protein requirements determined from fly feeding studies, suggesting that microbes enhance host protein nutrition by serving as protein-rich food. Microbes that enhance larval growth are also associated with the ability to better thrive on fly culture medium. Our results suggest an unanticipated range of microbial species that promote fly development and longevity and highlight microbial quantity as an important determinant of effects on physiology and lifespan during undernutrition.

RevDate: 2018-09-21

Kyburz A, Fallegger A, Zhang X, et al (2018)

Trans-maternal Helicobacter pylori exposure reduces allergic airway inflammation in offspring through regulatory T-cells.

The Journal of allergy and clinical immunology pii:S0091-6749(18)31297-1 [Epub ahead of print].

BACKGROUND: The trans-maternal exposure to tobacco, microbes, nutrients and other environmental factors shapes the fetal immune system through epigenetic processes. The gastric microbe Helicobacter pylori represents an ancestral constituent of the human microbiota that causes gastric disorders on the one hand, and is inversely associated with allergies and chronic inflammatory conditions on the other.

OBJECTIVE: Here, we investigate the consequences of trans-maternal exposure to H. pylori, in utero and/or during lactation, for susceptibility to viral and bacterial infection, predisposition to allergic airway inflammation, and the development of immune cell populations in the lung and lymphoid organs.

METHODS: We use experimental models of house dust mite- or ovalbumin-induced airway inflammation and influenza A virus or Citrobacter infection along with metagenomics analyses, multi-color flow cytometry and bilsufite pyrosequencing to study the effects of H. pylori on allergy severity and immunological and microbiome correlates thereof.

RESULTS: Perinatal exposure to H. pylori extract, or its immunomodulator VacA, confers robust protective effects against allergic airway inflammation not only in the first, but also the second offspring generation, but does not increase susceptibility to viral or bacterial infection. Immune correlates of allergy protection include skewing of regulatory over effector T-cells, expansion of Treg subsets expressing CXCR3 or RORγt, and demethylation of the FOXP3 locus. The composition and diversity of the gastrointestinal microbiota is measurably affected by perinatal H. pylori exposure.

CONCLUSION: We conclude that exposure to H. pylori has consequences not only for the carrier, but also for subsequent generations that may be exploited for interventional purposes.

RevDate: 2018-09-21

Archer NK, Jo JH, Lee SK, et al (2018)

Injury, dysbiosis and filaggrin deficiency drive skin inflammation via keratinocyte IL-1α release.

The Journal of allergy and clinical immunology pii:S0091-6749(18)31295-8 [Epub ahead of print].

BACKGROUND: Atopic dermatitis (AD) is associated with epidermal barrier defects, dysbiosis and skin injury from scratching. In particular, the barrier defective epidermis of AD patients with loss-of-function filaggrin mutations has increased IL-1α and IL-1β levels but the mechanisms by which IL-1α and/or IL-1β are induced and whether they contribute to the aberrant skin inflammation in AD is unknown.

OBJECTIVE: We sought to determine the mechanisms by which skin injury, dysbiosis and increased epidermal IL-1α and IL-1β contribute to the development of skin inflammation in a mouse model of injury-induced skin inflammation in filaggrin-deficient mice.

METHODS: Skin injury of wild-type, filaggrin-deficient (ft/ft), and MyD88-deficient ft/ft mice was performed and ensuing skin inflammation was evaluated by digital photography, histologic analysis and flow cytometry. IL-1α and IL-1β protein expression was measured by ELISA and visualized by immunofluorescence and immuno-electron microscopy. The composition of skin microbiome was determined by 16S rDNA sequencing.

RESULTS: Skin injury of ft/ft mice induced chronic skin inflammation involving dysbiosis-driven intracellular IL-1α release from keratinocytes. IL-1α was necessary and sufficient for skin inflammation in vivo and secreted from keratinocytes by various stimuli in vitro. Topical antibiotics or co-housing of ft/ft mice with unaffected wild-type mice to alter or intermix skin microbiota, respectively, resolved the skin inflammation and restored keratinocyte intracellular IL-1α localization.

CONCLUSIONS: Taken together, skin injury, dysbiosis and filaggrin deficiency triggered keratinocyte intracellular IL-1α release that was sufficient to drive chronic skin inflammation, which has implications for AD pathogenesis and for potential therapeutic targets.

RevDate: 2018-09-21

Harris L, van Zyl LJ, Kirby-McCullough BM, et al (2018)

Identification and sequence analysis of two novel cryptic plasmids isolated from the vaginal mucosa of South African women.

Plasmid pii:S0147-619X(18)30055-6 [Epub ahead of print].

The vaginal mucosa is dominated by Gram positive, rod shaped lactobacilli which serve as a natural barrier against infection. In both healthy- and bacterial vaginosis (BV)-infected women Lactobacillus crispatus and Lactobacillus jensenii have been found to be the predominant Lactobacillus species. Many studies have been conducted to assess factors influencing lactobacilli dominance in the vaginal microbiome. In the present study two plasmids, pLc4 and pLc17, isolated from vaginal Lactobacillus strains of both healthy and BV-infected women were characterized. The smaller plasmid, pLc4 (4224 bp in size), was detected in both L. crispatus and L. jensenii strains, while pLc17 was only detected in L. crispatus. Based on its nucleotide sequence pLc4 appears highly novel, with its replication protein having 44% identity to the replication initiation protein of pSMQ173b_03. Phylogenetic analysis with other Rolling Circle Replication plasmids confirmed that pLc4 shows a low degree of similarity to these plasmids. Plasmid pLc17 (16,663 bp in size) appears to carry both a RCR replicon and a theta replicon, which is rare in naturally occurring plasmids. pLc4 was maintained at a high copy number of 29, while pLc17 appears to be a medium copy number plasmid maintained at 11 copies per chromosome. While sequence analysis is a valuable tool to study cryptic plasmids, further function-based analysis will be required in order to fully elucidate the role of these plasmids within the vaginal milieu.

RevDate: 2018-09-21

Shulzhenko N, Dong X, Vyshenska D, et al (2018)

CVID enteropathy is characterized by exceeding low mucosal iga levels and interferon-driven inflammation possibly related to the presence of a pathobiont.

Clinical immunology (Orlando, Fla.) pii:S1521-6616(18)30294-8 [Epub ahead of print].

Common variable immunodeficiency (CVID), the most common symptomatic primary antibody deficiency, is accompanied in some patients by a duodenal inflammation and malabsorption syndrome known as CVID enteropathy (E-CVID). The goal of this study was to investigate the immunological abnormalities in CVID patients that lead to enteropathy as well as the contribution of intestinal microbiota to this process. We found that, in contrast to noE-CVID patients (without enteropathy), E-CVID patients have exceedingly low levels of IgA in duodenal tissues. In addition, using transkingdom network analysis of the duodenal microbiome, we identified Acinetobacter baumannii as a candidate pathobiont in E-CVID. Finally, we found that E-CVID patients exhibit a pronounced activation of immune genes and down-regulation of epithelial lipid metabolism genes. We conclude that in the virtual absence of mucosal IgA, pathobionts such as A. baumannii, may induce inflammation that re-directs intestinal molecular pathways from lipid metabolism to immune processes responsible for enteropathy.

RevDate: 2018-09-21

Cho Y, Abu-Ali G, Tashiro H, et al (2018)

Sex Differences in Pulmonary Responses to Ozone in Mice: Role of the Microbiome.

American journal of respiratory cell and molecular biology [Epub ahead of print].

We have previously reported that the mouse gut microbiome contributes to pulmonary responses to ozone, a common asthma trigger, and that short chain fatty acids, end products of bacterial fermentation, likely contribute to this role of the microbiome. A growing body of evidence indicates sex-related differences in gut microbiota and that these differences can have important functional consequences. The purpose of this study was to determine whether there were sex-related differences in the impact of the gut microbiota on pulmonary responses to ozone. After acute exposure to ozone, male mice developed greater airway hyperresponsiveness than female mice. This difference was abolished after antibiotic ablation of the gut microbiome. Moreover, weanling female pups housed in cages conditioned by adult male mice developed greater ozone-induced airway hyperresponsiveness than weanling female pups raised in cages conditioned by adult females. Finally, ad libitum oral administration via drinking water of the short chain fatty acid, propionate, resulted in augmented ozone-induced airway hyperresponsiveness in male but not in female mice. Overall, these data are consistent with the hypothesis that the microbiome contributes to sex differences in ozone-induced airway hyperresponsiveness, likely as a result of sex differences in the response to short chain fatty acids.

RevDate: 2018-09-21

Kuhar HN, Tajudeen BA, Mahdavinia M, et al (2018)

Relative abundance of nasal microbiota in chronic rhinosinusitis by structured histopathology.

International forum of allergy & rhinology [Epub ahead of print].

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disease process with several different phenotypes. Recent data has shown that CRS phenotypes maintain distinct nasal microbiota that may predict surgical outcomes. Nasal microbiota and structured histopathologic reporting have the potential to further differentiate subtypes and provide additional insight into the pathophysiology of CRS.

METHODS: Sinus swabs collected during functional endoscopic sinus surgery (FESS) were studied by polymerase chain reaction analysis of 16S ribosomal RNA. A structured histopathology report of 13 variables was utilized to analyze sinus tissue removed during FESS. Histopathology variables and relative abundance of nasal microbiota were compared among CRS patients.

RESULTS: A total of 51 CRS patients who underwent FESS were included. Relative abundance of the Firmicutes phylum in nasal microbiota of CRS patients was associated with presence of neutrophilic infiltrate (27.47 ± 44.75 vs 9.21 ± 11.84, p < 0.029), presence of mucosal ulceration (47.67 ± 45.52 vs 13.27 ± 26.48, p < 0.041), presence of squamous metaplasia (5562.70 ± 2715.66 vs 3563.73 ± 2580.84, p < 0.035), and absence of Charcot-Leyden crystals (5423.00 ± 3320.57 vs 679.94 ± 1653.66, p < 0.001). Relative abundance of the Bacteroidetes phylum in nasal microbiota of CRS patients was associated with increased severity of inflammatory degree (p < 0.004) and presence of mucosal ulceration (p < 0.004).

CONCLUSION: Distinct histopathologic features of CRS are associated with relative abundance of nasal microbiota phyla, specifically Firmicutes and Bacteroidetes. These findings contribute to the growing body of literature on microbiota in sinonasal disease and may have important implications for understanding pathophysiologic mechanisms of CRS subtypes and disease management.

RevDate: 2018-09-21

Florence VH, Kim P, Hugo R, et al (2018)

Mucin Degradation Niche as a Driver of Microbiome Composition and Akkermansia Muciniphila Abundance in a Dynamic Gut Model is Donor Independent.

FEMS microbiology ecology pii:5101425 [Epub ahead of print].

Akkermansia muciniphila, an abundant mucin degrading intestinal bacterium, has been correlated with human health in various studies. The in vitro SHIME model was used to reach a mechanistic understanding of A. muciniphila's colonization preferences and its response to environmental parameters such as colon pH and mucins. These insight can help to identify the optimal conditions for successful in vivo application. After a period of mucin deprivation, we found that mucin supplementation resulted in significantly different microbial communities, with more Akkermansia, Bacteroides and Ruminococcus. Mucin treatment accounted for 26% of the observed variation in the microbial community at OTU level (p=0.001), whereas the donor effect was limited (8%) (p=0.035), indicating mucins to constitute an important ecological niche shaping the microbiota composition. The effect of colonic pH had a less profound impact on the microbiome with both pH and donor origin explaining around 10% of the variability in the dataset. Yet, higher simulated colonic pH had a positive impact on Akkermansia abundance while short chain fatty acid analysis displayed a preference for propionate production with higher colonic pH. Our results show that mucins as nutritional resource are a more important modulator of the gut microbiome than colon pH as environmental factor.

RevDate: 2018-09-21

Kiernan MG, Coffey JC, McDermott K, et al (2018)

The human mesenteric lymph node microbiome differentiates between Crohn's disease and ulcerative colitis.

Journal of Crohn's & colitis pii:5098279 [Epub ahead of print].

Background and Aims: Mesenteric lymph nodes are sites in which translocated bacteria incite and progress immunological responses. For this reason, understanding the microbiome of mesenteric lymph nodes in inflammatory bowel disease is important. The bacterial profile of Crohn's disease mesenteric lymph nodes has been analysed using culture-independent methods in only one previous study. This study aimed to investigate the mesenteric lymph node microbiota from both Crohn's disease and ulcerative colitis patients.

Methods: Mesenteric lymph nodes were collected from Crohn's disease and ulcerative colitis patients undergoing resection. Total DNA was extracted from mesenteric lymph nodes and assessed for the presence of bacterial DNA (16S). All work was completed in a sterile environment using aseptic techniques. Samples positive for 16S DNA underwent next generation sequencing and the identity of bacterial phyla and species were determined.

Results: Crohn's disease mesenteric lymph nodes had a distinctly different microbial profile to that observed in ulcerative colitis. The relative abundance of Firmicutes was greater in nodes from ulcerative colitis patients while Proteobacteria were more abundant in Crohn's disease. Although species diversity was reduced in Crohn's disease mesenteric lymph nodes, they contained greater numbers of less dominant phyla, mainly Fusobacteria.

Conclusion: This study confirms that there are distinct differences between the Crohn's disease and ulcerative colitis mesenteric lymph node microbiomes. Such microbial differences could aid in the diagnosis of Crohn's disease or ulcerative colitis, particular in cases of indeterminate colitis at time of resection, or help explain their mechanisms of development and progression.

RevDate: 2018-09-21

Zinter MS, Dvorak CC, Mayday MY, et al (2018)

Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America pii:5098446 [Epub ahead of print].

Background: Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a highly sensitive metagenomic next generation sequencing assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children.

Methods: We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at three children's hospitals from 2014-2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the NCBI nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort.

Results: We identified a rich cross-domain pulmonary microbiome containing bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median 0.61, IQR 0.33-0.72 vs. median 0.96, IQR 0.94-0.96, p<0.001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (p<0.001).

Conclusions: An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease.

RevDate: 2018-09-21

Zou Q, Lin G, Jiang X, et al (2018)

Sequence clustering in bioinformatics: an empirical study.

Briefings in bioinformatics pii:5098604 [Epub ahead of print].

Sequence clustering is a basic bioinformatics task that is attracting renewed attention with the development of metagenomics and microbiomics. The latest sequencing techniques have decreased costs and as a result, massive amounts of DNA/RNA sequences are being produced. The challenge is to cluster the sequence data using stable, quick and accurate methods. For microbiome sequencing data, 16S ribosomal RNA operational taxonomic units are typically used. However, there is often a gap between algorithm developers and bioinformatics users. Different software tools can produce diverse results and users can find them difficult to analyze. Understanding the different clustering mechanisms is crucial to understanding the results that they produce. In this review, we selected several popular clustering tools, briefly explained the key computing principles, analyzed their characters and compared them using two independent benchmark datasets. Our aim is to assist bioinformatics users in employing suitable clustering tools effectively to analyze big sequencing data. Related data, codes and software tools were accessible at the link∼lg/clustering/.

RevDate: 2018-09-21

Le TN (2018)

Updates in vitamin D therapy in cystic fibrosis.

Current opinion in endocrinology, diabetes, and obesity [Epub ahead of print].

PURPOSE OF REVIEW: To summarize recent developments the role of vitamin D and treatment of vitamin D deficiency in cystic fibrosis.

RECENT FINDINGS: Although treatment of low vitamin D levels continues to be important for optimizing bone health in cystic fibrosis, increasing data on the extraskeletal effects of vitamin D are becoming available. Exploratory studies of vitamin D in modulation of respiratory and intestinal microbiomes, and the influence of vitamin D on the metabolomic signature of cystic fibrosis, suggest expanded roles for vitamin D in cystic fibrosis disease and treatment.

SUMMARY: Emerging developments in cystic fibrosis regarding therapeutics and effects of vitamin D on bone health, inflammation, microbiome, and the metabolome are summarized.

RevDate: 2018-09-21

Thapa S, Zhang Y, MS Allen (2018)

Effects of temperature on bacterial microbiome composition in Ixodes scapularis ticks.

MicrobiologyOpen [Epub ahead of print].

Ixodes scapularis, the blacklegged deer tick, is the principal vector of Lyme disease in North America. Environmental factors are known to influence regional and seasonal incidence of Lyme disease and possibly the endemicity of the disease to the northeastern and upper mid-western regions of the United States. With a goal to understand the impact of environmental temperature on microbial communities within the tick, we investigated the bacterial microbiome of colony-reared I. scapularis ticks statically incubated at different temperatures (4, 20, 30, and 37°C) at a constant humidity in a controlled laboratory setting by comparison of sequenced amplicons of the bacterial 16S V4 rRNA gene to that of the untreated baseline controls. The microbiomes of colony-reared I. scapularis males were distinct than that of females, which were entirely dominated by Rickettsia. In silico removal of Rickettsia sequences from female data revealed the underlying bacterial community, which is consistent in complexity with those seen among male ticks. The bacterial community composition of these ticks changes upon incubation at 30°C for a week and 37°C for more than 5 days. Moreover, the male ticks incubated at 30 and 37°C exhibited significantly different bacterial diversity compared to the initial baseline microbiome, and the change in bacterial diversity was dependent upon duration of exposure. Rickettsia-free data revealed a significantly different bacterial diversity in female ticks incubated at 37°C compared to that of 4 and 20°C treatments. These results provide experimental evidence that environmental temperature can impact the tick bacterial microbiome in a laboratory setting.

RevDate: 2018-09-21

Dieterle MG, Rao K, VB Young (2018)

Novel therapies and preventative strategies for primary and recurrent Clostridium difficile infections.

Annals of the New York Academy of Sciences [Epub ahead of print].

Clostridium difficile is the leading infectious cause of antibiotic-associated diarrhea and colitis. C. difficile infection (CDI) places a heavy burden on the healthcare system, with nearly half a million infections yearly and an approximate 20% recurrence risk after successful initial therapy. The high incidence has driven new research on improved prevention such as the emerging use of probiotics, intestinal microbiome manipulation during antibiotic therapies, vaccinations, and newer antibiotics that reduce the disruption of the intestinal microbiome. While the treatment of acute C. difficile is effective in most patients, it can be further optimized by adjuvant therapies that improve the initial treatment success and decrease the risk of subsequent recurrence. Finally, the high risk of recurrence has led to multiple emerging therapies that target toxin activity, recovery of the intestinal microbial community, and elimination of latent C. difficile in the intestine. In summary, CDIs illustrate the complex interaction among host physiology, microbial community, and pathogen that requires specific therapies to address each of the factors leading to primary infection and recurrence.

RevDate: 2018-09-21

Hahn A, Burrell A, Fanous H, et al (2018)

Antibiotic multidrug resistance in the cystic fibrosis airway microbiome is associated with decreased diversity.

Heliyon, 4(9):e00795 pii:e00795.

Background: Cystic fibrosis (CF) is associated with significant morbidity and early mortality due to recurrent acute and chronic lung infections. The chronic use of multiple antibiotics increases the possibility of multidrug resistance (MDR). Antibiotic susceptibility determined by culture-based techniques may not fully represent the resistance profile. The study objective was to detect additional antibiotic resistance using molecular methods and relate the presence of MDR to airway microbiome diversity and pulmonary function.

Methods: Bacterial DNA was extracted from sputum samples and amplified for the V4 region of the 16S rRNA gene. An qPCR array was used to detect antibiotic resistance genes. Clinical culture results and pulmonary function were also noted for each encounter.

Results: Six study participants contributed samples from 19 encounters. Those samples with MDR (n = 7) had significantly lower diversity measured by inverse Simpson's index than those without (n = 12) (2.193 ± 0.427 vs 6.023 ± 1.564, p = 0.035). Differential abundance showed that samples with MDR had more Streptococcus (p = 0.002) and Alcaligenaceae_unclassified (p = 0.002). Pulmonary function was also decreased when MDR was present (FEV1, 51 ± 22.9 vs 77 ± 26.7, p = 0.054; FVC, 64.5 ± 22.7 vs 91.6 ± 27.7, p = 0.047).

Conclusions: The presence of MDR within the CF airway microbiome was associated with decreased microbial diversity, the presence of Alcaligenes, and decreased pulmonary function.

RevDate: 2018-09-21

Dittoe DK, Ricke SC, AS Kiess (2018)

Organic Acids and Potential for Modifying the Avian Gastrointestinal Tract and Reducing Pathogens and Disease.

Frontiers in veterinary science, 5:216.

Recently, antibiotics have been withdrawn from some poultry diets; leaving the birds at risk for increased incidence of dysbacteriosis and disease. Furthermore, mortalities occurring from disease contribute between 10 to 20% of production cost in developed countries. Currently, numerous feed supplements are being proposed as effective antibiotic alternatives in poultry diets, such as prebiotics, probiotics, acidic compounds, competitive exclusion products, herbs, essential oils, and bacteriophages. However, acidic compounds consisting of organic acids show promise as antibiotic alternatives. Organic acids have demonstrated the capability to enhance poultry performance by altering the pH of the gastrointestinal tract (GIT) and consequently changing the composition of the microbiome. In addition, organic acids, by altering the composition of the microbiome, protect poultry from pH-sensitive pathogens. Protection is further provided to poultry by the ability of organic acids to potentially enhance the morphology and physiology of the GIT and the immune system. Thus, the objective of the current review is to provide an understanding of the effects organic acids have on the microbiome of poultry and the effect those changes have on the prevalence of pathogens and diseases in poultry. From data reviewed, it can be concluded that the efficacy of organic acids on shifting microbiome composition is limited to the time of administration, the composition of the organic acid product, and the current health conditions of poultry.

RevDate: 2018-09-21

Zhu L, Luo F, Hu W, et al (2018)

Bacterial Communities in the Womb During Healthy Pregnancy.

Frontiers in microbiology, 9:2163.

The idea that healthy uterine cavity is sterile is challenged nowadays. It is still debatable whether the bacteria present in the uterine cavity during pregnancy are residents or invaders. To reveal microbiome composition and its characteristics in the womb of pregnant women, 41 decidual tissue samples and 64 amniotic fluid samples were taken from pregnant Chinese women. DNA extraction was followed by pyrosequencing of the hypervariable V4 region of the 16S rDNA gene to characterize womb microbiome. Both types of samples had low diversity microbiome with Enterobacteriaceae being the dominant phylotypes at family level. To characterize the nature of colonization during pregnancy, the presence of endogenous biomass was confirmed by cultivation. Surprisingly, all of the 50 amniotic fluid samples studied were culture-negative, whereas 379 out of 1,832 placenta samples were culture-positive. Our results suggested that womb contained microbiome with low diversity. Culture-based investigation of amniotic fluid and placenta samples confirmed the presence of cultivable microorganisms in the placenta but not in amniotic fluid. Thus it suggests that bacterial colonization does occur during healthy pregnancy.

RevDate: 2018-09-21

Mulvey JJ, Littmann ER, Ling L, et al (2018)

The effects of amine-modified single-walled carbon nanotubes on the mouse microbiota.

International journal of nanomedicine, 13:5275-5286 pii:ijn-13-5275.

Background: Amine-modified carbon nanotubes are drug delivery platforms with great potential that have not yet been applied in human clinical trials. Although modified nanotube vectors have the ability to carry multiple effectors, targeting agents, and even wrapped RNA, reports on unmodified, insoluble carbon nanotubes have highlighted inflammation in organs, including the intestine, with disruption of its resident microbiota. Disruption of the microbiota may allow for colonization by pathogenic bacteria, such as Clostridoidies difficile, stimulate immunoinfiltrates into the lamina propria or alter the absorption of therapeutics. Most proposed nanotube drugs are soluble, modified structures that are administered parenterally, and the majority of these soluble macromolecules are renally excreted; however, some are released into the bile, gaining access to the gastrointestinal tract.

Methods: Using environmentally isolated BALB/C mice in oral and intraperitoneal dosing models, high dose (3.80 or 4.25 mg/week), we administered amine-modified, soluble carbon nanotubes for 7 or 8 weeks. The general health and weight of the mice were monitored weekly, and upon killing, the diversity and content of their colonic, cecal, and ileal microbiota were assessed using shotgun 16S DNA sequencing.

Results and conclusion: We show that while oral administration at suprapharmacological doses modestly altered the α- and β-diversity of the mouse microbiome, these changes did not result in observed changes in clinical end points. Intraperitoneally-dosed mice exhibited none of the toxicities assessed.

RevDate: 2018-09-21

Arrazuria R, Pérez V, Molina E, et al (2018)

Diet induced changes in the microbiota and cell composition of rabbit gut associated lymphoid tissue (GALT).

Scientific reports, 8(1):14103 pii:10.1038/s41598-018-32484-1.

The gut associated lymphoid tissue (GALT) is the largest immune organ of the body. Although the gut transient and mucosa-associated microbiota have been largely studied, the microbiota that colonizes the GALT has received less attention. The gut microbiome plays an important role in competitive exclusion of pathogens and in development and maturation of immunity. Diet is a key factor affecting the microbiota composition in the digestive tract. To investigate the relation between diet, microbiota and GALT, microbial and cell composition of vermiform appendix (VA) and sacculus rotundus (SR) were studied in two groups of New Zealand white rabbits on different diets. Diet shifted the lymphoid tissue microbiota affecting the presence and/or absence of certain taxa and their abundances. Immunohistochemistry revealed that a higher fibre content diet resulted in M cell hyperplasia and an increase of recently recruited macrophages, whereas T-cell levels remained unaltered in animals on both high fibre and standard diets. These findings indicate that diet has an impact on the microbiota and cell composition of the GALT, which could act as an important microbial recognition site where interactions with beneficial bacteria can take place favouring microbiota replacement after digestive dysregulations.

RevDate: 2018-09-21

Dong T, Chen T, White RA, et al (2018)

Meconium microbiome associates with the development of neonatal jaundice.

Clinical and translational gastroenterology, 9(9):182 pii:10.1038/s41424-018-0048-x.

OBJECTIVE: Neonatal jaundice is a common disease that affects up to 60% of newborns. Gut microbiota mediated the excretion of bilirubin from the human body. However, the relationship between early gut microbiome and development of neonatal jaundice is not fully understood. Here we sought to characterize meconium microbiome of newborns and to clarify its association with risk of neonatal jaundice.

METHODS: We conducted a nested case-control study with 301 newborns providing meconium samples from 2014 to 2015. The main outcome was the development of neonatal jaundice at 42 day follow-up. 16S rRNA gene sequencing was performed to profile the meconium microbiome. LEfSe was employed to identify different features between control and case groups. Logistic regression was used to estimate the risk effect of early gut microbiome on neonatal jaundice.

RESULTS: Logistic regression models suggested that higher ɑ-diversity was significantly associated with lower risk of jaundice in cesarean infants (OR 0.72, 95% CI 0.52-0.98), but not in infants born naturally. Higher relative abundance of Bifidobacterium pseudolongum in newborn meconium was significantly associated with lower risk of jaundice both in cesarean-born infants and in the total subjects (OR 0.24, 95% CI 0.07-0.68; OR 0.55, 95% CI 0.31-0.95, respectively). Spearman's correlations showed that relative abundance of B. pseudolongum was significantly correlated with ɑ-diversity (P < 0.01).

CONCLUSION: Preventive and treatment methods implying early gut microbiome intervention could be promising for the management of neonatal jaundice.

RevDate: 2018-09-21

Owada-Ozaki Y, Nishiyama K, Kobayashi T, et al (2018)

[A Study of Biomarkers in Immuno-Oncology - Correlation between Gut Microbiome Composition and the Effects of Immune Checkpoint Inhibitors].

Gan to kagaku ryoho. Cancer & chemotherapy, 45(9):1234-1237.

Currently, anti-PD-1 inhibitors(nivolumab and pembrolizumab)are used for patients with non-small cell lung cancer (NSCLC), although the role of this biomarker is not yet fully characterized. PD-L1 expression in the tumor has been established as a biomarker of the effects of pembrolizumab; however, a number of PD-L1-negative patients have benefited from nivolumab or other immune checkpoint inhibitors, suggesting that there might be additional relevant biomarkers. Notably, tumor mutation burden or tumor infiltrating lymphocytes might be useful biomarkers for these patients; the gut microbiome has received similar attention. It has been reported that mouse models of melanoma with certain types of microbiomes benefit from the use of immune checkpoint inhibitors. Even in human cases, those with certain types of microbiomes tended to benefit from immune checkpoint inhibitor treatment and exhibited elevated CD8-positive T cell counts. Additionally, when combined with antibiotics, the effect of the anti-PD-1 antibody was attenuated; conversely, mice that were treated with certain species of bacteria experienced beneficial outcomes from anti-PD-1 antibody treatment. This suggested that manipulation of the gut microbiome might alter treatment effects. Here, we analyzed the microbiome of 12 patients with advanced or recurrent NSCLC who were treated with anti-PD-1 antibody. There was no major difference between before and after administration in microbiome of each case. Cluster analysis indicated no significant differences in oral microbiomes among the patients before the administration of the anti-PD-1 antibody. Comparative analysis of the patients' gut microbiomes is ongoing. We plan to continue further examination to reveal whether the intestinal environment influences the effectiveness of immune checkpoint inhibitors in NSCLC patients.

RevDate: 2018-09-21

Liu Y, Wong KK, Ko EY, et al (2018)

Systematic Comparison of Bacterial Colonization of Endometrial Tissue and Fluid Samples in Recurrent Miscarriage Patients: Implications for Future Endometrial Microbiome Studies.

Clinical chemistry pii:clinchem.2018.289306 [Epub ahead of print].

BACKGROUND: A recent study has reported that the microbiota in endometrial fluid of patients receiving in vitro fertilization and embryo transfer (IVF-ET) may predict implantation and pregnancy rates. However, studies are lacking that simultaneously compare the microbiota between endometrial fluid and tissue samples. Whether the microbiota composition in endometrial fluid reflects that in the endometrial tissue remains unclear.

METHODS: We systematically profiled the microbiota in endometrial fluid and tissue samples of IVF-ET patients using massively parallel sequencing. The bacterial 16S ribosomal RNA gene (V4 region) was PCR-amplified. Sequencing reads with >98% nucleotide identity were clustered as a bacterial taxon. To account for the different number of reads per sample, we normalized the read counts of each taxon before comparing its relative abundances across samples.

RESULTS: Thirteen taxa, including Verrucomicrobiaceae, Brevundimonas, Achromobacter, Exiguobacterium, and Flavobacterium, were consistently detected only in endometrial tissue samples but not fluid samples. Eight taxa were detected in fluid but not tissue. Twenty-two taxa were differentially abundant between fluid and tissue samples (adjusted P values, 4.1 × 10-25 to 0.025). The numbers of taxa identified per 1000 sequencing reads, diversity, and evenness in fluid samples were smaller than those in tissue samples.

CONCLUSIONS: Our data suggest that the microbiota composition in endometrial fluid does not fully reflect that in endometrial tissue. Sampling from both endometrial fluid and biopsy allows a more comprehensive view of microbial colonization. Further efforts are needed to identify the preanalytical effects, including sampling sites, methods, and sequencing depth, on profiling endometrial microbiota.

RevDate: 2018-09-20

Colonetti K, Roesch LF, IVD Schwartz (2018)

The microbiome and inborn errors of metabolism: Why we should look carefully at their interplay?.

Genetics and molecular biology, 41(3):515-532.

Research into the influence of the microbiome on the human body has been shedding new light on diseases long known to be multifactorial, such as obesity, mood disorders, autism, and inflammatory bowel disease. Although inborn errors of metabolism (IEMs) are monogenic diseases, genotype alone is not enough to explain the wide phenotypic variability observed in patients with these conditions. Genetics and diet exert a strong influence on the microbiome, and diet is used (alone or as an adjuvant) in the treatment of many IEMs. This review will describe how the effects of the microbiome on the host can interfere with IEM phenotypes through interactions with organs such as the liver and brain, two of the structures most commonly affected by IEMs. The relationships between treatment strategies for some IEMs and the microbiome will also be addressed. Studies on the microbiome and its influence in individuals with IEMs are still incipient, but are of the utmost importance to elucidating the phenotypic variety observed in these conditions.

RevDate: 2018-09-20

Luo Z, Ogunrinde E, Li M, et al (2018)

Increased influenza-specific antibody avidity in HIV-infected females compared to HIV-infected males on antiretroviral therapy.

AIDS (London, England) [Epub ahead of print].

: It is recommended that HIV-infected individuals receive annual influenza vaccination due to their high susceptibility to influenza infection, especially among females. However, there have been few studies investigating sex-related responses to influenza vaccine in antiretroviral (ART)-treated HIV-infected subjects. In this study, 26 aviremic ART-treated HIV-infected subjects and 16 healthy controls were enrolled in the current study. Blood was collected prior to vaccination (D0), on days 7-10 (D7), and on days 14-21 (D14) following administration of the 2013-2014 seasonal influenza vaccine. A series of analyses evaluated the serological and cellular responses following influenza vaccination. Female HIV-infected subjects had increased influenza-specific antibody avidity relative to male HIV-infected subjects, but similar plasma levels of influenza-specific binding antibodies and neutralizing antibodies. Increased cycling B cells and follicular helper CD4+ T (Tfh) cells were observed in female HIV-infected subjects pre- and post-vaccination compared to male HIV-infected subjects, and cycling Tfh cells were directly correlated with influenza-specific antibody avidity. Moreover, plasma testosterone levels were inversely correlated with antibody avidity index. The magnitude of microbial translocation (plasma lipopolysaccharide (LPS)) level was directly correlated with influenza-specific antibody avidity. Circulating 16S rDNA microbiome showed that enrichment of specific species within Proteobacteria was associated with influenza-specific antibody avidity. These results, including differences based on sex and correlations, were only observed in HIV+ subjects but not in the healthy controls. This study demonstrated sex differences in influenza-specific antibody avidity in ART-treated HIV disease, and provides valuable information on vaccination strategy in the ART-treated HIV-infected population.

RevDate: 2018-09-20

Liebert A (2018)

Emerging Applications of Photobiomodulation Therapy: The Interaction Between Metabolomics and the Microbiome.

Photomedicine and laser surgery [Epub ahead of print].

RevDate: 2018-09-20

De Mulder T, Rasschaert G, Van Coillie E, et al (2018)

Impact of Cross-Contamination Concentrations of Doxycycline Hyclate on the Microbial Ecosystem in an Ex Vivo Model of the Pig's Cecum.

Microbial drug resistance (Larchmont, N.Y.) [Epub ahead of print].

AIMS: Cross-contamination of feed with antibiotics causes pigs to become unintentionally exposed to low concentrations of antibiotics. This study investigates the effect of residues of doxycycline hyclate (DOX) in an ex vivo model of the intestinal tract of pigs, focusing on the microbial community, microbial activity, and the enrichment of resistant bacteria and resistance genes.

RESULTS: The effect of three concentrations DOX were tested; 1 and 4 mg/L correspond to the intestinal concentrations when pigs are fed a compound feed containing 3% of a therapeutic dose, and a reference concentration of 16 mg/L. These were continuously administered to a chemostat, simulating the microbial ecosystem of the pig cecum and inoculated with cecal content of organically grown pigs. The administration of even the lowest DOX concentration caused a significant decrease in bacterial activity, while the microbial community profile appeared to remain unaffected by any of the concentrations. A concentration of 1 mg/L DOX caused minor selection pressure for tetracycline-resistant Escherichia coli but no other groups enumerated with plate cultivation, while 4 mg/L induced major enrichment of tetracycline-resistant E. coli, Enterobacteriaceae and total anaerobes. High abundances of tet(Q), tet(M), tet(W), tet(O), and tet(B) were detected in the inoculum and also before antibiotic administration in the chemostat and did not significantly increase during administration of 1 and 4 mg/L DOX. Only 16 mg/L DOX caused minor enrichments.

CONCLUSIONS: Cross-contamination concentrations of doxycycline, as a result of cross-contamination, cause a selection pressure for resistant bacteria and negatively affect microbial activity.

RevDate: 2018-09-20

Brugman S, Ikeda-Ohtsubo W, Braber S, et al (2018)

A Comparative Review on Microbiota Manipulation: Lessons From Fish, Plants, Livestock, and Human Research.

Frontiers in nutrition, 5:80.

During recent years the impact of microbial communities on the health of their host (being plants, fish, and terrestrial animals including humans) has received increasing attention. The microbiota provides the host with nutrients, induces host immune development and metabolism, and protects the host against invading pathogens (1-6). Through millions of years of co-evolution bacteria and hosts have developed intimate relationships. Microbial colonization shapes the host immune system that in turn can shape the microbial composition (7-9). However, with the large scale use of antibiotics in agriculture and human medicine over the last decades an increase of diseases associated with so-called dysbiosis has emerged. Dysbiosis refers to either a disturbed microbial composition (outgrowth of possible pathogenic species) or a disturbed interaction between bacteria and the host (10). Instead of using more antibiotics to treat dysbiosis there is a need to develop alternative strategies to combat disturbed microbial control. To this end, we can learn from nature itself. For example, the plant root (or "rhizosphere") microbiome of sugar beet contains several bacterial species that suppress the fungal root pathogen Rhizoctonia solani, an economically important fungal pathogen of this crop (11). Likewise, commensal bacteria present on healthy human skin produce antimicrobial molecules that selectively kill skin pathogen Staphylococcus aureus. Interestingly, patients with atopic dermatitis (inflammation of the skin) lacked antimicrobial peptide secreting commensal skin bacteria (12). In this review, we will give an overview of microbial manipulation in fish, plants, and terrestrial animals including humans to uncover conserved mechanisms and learn how we might restore microbial balance increasing the resilience of the host species.

RevDate: 2018-09-20

Wang Z, Zolnik CP, Qiu Y, et al (2018)

Comparison of Fecal Collection Methods for Microbiome and Metabolomics Studies.

Frontiers in cellular and infection microbiology, 8:301.

Background: Integrated microbiome and metabolomics analyses hold the potential to reveal interactions between host and microbiota in relation to disease risks. However, there are few studies evaluating how field methods influence fecal microbiome characterization and metabolomics profiling. Methods: Five fecal collection methods [immediate freezing at -20°C without preservative, OMNIgene GUT, 95% ethanol, RNAlater, and Flinders Technology Associates (FTA) cards] were used to collect 40 fecal samples from eight healthy volunteers. We performed gut microbiota 16S rRNA sequencing, untargeted metabolomics profiling, and targeted metabolomics focusing on short chained fatty acids (SCFAs). Metrics included α-diversity and β-diversity as well as distributions of predominant phyla. To evaluate the concordance with the "gold standard" immediate freezing, the intraclass correlation coefficients (ICCs) for alternate fecal collection systems were calculated. Correlations between SCFAs and gut microbiota were also examined. Results: The FTA cards had the highest ICCs compared to the immediate freezing method for α-diversity indices (ICCs = 0.96, 0.96, 0.76 for Shannon index, Simpson's Index, Chao-1 Index, respectively), followed by OMNIgene GUT, RNAlater, and 95% ethanol. High ICCs (all >0.88) were observed for all methods for the β-diversity metric. For untargeted metabolomics, in comparison to immediate freezing which detected 621 metabolites at ≥75% detectability level, 95% ethanol showed the largest overlapping set of metabolites (n = 430; 69.2%), followed by FTA cards (n = 330; 53.1%) and OMNIgene GUT (n = 213; 34.3%). Both OMNIgene GUT (ICCs = 0.82, 0.93, 0.64) and FTA cards (ICCs = 0.87, 0.85, 0.54) had acceptable ICCs for the top three predominant SCFAs (butyric acid, propionic acid and acetic acid). Nominally significant correlations between bacterial genera and SCFAs (P < 0.05) were observed in fecal samples collected by different methods. Of note, a high correlation between the genus Blautia (known butyrate producer) and butyric acid was observed for both immediate freezing (r = 0.83) and FTA cards (r = 0.74). Conclusions: Four alternative fecal collection methods are generally comparable with immediate freezing, but there are differences in certain measures of the gut microbiome and fecal metabolome across methods. Choice of method depends on the research interests, simplicity of fecal collection procedures and ease of transportation to the lab, especially for large epidemiological studies.

RevDate: 2018-09-20

Mendonça LABM, Dos Santos Ferreira R, de Cássia Avellaneda Guimarães R, et al (2018)

The Complex Puzzle of Interactions Among Functional Food, Gut Microbiota, and Colorectal Cancer.

Frontiers in oncology, 8:325.

Colorectal cancer exerts a strong influence on the epidemiological panorama worldwide, and it is directly correlated to etiologic factors that are substantiated by genetic and environmental elements. This complex mixture of factors also has a relationship involving the structural dependence and composition of the gut microbiome, leading to a dysbacteriosis process that may evolve to serious modifications in the intestinal lining, eventually causing the development of a neoplasm. The gastrointestinal tract presents defense strategies and immunological properties that interfere in intestinal permeability, inhibiting the bacterial translocation, thus maintaining the integrity of intestinal homeostasis. The modulation of the intestinal microbiome and the extinction of risk factors associated with intestinal balance losses, especially of environmental factors, make cell and defense alterations impossible. This modulation may be conducted by means of functional foods in the diet, especially soluble fibers, polyunsaturated fatty acids, antioxidants and prebiotics that signal immunomodulatory effects in the intestinal microbiota, with preventive and therapeutic action for colorectal cancer. In summary, this review focuses on the importance of dietary modulation of the intestinal microbiota as an instrument for dysbacteriosis and, consequently, for the prevention of colorectal cancer, suggesting anticarcinogenic, and antiangiogenic properties. Among the intestinal modulating agents considered here are functional foods, especially flaxseed, oat and soy, composing a Bioactive Food Compound.

RevDate: 2018-09-20

Lebovitz Y, Ringel-Scaia VM, Allen IC, et al (2018)

Emerging Developments in Microbiome and Microglia Research: Implications for Neurodevelopmental Disorders.

Frontiers in immunology, 9:1993.

From immunology to neuroscience, interactions between the microbiome and host are increasingly appreciated as potent drivers of health and disease. Epidemiological studies previously identified compelling correlations between perinatal microbiome insults and neurobehavioral outcomes, the mechanistic details of which are just beginning to take shape thanks to germ-free and antibiotics-based animal models. This review summarizes parallel developments from clinical and preclinical research that suggest neuroactive roles for gut bacteria and their metabolites. We also examine the nascent field of microbiome-microglia crosstalk research, which includes pharmacological and genetic strategies to inform functional capabilities of microglia in response to microbial programming. Finally, we address an emerging hypothesis behind neurodevelopmental disorders, which implicates microbiome dysbiosis in the atypical programming of neuroimmune cells, namely microglia.

RevDate: 2018-09-20

Black EM, CL Just (2018)

The Genomic Potentials of NOB and Comammox Nitrospira in River Sediment Are Impacted by Native Freshwater Mussels.

Frontiers in microbiology, 9:2061.

Freshwater mussel assemblages of the Upper Mississippi River (UMR) sequester tons of ammonia- and urea-based biodeposits each day and aerate sediment through burrowing activities, thus creating a unique niche for nitrogen (N) cycling microorganisms. This study explored how mussels impact the abundance of N-cycling species with an emphasis on Candidatus Nitrospira inopinata, the first microorganism known to completely oxidize ammonia (comammox) to nitrate. This study used metagenomic shotgun sequencing of genomic DNA to compare nitrogen cycling species in sediment under a well-established mussel assemblage and in nearby sediment without mussels. Metagenomic reads were aligned to the prokaryotic RefSeq non-redundant protein database using BLASTx, taxonomic binning was performed using the weighted lowest common ancestor algorithm, and protein-coding genes were categorized by metabolic function using the SEED subsystem. Linear discriminant analysis (LDA) effect sizes were used to determine which metagenomes and metabolic features explained the most differences between the mussel habitat sediment and sediment without mussels. Of the N-cycling species deemed differentially abundant, Nitrospira moscoviensis and "Candidatus Nitrospira inopinata" were responsible for creating a distinctive N-cycling microbiome in the mussel habitat sediment. Further investigation revealed that comammox Nitrospira had a large metabolic potential to degrade mussel biodeposits, as evidenced the top ten percent of protein-coding genes including the cytochrome c-type biogenesis protein required for hydroxylamine oxidation, ammonia monooxygenase, and urea decomposition SEED subsystems. Genetic marker analysis of these two Nitrospira taxons suggested that N. moscoviensis was most impacted by diverse carbon metabolic processes while "Candidatus Nitrospira inopinata" was most distinguished by multidrug efflux proteins (AcrB), NiFe hydrogenase (HypF) used in hydrogen oxidation and sulfur reduction coupled reactions, and a heme chaperone (CcmE). Furthermore, our research suggests that comammox and NOB Nitrospira likely coexisted by utilizing mixotrophic metabolisms. For example, "Candidatus Nitrospira inopinata" had the largest potentials for ammonia oxidation, nitrite reduction with NirK, and hydrogen oxidation, while NOB Nitrospira had the greatest potential for nitrite oxidation, and nitrate reduction possibly coupled with formate oxidation. Overall, our results suggest that this mussel habitat sediment harbors a niche for NOB and comammox Nitrospira, and ultimately impacts N-cycling in backwaters of the UMR.

RevDate: 2018-09-20

Thomsen M, Clarke S, L Vitetta (2018)

The role of adjuvant probiotics to attenuate intestinal inflammatory responses due to cancer treatments.

Beneficial microbes [Epub ahead of print].

Chemotherapy and radiotherapy treatment regimens for gastrointestinal, peritoneal and pelvic tumours can disrupt the intestinal microbiome and intestinal epithelia. Such disturbances can provoke symptoms such as diarrhoea, nausea and vomiting. Chemotherapy and radiotherapy induced gastrointestinal toxicity aggravating intestinal microbiome dysbiosis is postulated to adversely alter the intestinal microbiome, with a consequent induced pro-inflammatory effect that disrupts the intestinal microbiome-epithelia-mucosal immunity axis. Although not widely recognised, the intestinal mucosa is the largest and most densely and dynamically populated immune-environment. Cancer treatment adverse effects that affect intestinal and mucosal cells inadvertently target and disrupt resident intestinal macrophages, the cells that marshal immune activity in the intestinal mucosa by shaping pro-inflammatory and anti-inflammatory activities to control and eradicate infectious insults and maintain local homeostasis. Pathobionts (bacteria capable of pathogenic pro-inflammatory activity) and noxious environmental and bacterial antigens use the intestinal epithelia and gap junctions as a point of entry into the systemic circulation. This translocation movement promotes toxic sequelae that obstruct intestinal macrophage functions resulting in uncontrolled local and systemic pro-inflammatory activity, loss of phagocytic function and loss of expression of tight junction proteins. Probiotic bacteria as an adjunctive treatment shows efficacy in ameliorating enteropathies such as mucositis/diarrhoea resulting from chemotherapy or radiotherapy regimens. As such we posit that an important benefit that warrants a further focused research effort is the administration of adjuvant probiotics to help reduce the incidence of febrile neutropenia.

RevDate: 2018-09-20

Lu M, Z Wang (2018)

Microbiota and Aging.

Advances in experimental medicine and biology, 1086:141-156.

The human gut microbiota is a huge ecosystem that provides lots of functions for host development, immune system, and metabolism. Gut microbiota is linked to lots of diseases, including human metabolic diseases such as obesity, type 2 diabetes (T2D), irritable bowel syndrome, and cardiovascular disease (CVD). Few studies, however, have noted the relationship between aging and microbiota; the connection between aging and microbiota remains largely to be researched. In this review, recent research findings are summarized on the role of gut microbiota in aging processes with emphasis on therapeutic potential of microbiome-targeted interventions in antiaging medicine.

RevDate: 2018-09-20

Aguirre de Cárcer D (2018)

The human gut pan-microbiome presents a compositional core formed by discrete phylogenetic units.

Scientific reports, 8(1):14069 pii:10.1038/s41598-018-32221-8.

The complex community of microbes living in the human gut plays an important role in host wellbeing. However, defining a 'healthy' gut microbiome in terms of composition has remained an elusive task, despite its anticipated medical and scientific importance. In this regard, a central question has been if there is a 'core' microbiome consisting of bacterial groups common to all healthy humans. Recent studies have been able to define a compositional core in human gut microbiome datasets in terms of taxonomic assignments. However, the description of the core microbiome in terms of taxonomic assignments may not be adequate when considering subsequent analyses and applications. Through the implementation of a dynamic clustering approach in the meta-analyisis of comprehensive 16S rRNA marker gene datasets, this study found that the human gut pan-microbiome presents a preeminent compositional core comprised of discrete units of varying phylogenetic depth present in all individuals studied. Since both microbial traits and ecological coherence show signs of phylogenetic conservation, this outcome provides a new conceptual framework in the study of the ecosystem, as well as important practical considerations which should be taken into account in future research.

RevDate: 2018-09-20

Goltsman DSA, Sun CL, Proctor DM, et al (2018)

Metagenomic analysis with strain-level resolution reveals fine-scale variation in the human pregnancy microbiome.

Genome research pii:gr.236000.118 [Epub ahead of print].

Recent studies suggest that the microbiome has an impact on gestational health and outcome. However, characterization of the pregnancy-associated microbiome has largely relied on 16S rRNA gene amplicon-based surveys. Here, we describe an assembly-driven, metagenomics-based, longitudinal study of the vaginal, gut, and oral microbiomes in 292 samples from 10 subjects sampled every three weeks throughout pregnancy. Nonhuman sequences in the amount of 1.53 Gb were assembled into scaffolds, and functional genes were predicted for gene- and pathway-based analyses. Vaginal assemblies were binned into 97 draft quality genomes. Redundancy analysis (RDA) of microbial community composition at all three body sites revealed gestational age to be a significant source of variation in patterns of gene abundance. In addition, health complications were associated with variation in community functional gene composition in the mouth and gut. The diversity of Lactobacillus iners-dominated communities in the vagina, unlike most other vaginal community types, significantly increased with gestational age. The genomes of co-occurring Gardnerella vaginalis strains with predicted distinct functions were recovered in samples from two subjects. In seven subjects, gut samples contained strains of the same Lactobacillus species that dominated the vaginal community of that same subject and not other Lactobacillus species; however, these within-host strains were divergent. CRISPR spacer analysis suggested shared phage and plasmid populations across body sites and individuals. This work underscores the dynamic behavior of the microbiome during pregnancy and suggests the potential importance of understanding the sources of this behavior for fetal development and gestational outcome.

RevDate: 2018-09-20

Ingala MR, Simmons NB, SL Perkins (2018)

Bats Are an Untapped System for Understanding Microbiome Evolution in Mammals.

mSphere, 3(5): pii:3/5/e00397-18.

Mammals evolved in a microbial world, and consequently, microbial symbionts have played a role in their evolution. An exciting new subdiscipline of metagenomics considers the ways in which microbes, particularly those found in the gut, have facilitated the ecological and phylogenetic radiation of mammals. However, the vast majority of such studies focus on domestic animals, laboratory models, or charismatic megafauna (e.g., pandas and chimpanzees). The result is a plethora of studies covering few taxa across the mammal tree of life, leaving broad patterns of microbiome function and evolution unclear. Wildlife microbiome research urgently needs a model system in which to test hypotheses about metagenomic involvement in host ecology and evolution. We propose that bats (Order: Chiroptera) represent a model system ideal for comparative microbiome research, affording opportunities to examine host phylogeny, diet, and other natural history characteristics in relation to the evolution of the gut microbiome.

RevDate: 2018-09-20

Sharma V, Smolin J, Nayak J, et al (2018)

Mannose Alters Gut Microbiome, Prevents Diet-Induced Obesity, and Improves Host Metabolism.

Cell reports, 24(12):3087-3098.

Mannose is an important monosaccharide for protein glycosylation in mammals but is an inefficient cellular energy source. Using a C57BL6/J mouse model of diet-induced obesity, we show that mannose supplementation of high-fat-diet-fed mice prevents weight gain, lowers adiposity, reduces liver steatosis, increases endurance and maximal O2 consumption, and improves glucose tolerance. Mannose-supplemented mice have higher fecal energy content, suggesting reduced caloric absorption by the host. Mannose increases the Bacteroidetes to Firmicutes ratio in the gut microbiota, a signature associated with the lean phenotype. These beneficial effects of mannose are observed when supplementation is started early in life. Functional transcriptomic analysis of cecal microbiota revealed profound and coherent changes in microbial energy metabolism induced by mannose that are predicted to lead to reduced energy harvest from complex carbohydrates by gut microbiota. Our results suggest that the gut microbiota contributes to mannose-induced resistance to deleterious effects of a high-fat diet. VIDEO ABSTRACT.

RevDate: 2018-09-20

Michel AJ, Ward LM, Goffredi SK, et al (2018)

The gut of the finch: uniqueness of the gut microbiome of the Galápagos vampire finch.

Microbiome, 6(1):167 pii:10.1186/s40168-018-0555-8.

BACKGROUND: Darwin's finches are a clade of 19 species of passerine birds native to the Galápagos Islands, whose biogeography, specialized beak morphologies, and dietary choices-ranging from seeds to blood-make them a classic example of adaptive radiation. While these iconic birds have been intensely studied, the composition of their gut microbiome and the factors influencing it, including host species, diet, and biogeography, has not yet been explored.

RESULTS: We characterized the microbial community associated with 12 species of Darwin's finches using high-throughput 16S rRNA sequencing of fecal samples from 114 individuals across nine islands, including the unusual blood-feeding vampire finch (Geospiza septentrionalis) from Darwin and Wolf Islands. The phylum-level core gut microbiome for Darwin's finches included the Firmicutes, Gammaproteobacteria, and Actinobacteria, with members of the Bacteroidetes at conspicuously low abundance. The gut microbiome was surprisingly well conserved across the diversity of finch species, with one exception-the vampire finch-which harbored bacteria that were either absent or extremely rare in other finches, including Fusobacterium, Cetobacterium, Ureaplasma, Mucispirillum, Campylobacter, and various members of the Clostridia-bacteria known from the guts of carnivorous birds and reptiles. Complementary stable isotope analysis of feathers revealed exceptionally high δ15N isotope values in the vampire finch, resembling top marine predators. The Galápagos archipelago is also known for extreme wet and dry seasons, and we observed a significant seasonal shift in the gut microbial community of five additional finch species sampled during both seasons.

CONCLUSIONS: This study demonstrates the overall conservatism of the finch gut microbiome over short (< 1 Ma) divergence timescales, except in the most extreme case of dietary specialization, and elevates the evolutionary importance of seasonal shifts in driving not only species adaptation, but also gut microbiome composition.

RevDate: 2018-09-20

Vavourakis CD, Andrei AS, Mehrshad M, et al (2018)

A metagenomics roadmap to the uncultured genome diversity in hypersaline soda lake sediments.

Microbiome, 6(1):168 pii:10.1186/s40168-018-0548-7.

BACKGROUND: Hypersaline soda lakes are characterized by extreme high soluble carbonate alkalinity. Despite the high pH and salt content, highly diverse microbial communities are known to be present in soda lake brines but the microbiome of soda lake sediments received much less attention of microbiologists. Here, we performed metagenomic sequencing on soda lake sediments to give the first extensive overview of the taxonomic diversity found in these complex, extreme environments and to gain novel physiological insights into the most abundant, uncultured prokaryote lineages.

RESULTS: We sequenced five metagenomes obtained from four surface sediments of Siberian soda lakes with a pH 10 and a salt content between 70 and 400 g L-1. The recovered 16S rRNA gene sequences were mostly from Bacteria, even in the salt-saturated lakes. Most OTUs were assigned to uncultured families. We reconstructed 871 metagenome-assembled genomes (MAGs) spanning more than 45 phyla and discovered the first extremophilic members of the Candidate Phyla Radiation (CPR). Five new species of CPR were among the most dominant community members. Novel dominant lineages were found within previously well-characterized functional groups involved in carbon, sulfur, and nitrogen cycling. Moreover, key enzymes of the Wood-Ljungdahl pathway were encoded within at least four bacterial phyla never previously associated with this ancient anaerobic pathway for carbon fixation and dissimilation, including the Actinobacteria.

CONCLUSIONS: Our first sequencing effort of hypersaline soda lake sediment metagenomes led to two important advances. First, we showed the existence and obtained the first genomes of haloalkaliphilic members of the CPR and several hundred other novel prokaryote lineages. The soda lake CPR is a functionally diverse group, but the most abundant organisms in this study are likely fermenters with a possible role in primary carbon degradation. Second, we found evidence for the presence of the Wood-Ljungdahl pathway in many more taxonomic groups than those encompassing known homo-acetogens, sulfate-reducers, and methanogens. Since only few environmental metagenomics studies have targeted sediment microbial communities and never to this extent, we expect that our findings are relevant not only for the understanding of haloalkaline environments but can also be used to set targets for future studies on marine and freshwater sediments.

RevDate: 2018-09-20

Eggermont AMM, Crittenden M, J Wargo (2018)

Combination Immunotherapy Development in Melanoma.

American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting.

Melanoma has been the most important cancer to drive immunotherapy development of solid tumors. Since 2010, immunotherapy has been revolutionized by the concept of breaking tolerance. It represents a major paradigm shift and marks the beginning of a new era. The impact of the first immune checkpoint inhibitors, anti-CTLA-4 and anti-PD-1/anti-PD-L1, is unprecedented. In 7 years, it transformed advanced-stage melanoma into a curable disease in over 50% of patients. Another major step has been the development of the combination of BRAF inhibitors plus MEK inhibitors in the treatment of BRAF-mutant melanomas. For the treatment of advanced disease, approvals were obtained for the immune checkpoint inhibitors ipilimumab (2011), nivolumab (2014), pembrolizumab (2014), the combination ipilimumab plus nivolumab (2015), and the oncolytic virus vaccine laherparepvec (2015). The combination dabrafenib plus trametinib for BRAF-mutant melanoma was approved in 2014, with similar success for other BRAF plus MEK inhibitor combinations. Because of its unique therapeutic index (high efficacy and low toxicity) anti-PD-1 agents (nivolumab and pembrolizumab) have now been placed at the center of practically all combination therapy development strategies in melanoma. Anti-PD-1 agents are the central molecule for combinations with a great variety of other immunotherapeutics such as immune checkpoint inhibitors, agonists, IDO inhibitors, macrophage polarizing agents, monoclonal antibodies, vaccines, targeted agents, chemotherapeutics, radiation therapy, and even microbiome modulators.

RevDate: 2018-09-19

Liu J, Cui L, Yan X, et al (2018)

Analysis of Oral Microbiota Revealed High Abundance of Prevotella Intermedia in Gout Patients.

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 49(5):1804-1812 pii:000493626 [Epub ahead of print].

BACKGROUND/AIMS: Microbes reside in a number of body sites, including the oral cavity, and are associated with the progression of many systemic diseases. In this study, we aimed to investigate the effects of gout and hyperuricemia (HUA) on the composition of oral microbiomes.

METHODS: Analysis of the oral microbiota from 12 gout patients, 11 HUA patients, and 19 healthy control subjects was performed using a deep sequencing approach, and validation of significant changes in Prevotella intermedia and Serratia marcescens in new patient cohorts was performed using quantitative PCR (qPCR).

RESULTS: Our analysis indicated that both gout and HUA significantly altered the composition of the oral microbiome in patients. Patients with gout or HUA had significantly greater levels of salivary Prevotella intermedia but significantly lower levels of Serratia marcescens than healthy control subjects.

CONCLUSION: We demonstrated the association between the oral microbiome and gout and HUA for the first time. In particular, 16S sequencing and qPCR analysis revealed significantly higher levels of oral Prevotella intermedia in gout/HUA patients, which suggests that these patients might be at risk for the development of periodontitis.

RevDate: 2018-09-19

Beyer K, Zaura E, Brandt BW, et al (2018)

Subgingival microbiome of rheumatoid arthritis patients in relation to their disease status and periodontal health.

PloS one, 13(9):e0202278 pii:PONE-D-18-01606.

OBJECTIVE: Rheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases that share common risk factors. However, the bidirectional relationship between RA and periodontal disease is not fully understood. This study was undertaken to describe the bacterial component of the subgingival microbiome in RA patients and to relate this to RA disease activity and periodontal status.

METHODS: Patients with chronic established RA (N = 78) were periodontally examined and their subgingival plaque samples were collected; their clinical and laboratory data on RA status and medication were obtained from medical records. Bacterial DNA was quantified by universal 16S rDNA qPCR, and Porphyromonas gingivalis by species-specific qPCR. For microbiome assessment, 16S rDNA amplicon sequencing was performed.

RESULTS: Active RA was diagnosed in 58% of the patients and periodontitis in 82% (mild: 9%, moderate: 55%, severe: 18%). P. gingivalis was present in 14% of the samples. Different levels of gingival bleeding, periodontal probing depth, RA disease status, prednisolone use and smoking were associated with significantly different microbiome compositions. Two subgingival microbial community types were discerned.

CONCLUSION: In RA patients with active disease, anti-inflammatory medication as part of RA therapy was associated with better oral health status and a healthier subgingival microbiome compared to that of RA patients in remission, especially those in remission who were current smokers. RA patients in remission with current smoking status may particularly benefit from a systematic periodontal treatment program. The potential role of microbial community types in patient stratification and personalized therapy should be assessed in longitudinal studies.

RevDate: 2018-09-19

Little MS, Ervin SM, Walton WG, et al (2018)

Active Site Flexibility Revealed in Crystal Structures of Parabacteroides merdae β-Glucuronidase from the Human Gut Microbiome.

Protein science : a publication of the Protein Society [Epub ahead of print].

β-Glucuronidase (GUS) enzymes in the gastrointestinal tract are involved in maintaining mammalian-microbial symbiosis and can play key roles in drug efficacy and toxicity. Parabacteroides merdae GUS was identified as an abundant mini-Loop 2 (mL2) type GUS enzyme in the Human Microbiome Project gut metagenomic database. Here, we report the crystal structure of P. merdae GUS and highlight the differences between this enzyme and extant structures of gut microbial GUS proteins. We find that P. merdae GUS exhibits a distinct tetrameric quaternary structure and that the mL2 motif traces a unique path within the active site, which also includes two arginines distinctive to this GUS. We observe two states of the P. merdae GUS active site; a loop repositions itself by more than 50 Å to place a functionally-relevant residue into the enzyme's catalytic site. Finally, we find that P. merdae GUS is able to bind to homo- and heteropolymers of the polysaccharide alginic acid. Together, these data broaden our understanding of the structural and functional diversity in the GUS family of enzymes present in the human gut microbiome and point to specialization as an important feature of microbial GUS orthologs. This article is protected by copyright. All rights reserved.

RevDate: 2018-09-19

Nichols RG, Cai J, Murray IA, et al (2018)

Structural and Functional Analysis of the Gut Microbiome for Toxicologists.

Current protocols in toxicology [Epub ahead of print].

Characterizing the reciprocal interactions between toxicants, the gut microbiota, and the host, holds great promise for improving our mechanistic understanding of toxic endpoints. Advances in culture-independent sequencing analysis (e.g., 16S rRNA gene amplicon sequencing) combined with quantitative metabolite profiling (i.e., metabolomics) have provided new ways of studying the gut microbiome and have begun to illuminate how toxicants influence the structure and function of the gut microbiome. Developing a standardized protocol is important for establishing robust, reproducible, and importantly, comparative data. This protocol can be used as a foundation for examining the gut microbiome via sequencing-based analysis and metabolomics. Two main units follow: (1) analysis of the gut microbiome via sequencing-based approaches; and (2) functional analysis of the gut microbiome via metabolomics. © 2018 by John Wiley & Sons, Inc.

RevDate: 2018-09-19

Van der Jeught K, Xu HC, Li YJ, et al (2018)

Drug resistance and new therapies in colorectal cancer.

World journal of gastroenterology, 24(34):3834-3848.

Colorectal cancer (CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo- and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo- and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is α-amanitin antibody-drug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors.

RevDate: 2018-09-19

Oikonomou T, Papatheodoridis GV, Samarkos M, et al (2018)

Clinical impact of microbiome in patients with decompensated cirrhosis.

World journal of gastroenterology, 24(34):3813-3820.

Cirrhosis is an increasing cause of morbidity and mortality. Recent studies are trying to clarify the role of microbiome in clinical exacerbation of patients with decompensated cirrhosis. Nowadays, it is accepted that patients with cirrhosis have altered salivary and enteric microbiome, characterized by the presence of dysbiosis. This altered microbiome along with small bowel bacterial overgrowth, through translocation across the gut, is associated with the development of decompensating complications. Studies have analyzed the correlation of certain bacterial families with the development of hepatic encephalopathy in cirrhotics. In general, stool and saliva dysbiosis with reduction of autochthonous bacteria in patients with cirrhosis incites changes in bacterial defenses and higher risk for bacterial infections, such as spontaneous bacterial peritonitis, and sepsis. Gut microbiome has even been associated with oncogenic pathways and under circumstances might promote the development of hepatocarcinogenesis. Lately, the existence of the oral-gut-liver axis has been related with the development of decompensating events. This link between the liver and the oral cavity could be via the gut through impaired intestinal permeability that allows direct translocation of bacteria from the oral cavity to the systemic circulation. Overall, the contribution of the microbiome to pathogenesis becomes more pronounced with progressive disease and therefore may represent an important therapeutic target in the management of cirrhosis.

RevDate: 2018-09-19

Rupf S, Laczny CC, Galata V, et al (2018)

Comparison of initial oral microbiomes of young adults with and without cavitated dentin caries lesions using an in situ biofilm model.

Scientific reports, 8(1):14010 pii:10.1038/s41598-018-32361-x.

Dental caries is caused by acids released from bacterial biofilms. However, the in vivo formation of initial biofilms in relation to caries remains largely unexplored. The aim of this study was to compare the oral microbiome during the initial phase of bacterial colonization for individuals with (CC) and without (NC) cavitated dentin caries lesions. Bovine enamel slabs on acrylic splints were worn by the volunteers (CC: 14, NC: 13) for in situ biofilm formation (2 h, 4 h, 8 h, 1 ml saliva as reference). Sequencing of the V1/V2 regions of the 16S rRNA gene was performed (MiSeq). The relative abundances of individual operational taxonomic units (OTUs) were compared between samples from the CC group and the NC group. Random forests models were furthermore trained to separate the groups. While the overall heterogeneity did not differ substantially between CC and NC individuals, several individual OTUs were found to have significantly different relative abundances. For the 8 h samples, most of the significant OTUs showed higher relative abundances in the CC group, while the majority of significant OTUs in the saliva samples were more abundant in the NC group. Furthermore, using OTU signatures enabled a separation between both groups, with area-under-the-curve (AUC) values of ~0.8. In summary, the results suggest that initial oral biofilms provide the potential to differentiate between CC and NC individuals.

RevDate: 2018-09-19

Zhang M, Ma W, Zhang J, et al (2018)

Analysis of gut microbiota profiles and microbe-disease associations in children with autism spectrum disorders in China.

Scientific reports, 8(1):13981 pii:10.1038/s41598-018-32219-2.

Autism spectrum disorder (ASD) is a set of complex neurodevelopmental disorders. Recent studies reported that children with ASD have altered gut microbiota profiles compared with typical development (TD) children. However, few studies on gut bacteria of children with ASD have been conducted in China. Here, in order to elucidate changes of fecal microbiota in children with ASD, 16S rRNA sequencing was conducted and the 16S rRNA (V3-V4) gene tags were amplified. We investigated differences in fecal microbiota between 35 children with ASD and 6 TD children. At the phylum level, the fecal microbiota of ASD group indicated a significant increase of the Bacteroidetes/Firmicutes ratio. At the genus level, we found that the relative abundance of Sutterella, Odoribacter and Butyricimonas was much more abundant in the ASD group whereas the abundance of Veillonella and Streptococcus was decreased significantly compared to the control group. Functional analysis demonstrated that butyrate and lactate producers were less abundant in the ASD group. In addition, we downloaded the association data set of microbe-disease from human microbe-disease association database and constructed a human disease network including ASD using our gut microbiome results. In this microbe-disease network based on microbe similarity of diseases, we found that ASD is positively correlated with periodontal, negatively related to type 1 diabetes. Therefore, these results suggest that microbe-based disease analysis is able to predict novel connection between ASD and other diseases and may play a role in revealing the pathogenesis of ASD.

RevDate: 2018-09-19

Namasivayam S, Sher A, Glickman MS, et al (2018)

The Microbiome and Tuberculosis: Early Evidence for Cross Talk.

mBio, 9(5): pii:mBio.01420-18.

Tuberculosis (TB) is an ancient infectious disease of humans that has been extensively studied both clinically and experimentally. Although susceptibility to Mycobacterium tuberculosis infection is clearly influenced by factors such as nutrition, immune status, and both mycobacterial and host genetics, the variable pathogenesis of TB in infected individuals remains poorly understood. During the past two decades, it has become clear that the microbiota-the trillion organisms that reside at mucosal surfaces within and on the body-can exert a major influence on disease outcome through its effects on host innate and adaptive immune function and metabolism. This new recognition of the potentially pleiotropic participation of the microbiome in immune responses has raised the possibility that the microbiota may influence M. tuberculosis infection and/or disease. Similarly, treatment of TB may alter the healthy steady-state composition and function of the microbiome, possibly affecting treatment outcome in addition to other host physiological parameters. Herein, we review emerging evidence for how the microbiota may influence the transition points in the life cycle of TB infection, including (i) resistance to initial infection, (ii) initial infection to latent tuberculosis (LTBI), (iii) LTBI to reactivated disease, and (iv) treatment to cure. A major goal of this review is to frame questions to guide future scientific and clinical studies in this largely unexplored but increasingly important area of TB research.

RevDate: 2018-09-19

Rifaat M, Depmeier C, Jeger V, et al (2018)

[CME: Fusobacterium nucleatum/naviforme - a Rare but Serious Cause for Pyogenic Liver Abscesses].

Praxis, 107(19):1007-1012.

CME: Fusobacterium nucleatum/naviforme - a Rare but Serious Cause for Pyogenic Liver Abscesses Abstract. Pyogenic liver abscesses belong to the most common abdominal infections. Beside the most common pathogens, also rare forms like Fusobacteria, which can also be part of the natural oropharyngeal and enteral microbiome, may be considered to cause severe forms of abscesses of the liver. Since they may be more difficult to detect, they could become a challenge during diagnosis and therapy.

RevDate: 2018-08-22

Zhu Y, Zhao F, Li Z, et al (2018)

Current landscape and future directions of biomarkers for predicting responses to immune checkpoint inhibitors.

Cancer management and research, 10:2475-2488 pii:cmar-10-2475.

Immune checkpoint inhibitors (ICIs), represented by anti-CTLA-4 or anti-PD-1/anti-PD-L1 pathway antibodies, have led to a revolution in cancer treatment modalities. ICIs have unique clinical benefits, such as effectiveness against a broad range of tumor types, strong overall impact on survival, and persistent responses after the cessation of therapy. However, only a subset of patients responds to these therapies, and a small proportion of patients even experience rapid progression or an increased risk of death. Therefore, it is imperative to optimize patient selection for treatment. This review focuses on the mechanisms of tumor escape from immune surveillance, the composition and activity of a preexisting immune infiltrate, the degree of tumor foreignness (as reflected by the mutational burden, expression of viral genes, and driver gene mutations), and host factors (including peripheral blood biomarkers, genetic polymorphisms, and gut microbiome) to summarize current evidence on the biomarkers of responses to ICIs and explore the future prospects in this field.

RevDate: 2018-09-18

Johnson MM, S Fernandez-Bussy (2018)

Deciphering the Lung Microbiome: Implications for Lung Health and Disease.

Respiration; international review of thoracic diseases pii:000492753 [Epub ahead of print].

RevDate: 2018-09-18

Reininghaus EZ, Wetzlmair LC, Fellendorf FT, et al (2018)

The Impact of Probiotic Supplements on Cognitive Parameters in Euthymic Individuals with Bipolar Disorder: A Pilot Study.

Neuropsychobiology pii:000492537 [Epub ahead of print].

INTRODUCTION: Cognitive dysfunction is prevalent in depressive as well as manic episodes in individuals with Bipolar Disorder (BD). Even more, after symptom remission, many individuals with BD experience persisting cognitive impairment also in euthymic periods, leading to high illness burden and low quality of life. According to a recent research in animals and healthy humans, microbiota may influence cognitive processes via the brain-gut axis. A strategy to examine the role of the microbiota in different diseases is the intake of supplements that modulate the gut microbiome. The aim of this pilot study was to analyze the impact of probiotic supplements on cognitive parameters in a cohort of euthymic individuals with BD, receiving daily probiotic treatment over a time period of 3 months.

METHODS: A total of 20 euthymic individuals with BD received probiotic supplement over a time period of 3 months and completed a cognitive test battery at 3 time points (t1 at time of inclusion, t2 after one month and t3 after 3 months of probiotic intake).

RESULTS: We found a significant improvement of performance concerning attention and psychomotor processing speed measured with the Digit Symbol Test after one (t2) as well as after 3 months (t3) of treatment (F = 8.60; η2 = 0.49, p < 0.01). Furthermore, executive function measured with the TMT-B, increased significantly over 3 months (F = 3.68; η2 = 0.29, p < 0.05).

CONCLUSION: The results confirm the hypotheses that probiotic supplement might help stable individuals with BD to improve the cognitive function, which in turn might lead to better psychosocial, occupational, work and financial functioning. Nevertheless, the idea of this potential new treatment is challenging because of the variety of the human's gut microbiota.

RevDate: 2018-09-18

Crognale S, Casentini B, Amalfitano S, et al (2018)

Biological As(III) oxidation in biofilters by using native groundwater microorganisms.

The Science of the total environment, 651(Pt 1):93-102 pii:S0048-9697(18)33620-9 [Epub ahead of print].

Arsenic (As) contamination in drinking water represents a worldwide threat to human health. During last decades, the exploitation of microbial As-transformations has been proposed for bioremediation applications. Among biological methods for As-contaminated water treatment, microbial As(III)-oxidation is one of the most promising approaches since it can be coupled to commonly used adsorption removal technologies, without requiring the addition of chemicals and producing toxic by-products. Despite the As(III) oxidation capability has been described in several bacterial pure or enrichment cultures, very little is known about the real potentialities of this process when mixed microbial communities, naturally occurring in As contaminated waters, are used. This study highlighted the contribution of native groundwater bacteria to As(III)-oxidation in biofilters, under conditions suitable for a household-scale treatment system. This work elucidated the influence of a variety of experimental conditions (i.e., various filling materials, flow rates, As(III) inflow concentration, As(III):As(V) ratio, filter volumes) on the microbially-mediated As(III)-oxidation process in terms of oxidation efficiency and rate. The highest oxidation efficiencies (up to 90% in 3 h) were found on coarse sand biofilters treating total initial As concentration of 100 μg L-1. The detailed microbial characterization of the As(III) oxidizing biofilms revealed the occurrence of several OTUs affiliated with families known to oxidize As(III) (e.g., Burkholderiaceae, Comamonadaceae, Rhodobacteraceae, Xanthomonadaceae). Furthermore, As-related functional genes increased in biofilter systems in line with the observed oxidative performances.

RevDate: 2018-09-18

Ahn Y, Jung JY, Veach BT, et al (2018)

In vitro test systems to determine tetracycline residue binding to human feces.

Regulatory toxicology and pharmacology : RTP pii:S0273-2300(18)30235-6 [Epub ahead of print].

The use of antimicrobials, such as tetracycline, in food-producing animals may result in antimicrobial drug residues (ADR) in edible tissues from treated animals and contribute to the emergence of antibiotic resistant bacteria. The Veterinary International Conference on Harmonization (VICH) document (VICH GL36(R)/FDA-CVM Guidance for Industry#159) provides guidance on evaluating the safety of veterinary ADR in the human foods as related to effects on the human intestinal microbiome. One recognized research gap is a need for additional data and testing requirements to determine the fraction of an oral dose of ADR available to intestinal microorganisms. In the present study, we address this need by examining the binding of tetracycline to human feces using chemical and microbiological assays. High-performance liquid chromatography and liquid chromatography mass spectrometry assays showed that 25% (w/v) diluted steam sterilized feces dosed with 0.15 and 1.5 μg/ml tetracycline had binding of 58.2 ± 10.8% and 56.9 ± 9.1%, respectively. Tetracycline binding to fecal slurries gave similar results. Microbiological assays with two reference bacterial strains validated the results of the chemical assays. Based on data from chemical and microbiological assays methods, the fraction of dose available to microorganisms was 0.418 and 0.431 of the 0.15 and 1.5 μg/ml tetracycline treatments, respectively. This study also proposes factors to be considered when designing and conducting experiments to determine the percent of an antimicrobial agents that is available to microorganisms in the gastrointestinal tract.

RevDate: 2018-09-18

Wulff NAA, Fassini CG, Marques VV, et al (2018)

Molecular characterization and detection of 16SrIII group phytoplasma associated with Huanglongbing symptoms.

Phytopathology [Epub ahead of print].

When Huanglongbing (HLB) was found in Brazil in 2004, 'Candidatus Liberibacter americanus' (Lam) was infecting most of the trees while 'Ca. L. asiaticus' (Las) was present in minor proportion. Currently, 'Ca. L. asiaticus' is the predominant bacterium associated with HLB in citrus trees in São Paulo (SP) and Minas Gerais (MG) States, the major citrus growing regions in Brazil. A phytoplasma from 16Sr group IX was associated with HLB symptoms in Brazil in 2007, in plants free of Liberibacter. In this report, HLB-samples testing negative for Las, Lam and 16SrIX phytoplasma, were infected with 16SrIII phytoplasmas. Co-infection with Las and 16SrIII was also found. The 16S rRNA gene sequences from 22 samples were obtained and sequenced, confirming that 16Sr group III phytoplasma is associated with HLB symptoms in SP and MG States. Ten single nucleotide polymorphisms (SNPs) were found in the 1,427 bp 16SrDNA sequences from 16SrIII phytoplasmas from citrus, while none was detected in 16SrDNA sequences among 16SrIX phytoplasma from citrus. Ribosomal protein (rp) rpsSrplVrpsC gene sequences were amplified with 16SrIII group specific primers and sequenced from a subset of nine samples and assembled into three groups based on eight SNPs. SNPs in 16S rRNA and rp gene sequences are common in 16SrIII phytoplasmas from other hosts and this phytoplasma group is widespread in South America. 16SrIII phytoplasmas highly related are commonly found in Melia azedarach, a widespread tree in Brazil and Argentina. The finding of a new phytoplasma associated with HLB symptoms, belonging to the 16SrIII group reinforces the need to develop diagnostic tools to assess HLB associated microbiome.

RevDate: 2018-09-18

Wexler AG, Schofield WB, Degnan PH, et al (2018)

Human gut Bacteroides capture vitamin B12 via cell surface-exposed lipoproteins.

eLife, 7: pii:37138.

Human gut Bacteroides use surface-exposed lipoproteins to bind and metabolize complex polysaccharides. Although vitamins and other nutrients are also essential for commensal fitness, much less is known about how commensal bacteria compete with each other or the host for these critical resources. Unlike in Escherichia coli, transport loci for vitamin B12 (cobalamin) and other corrinoids in human gut Bacteroides are replete with conserved genes encoding proteins whose functions are unknown. Here we report that one of these proteins, BtuG, is a surface-exposed lipoprotein that is essential for efficient B12 transport in B. thetaiotaomicron. BtuG binds B12 with femtomolar affinity and can remove B12 from intrinsic factor, a critical B12 transport protein in humans. Our studies suggest that Bacteroides use surface-exposed lipoproteins not only for capturing polysaccharides, but also to acquire key vitamins in the gut.

RevDate: 2018-09-18

Dranse HJ, Zheng A, Comeau AM, et al (2018)

The impact of chemerin or chemokine-like receptor 1 loss on the mouse gut microbiome.

PeerJ, 6:e5494 pii:5494.

Chemerin is an adipocyte derived signalling molecule (adipokine) that serves as a ligand activator of Chemokine-like receptor 1(CMKLR1). Chemerin/CMKLR1 signalling is well established to regulate fundamental processes in metabolism and inflammation. The composition and function of gut microbiota has also been shown to impact the development of metabolic and inflammatory diseases such as obesity, diabetes and inflammatory bowel disease. In this study, we assessed the microbiome composition of fecal samples isolated from wildtype, chemerin, or CMKLR1 knockout mice using Illumina-based sequencing. Moreover, the knockout mice and respective wildtype mice used in this study were housed at different universities allowing us to compare facility-dependent effects on microbiome composition. While there was no difference in alpha diversity within samples when compared by either facility or genotype, we observed a dramatic difference in the presence and abundance of numerous taxa between facilities. There were minor differences in bacterial abundance between wildtype and chemerin knockout mice, but significantly more differences in taxa abundance between wildtype and CMKLR1 knockout mice. Specifically, CMKLR1 knockout mice exhibited decreased abundance of Akkermansia and Prevotella, which correlated with body weight in CMKLR1 knockout, but not wildtype mice. This is the first study to investigate a linkage between chemerin/CMKLR1 signaling and microbiome composition. The results of our study suggest that chemerin/CMKLR1 signaling influences metabolic processes through effects on the gut microbiome. Furthermore, the dramatic difference in microbiome composition between facilities might contribute to discrepancies in the metabolic phenotype of CMKLR1 knockout mice reported by independent groups. Considered altogether, these findings establish a foundation for future studies to investigate the relationship between chemerin signaling and the gut microbiome on the development and progression of metabolic and inflammatory disease.

RevDate: 2018-09-18

Randolph TW, Zhao S, Copeland W, et al (2018)


The annals of applied statistics, 12(1):540-566.

The analysis of human microbiome data is often based on dimension-reduced graphical displays and clusterings derived from vectors of microbial abundances in each sample. Common to these ordination methods is the use of biologically motivated definitions of similarity. Principal coordinate analysis, in particular, is often performed using ecologically defined distances, allowing analyses to incorporate context-dependent, non-Euclidean structure. In this paper, we go beyond dimension-reduced ordination methods and describe a framework of high-dimensional regression models that extends these distance-based methods. In particular, we use kernel-based methods to show how to incorporate a variety of extrinsic information, such as phylogeny, into penalized regression models that estimate taxonspecific associations with a phenotype or clinical outcome. Further, we show how this regression framework can be used to address the compositional nature of multivariate predictors comprised of relative abundances; that is, vectors whose entries sum to a constant. We illustrate this approach with several simulations using data from two recent studies on gut and vaginal microbiomes. We conclude with an application to our own data, where we also incorporate a significance test for the estimated coefficients that represent associations between microbial abundance and a percent fat.

RevDate: 2018-09-18

Tun MH, Tun HM, Mahoney JJ, et al (2018)

Postnatal exposure to household disinfectants, infant gut microbiota and subsequent risk of overweight in children.

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, 190(37):E1097-E1107.

BACKGROUND: Emerging links between household cleaning products and childhood overweight may involve the gut microbiome. We determined mediating effects of infant gut microbiota on associations between home use of cleaning products and future overweight.

METHODS: From the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort, we tested associations between maternal report of cleaning product use and overweight at age 3, and whether associations were mediated by microbial profiles of fecal samples in 3- to 4-month-old infants.

RESULTS: Among 757 infants, the abundance of specific gut microbiota was associated with household cleaning with disinfectants and eco-friendly products in a dose-dependent manner. With more frequent use of disinfectants, Lachnospiraceae increasingly became more abundant (highest v. lowest quintile of use: adjusted odds ratio [AOR] 1.93, 95% confidence interval [CI] 1.08 to 3.45) while genus Haemophilus declined in abundance (highest v. lowest quintile of use: AOR 0.36, 95% CI 0.20 to 0.65). Enterobacteriaceae were successively depleted with greater use of eco-friendly products (AOR 0.45, 95% CI 0.27 to 0.74). Lachnospiraceae abundance significantly mediated associations of the top 30th centile of household disinfectant use with higher body mass index (BMI) z score (p = 0.02) and with increased odds of overweight or obesity (p = 0.04) at age 3. Use of eco-friendly products was associated with decreased odds of overweight or obesity independently of Enterobacteriaceae abundance (AOR 0.44, 95% CI 0.22 to 0.86), with no significant mediation (p = 0.2).

INTERPRETATION: Exposure to household disinfectants was associated with higher BMI at age 3, mediated by gut microbial composition at age 3-4 months. Although child overweight was less common in households that cleaned with eco-friendly products, the lack of mediation by infant gut microbiota suggests another pathway for this association.

RevDate: 2018-09-18

Leiva-Gea I, Sánchez-Alcoholado L, Martín-Tejedor B, et al (2018)

Gut Microbiota Differs in Composition and Functionality Between Children With Type 1 Diabetes, MODY2, and Healthy Control Subjects: A Case-Control Study.

Diabetes care pii:dc18-0253 [Epub ahead of print].

OBJECTIVE: Type 1 diabetes is associated with compositional differences in gut microbiota. To date, no microbiome studies have been performed in maturity-onset diabetes of the young 2 (MODY2), a monogenic cause of diabetes. Gut microbiota of type 1 diabetes, MODY2, and healthy control subjects was compared.

RESEARCH DESIGN AND METHODS: This was a case-control study in 15 children with type 1 diabetes, 15 children with MODY2, and 13 healthy children. Metabolic control and potential factors modifying gut microbiota were controlled. Microbiome composition was determined by 16S rRNA pyrosequencing.

RESULTS: Compared with healthy control subjects, type 1 diabetes was associated with a significantly lower microbiota diversity, a significantly higher relative abundance of Bacteroides, Ruminococcus, Veillonella, Blautia, and Streptococcus genera, and a lower relative abundance of Bifidobacterium, Roseburia, Faecalibacterium, and Lachnospira. MODY2 showed a significantly higher Prevotella abundance and a lower Ruminococcus and Bacteroides abundance. Proinflammatory cytokines and lipopolisaccharides were increased in type 1 diabetes, and gut permeability (determined by zonulin levels) was significantly increased in type 1 diabetes and MODY2. The PICRUSt analysis found an increment of genes related to lipid and amino acid metabolism, ABC transport, lipopolysaccharide biosynthesis, arachidonic acid metabolism, antigen processing and presentation, and chemokine signaling pathways in type 1 diabetes.

CONCLUSIONS: Gut microbiota in type 1 diabetes differs at taxonomic and functional levels not only in comparison with healthy subjects but fundamentally with regard to a model of nonautoimmune diabetes. Future longitudinal studies should be aimed at evaluating if the modulation of gut microbiota in patients with a high risk of type 1 diabetes could modify the natural history of this autoimmune disease.

RevDate: 2018-09-18

Carthey AJR, Gillings MR, DT Blumstein (2018)

The Extended Genotype: Microbially Mediated Olfactory Communication.

Trends in ecology & evolution pii:S0169-5347(18)30203-9 [Epub ahead of print].

Microbes are now known to influence inter- and intraspecific olfactory signaling systems. They do so by producing metabolites that function as odorants. A unique attribute of such odorants is that they arise as a product of microbial-host interactions. These interactions need not be mutualistic, and indeed can be antagonistic. We develop an integrated ecoevolutionary model to explore microbially mediated olfactory communication and a process model that illustrates the various ways that microbial products might contribute to odorants. This novel approach generates testable predictions, including that selection to incorporate microbial products should be a common feature of infochemicals that communicate identity but not those that communicate fitness or quality. Microbes extend an individual's genotype, but also enhance vulnerability to environmental change.

RevDate: 2018-09-18

Bredon M, Dittmer J, Noël C, et al (2018)

Lignocellulose degradation at the holobiont level: teamwork in a keystone soil invertebrate.

Microbiome, 6(1):162 pii:10.1186/s40168-018-0536-y.

BACKGROUND: Woodlice are recognized as keystone species in terrestrial ecosystems due to their role in the decomposition of organic matter. Thus, they contribute to lignocellulose degradation and nutrient cycling in the environment together with other macroarthropods. Lignocellulose is the main component of plants and is composed of cellulose, lignin and hemicellulose. Its digestion requires the action of multiple Carbohydrate-Active enZymes (called CAZymes), typically acting together as a cocktail with complementary, synergistic activities and modes of action. Some invertebrates express a few endogenous lignocellulose-degrading enzymes but in most species, an efficient degradation and digestion of lignocellulose can only be achieved through mutualistic associations with endosymbionts. Similar to termites, it has been suspected that several bacterial symbionts may be involved in lignocellulose degradation in terrestrial isopods, by completing the CAZyme repertoire of their hosts.

RESULTS: To test this hypothesis, host transcriptomic and microbiome shotgun metagenomic datasets were obtained and investigated from the pill bug Armadillidium vulgare. Many genes of bacterial and archaeal origin coding for CAZymes were identified in the metagenomes of several host tissues and the gut content of specimens from both laboratory lineages and a natural population of A. vulgare. Some of them may be involved in the degradation of cellulose, hemicellulose, and lignin. Reconstructing a lignocellulose-degrading microbial community based on the prokaryotic taxa contributing relevant CAZymes revealed two taxonomically distinct but functionally redundant microbial communities depending on host origin. In parallel, endogenous CAZymes were identified from the transcriptome of the host and their expression in digestive tissues was demonstrated by RT-qPCR, demonstrating a complementary enzyme repertoire for lignocellulose degradation from both the host and the microbiome in A. vulgare.

CONCLUSIONS: Our results provide new insights into the role of the microbiome in the evolution of terrestrial isopods and their adaptive radiation in terrestrial habitats.

RevDate: 2018-09-18

Sitaraman R (2018)

Prokaryotic horizontal gene transfer within the human holobiont: ecological-evolutionary inferences, implications and possibilities.

Microbiome, 6(1):163 pii:10.1186/s40168-018-0551-z.

The ubiquity of horizontal gene transfer in the living world, especially among prokaryotes, raises interesting and important scientific questions regarding its effects on the human holobiont i.e., the human and its resident bacterial communities considered together as a unit of selection. Specifically, it would be interesting to determine how particular gene transfer events have influenced holobiont phenotypes in particular ecological niches and, conversely, how specific holobiont phenotypes have influenced gene transfer events. In this synthetic review, we list some notable and recent discoveries of horizontal gene transfer among the prokaryotic component of the human microbiota, and analyze their potential impact on the holobiont from an ecological-evolutionary viewpoint. Finally, the human-Helicobacter pylori association is presented as an illustration of these considerations, followed by a delineation of unresolved questions and avenues for future research.

RevDate: 2018-09-18

Lin H, He QY, Shi L, et al (2018)

Proteomics and the microbiome: pitfalls and potential.

Expert review of proteomics [Epub ahead of print].

INTRODUCTION: Human symbiotic microbiota are now known to play important roles in human health and disease. Significant progress in our understanding of the human microbiome has been driven by recent technological advances in the fields of genomics, transcriptomics and proteomics. As a complementary method to metagenomics, proteomics is enabling detailed protein profiling of the microbiome to decipher its structure and function and to analyse its relationship with the human body. Faecal proteomics is being increasingly applied to discover and validate potential health and disease biomarkers, and TGA approved instrumentation and a range of clinical assays are being developed that will collectively play key roles in advancing personalized medicine. Areas covered: This review will introduce the complexity of the microbiome and its role in health and disease (in particular the gastrointestinal tract or gut microbiome), discuss current genomic and proteomic methods for studying this system, including the discovery of potential biomarkers, and outline the development of clinically accepted protocols leading to personalized medicine. Expert commentary: Recognition of the important role the microbiome plays in both health and disease is driving current research in this key area. A proteogenomics approach will be essential to unravel the biologies underlying this complex network.

RevDate: 2018-09-18

Lee SH, Yun Y, Kim SJ, et al (2018)

Association between Cigarette Smoking Status and Composition of Gut Microbiota: Population-Based Cross-Sectional Study.

Journal of clinical medicine, 7(9): pii:jcm7090282.

There have been few large-scale studies on the relationship between smoking and gut microbiota. We investigated the relationship between smoking status and the composition of gut microbiota. This was a population-based cross-sectional study using Healthcare Screening Center cohort data. A total of 758 men were selected and divided into three groups: never (n = 288), former (n = 267), and current smokers (n = 203). Among the three groups, there was no difference in alpha diversity, however, Jaccard-based beta diversity showed significant difference (p = 0.015). Pairwise permutational multivariate analysis of variance (PERMANOVA) tests between never and former smokers did not show a difference; however, there was significant difference between never and current smokers (p = 0.017) and between former and current smokers (p = 0.011). Weighted UniFrac-based beta diversity also showed significant difference among the three groups (p = 0.038), and pairwise PERMANOVA analysis of never and current smokers showed significant difference (p = 0.01). In the analysis of bacterial composition, current smokers had an increased proportion of the phylum Bacteroidetes with decreased Firmicutes and Proteobacteria compared with never smokers, whereas there were no differences between former and never smokers. In conclusion, gut microbiota composition of current smokers was significantly different from that of never smokers. Additionally, there was no difference in gut microbiota composition between never and former smokers.

RevDate: 2018-09-17

Mörkl S, Wagner-Skacel J, Lahousen T, et al (2018)

The Role of Nutrition and the Gut-Brain Axis in Psychiatry: A Review of the Literature.

Neuropsychobiology pii:000492834 [Epub ahead of print].

INTRODUCTION: Individuals suffering from psychiatric disorders experience high levels of illness burden and a significantly reduced quality of life. Despite targeted psychopharmacological strategies and complementary psychotherapeutic procedures only moderate effects are obtained, and the risk of relapse is high in many patients. Worldwide, psychiatric diseases such as depression are continuously increasing, challenging the personal life of the affected as well as their families, but also whole societies by increasing disability, early retirement and hospitalization. According to current scientific knowledge psychiatric disorders are caused by a multifactorial pathogenesis, including genetics, inflammation and neurotransmitter imbalance; furthermore, also lifestyle-associated factors gain rising importance. In line with this, there is growing evidence that the gut microbiota and nutrition have an impact on the onset and course of psychiatric disorders.

AIM: This narrative review highlights the important role of nutrition in psychiatric care and underlines the significance of nutritional advice in the multifactorial, biopsychosocial treatment of patients. It focuses on current dietary interventions such as the Mediterranean diet, dietary supplements and modifications of the gut microbiota with pre-, pro- and postbiotics.

RESULTS: Recent studies support the connection between the quality of diet, gut microbiota and mental health through regulation of metabolic functions, anti-inflammatory and antiapoptotic properties and the support of neurogenesis. Dietary coaching to improve mental health seems to be an additional, cost-effective, practical, nonpharmacological intervention for individuals with psychiatric disorders.

CONCLUSION: The use of nutritional interventions in psychiatry equips therapists with a promising tool for both the prevention and treatment of psychiatric disorders. Besides pharmacological therapy, psychotherapy and physical activity, nutritional interventions are an important pillar in the multifactorial, biopsychosocial treatment of psychiatric disease and could be used as a potential therapeutic target.

RevDate: 2018-09-17

Heilmann RM, JM Steiner (2018)

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs.

Journal of veterinary internal medicine [Epub ahead of print].

Chronic inflammatory enteropathies (CIE) in dogs are a group of disorders that are characterized by chronic persistent or recurrent signs of gastrointestinal disease and histologic evidence of mucosal inflammation. These CIEs are classified as either food-responsive, antibiotic-responsive, or immunosuppressant-responsive enteropathy. Patients not clinically responding to immunomodulatory treatment are grouped as nonresponsive enteropathy and dogs with intestinal protein loss as protein-losing enteropathy. Disease-independent clinical scoring systems were established in dogs for assessment of clinical disease severity and patient monitoring during treatment. Histopathologic and routine clinicopathologic findings are usually not able to distinguish the subgroups of CIE. Treatment trials are often lengthy and further diagnostic tests are usually at least minimally invasive. Biomarkers that can aid in defining the presence of disease, site of origin, severity of the disease process, response to treatment, or a combination of these would be clinically useful in dogs with CIE. This article summarizes the following biomarkers that have been evaluated in dogs with CIE during the last decade, and critically evaluates their potential clinical utility in dogs with CIE: functional biomarkers (cobalamin, methylmalonic acid, folate, α1 -proteinase inhibitor, immunoglobulin A), biochemical biomarkers (C-reactive protein, perinuclear anti-neutrophilic cytoplasmic antibodies, 3-bromotyrosine, N-methylhistamine, calprotectin, S100A12, soluble receptor of advanced glycation end products, cytokines and chemokines, alkaline phosphatase), microbiomic biomarkers (microbiome changes, dysbiosis index), metabolomic biomarkers (serum metabolome), genetic biomarkers (genomic markers, gene expression changes), and cellular biomarkers (regulatory T cells). In addition, important performance criteria of diagnostic tests are briefly reviewed.

RevDate: 2018-09-17

Sikora M, Chrabąszcz M, Maciejewski C, et al (2018)

Intestinal barrier integrity in patients with plaque psoriasis.

The Journal of dermatology [Epub ahead of print].

Psoriasis is a chronic inflammatory systemic disease. Growing evidence suggests that human homeostasis depends on a mutualistic relationship with gut bacteria that produce a number of biologically active compounds. Therefore, enteric microbiota dysbiosis with gut barrier disruption may be an important factor in the development of chronic inflammatory diseases. The aim of our study was to assess non-invasive markers of intestinal barrier integrity in patients with moderate to severe psoriasis. Concentrations of claudin-3 (intestinal epithelial tight junction structure) and intestinal fatty acid binding protein (I-FABP; marker of enterocyte damage) were determined in the blood of patients with chronic plaque psoriasis (n = 20) and healthy individuals (n = 20) using commercially available enzyme-linked immunoassay test kits. Claudin-3 concentration was higher in patients with psoriasis compared with healthy control (median, 54.07 vs 42.36 ng/mL; P < 0.001). Patients with psoriasis also had elevated concentration of plasma I-FABP (median, 708.8 vs 147.1 pg/mL; P < 0.05). Our results support the hypothesis that dysfunction of the intestinal barrier in psoriasis disturbs the homeostatic equilibrium between the microbiota and immune system. Further studies are needed in order to develop new therapeutic interventions based on modulation of intestinal permeability.

RevDate: 2018-09-17

Vida A, Kardos G, Kovács T, et al (2018)

Deletion of poly(ADP‑ribose) polymerase-1 changes the composition of the microbiome in the gut.

Molecular medicine reports [Epub ahead of print].

Poly(adenosine diphosphate‑ribose) polymerase (PARP)‑1 is the prototypical PARP enzyme well known for its role in DNA repair and as a pro‑inflammatory protein. Since PARP1 is an important co‑factor of several other pro‑inflammatory proteins, in the present study the possible changes in microbial flora of PARP1 knockout mice were investigated. Samples from the duodenum, cecum and feces from wild type and PARP1 knockout C57BL/6J male mice were collected and 16S ribosomal RNA genes were sequenced. Based on the sequencing results, the microbiome and compared samples throughout the lower part of the gastrointestinal system were reconstructed. The present results demonstrated that the lack of PARP1 enzyme only disturbed the microbial flora of the duodenum, where the biodiversity increased in the knockout animals on the species level but decreased on the order level. The most prominent change was the overwhelming abundance of the family Porphyromonadaceae in the duodenum of PARP1‑/‑ animals, which disappeared in the cecum and feces where families were spread out more evenly than in the wild type animals. The findings of the present study may improve current understanding of the role of PARP1 in chronic inflammatory diseases.

RevDate: 2018-09-17

Vargas-Albores F, Martínez-Córdova LR, Martínez-Porchas M, et al (2018)

Functional metagenomics: a tool to gain knowledge for agronomic and veterinary sciences.

Biotechnology & genetic engineering reviews [Epub ahead of print].

The increased global demand for food production has motivated agroindustries to increase their own levels of production. Scientific efforts have contributed to improving these production systems, aiding to solve problems and establishing novel conceptual views and sustainable alternatives to cope with the increasing demand. Although microorganisms are key players in biological systems and may drive certain desired responses toward food production, little is known about the microbial communities that constitute the microbiomes associated with agricultural and veterinary activities. Understanding the diversity, structure and in situ interactions of microbes, together with how these interactions occur within microbial communities and with respect to their environments (including hosts), constitutes a major challenge with an enormous relevance for agriculture and biotechnology. The emergence of high-throughput sequencing technologies, together with novel and more accessible bioinformatics tools, has allowed researchers to learn more about the functional potential and functional activity of these microbial communities. These tools constitute a relevant approach for understanding the metabolic processes that can occur or are currently occurring in a given system and for implementing novel strategies focused on solving production problems or improving sustainability. Several 'omics' sciences and their applications in agriculture are discussed in this review, and the usage of functional metagenomics is proposed to achieve substantial advances for food agroindustries and veterinary sciences.

RevDate: 2018-09-17

Zhou D, Huang XF, Guo J, et al (2018)

Trichoderma gamsii affected herbivore feeding behaviour on Arabidopsis thaliana by modifying the leaf metabolome and phytohormones.

Microbial biotechnology [Epub ahead of print].

Plants can re-programme their transcriptome, proteome and metabolome to deal with environmental and biotic stress. It has been shown that the rhizosphere microbiome has influence on the plant metabolome and on herbivore behaviour. In the present study, Trichoderma gamsii was isolated from Arabidopsis thaliana rhizosphere soil. The inoculation of roots of Arabidopsis thaliana with T. gamsii significantly inhibited the feeding behaviour of Trichoplusia ni and affected the metabolome as well as the content of phytohormones in Arabidopsis leaves. T. gamsii-treated plant leaves had higher levels of amino acids and lower concentrations of sugars. In addition, T. gamsii-treated plant leaves had more abscisic acid (ABA) and lower levels of salicylic acid (SA) and indole-3-acetic acid (IAA) in comparison with the untreated plants. Furthermore, the inoculation with T. gamsii on different signalling mutants showed that the induction of defences were SA-dependent. These findings indicate that T. gamsii has potential as a new type of biocontrol agent to promote plant repellence to insect attacks.

RevDate: 2018-09-17

Holtorf A, Conrad A, Holzmann B, et al (2018)

Cell-type specific MyD88 signaling is required for intestinal tumor initiation and progression to malignancy.

Oncoimmunology, 7(8):e1466770 pii:1466770.

The signal adapter MyD88, an essential component of Toll-like receptor (TLR) signaling, is important for gut-microbiome interactions. However, its contribution to cancer and its cell-type specific functions are controversially discussed. Therefore, we generated new tissue-specific mouse models and analyzed the clinical importance in human colorectal cancer. A gene-trap was inserted into the murine Myd88 gene (Myd88LSL), yielding MyD88-deficient background with Cre-mediated re-expression in myeloid (MYEL) or intestinal epithelial cells (IECs). These lines were bred with the Apc1638N model that develops invasive adenocarcinoma and analyzed at 12 months. Further, two patient collectives of colorectal cancer (n = 61, and n = 633) were analyzed for expression of Myd88 and TLRs. MyD88 expression was significantly increased in carcinomas, and increased intratumoral levels of MyD88 and TLR pathway components were associated with significantly shorter disease-free (P = .011), and overall survival (P < .0001). In accordance, fully MyD88-deficient mice showed highly significantly decreased tumor incidence, tumor numbers, increased survival, and, importantly, fully lacked malignant lesions. Thus, MyD88 is essential for tumorigenesis and especially progression to malignancy. Tissue-specific re-expression of MyD88 highly significantly increased tumor initiation by differing mechanisms. In intestinal epithelia, MyD88 enhanced epithelial turnover, whereas in myeloid cells, it led to increased production of tumor- and stemness-enhancing cytokines, significantly associated with altered expression of adaptive immune genes. However, neither re-expression of MyD88 in IECs or myeloid cells was sufficient for malignant progression to carcinoma. Thus, MyD88 crucially contributes to colorectal cancer initiation and progression with non-redundant and cell-type specific functions, constituting an attractive therapeutic target.

RevDate: 2018-09-17

Dhoble AS, Lahiri P, KD Bhalerao (2018)

Machine learning analysis of microbial flow cytometry data from nanoparticles, antibiotics and carbon sources perturbed anaerobic microbiomes.

Journal of biological engineering, 12:19 pii:112.

Background: Flow cytometry, with its high throughput nature, combined with the ability to measure an increasing number of cell parameters at once can surpass the throughput of prevalent genomic and metagenomic approaches in the study of microbiomes. Novel computational approaches to analyze flow cytometry data will result in greater insights and actionability as compared to traditional tools used in the analysis of microbiomes. This paper is a demonstration of the fruitfulness of machine learning in analyzing microbial flow cytometry data generated in anaerobic microbiome perturbation experiments.

Results: Autoencoders were found to be powerful in detecting anomalies in flow cytometry data from nanoparticles and carbon sources perturbed anaerobic microbiomes but was marginal in predicting perturbations due to antibiotics. A comparison between different algorithms based on predictive capabilities suggested that gradient boosting (GB) and deep learning, i.e. feed forward artificial neural network with three hidden layers (DL) were marginally better under tested conditions at predicting overall community structure while distributed random forests (DRF) worked better for predicting the most important putative microbial group(s) in the anaerobic digesters viz. methanogens, and it can be optimized with better parameter tuning. Predictive classification patterns with DL (feed forward artificial neural network with three hidden layers) were found to be comparable to previously demonstrated multivariate analysis. The potential applications of this approach have been demonstrated for monitoring the syntrophic resilience of the anaerobic microbiomes perturbed by synthetic nanoparticles as well as antibiotics.

Conclusion: Machine learning can benefit the microbial flow cytometry research community by providing rapid screening and characterization tools to discover patterns in the dynamic response of microbiomes to several stimuli.

RevDate: 2018-09-17

Dickson K, Liu S, Zhou J, et al (2018)

Selective sensitivity of the gut microbiome to iron chelators in polybacterial abdominal sepsis.

Medical hypotheses, 120:68-71.

Iron chelation has been proposed as a potential therapy for polybacterial abdominal sepsis. Treatment with iron chelation is known to be able to attenuate bacterial growth. It is hypothesized that the different types of bacteria will exhibit variations in their sensitivity to iron chelation based on differences in their iron metabolism. Bacteria with weaker iron access systems might have their growth reduced initially, but stronger species may also be suppressed. Gram-positive and Gram-negative bacteria are known to possess different iron acquisition systems, which may affect their response to iron chelation. Bacteria which can produce siderophores are at a particular advantage for iron acquisition. Novel iron chelators, which do not act as xenosiderophores, may be effective in depriving these bacteria of iron. This has implications for the treatment of polybacterial sepsis, which might be enhanced if the sensitivity to iron chelation of the primary causative agents is known.

RevDate: 2018-09-17

Sandgren AM, RJM Brummer (2018)

ADHD-originating in the gut? The emergence of a new explanatory model.

Medical hypotheses, 120:135-145.

The microbiome-gut-brain axis paradigm explains that alterations in the central nervous system and behavior may be secondary to functional changes in the gut in general and more specifically the enteric nervous system. An unfavorable development of the intestinal microbial ecosystem, leading to e.g. a diminished microbial diversity, may play a central role. This paper outlines, and describes the theoretical basis of, a novel integrative model explaining the etiology and pathogenesis of ADHD in a microbiota-gut-brain context, taking into account the complexity of the bi-directional signaling between the gut and the brain.


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 )