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Bibliography on: Microbiome

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ESP: PubMed Auto Bibliography 20 Mar 2019 at 01:43 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: 2019-03-19

Cui HL, Duan GL, Zhang H, et al (2019)

Microbiota in Non-flooded and Flooded Rice Culms.

FEMS microbiology ecology pii:5393367 [Epub ahead of print].

Rice plants are the habitat for large and diverse populations of microbes, which play important roles on rice health and productivity. However, the response of microbiome on rice culm to water flooding is poorly understood. In this study, the bacterial community on non-flooded (RSA) and flooded (RSB) rice culms was investigated through 16S rRNA gene sequencing. The results showed that RSA and RSB had significantly distinct bacterial communities. In RSA, Gammaproteobacteria and Pantoea were the most abundant class (57%), genus (37.06%), respectively, while in RSB, the most abundant phylum and genus was Firmicutes (54%) and Bacillus (52.63%), respectively. Compared with RSA, the abundance of 27 genera significantly increased and 21 genera significantly decreased in RSB, and some remarkably changed species, such as Aeromonas, Bacillus were identified, which are sensitive to non-flooded or flooded conditions. In addition, rare operational taxonomic units (OTUs) was much more than abundant OTUs in all samples, and RSB had significantly higher bacterial richness than RSA due to having more rare taxa. Our study would advance the insights into the microbiome of rice culms and its response to flooding, which would help to identify potential beneficial bacteria for improving crop health and sustainable productivity in agroecosystems.

RevDate: 2019-03-19

Portillo A, Palomar AM, de Toro M, et al (2019)

Exploring the bacteriome in anthropophilic ticks: To investigate the vectors for diagnosis.

PloS one, 14(3):e0213384 pii:PONE-D-18-28858.

OBJECTIVE: The aim of this study was to characterize the bacterial microbiome of hard ticks with affinity to bite humans in La Rioja (North of Spain).

METHODS: A total of 88 adult ticks (22 Rhipicephalus sanguineus sensu lato, 27 Haemaphysalis punctata, 30 Dermacentor marginatus and 9 Ixodes ricinus) and 120 I. ricinus nymphs (CRETAV collection, La Rioja, Spain), representing the main anthropophilic species in our environment, were subjected to a metagenomic analysis of the V3-V4 region of the 16S rRNA gene using an Illumina MiSeq platform. Data obtained with Greengenes database were refined with BLAST. Four groups of samples were defined, according to the four tick species.

RESULTS: Proteobacteria was the predominant phylum observed in all groups. Gammaproteobacteria was the most abundant class, followed by Alphaproteobacteria for R. sanguineus, H. punctata and D. marginatus but the relative abundance of reads for these classes was reversed for I. ricinus. This tick species showed more than 46% reads corresponding to 'not assigned' OTUs (Greengenes), and >97% of them corresponded to 'Candidatus Midichloriaceae' using BLAST. Within Rickettsiales, 'Candidatus Midichloria', Rickettsia, Ehrlichia, 'Candidatus Neoehrlichia' and Wolbachia were detected. I. ricinus was the most alpha-diverse species. Regarding beta-diversity, I. ricinus and H. punctata samples grouped according to their tick species but microbial communities of some R. sanguineus and D. marginatus specimens clustered together.

CONCLUSIONS: The metagenomics approach seems useful to discover the spectrum of tick-related bacteria. More studies are needed to identify and differentiate bacterial species, and to improve the knowledge of tick-borne diseases in Spain.

RevDate: 2019-03-19

Foysal MJ, Momtaz F, Kawser AQMR, et al (2019)

Microbiome patterns reveal the transmission of pathogenic bacteria in hilsa fish (Tenualosa ilisha) marketed for human consumption in Bangladesh.

Journal of applied microbiology [Epub ahead of print].

AIMS: This study conducted bacterial community, virulence and antibiogram profiling inside the hindgut and skin of freshly caught hilsa fish and those sold at markets.

METHODS AND RESULTS: The results of 16S rRNA-based high-throughput sequencing showed a higher number of bacterial genera in marketed fish samples than in fresh fish samples. The total operational taxonomic units (OTU), genus counts and diversity index were significantly higher (p > 0.05) in marketed fish, which also had abundant pathogenic bacterial groups. Skin samples had a lower profusion of pathogenic bacteria than gut samples. A total of 52 bacterial isolates from nine species were identified in this study, of which 25 were from a Chittagong market and 22 were from a Dhaka market, while only five were from fresh hilsa. The PCR amplification of 12 species-specific virulence genes in the 52 isolates, namely, aer, hly, chxA, toxB, rtxC, sfa, uge, norB, trx, toxA, ipaH, sigA and coa, indicated a high number of positive samples containing Vibrio cholerae, Aeromonas spp., Klebsiella pneumoniae, Escherichia coli and Staphylococcus aureus. Antibiogram profiling of these bacteria against ten commercial antibiotics showed high resistance patterns of the isolates against sulfamethoxazole, kanamycin, neomycin, ampicillin and tetracycline.

CONCLUSION: The results reveal the spread of multidrug-resistant bacteria in hilsa fish marketed for human consumption in Bangladesh.

The present study highlights the risk of spreading environmentally- and clinically-pathogenic bacteria in fish sold for human consumption in Bangladesh. Such bacteria come from aquatic pollution and poor handling, storage and transportation practices that may predispose fish to major outbreaks of infectious and waterborne diseases. This article is protected by copyright. All rights reserved.

RevDate: 2019-03-19

Wang G, Yu Y, Wang YZ, et al (2019)

Role of SCFAs in gut microbiome and glycolysis for colorectal cancer therapy.

Journal of cellular physiology [Epub ahead of print].

Increased risk of colorectal cancer (CRC) is associated with altered intestinal microbiota as well as short-chain fatty acids (SCFAs) reduction of output The energy source of colon cells relies mainly on three SCFAs, namely butyrate (BT), propionate, and acetate, while CRC transformed cells rely mainly on aerobic glycolysis to provide energy. This review summarizes recent research results for dysregulated glucose metabolism of SCFAs, which could be initiated by gut microbiome of CRC. Moreover, the relationship between SCFA transporters and glycolysis, which may correlate with the initiation and progression of CRC, are also discussed. Additionally, this review explores the linkage of BT to transport of SCFAs expressions between normal and cancerous colonocyte cell growth for tumorigenesis inhibition in CRC. Furthermore, the link between gut microbiota and SCFAs in the metabolism of CRC, in addition, the proteins and genes related to SCFAs-mediated signaling pathways, coupled with their correlation with the initiation and progression of CRC are also discussed. Therefore, targeting the SCFA transporters to regulate lactate generation and export of BT, as well as applying SCFAs or gut microbiota and natural compounds for chemoprevention may be clinically useful for CRCs treatment. Future research should focus on the combination these therapeutic agents with metabolic inhibitors to effectively target the tumor SCFAs and regulate the bacterial ecology for activation of potent anticancer effect, which may provide more effective application prospect for CRC therapy.

RevDate: 2019-03-19

Wang L, M Mazzola (2019)

Field evaluation of reduced rate Brassicaceae seed meal amendment and rootstock genotype on the microbiome and control of apple replant disease.

Phytopathology [Epub ahead of print].

An orchard field trial was conducted to assess the utility of reduced rate Brassicaceae seed meal (SM) amendment in concert with specific rootstock genotypes for effective control of apple replant disease. Three amendment rates of a 1:1 formulation of Brassica juncea/Sinapis alba SM were compared to pre-plant 1,3-dichloropropene/chloropicrin soil fumigation for disease control efficacy. When applied at the highest rate (6.6 t ha-1) in the spring of planting, SM caused significant phytotoxicity and tree mortality, which was higher for Gala.M26 than Gala.G41 but was not observed at SM application rates of 2.2 or 4.4 t ha-1. SM treatment resulted in growth and yield increases of Gala.M.26 and Gala.G.41 trees in a manner similar to the fumigation treatment and significantly greater than the no treatment control. Tree growth in soils treated with SM at 4.4 t ha-1 was similar or superior to that obtained with SM at 6.6 t ha-1 and superior to that attained at a SM application rate of 2.2 t ha-1. Soil fumigation and all SM treatments reduced Pratylenchus penetrans root infestation relative to the control treatment at the end of the initial growing season. Lesion nematode root densities in the fumigation treatment, but not SM treatments, rapidly recovered and were indistinguishable from the control at the end of the second growing season. Soil fumigation and all SM treatments significantly suppressed Pythium spp. root infection relative to the control. Trees grafted to rootstock G.41 possessed lower P. penetrans root densities relative to trees grafted to rootstock M.26. One year after planting, composition of microbial communities from SM-amended soils was distinct from those detected in control and fumigated soils, and the differences were amplified with increasing SM application rate. Specific fungal and bacterial phyla associated with suppression of plant pathogens were more abundant in SM-treated soil relative to the control and were similar in abundance in 4.4 and 6.6 t ha-1 SM treatments. Findings from this study demonstrated that use of the appropriate apple rootstock genotype will allow for effective replant disease control at SM application rates significantly less than that utilized previously (6.6 t ha-1).

RevDate: 2019-03-19

Dąbrowska K (2019)

Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review.

Medicinal research reviews [Epub ahead of print].

Bacteriophages are not forgotten viruses anymore: scientists and practitioners seek to understand phage pharmacokinetics in animals and humans, investigating bacteriophages as therapeutics, nanocarriers or microbiome components. This review provides a comprehensive overview of factors that determine phage circulation, penetration, and clearance, and that in consequence determine phage applicability for medicine. It makes use of experimental data collected by the phage community so far (PubMed 1924-2016, including non-English reports), combining elements of critical and systematic review. This study covers phage ability to enter a system by various routes of administration, how (and if) the phage may access various tissues and organs, and finally what mechanisms determine the courses of phage clearance. The systematic review method was applied to analyze (i) phage survival in the gut (gut transit) and (ii) phage ability to enter the mammalian system by many administration routes. Aspects that have not yet been covered by a sufficient number of reports for mathematical analysis, as well as mechanisms underlying trends, are discussed in the form of a critical review. In spite of the extraordinary diversity of bacteriophages and possible phage applications, the analysis revealed that phage morphology, phage specificity, phage dose, presence of sensitive bacteria or the characteristics of treated individuals (age, taxonomy) may affect phage bioavailability in animals and humans. However, once phages successfully enter the body, they reach most organs, including the central nervous system. Bacteriophages are cleared mainly by the immune system: innate immunity removes phages even when no specific response to bacteriophages has yet developed.

RevDate: 2019-03-19

Fayfman M, Flint K, S Srinivasan (2019)

Obesity, Motility, Diet, and Intestinal Microbiota-Connecting the Dots.

Current gastroenterology reports, 21(4):15 pii:10.1007/s11894-019-0680-y.

PURPOSE OF REVIEW: The goal of the present review is to explore the relationship between dietary changes and alterations in gut microbiota that contribute to disorders of gut motility and obesity.

RECENT FINDINGS: We review the microbiota changes that are seen in obesity, diarrhea, and constipation and look at potential mechanisms of how dysbiosis can predispose to these. We find that microbial metabolites, particularly short chain fatty acids, can lead to signaling changes in the host enterocytes. Microbial alteration leading to both motility disorders and obesity may be mediated by the release of hormones including glucagon-like peptides 1 and 2 (GLP-1, GLP-2) and polypeptide YY (PYY). These pathways provide avenues for microbiota-targeted interventions that can treat both disorders of motility and obesity. In summary, multiple mechanisms contribute to the interplay between the microbial dysbiosis, obesity, and dysmotility.

RevDate: 2019-03-19

Gu L, Xu Y, Xu W, et al (2019)

The exosome secretion inhibitor neticonazole suppresses intestinal dysbacteriosis-induced tumorigenesis of colorectal cancer.

Investigational new drugs pii:10.1007/s10637-019-00759-7 [Epub ahead of print].

Colorectal cancer (CRC) is the most frequently encountered malignancy associated with the rectum or colon, and accumulating evidences have implicated intestinal dysbacteriosis (IDB, disruption of gut microbiome) and exosomes in the pathology of CRC. We aimed to investigate the effect of IDB on exosome secretion in a CRC xenograft mouse model. An IDB mouse model was established and was inoculated with the CRC cell line SW480 as a xenograft tumor. Tumor growth was monitored for 15 days in sham and IDB mice, after which blood was collected to assess serum exosome secretion. A novel exosome secretion inhibitor, neticonazole, was administered to IDB mice bearing CRC xenograft tumors, followed by monitoring of tumor growth and mouse survival. Western blot analysis was performed in xenograft tumors to investigate the underlying molecular mechanism. IDB promoted CRC xenograft tumor growth and exosome secretion, which could be inhibited by the exosome secretion inhibitor neticonazole. Moreover, neticonazole treatment significantly improved the survival of IDB mice with CRC xenograft tumors, likely through increasing apoptosis of CRC xenograft tumor cells. The exosome secretion inhibitor neticonazole may serve as a promising therapeutic candidate against CRC by suppressing IDB-induced CRC tumorigenesis.

RevDate: 2019-03-19

Gong J, Chehrazi-Raffle A, Placencio-Hickok V, et al (2019)

The gut microbiome and response to immune checkpoint inhibitors: preclinical and clinical strategies.

Clinical and translational medicine, 8(1):9 pii:10.1186/s40169-019-0225-x.

There is growing interest in identifying predictive biomarkers for inhibitors of programmed cell death protein 1 receptor (PD-1), programmed death ligand 1 (PD-L1), and cytotoxic T-lymphocyte associated protein 4 (CTLA-4). Given the links between the stool microbiota, anticancer immunosurveillance, and general health, the composition of the gut microbiome has recently undergone investigation as a biomarker for immunotherapy. In this review, we highlight published results from preclinical and clinical studies to date supporting a relationship between the gut microbiome and antitumor efficacy of immune checkpoint inhibitors. Despite the promising and hypothesis-generating findings that have been produced in this arena to date, there remain some inconsistencies amongst present data that may need to be resolved to contribute to further development. Among these, a better understanding of the immunomodulatory function of the microbiome, standardization in sampling, sequencing techniques, and data analysis, and ensuring uniformity across various aspects of study design are warranted in conducting future prospective studies seeking to validate the gut microbiome as a potential biomarker of response to checkpoint blockade.

RevDate: 2019-03-19

Eisenhofer R, LS Weyrich (2019)

Assessing alignment-based taxonomic classification of ancient microbial DNA.

PeerJ, 7:e6594 pii:6594.

The field of palaeomicrobiology-the study of ancient microorganisms-is rapidly growing due to recent methodological and technological advancements. It is now possible to obtain vast quantities of DNA data from ancient specimens in a high-throughput manner and use this information to investigate the dynamics and evolution of past microbial communities. However, we still know very little about how the characteristics of ancient DNA influence our ability to accurately assign microbial taxonomies (i.e. identify species) within ancient metagenomic samples. Here, we use both simulated and published metagenomic data sets to investigate how ancient DNA characteristics affect alignment-based taxonomic classification. We find that nucleotide-to-nucleotide, rather than nucleotide-to-protein, alignments are preferable when assigning taxonomies to short DNA fragment lengths routinely identified within ancient specimens (<60 bp). We determine that deamination (a form of ancient DNA damage) and random sequence substitutions corresponding to ∼100,000 years of genomic divergence minimally impact alignment-based classification. We also test four different reference databases and find that database choice can significantly bias the results of alignment-based taxonomic classification in ancient metagenomic studies. Finally, we perform a reanalysis of previously published ancient dental calculus data, increasing the number of microbial DNA sequences assigned taxonomically by an average of 64.2-fold and identifying microbial species previously unidentified in the original study. Overall, this study enhances our understanding of how ancient DNA characteristics influence alignment-based taxonomic classification of ancient microorganisms and provides recommendations for future palaeomicrobiological studies.

RevDate: 2019-03-19

Scott JE, GA O'Toole (2019)

The Yin and Yang of Streptococcus Lung Infections in Cystic Fibrosis: A Model for Studying Polymicrobial Interactions.

Journal of bacteriology pii:JB.00115-19 [Epub ahead of print].

The streptococci are increasingly recognized as a core component of the cystic fibrosis (CF) lung microbiome, yet the role that they play in CF lung disease is unclear. The presence of Streptococcus milleri group (SMG, also known as the anginosus group streptococci, AGS) correlates with exacerbation when these microbes are the predominant species in the lung. In contrast, microbiome studies have indicated that increased relative abundance of streptococci in the lung, including members of the oral microflora, correlates with less severe impacts on lung disease compared to other CF-associated microflora, indicating a complex role for this genus in the context of CF. Recent findings suggest that streptococci in the CF lung microenvironment may influence the growth and/or virulence of other CF pathogens as evidenced by increased virulence factor production by Pseudomonas aeruginosa when grown in coculture with oral streptococci. Conversely, the presence of P. aeruginosa can enhance the growth of streptococci, including members of the SMG, a phenomenon that could be exacerbated by the fact that streptococci are not susceptible to some of the front-line antibiotics used to treat P. aeruginosa Collectively, these studies indicate the necessity for further investigation into the role of streptococci in the CF airway to determine how these microbes, alone or via interactions with other CF-associated pathogens, might influence CF lung disease, for better or for worse. We also propose that studying the interactions of streptococci with other CF pathogens is an ideal model to study clinically relevant microbial interactions.

RevDate: 2019-03-19

Kirakodu S, Chen J, Gonzalez Martinez J, et al (2019)

Microbiome Profiles of Ligature-Induced Periodontitis in Nonhuman Primates Across the Lifespan.

Infection and immunity pii:IAI.00067-19 [Epub ahead of print].

This investigation compared the microbiome colonizing teeth during the initiation, progression and resolution of periodontitis in nonhuman primates (Macaca mulatta) at different ages. Subgingival plaque samples were collected at baseline, and at 0.5, 1 and 3 months following ligature-induced periodontitis and following naturally-occurring disease resolution at 5 months. Samples were analyzed using 16S amplicon sequencing to identify bacterial profiles across age groups: young (<3 yrs), adolescent (3-7 yrs.), adult (12-15 yrs.) aged (17-23 yrs.). α-diversity of the microbiomes was greater in the adult/aged samples compared to the young/adolescent samples. β-diversity of the samples demonstrated clear age group differences, albeit, individual variation in microbiomes between animals within the age categories was noted. Phyla distribution differed between the young/adolescent group animals and the adult/aged animals at each of the time points showing an enrichment of Spirochetes, Fusobacteria, and Bacteroidetes phyla associated with periodontitis. Major differences in the top 50 OTUs were noted in the young and adolescent microbiomes during the initiation and progression post-ligation compared to the adult and aged animals. A large number of species in the top 50 OTUs were lower at baseline and in resolved disease microbiomes in the young samples, while profiles in adolescent animals were more consistent with the disease microbiomes. Microbiome profiles for resolution for adults and aged animals appeared more resilient and generally maintained a pattern similar to disease. Use of the model can expand our understanding of the crucial interactions of the oral microbiome and host responses in periodontitis.

RevDate: 2019-03-19

Christian LM (2019)

At the Forefront of Psychoneuroimmunology in Pregnancy: Implications for Racial Disparities in Birth Outcomes: PART 2: Biological Mechanisms.

Neuroscience and biobehavioral reviews pii:S0149-7634(18)30551-7 [Epub ahead of print].

As reviewed in Part I of this two part review, birth prior to full term is a substantial public health issue. In the US, ˜400,000 babies per year are born preterm (< 37 weeks), while >1 million are early term (37-386/7 weeks) and remarkable racial disparities in shortened gestation are observed among African Americans as compared to Whites. Biomechanisms linking stressor exposures with birth outcomes are increasingly being explicated. The current paper reviews the mechanistic role of maternal biological functioning in the link between behavioral exposures and birth outcomes. These include the inter-related roles of neuroendocrine function, inflammatory regulation, biological aging, and the microbiome. An integrative approach which addresses both behavioral and biological factors within the same study, carefully considers the role of race/ethnicity, and rigorously defines birth outcomes (e.g., spontaneous versus medically-indicated and inclusive of early term birth) is needed to move research in this field toward better mechanistic understanding and clinical application.

RevDate: 2019-03-19

Sampson T (2019)

The impact of indigenous microbes on Parkinson's disease.

Neurobiology of disease pii:S0969-9961(19)30069-5 [Epub ahead of print].

The gastrointestinal tract is inhabited by trillions of individual microbes, representing hundreds to thousands of distinct species. These indigenous organisms are not simply spectators to host activity, but instead actively modulate critical aspects of host physiology. From digestion and the production of small molecules, to the maturation and tuning of immune responses, the gastrointestinal microbiome influences every organ system in the body. Growing experimental evidence demonstrates microbial influence on neurological function in both health and disease. Furthermore, sequencing of the intestinal microbe population reveals altered community structures in various neurological conditions. Here, we provide a perspective on the potential roles for the intestinal microbiome in modulating Parkinson's disease. While Parkinson's disease has been historically studied as a disease of the central nervous system, there is growing appreciation for the roles of both gastrointestinal function and its resident microbes within this disease state. Recent studies focused on the microbiome during Parkinson's disease may advance our understanding of disease etiology and provide perspective for previously unrecognized therapeutic avenues through modulation of intestinal microbes.

RevDate: 2019-03-19

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

MetaPheno: A Critical Evaluation of Deep Learning and Machine Learning in Metagenome-Based Disease Prediction.

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

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

RevDate: 2019-03-19

Hildonen M, Kodama M, Puetz L, et al (2019)

A comparison of storage methods for gut microbiome studies in teleosts: Insights from rainbow trout (Oncorhynchus mykiss).

Journal of microbiological methods pii:S0167-7012(19)30122-8 [Epub ahead of print].

Immediate freezing is perhaps the most preferred method used for preserving gut microbial samples, but research on sample preservation has been principally based around samples from mammalian species, and little is known about the advantages or disadvantages relating to different storage methods for fish guts. Fish gut samples may pose additional challenges due to the different chemical and enzymatic profile, as well as the higher water content, which might affect the yield and purity of DNA recovered. To explore this, we took gut content and mucosal scrape samples from 10 rainbow trout (Oncorhynchus mykiss), and tested whether different preservation methods have any effect on the ability to construct high quality genomic libraries for shotgun and 16S rRNA gene sequencing. Four different storage methods were compared for the gut content samples (immediate freezing on dry ice, 96% ethanol, RNAlater and DNA/RNA shield), while two different methods were compared for mucosal scrape samples (96% ethanol and RNAlater). The samples were thereafter stored at -80 °C. Our findings concluded that 96% ethanol outperforms the other storage methods when considering DNA quantity, quality, cost and labor. Ethanol works consistently well for both gut content and mucosal scrape samples, and enables construction of DNA sequencing libraries of sufficient quantity and with a fragment length distribution suitable for shotgun sequencing. Two main conclusions from our study are i) sample storage optimisation is an important part of establishing a microbiome research program in a new species or sample type system, and ii) 96% ethanol is the preferred method for storing rainbow trout gut content and mucosal scrape samples.

RevDate: 2019-03-19

Rogers GB (2019)

The nasopharyngeal microbiome and LRTIs in infants.

The Lancet. Respiratory medicine pii:S2213-2600(18)30495-8 [Epub ahead of print].

RevDate: 2019-03-19

Kokai-Kun JF, Roberts T, Coughlin O, et al (2019)

Use of ribaxamase (SYN-004), a β-lactamase, to prevent Clostridium difficile infection in β-lactam-treated patients: a double-blind, phase 2b, randomised placebo-controlled trial.

The Lancet. Infectious diseases pii:S1473-3099(18)30731-X [Epub ahead of print].

BACKGROUND: Infections with Clostridium difficile are a health threat, yet no products are currently licensed for prevention of primary C difficile infections. Intravenous β-lactam antibiotics are considered to confer a high risk of C difficile infection because of their biliary excretion into the gastrointestinal tract and disruption of the gut microbiome. ribaxamase (SYN-004) is an orally administered β-lactamase that was designed to be given with intravenous β-lactam antibiotics to degrade excess antibiotics in the upper gastrointestinal tract before they disrupt the gut microbiome and lead to C difficile infection. We therefore aimed to determine whether administration of ribaxamase could prevent C difficile infection in patients being treated with intravenous ceftriaxone for a lower respiratory tract infection, thereby supporting continued clinical development.

METHODS: In this parallel-group, double-blind, multicentre, phase 2b, randomised placebo-controlled trial, we recruited patients who had been admitted to a hospital with a lower respiratory tract infection with a pneumonia index score of 90-130 and who were expected to be treated with ceftriaxone for at least 5 days. Patients were recruited from 54 clinical sites in the USA, Canada, Bulgaria, Hungary, Poland, Romania, and Serbia. We randomly assigned patients older than 50 years to groups (1:1) in blocks of four by use of an interactive web portal; these groups were assigned to receive either 150 mg ribaxamase or placebo four times per day during, and for 72 h after, treatment with ceftriaxone. All patients, clinical investigators, study staff, and sponsor personnel were masked to the study drug assignments. The primary endpoint was the incidence of C difficile infection, as diagnosed by the local laboratory, in patients who received at least one treatment dose, and this outcome was assessed during treatment and for 4 weeks after treatment. This study is registered with, number NCT02563106.

FINDINGS: Between Nov 16, 2015, and Nov 10, 2016, we screened 433 patients for inclusion in the study. Of these patients, 20 (5%) patients were excluded from the study (16 [4%] patients did not meet inclusion criteria; four [1%] patients because of dosing restrictions). We enrolled and randomly assigned 413 patients to groups, of whom 207 patients were assigned to receive ceftriaxone plus ribaxamase and 206 patients were assigned to receive ceftriaxone plus placebo. However, one (<1%) patient in the ribaxamase group withdrew consent and was not treated with ribaxamase. During the study and within the 4 weeks after antibiotic treatment, two (1·0%) patients in the ribaxamase group and seven (3·4%) patients in the placebo group were diagnosed with an infection with C difficile (risk reduction 2·4%, 95% CI -0·6 to 5·9; one-sided p=0·045). Adverse events were similar between groups but more deaths were reported in the ribaxamase group (11 deaths vs five deaths in the placebo group). This disparity was due to the higher incidence of deaths attributed to cardiac-associated causes in the ribaxamase group (six deaths vs one death in the placebo group).

INTERPRETATION: In patients treated with intravenous ceftriaxone for lower respiratory tract infections, oral ribaxamase reduced the incidence of C difficile infections compared with placebo. The imbalance in deaths between the groups appeared to be related to the underlying health of the patients. Ribaxamase has the potential to prevent C difficile infection in patients treated with intravenous β-lactam antibiotics, and our findings support continued clinical development of ribaxamase to prevent C difficile infection.

FUNDING: Synthetic Biologics.

RevDate: 2019-03-19

Goldenberg SD (2019)

A solution to the problem of antibiotic induced collateral damage to the gut microbiome.

The Lancet. Infectious diseases pii:S1473-3099(18)30784-9 [Epub ahead of print].

RevDate: 2019-03-19

Zhao S, Gao G, Li W, et al (2019)

Antibiotics are associated with attenuated efficacy of anti-PD-1/PD-L1 therapies in Chinese patients with advanced non-small cell lung cancer.

Lung cancer (Amsterdam, Netherlands), 130:10-17.

OBJECTIVES: Gut microbiome plays a dominant role in modulating therapeutic efficacy of immune checkpoint inhibitors (ICIs) targeting the programmed cell death receptor/ligand-1 (PD-1/PD-L1) pathway, suggesting that co-administration of antibiotics (Abx), which might result in dysbacteriosis, can attenuate the clinical outcomes of ICIs. The current study aimed to investigate the predictive role of Abx on ICIs treatment in patients with advanced non-small cell lung cancer (NSCLC). The impact of proton pump inhibitors (PPIs), another medication that can induce dysbacteriosis, was also investigated.

MATERIALS AND METHODS: We retrospectively reviewed the medical records of eligible patients who received anti-PD-1-based therapies in our hospital. Tumor responses, patients' survival, the incidence of immune-related adverse events (irAEs) and other baseline variables were examined. The application of Abx or PPIs treatment were also collected. Clinical outcomes and clinicopathologic features were compared according to the status of Abx or PPIs co-administration.

RESULTS: A total of 109 patients were included. Of them, 20 (18.3%) patients were categorized in Abx-treated group. No major difference in baseline characteristics was observed between Abx-treated and -untreated groups. Concomitant Abx treatment was significantly associated with shorter progression-free survival (PFS) (p < 0.0001) and overall survival (OS) (p = 0.0021). And primary disease progression tended to increase in Abx-treated group (p = 0.092). Yet, the occurrence and grades of irAEs were comparable between two groups. In multivariable analysis, Abx treatment was markedly associated with worse PFS (HR=0.32, 95%CI 0.18-0.59, p < 0.0001) and OS (HR=0.35, 95%CI 0.16-0.77, p = 0.009). Regarding the use of PPIs, no significant difference was observed in clinical outcomes between the patients with or without concomitant PPIs treatment.

CONCLUSIONS: Abx treatment was significantly associated with attenuated clinical outcomes derived from anti-PD-1-based ICIs in a Chinese cohort of patients with advanced NSCLC.

RevDate: 2019-03-19

Prodan A, Levin E, M Nieuwdorp (2019)

Does disease start in the mouth, the gut or both?.

eLife, 8: pii:45931.

Oral bacteria colonize the gut more frequently than previously thought.

RevDate: 2019-03-19

Westreich ST, Ardeshir A, Alkan Z, et al (2019)

Fecal metatranscriptomics of macaques with idiopathic chronic diarrhea reveals altered mucin degradation and fucose utilization.

Microbiome, 7(1):41 pii:10.1186/s40168-019-0664-z.

BACKGROUND: Idiopathic chronic diarrhea (ICD) is a common cause of morbidity and mortality among juvenile rhesus macaques. Characterized by chronic inflammation of the colon and repeated bouts of diarrhea, ICD is largely unresponsive to medical interventions, including corticosteroid, antiparasitic, and antibiotic treatments. Although ICD is accompanied by large disruptions in the composition of the commensal gut microbiome, no single pathogen has been concretely identified as responsible for the onset and continuation of the disease.

RESULTS: Fecal samples were collected from 12 ICD-diagnosed macaques and 12 age- and sex-matched controls. RNA was extracted for metatranscriptomic analysis of organisms and functional annotations associated with the gut microbiome. Bacterial, fungal, archaeal, protozoan, and macaque (host) transcripts were simultaneously assessed. ICD-afflicted animals were characterized by increased expression of host-derived genes involved in inflammation and increased transcripts from bacterial pathogens such as Campylobacter and Helicobacter and the protozoan Trichomonas. Transcripts associated with known mucin-degrading organisms and mucin-degrading enzymes were elevated in the fecal microbiomes of ICD-afflicted animals. Assessment of colon sections using immunohistochemistry and of the host transcriptome suggests differential fucosylation of mucins between control and ICD-afflicted animals. Interrogation of the metatranscriptome for fucose utilization genes reveals possible mechanisms by which opportunists persist in ICD. Bacteroides sp. potentially cross-fed fucose to Haemophilus whereas Campylobacter expressed a mucosa-associated transcriptome with increased expression of adherence genes.

CONCLUSIONS: The simultaneous profiling of bacterial, fungal, archaeal, protozoan, and macaque transcripts from stool samples reveals that ICD of rhesus macaques is associated with increased gene expression by pathogens, increased mucin degradation, and altered fucose utilization. The data suggest that the ICD-afflicted host produces fucosylated mucins that are leveraged by potentially pathogenic microbes as a carbon source or as adhesion sites.

RevDate: 2019-03-19

Spence JD (2019)

Nutrition and Risk of Stroke.

Nutrients, 11(3): pii:nu11030647.

Nutrition is far more important in stroke risk than most physcians suppose. Healthy lifestyle choices reduce the risk of stroke by ~80%, and of the factors that increase the risk of stroke, the worst is diet: only ~0.1% of Americans consume a healthy diet, and only 8.3% consume a somewhat healthy diet. The situation is probably not much better in most other countries. A Cretan Mediterranean diet, high in olive oil, whole grains, fruits, vegetables and legumes, and low in cholesterol and saturated fat, can reduce stroke by 40% or more in high-risk patients. The role of the intestinal microbiome in cardiovascular risk is emerging; high levels of toxic metabolites produced by intestinal bacteria from meat (particularly red meat) and egg yolk are renally excreted. Patients with renal impairment, including the elderly, should limit red meat and avoid egg yolk, as should other patients at high risk of stroke. Salt intake should be limited to 2⁻3 grams per day. Metabolic B12 deficiency is common and usually missed. It has serious neurological consequences, including an increase in the risk of stroke. It now clear that B vitamins to lower homocysteine reduce the risk of stroke, but we should probably be using methylcobalamin instead of cyanocobalamin.

RevDate: 2019-03-19

Blanco-Míguez A, Fdez-Riverola F, Lourenço A, et al (2019)

In silico prediction reveals the existence of potential bioactive neuropeptides produced by the human gut microbiota.

Food research international (Ottawa, Ont.), 119:221-226.

This work reports on a large-scale potential neuropeptide activity screening in human gut microbiomes deposited in public databases. In our experimental approach, the sequences of the bioactive peptides collected in the MAHMI database, mainly predicted as immunomodulatory or antitumoral, were crossed with those of the neuroactive/digestive peptides. From 91,325,790 potential bioactive peptides, only 581 returned a match when crossed against the 5949 neuroactive peptides from the NeuroPep database and the 15 digestive hormones. Relevant bacterial taxa, such as Ruminococcus sp., Clostridium sp. were found among the main producers of the matching sequences, and many of the matches corresponded to adiponectin and the hormone produced by adipocites, which is involved in glucose homeostasis. These results show, for the first time, the presence of potentially bioactive peptides produced by gut microbiota members over the nervous cells, most notably, peptides with already predicted immunomodulatory or anti-inflammatory activity. Classical (Lactobacillus sp.) and next-generation (Faecalibacterium sp.) probiotics are shown to produce these peptides, which are proposed as a potential mechanism of action of psychobiotics. Our previous experimental results showed that many of these peptides were active when incubated with immune cells, such as dendritic cells, so their effect over the nervous system innervating the gut mucosa holds significant potential and should be explored.

RevDate: 2019-03-18

Siemer S, Hahlbrock A, Vallet C, et al (2018)

Nanosized food additives impact beneficial and pathogenic bacteria in the human gut: a simulated gastrointestinal study.

NPJ science of food, 2(1):22.

Nanotechnology provides the food industry with new ways to modulate various aspects of food. Hence, engineered nanoparticles (NPs) are increasingly added to food and beverage products as functional ingredients. However, the impact of engineered as well as naturally occurring NPs on both commensal and pathogenic microorganisms within the gastrointestinal tract (GI) is not fully understood. Here, well-defined synthetic NPs and bacterial models were used to probe nanoparticle-bacteria interactions, from analytical to in situ to in vitro. NP-bacteria complexation occurred most efficiently for small NPs, independent of their core material or surface charge, but could be reduced by NPs' steric surface modifications. Adsorption to bacteria could also be demonstrated for naturally occurring carbon NPs isolated from beer. Complex formation affected the (patho)biological behavior of both the NPs and bacteria, including their cellular uptake into epithelial cells and phagocytes, pathogenic signaling pathways, and NP-induced cell toxicity. NP-bacteria complex formation was concentration-dependently reduced when the NPs became coated with biomolecule coronas with sequential simulation of first oral uptake and then the GI. However, efficient NP adsorption was restored when the pH was sufficiently low, such as in simulating the conditions of the stomach. Collectively, NP binding to enteric bacteria may impact their (patho)biology, particularly in the stomach. Nanosized-food additives as well as naturally occurring NPs may be exploited to (rationally) shape the microbiome. The information contained in this article should facilitate a "safe by design" strategy for the development and application of engineered NPs as functional foods ingredients.

RevDate: 2019-03-18

Dolan KE, Pizano JM, Gossard CM, et al (2017)

Probiotics and Disease: A Comprehensive Summary-Part 6, Skin Health.

Integrative medicine (Encinitas, Calif.), 16(4):32-41.

This article series provides a literature review of the disease-specific probiotic strains associated with dermatological disorders and conditions that have been studied in published clinical trials in humans and animals. This is not an exhaustive review. The table design allows for quick access to supportive data and will be helpful as a guide for both researchers and clinicians. The goal of the probiotics and disease series is to provide clinically useful tools. The first article (part 1) focused on mental health and neurological conditions, and the second article (part 2) explored cultured and fermented foods that are commonly available in the United States. The third article (part 3) explored the relationship between bacterial strains and 2 of the most prevalent diseases we have in modern society: cardiometabolic disease and fatigue syndromes. The fourth article (part 4) elucidated the role of the microbiome in infectious diseases, and the fifth article (part 5) examined respiratory conditions and conditions of the ears, nose, and throat. This sixth article (part 6) article explores the relationship between the microbiome and skin disorders. Future articles will review conditions related to autoimmunity and dermatological conditions; the influence of the microbiome on cancer development and prognosis, gastrointestinal and genitourinary diseases associated with dysbiosis conditions; followed by an article focused on probiotic supplements. This literature review is specific to disease condition, probiotic classification, and individual strain.

RevDate: 2019-03-18

Jiang CL, Jin WZ, Tao XH, et al (2019)

Black soldier fly larvae (Hermetia illucens) strengthen the metabolic function of food waste biodegradation by gut microbiome.

Microbial biotechnology [Epub ahead of print].

Vermicomposting using black soldier fly (BSF) larvae (Hermetia illucens) has gradually become a promising biotechnology for waste management, but knowledge about the larvae gut microbiome is sparse. In this study, 16S rRNA sequencing, SourceTracker, and network analysis were leveraged to decipher the influence of larvae gut microbiome on food waste (FW) biodegradation. The microbial community structure of BSF vermicompost (BC) changed greatly after larvae inoculation, with a peak colonization traceable to gut bacteria of 66.0%. The relative abundance of 11 out of 21 metabolic function groups in BC were significantly higher than that in natural composting (NC), such as carbohydrate-active enzymes. In addition, 36.5% of the functional genes in BC were significantly higher than those in NC. The changes of metabolic functions and functional genes were significantly correlated with the microbial succession. Moreover, the bacteria that proliferated in vermicompost, including Corynebacterium, Vagococcus, and Providencia, had strong metabolic abilities. Systematic and complex interactions between the BSF gut and BC bacteria occurred over time through invasion, altered the microbial community structure, and thus evolved into a new intermediate niche favourable for FW biodegradation. The study highlights BSF gut microbiome as an engine for FW bioconversion, which is conducive to bioproducts regeneration from wastes.

RevDate: 2019-03-18

Fernández I, Cosme M, Stringlis IA, et al (2019)

Molecular dialogue between arbuscular mycorrhizal fungi and the non-host plant Arabidopsis thaliana switches from initial detection to antagonism.

The New phytologist [Epub ahead of print].

Approximately 29% of all vascular plant species are unable to establish an arbuscular mycorrhizal (AM) symbiosis. Despite this, AM fungi (Rhizophagus spp.) are enriched in the root microbiome of the non-host Arabidopsis thaliana and Arabidopsis roots become colonized when AM networks nurtured by host plants are available. Here, we investigated the non-host-AM fungus interaction by analyzing transcriptional changes in Rhizophagus, Arabidopsis, and the host plant Medicago truncatula while growing in the same mycorrhizal network. In early interaction stages, Rhizophagus activated the Arabidopsis strigolactone biosynthesis genes CCD7 and CCD8, suggesting that detection of AM fungi is not completely impaired. However, in colonized Arabidopsis roots, fungal nutrient transporter genes GintPT, GintAMT2, GintMST2 and GintMST4, essential for AM symbiosis, were not activated. RNA-seq transcriptome analysis pointed to activation of costly defenses in colonized Arabidopsis roots. Moreover, Rhizophagus colonization caused a 50% reduction in shoot biomass, but also led to enhanced systemic immunity against Botrytis cinerea. This suggests that early signaling between AM fungi and Arabidopsis is not completely impaired and that incompatibility appears at later interaction stages. Moreover, Rhizophagus-mediated defenses coincide with reduced Arabidopsis growth, but also with systemic disease resistance, highlighting the multifunctional role of AM fungi in host and non-host interactions. This article is protected by copyright. All rights reserved.

RevDate: 2019-03-18

Sugino KY, Paneth N, SS Comstock (2019)

Michigan cohorts to determine associations of maternal pre-pregnancy body mass index with pregnancy and infant gastrointestinal microbial communities: Late pregnancy and early infancy.

PloS one, 14(3):e0213733 pii:PONE-D-18-22520.

BACKGROUND: About 25% of women in the United States are obese prior to becoming pregnant. Although there is some knowledge about the relationship between the gastrointestinal microbiota and obesity, little is known about the relationship between pre-pregnancy obesity and the gastrointestinal microbiota in pregnancy or its impact on infant gut microbiota. However, the composition of the gut microbiota early in life may influence childhood health. Thus, the objective of this research was to identify associations between maternal pre-pregnancy obesity and the pregnancy (n = 39) or early infancy (n = 39) microbiotas.

RESULTS: Fecal bacterial communities from overweight women had lower microbiota diversity (Chao1: p = 0.02; inverse Simpson: p = 0.05; Shannon: p = 0.02) than communities from normal weight or obese women. The within-group microbiota composition of overweight women differed from those of normal and obese women at the genus and phylum levels (p = 0.003 and p = 0.02, respectively). Pre-pregnancy overweight women had higher abundances of Bacteroides and lower Phascolarctobacterium than women who were normal weight or obese prior to becoming pregnant. Normal weight women had lower abundances of Acidaminococcus and Dialister than overweight and obese women. Infant community composition tended to differ in membership (Sorensen index) by maternal pre-pregnancy BMI category, and significantly differed by delivery mode and breastfeeding exclusivity (p = 0.06, p = 0.001, p = 0.008, respectively). Infants from normal weight women had lower abundances of Megasphaera than infants from overweight or obese women. Streptococcus was lowest in infants from overweight women, and Staphylococcus was lowest in infants from obese women.

CONCLUSION: Maternal and infant microbiotas are associated with and might be affected by maternal pre-pregnancy BMI. Future work should determine if there are also functional differences in the infant microbiome, if those functional differences are related to maternal pre-pregnancy BMI, and whether differences in composition or traits persist over time.

RevDate: 2019-03-18

Mailing LJ, Allen JM, Buford TW, et al (2019)

Exercise and the Gut Microbiome: A Review of the Evidence, Potential Mechanisms, and Implications for Human Health.

Exercise and sport sciences reviews, 47(2):75-85.

The gastrointestinal tract contains trillions of microbes (collectively known as the gut microbiota) that play essential roles in host physiology and health. Studies from our group and others have demonstrated that exercise independently alters the composition and functional capacity of the gut microbiota. Here, we review what is known about the gut microbiota, how it is studied, and how it is influenced by exercise training and discuss the potential mechanisms and implications for human health and disease.

RevDate: 2019-03-18

Neu J (2019)

Multiomics-based strategies for taming intestinal inflammation in the neonate.

Current opinion in clinical nutrition and metabolic care [Epub ahead of print].

PURPOSE OF REVIEW: The purpose of this review is to discuss evolving research into intestinal inflammatory responses as they relate to the developing microbiome and to provide insights into developing multiomic tools that are being used to describe these relationships. Intestinal inflammatory conditions are common, and in the neonate present special challenges, especially in the form of necrotizing enterocolitis (NEC) and other conditions that involve damage or breakdown of the mucosal barrier, leading to systemic inflammation and damage to distal sites, such as the liver and brain.

RECENT STUDIES: Recent studies show that when a dysbiosis (microbial imbalance or impaired microbiota) occurs, an inflammatory response that can affect the entire body is frequently the result. We are recognizing that not only the microbial diversity and relative abundance of certain taxa play a role in dysbiosis and inflammation, but their functional capabilities in terms of metabolite production and interaction with the immune system of the host afre critical in future health and disease.

SUMMARY: A multiomic approach to evaluate these microorgansims as well as their interaction with the host by using systems-based concepts is becoming possible and is likely to shed new light on various disease entities and how we can best prevent and treat them.

RevDate: 2019-03-18

Man WH, Clerc M, de Steenhuijsen Piters WAA, et al (2019)

Loss of Microbial Topography between Oral and Nasopharyngeal Microbiota and Development of Respiratory Infections Early in Life.

American journal of respiratory and critical care medicine [Epub ahead of print].

RATIONALE: The respiratory microbiota is increasingly being appreciated as an important mediator in the susceptibility to childhood respiratory tract infections (RTIs). Pathogens are presumed to originate from the nasopharyngeal ecosystem.

OBJECTIVES: To investigate the association between early-life respiratory microbiota and development of childhood RTIs.

METHODS: In a prospective birth cohort (Microbiome Utrecht Infant Study: MUIS), we characterized the oral microbiota longitudinally from birth until six months of age of 112 infants (9 regular samples/subject) and compared them with nasopharyngeal microbiota using 16S-rRNA-based sequencing. We also characterized oral and nasopharynx samples during RTI episodes in the first half year of life.

MEASUREMENTS AND MAIN RESULTS: Oral microbiota were driven mostly by feeding type, followed by age, mode of delivery and season of sampling. In contrast to our previously published associations between nasopharyngeal microbiota development and susceptibility to RTIs, oral microbiota development was not directly associated with susceptibility to RTI development. However, we did observe an influx of oral taxa, such as Neisseria lactamica, Streptococcus, Prevotella nanceiensis, Fusobacterium and Janthinobacterium lividum, in the nasopharyngeal microbiota prior to and during RTIs, which was accompanied by reduced presence and abundance of Corynebacterium, Dolosigranulum and Moraxella spp. Moreover, this phenomenon was accompanied by reduced niche differentiation indicating loss of ecological topography preceding confirmed RTIs. This loss of ecological topography was further augmented by start of daycare, and linked to consecutive development of symptomatic infections.

CONCLUSIONS: Together, our results link the loss of topography to subsequent development of RTI episodes. This may lead to new insights for prevention of RTIs and antibiotic utilization in childhood.

RevDate: 2019-03-18

Ferrarello D, Froh EB, Hinson TD, et al (2019)

Nurses' Views on Using Pasteurized Donor Human Milk for Hypoglycemic Term Infants.

MCN. The American journal of maternal child nursing [Epub ahead of print].

PURPOSE: The purpose of this study was to explore maternal child nurses' knowledge and beliefs about using pasteurized donor human milk (PDHM) to treat newborns with hypoglycemia. Pasteurized donor human milk has been used for decades in neonatal intensive care units, but its use is relatively new in the well-baby population.

STUDY DESIGN AND METHODS: Focus groups of maternal child nurses were conducted to explore this topic.

RESULTS: Six focus groups that included a total 20 nurses were held. Four themes were identified: 1) nurses presumed safety of PDHM but lacked knowledge, 2) nurses' role as patient-family advocate, 3) nurses' logistical concerns about implementation of PDHM, and 4) nurses lacked clarity on formal milk sharing versus PDHM.

CLINICAL IMPLICATIONS: As the use of PDHM increases for well babies, nurses will need more education about PDHM, its safety profile, its use in breastfeeding support and protection of the infant microbiome, and how PDHM differs from informal milk sharing. Nurses play an important role in helping parents weigh risks and benefits of using PDHM or formula when supplementation is needed during the hospital stay. It is important that nurses feel confident in their own knowledge and ability to address parental concerns so they can advocate for their patients and support parental decisionmaking.

RevDate: 2019-03-18

Shaw L, N Klein (2019)

The Microbiome-The Explanation for (Almost) Everything?.

The Pediatric infectious disease journal, 38(4):e69-e71.

RevDate: 2019-03-18

Maurice JB, Garvey L, Tsochatzis EA, et al (2019)

Monocyte-macrophage activation is associated with nonalcoholic fatty liver disease and liver fibrosis in HIV monoinfection independently of the gut microbiome and bacterial translocation.

AIDS (London, England), 33(5):805-814.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is common among people living with HIV. There are limited data available on the pathophysiology of NAFLD and the development of fibrosis in this population.

OBJECTIVES: The aim of this study was to investigate the association of bacterial translocation, adipose tissue dysfunction, monocyte activation and gut dysbiosis in patients with HIV monoinfection and NAFLD.

METHODS: Cases with biopsy-proven NAFLD and HIV monoinfection were age and sex-matched to HIV-positive and HIV-negative controls. Markers of bacterial translocation [lipopolysaccharide-binding protein (LBP), bacterial DNA and lipopolysaccharide (LPS)], adipose tissue dysfunction (leptin, adiponectin) and monocyte activation (sCD14 and sCD163) were measured by ELISA. Hepatic patterns of macrophage activation were explored with immunohistochemistry. 16 s rRNA sequencing was performed with stool.

RESULTS: Thirty-three cases were included (≥F2 fibrosis n = 16), matched to HIV-positive (n = 29) and HIV-negative (n = 17) controls. Cases with NAFLD were more obese (BMI 31.0 ± 4.4 vs. 24.1 ± 2.8 kg/m, P < 0.001) and had significantly increased levels of sCD14, sCD163 and higher leptin to adiponectin ratio vs. HIV-positive controls. Cases with ≥F2 verses < F2 fibrosis had increased sCD14 (1.4 ± 0.4 vs. 1.1 ± 0.3 μg/ml, P = 0.023) and sCD163 (1.0 ± 0.3 vs. 0.8 ± 0.3 μg/ml, P = 0.060), which correlated with waist circumference (sCD14 P = 0.022, sCD163 P = 0.011). Immunohistochemistry showed increased hepatic portal macrophage clusters in patients with fibrosis. No markers of bacterial translocation or changes to the microbiome were associated with NAFLD or fibrosis.

CONCLUSION: NAFLD fibrosis stage in HIV monoinfected patients is associated with monocyte activation in the context of obesity, which may be independent of bacterial translocation and gut microbiome.

RevDate: 2019-03-18

Wang Z, Xu CM, Liu YX, et al (2019)

Characteristic dysbiosis of gut microbiota of chinese patients with diarrhea-predominant irritable bowel syndrome by an insight into the pan-microbiome.

Chinese medical journal [Epub ahead of print].

BACKGROUND: Irritable bowel syndrome (IBS) is reported associated with the alteration of gut microbial composition termed as dysbiosis. However, the pathogenic mechanism of IBS remains unclear, while the studies of Chinese individuals are scarce. This study aimed to understand the concept of dysbiosis among Chinese diarrhea-predominant IBS (IBS-D) patients, as a degree of variance between the gut microbiomes of IBS-D population and that of healthy population.

METHODS: The IBS-D patients were recruited (assessed according to the Rome III criteria, by IBS symptom severity score) from the Outpatient Department of Gastroenterology of Peking University Third Hospital, and volunteers as healthy controls (HC) were enrolled, during 2013. The 16S rRNA sequences were extracted from fecal samples. RDP resources, BLAST and SparCC software were used to obtain the phylotype composition of samples and the internal interactions of the microbial community. Herein, the nonparametric test, Wilcoxon rank-sum test was carried out to find the statistical significance between HC and IBS-D groups. All the P values were adjusted to q values to decrease the error rate.

RESULTS: The study characterized the gut microbiomes of Chinese IBS-D patients, and demonstrated that the dysbiosis could be characterized as directed alteration of the microbiome composition leading to greater disparity between relative abundance of two phyla, Bacteroidetes (Z = 4.77, q = 1.59 × 10) and Firmicutes (Z = -3.87, q = 5.83 × 10). Moreover it indicated that the IBS symptom features were associated with the dysbiosis of whole gut microbiome, instead of one or several certain genera even they were dominating. Two genera, Bacteroides and Lachnospiracea incertae sedis, were identified as the core genera, meanwhile the non-core genera contribute to a larger pan-microbiome of the gut microbiome. Furthermore the dysbiosis in IBS-D patients was associated with a reduction of network complexity of the interacted microbial community (HC vs. IBS-D: 639 vs. 154). The disordered metabolic functions of IBS-D patients were identified as the potential influence of gut microbiome on the host (significant difference with q < 0.01 between HC and IBS-D).

CONCLUSIONS: This study supported the view of the potential influence of gut microbiome on the symptom of Chinese IBS-D patients, and further characterized dysbiosis in Chinese IBS-D patients, thus provided more pathological evidences for IBS-D with the further understanding of dysbiosis.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

RevDate: 2019-03-18

Mima K, H Baba (2019)

The gut microbiome, antitumor immunity, and liver cancer.

Hepatobiliary surgery and nutrition, 8(1):67-68.

RevDate: 2019-03-18

Tribble GD, Angelov N, Weltman R, et al (2019)

Frequency of Tongue Cleaning Impacts the Human Tongue Microbiome Composition and Enterosalivary Circulation of Nitrate.

Frontiers in cellular and infection microbiology, 9:39.

The oral microbiome has the potential to provide an important symbiotic function in human blood pressure physiology by contributing to the generation of nitric oxide (NO), an essential cardiovascular signaling molecule. NO is produced by the human body via conversion of arginine to NO by endogenous nitric oxide synthase (eNOS) but eNOS activity varies by subject. Oral microbial communities are proposed to supplement host NO production by reducing dietary nitrate to nitrite via bacterial nitrate reductases. Unreduced dietary nitrate is delivered to the oral cavity in saliva, a physiological process termed the enterosalivary circulation of nitrate. Previous studies demonstrated that disruption of enterosalivary circulation via use of oral antiseptics resulted in increases in systolic blood pressure. These previous studies did not include detailed information on the oral health of enrolled subjects. Using 16S rRNA gene sequencing and analysis, we determined whether introduction of chlorhexidine antiseptic mouthwash for 1 week was associated with changes in tongue bacterial communities and resting systolic blood pressure in healthy normotensive individuals with documented oral hygiene behaviors and free of oral disease. Tongue cleaning frequency was a predictor of chlorhexidine-induced changes in systolic blood pressure and tongue microbiome composition. Twice-daily chlorhexidine usage was associated with a significant increase in systolic blood pressure after 1 week of use and recovery from use resulted in an enrichment in nitrate-reducing bacteria on the tongue. Individuals with relatively high levels of bacterial nitrite reductases had lower resting systolic blood pressure. These results further support the concept of a symbiotic oral microbiome contributing to human health via the enterosalivary nitrate-nitrite-NO pathway. These data suggest that management of the tongue microbiome by regular cleaning together with adequate dietary intake of nitrate provide an opportunity for the improvement of resting systolic blood pressure.

RevDate: 2019-03-18

Ashton JJ, Mossotto E, Ennis S, et al (2019)

Personalising medicine in inflammatory bowel disease-current and future perspectives.

Translational pediatrics, 8(1):56-69.

Up to 25% of inflammatory bowel disease (IBD) presents during childhood, often with severe and extensive disease, leading to significant morbidity including delayed growth and nutritional impairment. The classical approach to management has centred on differentiation into Crohn's disease (CD) or ulcerative colitis (UC), with subsequent treatment based on symptoms, results and complications. However, IBD is a heterogeneous condition with substantial variation in phenotype, disease course and outcome, so whilst effective treatment exists one size does not fit all. The ability to predict disease course at diagnosis, alongside tailoring medications based on response gives the potential for a more 'personalised approach'. The move to a pre-emptive strategy to prevent IBD-related complications, whilst simultaneously minimising side effects and long-term toxicity from therapy, particularly in those with relatively indolent disease, has the potential to revolutionise care. In very early-onset IBD, personalised approaches to diagnosis and management have become the standard of treatment enabling clinicians to significantly alter the outcomes of the few children with monogenic disease. However, the promise of discoveries in genomics, microbiome and transcriptomics in paediatric IBD has not yet translated to clinical application for the vast majority of patients. Despite this, the opportunity presents itself to apply data gathered at diagnosis and follow-up to predict which patients are likely to progress to complicated disease, which will respond well and which will require additional therapy. Using complex mathematics and innovative, cutting-edge machine learning (ML) techniques gives the potential to use this data to develop personalised clinical care algorithms to treat patients more effectively, reduce toxicity and improve outcome. In this review, we will consider current management of paediatric IBD, discuss how precision medicine is making inroads into clinical practice already, examine the contemporary studies applying data to stratify patients and explore how future management may be revolutionised by personalisation with clinical, genomic and other multi-omic data.

RevDate: 2019-03-18

Ledder O (2019)

Antibiotics in inflammatory bowel diseases: do we know what we're doing?.

Translational pediatrics, 8(1):42-55.

Despite the revolution in inflammatory bowel disease (IBD) treatment over the past two decades with the advent of biological therapies, there remains a substantial proportion of patients with inadequate or unsustained response to existent therapies. The overwhelming focus of IBD therapeutics has been targeting mucosal immunity, however with the developing evidence base pointing to the role of gut microbes in the inflammatory process, renewed focus should be placed on the impact of manipulating the microbiome in IBD management. This review provides an overview of the evidence implicating bacteria in the pathogenesis of gut inflammation in IBD and provides an overview of the evidence of antibiotics in IBD treatment. We also suggest a potential role of antibiotics in clinical practice based on available evidence and clinical experience.

RevDate: 2019-03-18

Dohlman AB, X Shen (2019)

Mapping the microbial interactome: Statistical and experimental approaches for microbiome network inference.

Experimental biology and medicine (Maywood, N.J.) [Epub ahead of print].

IMPACT STATEMENT: This review provides a comprehensive description of experimental and statistical tools used for network analyses of the human gut microbiome. Understanding the system dynamics of microbial interactions may lead to the improvement of therapeutic approaches for managing microbiome-associated diseases. Microbiome network inference tools have been developed and applied to both cross-sectional and longitudinal experimental designs, as well as to multi-omic datasets, with the goal of untangling the complex web of microbe-host, microbe-environmental, and metabolism-mediated microbial interactions. The characterization of these interaction networks may lead to a better understanding of the systems dynamics of the human gut microbiome, augmenting our knowledge of the microbiome's role in human health, and guiding the optimization of effective, precise, and rational therapeutic strategies for managing microbiome-associated disease.

RevDate: 2019-03-18

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

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

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

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

RevDate: 2019-03-18

Nunn KL, Ridenhour BJ, Chester EM, et al (2019)

Vaginal Glycogen, Not Estradiol, Is Associated With Vaginal Bacterial Community Composition in Black Adolescent Women.

The Journal of adolescent health : official publication of the Society for Adolescent Medicine pii:S1054-139X(19)30025-4 [Epub ahead of print].

PURPOSE: The purpose of this study was to characterize the composition of vaginal bacterial communities in a cohort of black adolescent women and to determine how the species composition of these communities correlates with levels of estradiol, glycogen, and stress.

METHODS: Twenty-one black adolescent women were sampled longitudinally. The composition of their vaginal communities was determined by analyzing the sequences of the V1-V3 regions of 16S rRNA genes, and they were grouped based on patterns in species abundances. The relationships between estradiol, glycogen, psychosocial stress, and the composition of these communities were assessed.

RESULTS: Vaginal communities could be distinguished and classified into three groups that differed in the abundances of Lactobacillus. Eighty-one percent of study participants had communities dominated by species of Lactobacillus. Glycogen levels were higher in communities dominated by one or multiple species of Lactobacillus compared with those having low proportions of Lactobacillus. Estradiol and psychosocial stress measurements did not differ among the three groups, whereas estradiol and glycogen exhibited a weak positive relationship that was not statistically significant.

CONCLUSIONS: The findings of this pilot study suggest that glycogen levels are associated with vaginal community composition in young black women; however, estradiol and psychosocial stress are not. In addition, the results suggest there is no simple relationship between levels of estradiol and the production of vaginal glycogen.

RevDate: 2019-03-18

Kates AE, Zimbric ML, Mitchell K, et al (2019)

The impact of chlorhexidine gluconate on the skin microbiota of children and adults: A pilot study.

American journal of infection control pii:S0196-6553(19)30066-5 [Epub ahead of print].

We examined the effect of chlorhexidine gluconate (CHG) bathing on the skin microbiota of adult and pediatric patients. We observed no differences in pediatric patients; however, multiple genera of bacteria were observed to be significantly less abundant in the adults bathing with CHG. Further research is needed to determine the long-term impact of CHG use on the skin microbiota.

RevDate: 2019-03-17

Mari A, Abu Backer F, Mahamid M, et al (2019)

Bloating and Abdominal Distension: Clinical Approach and Management.

Advances in therapy pii:10.1007/s12325-019-00924-7 [Epub ahead of print].

Functional abdominal bloating and distension (FABD) are common gastrointestinal complaints, encountered on a daily basis by gastroenterologists and healthcare providers. Functional abdominal bloating is a subjective sensation that is commonly associated with an objective abdominal distension. FABD may be diagnosed as a single entity (the sole or cardinal complaint) or may overlap with other functional gastrointestinal disorders such as functional constipation, irritable bowel syndrome, and functional dyspepsia. The pathophysiology of FABD is not completely understood. Proposed underlying mechanisms include visceral hypersensitivity, behavioral induced abnormal abdominal wall-phrenic reflexes, the effect of poorly absorbed fermentable carbohydrates, and microbiome alterations. Management includes behavioral therapy, dietary interventions, microbiome modulation, and medical therapy. This review presents the current knowledge on the pathophysiology, evaluation, and management of FABD.

RevDate: 2019-03-17

Sheflin AM, Kirkwood JS, Wolfe LM, et al (2019)

High-throughput quantitative analysis of phytohormones in sorghum leaf and root tissue by ultra-performance liquid chromatography-mass spectrometry.

Analytical and bioanalytical chemistry pii:10.1007/s00216-019-01658-9 [Epub ahead of print].

Plant development, growth, and adaptation to stress are regulated by phytohormones, which can influence physiology even at low concentrations. Phytohormones are chemically grouped according to both structure and function as auxins, cytokinins, abscisic acid, jasmonates, salicylates, gibberellins, and brassinosteroids, among others. This chemical diversity and requirement for highly sensitive detection in complex matrices create unique challenges for comprehensive phytohormone analysis. Here, we present a robust and efficient quantitative UPLC-MS/MS assay for 17 phytohormones, including jasmonates, salicylates, abscisic acid, gibberellins, cytokinins, and auxins. Using this assay, 12 phytohormones were detected and quantified in sorghum plant tissue without the need for solid phase extraction (SPE) or liquid-liquid extraction. Variation of phytohormone profiles was explored in both root and leaf tissues between three genotypes, harvested at two different developmental time points. The results highlight the importance of tissue type, sampling time, and genetic factors when designing experiments that involve phytohormone analysis of sorghum. This research lays the groundwork for future studies, which can combine phytohormone profiling with other datasets such as transcriptome, soil microbiome, genome, and metabolome data, to provide important functional information about adaptation to stress and other environmental variables.

RevDate: 2019-03-17

Iwamoto K, Moriwaki M, Miyake R, et al (2019)

Staphylococcus aureus in atopic dermatitis: Strain-specific cell wall proteins and skin immunity.

Allergology international : official journal of the Japanese Society of Allergology pii:S1323-8930(19)30019-X [Epub ahead of print].

Atopic dermatitis (AD) is a common chronic skin disease. The presence of the bacterium Staphylococcus aureus (S. aureus) is frequently detected on skin affected with AD. In this review, we focused on the characteristics of S. aureus strains isolated from AD skin, particularly the proteins on the cell surface that modulates the interactions between Langerhans cell, keratinocyte, and S. aureus. The skin microbiome plays an important role in maintaining homeostasis of the skin, and colonization of S. aureus in AD is considered to be deeply involved in the clinical manifestation and pathogenesis of skin flares. Colonizing S. aureus strains in AD harbor different surface proteins at the strain level, which are indicated as clonal complexes. Moreover, the cell wall proteins of S. aureus affect skin adhesion and induce altered immune responses. S. aureus from AD skin (AD strain) exhibits internalization into keratinocytes and induces imbalanced Th1/Th2 adaptive immune responses via Langerhans cells. AD strain-derived cell wall proteins and secreted virulence factors are expected to represent therapeutic targets. In addition, the microbiome on the AD skin surface is associated with skin immunity; thus, microbiome-based immunotherapy, whose mechanism of action completely differs from that of typical steroid ointments, are expected to be developed in the future.

RevDate: 2019-03-16

Forgie AJ, Gao Y, Ju T, et al (2019)

Pea polyphenolics and hydrolysis processing alter microbial community structure and early pathogen colonization in mice.

The Journal of nutritional biochemistry, 67:101-110 pii:S0955-2863(18)30661-2 [Epub ahead of print].

Health benefits associated with pea consumption have been attributed to the fiber and polyphenolic content concentrated within the pea seed coat. However, the amount of pea polyphenols can vary between cultivars, and it has yet to be studied whether pea polyphenols impact the intestinal microbiota. We hypothesized that pea polyphenols promote a healthy microbiome that supports intestinal integrity and pathogen colonization resistance. To investigate the effects of pea polyphenols, pea cultivars rich and poor in proanthocyanidins were supplemented in raw or acid hydrolyzed form to an isocaloric diet in mice. Acid hydrolysis increases the absorption of pea polyphenols by cleaving polymeric proanthocyanidins to their readily absorbable anthocyanidin monomers. After 3 weeks of diet, mice were challenged with Citrobacter rodentium and pathogen colonization and inflammation were assessed. Counter to our hypothesis, pea seed coat fraction supplementation, especially the non-hydrolyzed proanthocyanidin-rich fraction diet adversely increased C. rodentium pathogen load and inflammation. Ileal, cecal and colon microbial communities were notably distinct between pea seed cultivar and hydrolysis processing. The consumption of intact proanthocyanidins decreased microbial diversity indicating that proanthocyanidins have antimicrobial properties. Together our results indicate supplementation of raw pea seed coat rich in proanthocyanidins adversely affect intestinal integrity. However, acid hydrolysis processing restored community structure and colonization resistance, and the anthocyanidin-rich fractions reduced weight gain on a high fat diet. Establishing a clear understanding of the effects of pea fiber and polyphenolic form on health will help to develop research-based pea products and dietary recommendations.

RevDate: 2019-03-16

Kobayashi T, K Nagao (2019)

Host-microbial Dialogues in Atopic Dermatitis.

International immunology pii:5381976 [Epub ahead of print].

Recent advances in sequencing technologies have revealed the diversity of microbes that reside on skin surface which has enhanced our understanding on skin as an ecosystem, wherein the epidermis, immune cells and the microbiota engage in active dialogues that maintain barrier integrity and functional immunity. This mutual dialogue is altered in atopic dermatitis (AD), in which impaired epidermal barrier, the skin microbial flora and aberrant immunity can form a vicious cycle that leads to clinical manifestation as eczematous dermatitis. Microbiome studies have revealed altered microbial landscape in AD and genetic studies have identified genes that underlie barrier impairment and immune dysregulation. Shifting from the long-standing notion that AD was mediated by conventional allergic responses, emerging data suggest that it is a disorder of altered host-microbial relationship with sophisticated pathophysiology. In this review, we will discuss recent advancements that suggest the roles of skin microbiota in AD pathophysiology, genetic factors that mediate barrier impairment, dysbiosis and inflammation. Studies in mice, classic AD and monogenic disorders that manifest as AD collectively facilitate our understanding of AD pathophysiology and provide foundation for novel therapeutic strategies.

RevDate: 2019-03-16

Hollingshead S, CM Tang (2019)

An Overview of Neisseria meningitidis.

Methods in molecular biology (Clifton, N.J.), 1969:1-16.

Neisseria meningitidis (the meningococcus) is a member of the normal nasopharyngeal microbiome in healthy individuals, but can cause septicemia and meningitis in susceptible individuals. In this chapter we provide an overview of the disease caused by N. meningitidis and the schemes used to type the meningococcus. We also review the adhesions, virulence factors, and phase variable genes that enable it to successfully colonize the human host. Finally, we outline the history and current status of meningococcal vaccines and highlight the importance of continued molecular investigation of the epidemiology and the structural analysis of the antigens of this pathogen to aid future vaccine development.

RevDate: 2019-03-16

Frank AC (2019)

Molecular host mimicry and manipulation in bacterial symbionts.

FEMS microbiology letters, 366(4):.

It is common among intracellular bacterial pathogens to use eukaryotic-like proteins that mimic and manipulate host cellular processes to promote colonization and intracellular survival. Eukaryotic-like proteins are bacterial proteins with domains that are rare in bacteria, and known to function in the context of a eukaryotic cell. Such proteins can originate through horizontal gene transfer from eukaryotes or, in the case of simple repeat proteins, through convergent evolution. Recent studies of microbiomes associated with several eukaryotic hosts suggest that similar molecular strategies are deployed by cooperative bacteria that interact closely with eukaryotic cells. Some mimics, like ankyrin repeats, leucine rich repeats and tetratricopeptide repeats are shared across diverse symbiotic systems ranging from amoebae to plants, and may have originated early, or evolved independently in multiple systems. Others, like plant-mimicking domains in members of the plant microbiome are likely to be more recent innovations resulting from horizontal gene transfer from the host, or from microbial eukaryotes occupying the same host. Host protein mimics have only been described in a limited set of symbiotic systems, but are likely to be more widespread. Systematic searches for eukaryote-like proteins in symbiont genomes could lead to the discovery of novel mechanisms underlying host-symbiont interactions.

RevDate: 2019-03-16

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

Modelling microbiome recovery after antibiotics using a stability landscape framework.

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

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

RevDate: 2019-03-16

Chan CYL, Hiong KC, Choo CYL, et al (2019)

With illumination, the fluted giant clam, Tridacna squamosa, upregulates the protein abundance of an apical Na+: glucose cotransporter 1 homolog in its ctenidium, and increases exogenous glucose absorption that can be impeded by urea.

The Journal of experimental biology pii:jeb.195644 [Epub ahead of print].

Giant clams contain phototrophic zooxanthellae, and live in nutrient-deficient tropical waters where light is available. We had obtained the complete cDNA coding sequence of a homolog of Na+:Glucose Cotransporter 1 (SGLT1-like) from the ctenidium of the fluted giant clam, Tridacna squamosaSGLT1-like had a host origin and was expressed predominantly in the ctenidium. Molecular characterizations reveal that SGLT1-like of T. squamosa could transport urea, in addition to glucose, as other SGLT1s do. It has an apical localization in the epithelium of ctenidial filaments and water channels, and the apical anti-SGLT1-like immunofluorescence was stronger in individuals exposed to light than to darkness. Furthermore, the protein abundance of SGLT1-like increased significantly in the ctenidium of individuals exposed to light for 12 h, despite the SGLT1-like transcript level remained unchanged. As expected, T. squamosa, could perform light-enhanced glucose absorption, which was impeded by exogenous urea. These results denote the close relationships between light-enhanced glucose absorption and light-enhanced SGLT1-like expression in the ctenidium of T. squamosa Although glucose absorption could be trivial compared with the donation of photosynthates from zooxanthellae in symbiotic adults, SGLT1-like might be essential for the survival of aposymbiotic larvae, leading to its retention in the symbiotic stage. A priori, glucose uptake through SGLT1-like might be augmented by the surface microbiome through nutrient cycling, and the absorbed glucose could partially fulfill the metabolic needs of the ctenidial cells. Additionally, SGLT1-like could partake in urea absorption, as T. squamosa is known to conduct light-enhanced urea uptake to benefit the nitrogen-deficient zooxanthellae.

RevDate: 2019-03-16

Labourel A, Baslé A, Munoz-Munoz J, et al (2019)

Structural and functional analysis of glycoside hydrolase 138 enzymes targeting chain A galacturonic acid in the complex pectin rhamnogalacturonan II.

The Journal of biological chemistry pii:RA118.006626 [Epub ahead of print].

The metabolism of carbohydrate polymers drives microbial diversity in the human gut microbiome. The selection pressures in this environment have spurred the evolution of a complex reservoir of microbial genes encoding carbohydrate-active enzymes (CAZymes). Previously, we have shown that the human gut bacterium Bacteroides thetaiotaomicron (Bt) can depolymerize the most structurally complex glycan, the plant pectin rhamnogalacturonan II (RGII), commonly found in the human diet. Previous investigation of the RGIIdegrading apparatus in Bt identified BT0997 as a new CAZyme family, classified as glycoside hydrolase 138 (GH138). The mechanism of substrate recognition by GH138, however, remains unclear. Here, using synthetic substrates and biochemical assays, we show that BT0997 targets the D-galacturonic acid-α-1,2-L-rhamnose linkage in chain A of RGII and that it absolutely requires the presence of a second D-galacturonic acid side chain (linked β-1,3 to L-rhamnose) for activity. NMR analysis revealed that BT0997 operates through a double-displacement, retaining mechanism. We also report the crystal structure of a BT0997 homolog, BPA0997 from Bacteroides paurosaccharolyticus, in complex with ligands at 1.6 Å resolution. The structure disclosed that the enzyme comprises four domains, including a catalytic TIM (α/β)8 barrel. Characterization of several BT0997 variants identified Glu-294 and Glu361 as the catalytic acid/base and nucleophile, respectively, and we observed a chloride ion close to the active site. The three-dimensional structure and bioinformatic analysis revealed that two arginines, Arg-332 and Arg-521, are key specificity determinants of BT0997 in targeting D-galacturonic acid residues. In summary, our study reports the first structural and mechanistic analyses of GH138 enzymes.

RevDate: 2019-03-16

Nobs SP, Tuganbaev T, E Elinav (2019)

Microbiome diurnal rhythmicity and its impact on host physiology and disease risk.

EMBO reports pii:embr.201847129 [Epub ahead of print].

Host-microbiome interactions constitute key determinants of host physiology, while their dysregulation is implicated in a wide range of human diseases. The microbiome undergoes diurnal variation in composition and function, and this in turn drives oscillations in host gene expression and functions. In this review, we discuss the newest developments in understanding circadian host-microbiome interplays, and how they may be relevant in health and disease contexts. We summarize the molecular mechanisms by which the microbiome influences host function in a diurnal manner, and inversely describe how the host orchestrates circadian rhythmicity of the microbiome. Furthermore, we highlight the future perspectives and challenges in studying this new and exciting facet of host-microbiome interactions. Finally, we illustrate how the elucidation of the microbiome chronobiology may pave the way for novel therapeutic approaches.

RevDate: 2019-03-16

Uchiyama K, Naito Y, T Takagi (2019)

Intestinal microbiome as a novel therapeutic target for local and systemic inflammation.

Pharmacology & therapeutics pii:S0163-7258(19)30045-2 [Epub ahead of print].

Recently, the pathogenesis of systemic inflammatory disease such as inflammatory bowel disease (IBD), multiple sclerosis (MS), systemic inflammatory arthritis, asthma, and non-alcoholic fatty liver disease has been reported to be related to the dysbiosis of gut microbiota. The contribution of special bacteria for the development of those diseases has been elucidated by disease animal models such as germ-free mice. Besides, the contribution by several bacteria for the pathogenesis of those diseases has been suggested by detailed analysis of the 16 small ribosomal subunit RNA (16S rRNA) from stool samples of the patients. Gut microbiota-targeted treatment for systemic inflammatory diseases such as fecal microbiota transplant (FMT), and probiotics has been now reported. Though there are several issues to be understood, these treatments have been highlighted as an innovative approach to intractable systemic inflammatory disease. In the present review, recent reports regarding the relation between gut microbiota and systemic inflammatory diseases are discussed with treatments to target gut microbiota.

RevDate: 2019-03-16

Douillard FP, WM de Vos (2019)

Biotechnology of health-promoting bacteria.

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

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

RevDate: 2019-03-16

Lebeer S, I Spacova (2019)

Exploring human host-microbiome interactions in health and disease-how to not get lost in translation.

Genome biology, 20(1):56 pii:10.1186/s13059-019-1669-4.

A meeting report on the 7th Wellcome Trust conference on Exploring Human Host-Microbiome Interactions in Health and Disease, held at Hinxton, UK, 5-7 December 2018.

RevDate: 2019-03-16

Giannella M, Pascale R, Gutiérrez-Gutiérrez B, et al (2019)

The use of predictive scores in the management of patients with carbapenem resistant Klebsiella pneumoniae infection.

Expert review of anti-infective therapy [Epub ahead of print].

INTRODUCTION: Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections are associated with high morbidity and mortality rates. A therapeutic approach based on the patient risk stratification could improve outcome and avoid antibiotic misuse. Area covered: English literature search, from 2008 to 2018, was done using PubMed database. Risk factors for developing CR-KP infection in several settings were reviewed. Since, rectal carriage was a main risk factor for developing infection, we revised in deep clinical score to predict infection among colonized patients. Furthermore, we investigated overall and treatment-related risk factors for poor outcome in patients with CR-KP infection, in particular the carbapenem producing Enterobacteriacieae (CPE)-INCREMENT score. Finally, an algorithm, based on such scores, for the therapeutic management of patients with CR-KP colonization was commented. Expert opinion: The therapeutic approach analyzed in this review could help physicians to avoid antibiotic overuse as well as to start promptly with the most appropriate antibiotic regimen. However, it has to be validated in further studies, mainly among special population such as immunocompromised patients. The availability of new drugs, fast microbiology and analysis of gut microbiome could significantly improve the management of CR-KP colonized and/or infected patients.

RevDate: 2019-03-16

Uritskiy G, J DiRuggiero (2019)

Applying Genome-Resolved Metagenomics to Deconvolute the Halophilic Microbiome.

Genes, 10(3): pii:genes10030220.

In the past decades, the study of microbial life through shotgun metagenomic sequencing has rapidly expanded our understanding of environmental, synthetic, and clinical microbial communities. Here, we review how shotgun metagenomics has affected the field of halophilic microbial ecology, including functional potential reconstruction, virus⁻host interactions, pathway selection, strain dispersal, and novel genome discoveries. However, there still remain pitfalls and limitations from conventional metagenomic analysis being applied to halophilic microbial communities. Deconvolution of halophilic metagenomes has been difficult due to the high G + C content of these microbiomes and their high intraspecific diversity, which has made both metagenomic assembly and binning a challenge. Halophiles are also underrepresented in public genome databases, which in turn slows progress. With this in mind, this review proposes experimental and analytical strategies to overcome the challenges specific to the halophilic microbiome, from experimental designs to data acquisition and the computational analysis of metagenomic sequences. Finally, we speculate about the potential applications of other next-generation sequencing technologies in halophilic communities. RNA sequencing, long-read technologies, and chromosome conformation assays, not initially intended for microbiomes, are becoming available in the study of microbial communities. Together with recent analytical advancements, these new methods and technologies have the potential to rapidly advance the field of halophile research.

RevDate: 2019-03-15

Ayuningrum D, Liu Y, Riyanti , et al (2019)

Tunicate-associated bacteria show a great potential for the discovery of antimicrobial compounds.

PloS one, 14(3):e0213797 pii:PONE-D-18-30835.

Tunicates (Ascidians, sea squirts) are marine protochordates, which live sedentary or sessile in colonial or solitary forms. These invertebrates have to protect themselves against predators and invaders. A most successful strategy, to not being eaten by predators and prevent pathogenic microorganisms to settle, is the usage of chemical molecules for defence. To accomplish this, tunicates take advantage of the specialized metabolites produced by the bacteria associated with them. Therefore, the microbiome of the tunicates can be regarded as a promising bioresource for bacterial strains producing compounds with antibacterial activity. The aim of this study was to test this hypothesis by (i) isolation of tunicate-associated bacteria, (ii) analysis of the antibacterial activities of these strains, and (iii) purification and structure elucidation of an active compound derived from this bioresource. In total, 435 bacterial strains were isolated and thereof 71 (16%) showed antibacterial activity against multidrug resistant (MDR) bacteria. Therefrom, the ethyl acetate crude extracts from liquid fermentations of 25 strains showed activity against MDR Extended-Spectrum Beta-Lactamase (MDR-ESBL) Escherichia coli, MDR Bacillus cereus, Micrococcus luteus, and Bacillus megaterium. Phenotypic analysis based on 16S rDNA sequencing revealed the active strains belonging to different genera and phyla, like Bacillus, Pantoea, Pseudoalteromonas, Salinicola, Streptomyces, Vibrio and Virgibacillus. To obtain first insights into the molecules responsible for the antibacterial activities observed, strain Pseudoalteromonas rubra TKJD 22 was selected for large-scale fermentation and the active compound was isolated. This allowed the purification and structure elucidation of isatin, a compound known for its strong biological effects, thereunder inhibition of Gram-positive and Gram-negative pathogens.

RevDate: 2019-03-15

Topcuoglu N, Erdem AP, Karacan I, et al (2019)

Oral microbial dysbiosis in patients with Kostmann syndrome.

Journal of medical microbiology [Epub ahead of print].

PURPOSE: The oral microbiome is maintained by host- and microbe-derived factors. A shift in microbial composition, as a result of diseases related to the immune system, is the most important step in the development of oral and dental diseases. The aim of this study was to investigate the oral microbial composition of patients with Kostmann syndrome, who have severe neutropenia, compared with healthy children.

METHODOLOGY: A group of nine Kostmann syndrome patients and a group of nine healthy controls participated. After clinical investigation, DNA from stimulated saliva specimens was examined by high-throughput sequencing of the V3-V4 hypervariable region of the 16S rRNA gene using Illumina sequencing. The QIIME software package was used for 16 S rRNA amplicon analysis, while the Greengenes database was used for taxonomic classification.

RESULTS: The periodontal pocket depths, plaque indices and bleeding-on-probing percentages and caries status on the deciduous teeth of the patients with Kostmann syndrome were statistically higher than those for the healthy controls. Patients with Kostmann syndrome had significantly lower bacterial diversity as compared to the controls. The presence of Firmicutes was statistically higher in patients with Kostmann syndrome, while that for Proteobacteria was higher in samples from the healthy controls (P<0.05). Streptococcus, Rothia, Granulicatella, Actinomyces, and genera from the family Gemellaceae were present as the core microbiome (abundance >1 % in at least 75 % of samples) in all groups, whereas the genus Porphyromonas was only detected as a member of the core microbiome in Kostmann patients.

CONCLUSIONS: The evidence of lower bacterial diversity and differences in microbial profile for patients with Kostmann syndrome not only shows the impact of immune system-related diseases on oral microbiota, but also endorses the ecological plaque hypothesis proposed for the aetiology of oral diseases such as dental caries and periodontitis.

RevDate: 2019-03-15

Taylor SL, Leong LEX, Mobegi FM, et al (2019)

Long-Term Azithromycin Reduces Haemophilus influenzae and Increases Antibiotic Resistance in Severe Asthma.

American journal of respiratory and critical care medicine [Epub ahead of print].

Rationale The macrolide antibiotic, azithromycin, reduces exacerbations in adults with persistent symptomatic asthma. However, owing to the pleotropic properties of macrolides, unintended bacteriological consequences such as augmented pathogen colonization or dissemination of antibiotic-resistant organisms can occur, calling into question the long-term safety of azithromycin maintenance therapy. Objectives To assess the effects of azithromycin on the airway microbiota, pathogen abundance, and carriage of antibiotic-resistance genes. Methods 16S rRNA sequencing and quantitative PCR (qPCR) were performed to assess the effect of azithromycin on sputum microbiology from participants of the AMAZES trial: a 48-week, double-blind, placebo-controlled trial of thrice-weekly 500mg oral azithromycin in adults with persistent uncontrolled asthma. Pooled-template shotgun metagenomic sequencing, qPCR, and isolate whole genome sequencing were performed to assess antibiotic resistance. Measurements and Main Results Paired sputum was available from 61 patients (n=34 placebo, n=27 azithromycin). Azithromycin did not affect bacterial load (p=0.37) but did significantly decrease Faith's bacterial diversity (p=0.026) and Haemophilus influenzae load (p<0.001). Azithromycin did not significantly affect levels of Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa or Moraxella catarrhalis. Of the 89 antibiotic resistance genes detected, macrolide resistance genes (erm(B), erm(F), msr(E), mef(A), and mel) and tetracycline resistance genes (tet(M) and tet(W)) were increased significantly. Conclusions In patients with persistent uncontrolled asthma, addition of azithromycin reduced airway H. influenzae load, with no changes to total or pathogenic bacterial loads. Macrolide resistance increased, reflecting previous studies. These results highlight the need for studies assessing the efficacy of non-antibiotic macrolides as long-term therapy for patients with persistent uncontrolled asthma.

RevDate: 2019-03-15

Cryan JF, Boehme M, TG Dinan (2019)

Is the fountain of youth in the gut microbiome?.

The Journal of physiology [Epub ahead of print].

RevDate: 2019-03-15

Yerevanian A, AA Soukas (2019)

Metformin: Mechanisms in Human Obesity and Weight Loss.

Current obesity reports pii:10.1007/s13679-019-00335-3 [Epub ahead of print].

PURPOSE OF REVIEW: Metformin has multiple benefits for health beyond its anti-hyperglycemic properties. The purpose of this manuscript is to review the mechanisms that underlie metformin's effects on obesity.

RECENT FINDINGS: Metformin is a first-line therapy for type 2 diabetes. Large cohort studies have shown weight loss benefits associated with metformin therapy. Metabolic consequences were traditionally thought to underlie this effect, including reduction in hepatic gluconeogenesis and reduction in insulin production. Emerging evidence suggests that metformin-associated weight loss is due to modulation of hypothalamic appetite regulatory centers, alteration in the gut microbiome, and reversal of consequences of aging. Metformin is also being explored in the management of obesity's sequelae such as hepatic steatosis, obstructive sleep apnea, and osteoarthritis. Multiple mechanisms underlie the weight loss-inducing and health-promoting effects of metformin. Further exploration of these pathways may be important in identifying new pharmacologic targets for obesity and other aging-associated metabolic diseases.

RevDate: 2019-03-15

Seidler U, K Nikolovska (2019)

Slc26 Family of Anion Transporters in the Gastrointestinal Tract: Expression, Function, Regulation, and Role in Disease.

Comprehensive Physiology, 9(2):839-872.

SLC26 family members are multifunctional transporters of small anions, including Cl- , HCO3- , sulfate, oxalate, and formate. Most SLC26 isoforms act as secondary (coupled) anion transporters, while others mediate uncoupled electrogenic transport resembling Cl- channels. Of the 11 described SLC26 isoforms, the SLC26A1,2,3,6,7,9,11 are expressed in the gastrointestinal tract, where they participate in salt and water transport, surface pH-microclimate regulation, affect the microbiome composition, the absorption, and secretion of oxalate and sulfate, and other functions that require further study. Several intestinal or extra-intestinal diseases are related to SLC26A mutations. Patients with congenital chloride diarrhea (CLD) suffer from Cl- -rich acidic diarrhea and systemic alkalosis due to SLC26A3 mutations. Patients with osteochondrodysplastic syndromes experience skeletal defects due to SLC26A2 mutations, resulting in defective sulfate absorption in enterocytes and sulfate uptake in chondrocytes. Because of functional interactions between SLC26 and other proteins, such as the Cl- channel CFTR, some of the intestinal cystic fibrosis manifestations may be attributed to impaired SLC26 isoform localization and function. The altered expression of SLC26 members due to inflammation or operative procedures have important consequences on intestinal transport and barrier function in common diseases as inflammatory bowel disease or bariatric surgery. The present review gives an overview on the current state of knowledge of the intestinally expressed SLC26A isoforms (SLC26A1,2,3,6,7,9,11) from the history of their functional identification, cloning and expression, the insights into their function, interaction partners and regulation gained in heterologous expression systems and Slc26a-deficient mice, to information about their transcriptional regulation and roles in gastrointestinal disease manifestations. © 2019 American Physiological Society. Compr Physiol 9:839-872, 2019.

RevDate: 2019-03-15

Wang B, Ma MP, Diao QY, et al (2019)

Saponin-Induced Shifts in the Rumen Microbiome and Metabolome of Young Cattle.

Frontiers in microbiology, 10:356.

The aim of this study was to explore the effects of saponins on the rumen microbiota and the ruminal metabolome. Alfalfa hay (AH) and soybean hulls (SH) were used as fiber sources for the control diets. The AH and SH diets were supplemented with tea saponins resulting in two additional diets named AHS and SHS, respectively. These 4 diets were fed to 24 young male Holstein cattle (n = 6 per diet). After 28 days of feeding, the rumen fluid from these cattle was collected using an oral stomach tube. Illumina MiSeq sequencing and ultrahigh-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) were used to investigate the changes in the ruminal microbes and their metabolites. The relative abundance of Prevotellaceae_YAB2003 increased, while Ruminococcaceae_NK4A214 and Lachnospiraceae_NK3A20 decreased in SHS and AHS compared to SH and AHS, respectively. Feeding SHS resulted in higher ruminal concentrations of squalene, lanosterol, 3-phenylpropanoic acid, and citrulline compared to SH. The different microbial genes predicted by Tax4Fun were involved in amino sugar and nucleotide sugar metabolism. The pathways of arginine and proline metabolism, purine metabolism, and pyrimidine metabolism were enriched by different metabolites. Moreover, in the SH group, a positive correlation was observed between Prevotella_1 (Bacteroidetes), Prevotellaceae_YAB2003 (Bacteroidetes), and Christensenellaceae_R.7 (Firmicutes), and the metabolites, including citrulline, lanosterol, and squalene. The increased abundances of Prevotella_1, Ruminococcaceae_UCG.002, and Prevotellaceae_YAB2003 might result in increased fiber digestion and nutrient utilization but nutrient digestion was not measured in the current study. In summary, saponins have the ability to modulate the ruminal microbial community and ruminal metabolites and thus affect the rumen environment. However, the response seems to be dependent on the composition of the basal diet. This study provides a comprehensive overview of the microbial and biochemical changes in the rumen of cattle fed saponins.

RevDate: 2019-03-15

Li H, Cai X, Gong J, et al (2019)

Long-Term Organic Farming Manipulated Rhizospheric Microbiome and Bacillus Antagonism Against Pepper Blight (Phytophthora capsici).

Frontiers in microbiology, 10:342.

Soil-borne diseases are often less severe in organic farms, possibly because of the recruitment of beneficial microorganisms by crops. Here, the suppressiveness of organic, integrated, and conventionally managed soils to pepper blight (Phytophthora capsici) was studied in growth chamber experiments. Disease incidence was 41.3 and 34.1% lower in the soil from an organic farming system than in either the soil from the integrated or from the conventional farming systems, respectively. Beta-diversity of rhizospheric microbial communities differed among treatments, with enrichment of Bacillus, Sporosarcina, Acidobacteria Gp5, Gp6, Gp22, and Ignavibacterium by the organic soil. Cultivation-dependent analysis indicated that 50.3% of in vitro antagonists of P. capsici isolated from the rhizosphere of healthy peppers were affiliated to Bacillus. An integration of in vitro antagonists and bacterial diversity analyses indicated that Bacillus antagonists were higher in the rhizosphere of pepper treated by the organic soil. A microbial consortium of 18 in vitro Bacillus antagonists significantly increased the suppressiveness of soil from the integrated farming system against pepper blight. Overall, the soil microbiome under the long-term organic farming system was more suppressive to pepper blight, possibly owing to Bacillus antagonism in the rhizosphere. This study provided insights into microbiome management for disease suppression under greenhouse conditions.

RevDate: 2019-03-15

Johnston J, LaPara T, S Behrens (2019)

Composition and Dynamics of the Activated Sludge Microbiome during Seasonal Nitrification Failure.

Scientific reports, 9(1):4565 pii:10.1038/s41598-019-40872-4.

Wastewater treatment plants in temperate climate zones frequently undergo seasonal nitrification failure in the winter month yet maintain removal efficiency for other contaminants. We tested the hypothesis that nitrification failure can be correlated to shifts in the nitrifying microbial community. We monitored three parallel, full-scale sequencing batch reactors over the course of a year with respect to reactor performance, microbial community composition via 16S rRNA gene amplicon sequencing, and functional gene abundance using qPCR. All reactors demonstrated similar changes to their core microbiome, and only subtle variations among seasonal and transient taxa. We observed a decrease in species richness during the winter, with a slow recovery of the activated sludge community during spring. Despite the change in nitrification performance, ammonia monooxygenase gene abundances remained constant throughout the year, as did the relative sequence abundance of Nitrosomonadacae. This suggests that nitrification failure at colder temperatures might result from different reaction kinetics of nitrifying taxa, or that other organisms with strong seasonal shifts in population abundance, e.g. an uncultured lineage of Saprospiraceae, affect plant performance in the winter. This research is a comprehensive analysis of the seasonal microbial community dynamics in triplicate full-scale sequencing batch reactors and ultimately strengthens our basic understanding of the microbial ecology of activated sludge communities by revealing seasonal succession patterns of individual taxa that correlate with nutrient removal efficiency.

RevDate: 2019-03-15

Gaiser RA, Halimi A, Alkharaan H, et al (2019)

Enrichment of oral microbiota in early cystic precursors to invasive pancreatic cancer.

Gut pii:gutjnl-2018-317458 [Epub ahead of print].

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cysts that can progress to invasive pancreatic cancer. Associations between oncogenesis and oral microbiome alterations have been reported. This study aims to investigate a potential intracystic pancreatic microbiome in a pancreatic cystic neoplasm (PCN) surgery patient cohort.

DESIGN: Paired cyst fluid and plasma were collected at pancreatic surgery from patients with suspected PCN (n=105). Quantitative and qualitative assessment of bacterial DNA by qPCR, PacBio sequencing (n=35), and interleukin (IL)-1β quantification was performed. The data were correlated to diagnosis, lesion severity and clinical and laboratory profile, including proton-pump inhibitor (PPI) usage and history of invasive endoscopy procedures.

RESULTS: Intracystic bacterial 16S DNA copy number and IL-1β protein quantity were significantly higher in IPMN with high-grade dysplasia and IPMN with cancer compared with non-IPMN PCNs. Despite high interpersonal variation of intracystic microbiota composition, bacterial network and linear discriminant analysis effect size analyses demonstrated co-occurrence and enrichment of oral bacterial taxa including Fusobacterium nucleatum and Granulicatella adiacens in cyst fluid from IPMN with high-grade dysplasia. The elevated intracystic bacterial DNA is associated with, but not limited to, prior exposure to invasive endoscopic procedures, and is independent from use of PPI and antibiotics.

CONCLUSIONS: Collectively, these findings warrant further investigation into the role of oral bacteria in cystic precursors to pancreatic cancer and have added values on the aetiopathology as well as the management of pancreatic cysts.

RevDate: 2019-03-15

Li Y, Wang H, Li X, et al (2019)

Disordered intestinal microbes are associated with the activity of Systemic Lupus Erythematosus.

Clinical science (London, England : 1979) pii:CS20180841 [Epub ahead of print].

Intestinal dysbiosis is implicated in Systemic lupus erythematosus (SLE). However, the evidence of gut microbiome changes in SLE is limited, and the association of changed gut microbiome with the activity of SLE, as well as its functional relevance with SLE still remains unknown. Here, we sequenced 16S rRNA amplicon on fecal samples from 40 SLE patients (19 active patients, 21 remissive patients), 20 disease controls (Rheumatoid Arthritis patients), and 22 healthy controls, and investigated the association of functional categories with taxonomic composition by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). We demonstrated that SLE patients, particularly those active patients, had significant dysbiosis in gut microbiota with reduced bacterial diversity and biased community constitutions. Among the disordered microbiota, the genera Streptococcus , Campylobacter , Veillonella , the species anginosus and dispar , were positively correlated with lupus activity, while the genus Bifidobacterium was negatively associated with disease activity. PICRUSt analysis showed that metabolic pathways were different between SLE and healthy controls, and between active and remissive SLE patients. Moreover, we revealed that a random forest model could distinguish SLE from RA and healthy controls (AUC = 0.792), and another random forest model could well predict the activity of SLE patients (AUC = 0.811). In summary, SLE patients, especially the active patients, show an obvious dysbiosis in gut microbiota and its related metabolic pathways. Among the disordered microflora, 4 genera and 2 species are associated with lupus activity. Furthermore, the random forest models are able to diagnose SLE and predict disease activity.

RevDate: 2019-03-15

Alikhan A, Sayed C, Alavi A, et al (2019)

North American Clinical Management Guidelines for Hidradenitis Suppurativa: a Publication from the United States and Canadian Hidradenitis Suppurativa Foundations. Part I: Diagnosis, Evaluation, and the use of Complementary and Procedural Management.

Journal of the American Academy of Dermatology pii:S0190-9622(19)30367-6 [Epub ahead of print].

Hidradenitis suppurativa is a chronic inflammatory disorder affecting hair follicles with profoundly negative impact on patient quality of life. Evidence informing ideal evaluation and management of patients with hidradenitis suppurativa is still sparse in many areas, but has grown substantially in the last decade. Part I of this evidence-based guideline is presented to support health care practitioners as they select optimal management strategies including diagnostic testing, comorbidity screening, and both complementary and procedural treatment options. Recommendations and evidence grading based on the evidence available at the time of the review are provided.

RevDate: 2019-03-15

Alikhan A, Sayed C, Alavi A, et al (2019)

North American Clinical Management Guidelines for Hidradenitis Suppurativa: a Publication from the United States and Canadian Hidradenitis Suppurativa Foundations. Part II: Topical, Intralesional, and Systemic medical Management.

Journal of the American Academy of Dermatology pii:S0190-9622(19)30368-8 [Epub ahead of print].

Hidradenitis suppurativa is a severe and debilitating dermatologic disease. Clinical management is challenging and consists of both medical and surgical approaches, which must often be combined for best outcomes. Therapeutic approaches have evolved rapidly in the last decade and include the use of topical therapies, systemic antibiotics, hormonal therapies, and a wide range of immunomodulating medications. An evidence-based guideline is presented to support health care practitioners as they select optimal medical management strategies is reviewed in this second part of the management guidelines. A therapeutic algorithm informed by the evidence available at the time of the review is provided.

RevDate: 2019-03-15

Minot SS (2019)

De novo Assembly Vastly Expands the Known Microbial Universe.

Trends in microbiology pii:S0966-842X(19)30058-7 [Epub ahead of print].

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

RevDate: 2019-03-15

Ni YH (2019)

Bugs to debug? The exploration of gut microbiome in human health and diseases.

Journal of the Formosan Medical Association = Taiwan yi zhi, 118 Suppl 1:S1-S2.

RevDate: 2019-03-15

Meindl-Beinker NM, Betge J, Gutting T, et al (2019)

A multicenter open-label phase II trial to evaluate nivolumab and ipilimumab for 2nd line therapy in elderly patients with advanced esophageal squamous cell cancer (RAMONA).

BMC cancer, 19(1):231 pii:10.1186/s12885-019-5446-2.

BACKGROUND: Advanced esophageal squamous cell cancer (ESCC) is frequently diagnosed in elderly patients. The impact of 2nd line chemotherapy is poorly defined. Recent data demonstrated effectiveness of checkpoint inhibitors in different squamous cell carcinomas. Therefore, we assess combined nivolumab/ipilimumab as 2nd line therapy in elderly ESCC patients.

METHODS: RAMONA is a multicenter open-label phase II trial. The primary objective is to demonstrate a significant survival benefit of nivolumab/ipilimumab in advanced ESCC compared to historical data of standard chemotherapy. Primary endpoint is therefore overall survival (OS). Major secondary objective is the evaluation of tolerability. Time to QoL deterioration will thus be determined as key secondary endpoint. Further secondary endpoints are tumor response, PFS and safety. We aim to recruit a total of n = 75 subjects that have to be > 65 years old. Eligibility is determined by the geriatric status (G8 screening and Deficit Accumulation Frailty Index (DAFI)). A safety assessment will be performed after a 3 cycle run-in phase of nivolumab (240 mg Q2W) to justify escalation for eligible patients to combined nivolumab (240 mg Q2W) and ipilimumab (1 mg/kg Q6W), while the other patients will remain on nivolumab only. RAMONA also includes translational research sub-studies to identify predictive biomarkers, including PD-1 and PD-L1 evaluation at different time points, establishment of organoid cultures and microbiome analyses for response prediction.

DISCUSSION: The RAMONA trial aims to implement checkpoint inhibitors for elderly patients with advanced ESCC as second line therapy. Novel biomarkers for checkpoint-inhibitor response are analyzed in extensive translational sub-studies.

TRIAL REGISTRATION: EudraCT Number: 2017-002056-86 ; NCT03416244 , registered: 31.1.2018.

RevDate: 2019-03-15

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

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

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

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

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

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

RevDate: 2019-03-15

Torres PJ, Skarra DV, Ho BS, et al (2019)

Letrozole treatment of adult female mice results in a similar reproductive phenotype but distinct changes in metabolism and the gut microbiome compared to pubertal mice.

BMC microbiology, 19(1):57 pii:10.1186/s12866-019-1425-7.

BACKGROUND: A majority of women with polycystic ovary syndrome (PCOS) have metabolic dysfunction that results in an increased risk of type 2 diabetes. We previously developed a pubertal mouse model using the aromatase inhibitor, letrozole, which recapitulates many of the reproductive and metabolic features of PCOS. To further our understanding of the effects of androgen excess, we compared the effects of letrozole treatment initiated in puberty versus adulthood on reproductive and metabolic phenotypes as well as on the gut microbiome.

RESULTS: Letrozole treatment of both pubertal and adult female mice resulted in reproductive hallmarks of PCOS, including hyperandrogenemia, anovulation and polycystic ovaries. However, unlike pubertal mice, treatment of adult female mice resulted in modest weight gain and abdominal adiposity, minimal elevation in fasting blood glucose and insulin levels, and no detectable insulin resistance. In addition, letrozole treatment of adult mice was associated with a distinct shift in gut microbial diversity compared to letrozole treatment of pubertal mice.

CONCLUSIONS: Our results indicate that dysregulation of metabolism and the gut microbiome in PCOS may be influenced by the timing of androgen exposure. In addition, the minimal weight gain and lack of insulin resistance in adult female mice after letrozole treatment indicates that this model may be useful for investigating the effects of hyperandrogenemia on the hypothalamic-pituitary-gonadal axis and the periphery without the influence of substantial metabolic dysregulation.

RevDate: 2019-03-15

Dong TS, JP Jacobs (2019)

Nonalcoholic fatty liver disease and the gut microbiome: Are bacteria responsible for fatty liver?.

Experimental biology and medicine (Maywood, N.J.) [Epub ahead of print].

IMPACT STATEMENT: This invited minireview for the upcoming thematic issue on the microbiome addresses the role of the microbiome in nonalcoholic fatty liver disease (NAFLD). The incidence of NAFLD has increased greatly in recent years in parallel with the rise in obesity and is now believed to have a population prevalence of 20-40%. It is anticipated to soon become the primary cause of liver-related morbidity and mortality, and unfortunately, there are few treatment options. Therefore, there is a critical need for improved understanding of NAFLD pathophysiology to provide new avenues for therapeutic intervention. In this paper, we have reviewed evidence from human and animal model studies that have associated microbiome composition and microbial metabolites with development and progression of NAFLD. We have also discussed proposed mechanisms by which the microbiome could contribute to NAFLD pathogenesis and addressed future directions for this field.

RevDate: 2019-03-15

Gurwara S, Ajami NJ, Jang A, et al (2019)

Dietary Nutrients Involved in One-Carbon Metabolism and Colonic Mucosa-Associated Gut Microbiome in Individuals with an Endoscopically Normal Colon.

Nutrients, 11(3): pii:nu11030613.

One carbon (1C) metabolism nutrients influence epigenetic regulation and they are supplied by diet and synthesized by gut microbiota. We examined the association between dietary consumption of methyl donors (methionine, betaine and choline) and B vitamins (folate, B2, B6, and B12) and the community composition and structure of the colonic mucosa-associated gut microbiota determined by 16S rRNA gene sequencing in 97 colonic biopsies of 35 men. We used the food frequency questionnaire to assess daily consumption of nutrients, and the UPARSE and SILVA databases for operational taxonomic unit classification. The difference in bacterial diversity and taxonomic relative abundance were compared between low versus high consumption of these nutrients. False discover rate (FDR) adjusted p value < 0.05 indicated statistical significance. The bacterial richness and composition differed significantly by the consumption of folate and B vitamins (p < 0.001). Compared with higher consumption, a lower consumption of these nutrients was associated with a lower abundance of Akkermansia (folate), Roseburia (vitamin B2), and Faecalibacterium (vitamins B2, B6, and B12) but a higher abundance of Erysipelatoclostridium (vitamin B2) (FDR p values < 0.05). The community composition and structure of the colonic bacteria differed significantly by dietary consumption of folate and B vitamins.

RevDate: 2019-03-15

Murtaza N, Burke LM, Vlahovich N, et al (2019)

Analysis of the Effects of Dietary Pattern on the Oral Microbiome of Elite Endurance Athletes.

Nutrients, 11(3): pii:nu11030614.

Although the oral microbiota is known to play a crucial role in human health, there are few studies of diet x oral microbiota interactions, and none in elite athletes who may manipulate their intakes of macronutrients to achieve different metabolic adaptations in pursuit of optimal endurance performance. The aim of this study was to investigate the shifts in the oral microbiome of elite male endurance race walkers from Europe, Asia, the Americas and Australia, in response to one of three dietary patterns often used by athletes during a period of intensified training: a High Carbohydrate (HCHO; n = 9; with 60% energy intake from carbohydrates; ~8.5 g kg-1 day-1 carbohydrate, ~2.1 g kg-1 day-1 protein, 1.2 g kg-1 day-1 fat) diet, a Periodised Carbohydrate (PCHO; n = 10; same macronutrient composition as HCHO, but the intake of carbohydrates is different across the day and throughout the week to support training sessions with high or low carbohydrate availability) diet or a ketogenic Low Carbohydrate High Fat (LCHF; n = 10; 0.5 g kg-1 day-1 carbohydrate; 78% energy as fat; 2.1 g kg-1 day-1 protein) diet. Saliva samples were collected both before (Baseline; BL) and after the three-week period (Post treatment; PT) and the oral microbiota profiles for each athlete were produced by 16S rRNA gene amplicon sequencing. Principal coordinates analysis of the oral microbiota profiles based on the weighted UniFrac distance measure did not reveal any specific clustering with respect to diet or athlete ethnic origin, either at baseline (BL) or following the diet-training period. However, discriminant analyses of the oral microbiota profiles by Linear Discriminant Analysis (LDA) Effect Size (LEfSe) and sparse Partial Least Squares Discriminant Analysis (sPLS-DA) did reveal changes in the relative abundance of specific bacterial taxa, and, particularly, when comparing the microbiota profiles following consumption of the carbohydrate-based diets with the LCHF diet. These analyses showed that following consumption of the LCHF diet the relative abundances of Haemophilus, Neisseria and Prevotella spp. were decreased, and the relative abundance of Streptococcus spp. was increased. Such findings suggest that diet, and, in particular, the LCHF diet can induce changes in the oral microbiota of elite endurance walkers.

RevDate: 2019-03-15

Yan H, Zhang L, Guo Z, et al (2019)

Production Phase Affects the Bioaerosol MicrobialComposition and Functional Potential in SwineConfinement Buildings.

Animals : an open access journal from MDPI, 9(3): pii:ani9030090.

Bioaerosols from swine confinement buildings (SCBs) pose a challenge to public health,and microorganisms within the SCBs bioaerosols originate from swine feces, of which the microbialcomposition is associated with the production phase. The present study adopted the wholemetagenome shotgun sequencing approach, to assess the effects of the production phase on thecomposition and functional potential of microbial populations in SCBs bioaerosols. Most annotatedproteins were assigned into domain bacteria, within which the predominant phylum was Firmicutes.The taxonomical profiles of bioaerosols from different types of piggeries showed that buildingshousing weaning piglets (WP) exhibited higher abundances of Bacteroidetes and Proteobacteria thanbuildings housing finishing pigs (FP), gestating sows (GS), farrowing sows (FS), and breeding boars(BB). Regarding the functional potential, the WP bioaerosol had more genes involved in the proteinturnover and fewer genes involved in the carbohydrate metabolism than bioaerosols from othertypes of SCBs. Furthermore, production phase influenced the antibiotic resistance genes (ARGs)profile of the SCBs bioaerosols. Bioaerosol microbiome of BB, shared a high similarity with GS, andWP bioaerosol microbiome was more similar to FP than other types of SCBs. Our study suggeststhat the production phase plays a key role in the SCBs bioaerosol microbiome.

RevDate: 2019-03-15

Lin JH, Wu ZY, Gong L, et al (2019)

Complex Microbiome in Brain Abscess Revealed by Whole-Genome Culture-Independent and Culture-Based Sequencing.

Journal of clinical medicine, 8(3): pii:jcm8030351.

Brain abscess is a severe infectious disease with high mortality and mobility. Although culture-based techniques have been widely used for the investigation of microbial composition of brain abscess, these approaches are inherent biased. Recent studies using 16S ribosomal sequencing approaches revealed high complexity of the bacterial community involved in brain abscess but fail to detect fungal and viral composition. In the study, both culture-independent nanopore metagenomic sequencing and culture-based whole-genome sequencing using both the Illumina and the Nanopore platforms were conducted to investigate the microbial composition and genomic characterization in brain abscess. Culture-independent metagenomic sequencing revealed not only a larger taxonomic diversity of bacteria but also the presence of fungi and virus communities. The culture-based whole-genome sequencing identified a novel species in Prevotella and reconstructs a Streptococcus constellatus with a high GC-skew genome. Antibiotic-resistance genes CfxA and ErmF associated with resistance to penicillin and clindamycin were also identified in culture-based and culture-free sequencing. This study implies current understanding of brain abscess need to consider the broader diversity of microorganisms.

RevDate: 2019-03-15

Li D, Chen H, Zhao J, et al (2019)

Potential Functions of the Gastrointestinal Microbiome Inhabiting the Length of the Rat Digest Tract.

International journal of molecular sciences, 20(5): pii:ijms20051232.

The rat is an important model animal used frequently in biological researches exploring the correlations between gut microbiome and a wide array of diseases. In this study, we used an extended ancestral-state reconstruction algorithm to predict the functional capabilities of the rat gastrointestinal microbiome. Our results indicate an apparent tendency toward metabolic heterogeneity along the longitudinal and transverse axes of the rat gastrointestinal tract (GIT). This heterogeneity was suggested by the enriched small-molecule transport activity and amino acid metabolism in the upper GIT, the aerobic energy metabolism in the stomach and the mucolysis-related metabolism in the lower GIT mucus layer. In contrast to prior results, many functional overlaps were observed when the gastrointestinal microbiomes of different hosts were compared. These overlaps implied that although both the biogeographic location and host genotype were prominent driving forces in shaping the gastrointestinal microbiota, the microbiome functions were similar across hosts when observed under similar physicochemical conditions at identical anatomical sites. Our work effectively complements the rat microbial biogeography dataset we released in 2017 and, thus, contributes to a better understanding and prediction of disease-related alterations in microbial community function.

RevDate: 2019-03-14

Sun J (2017)

Intestinal organoid as an in vitro model in studying host-microbial interactions.

Frontiers in biology, 12(2):94-102.

Background: Organoid is an in vitro three-dimensional organ-bud that shows realistic microanatomy and physiologic relevance. The progress in generating organoids that faithfully recapitulate human in vivo tissue composition has extended organoid applications from being just a basic research tool to a translational platform with a wide range of uses. Study of host-microbial interactions relies on model systems to mimic the in vivo infection. Researchers have developed various experimental models in vitro and in vivo to examine the dynamic host-microbial interactions. For some infectious pathogens, model systems are lacking whereas some of the used systems are far from optimal.

Objective: In the present work, we will review the brief history and recent findings using organoids for studying host-microbial interactions.

Methods: A systematic literature search was performed using the PubMed search engine. We also shared our data and research contribution to the field.

Results: we summarize the brief history of 3D organoids. We discuss the feasibility of using organoids in studying host-microbial interactions, focusing on the development of intestinal organoids and gastric organoids. We highlight the advantage and challenges of the new experimental models. Further, we discuss the future direction in using organoids in studying host-microbial interactions and its potential application in biomedical studies.

Conclusion: In combination with genetic, transcriptome and proteomic profiling, both murine- and human-derived organoids have revealed crucial aspects of development, homeostasis and diseases. Specifically, human organoids from susceptible host will be used to test their responses to pathogens, probiotics, and drugs. Organoid system is an exciting tool for studying infectious disease, microbiome, and therapy.

RevDate: 2019-02-28

Salter SJ, Scott P, Page AJ, et al (2019)

'Candidatus Ornithobacterium hominis': insights gained from draft genomes obtained from nasopharyngeal swabs.

Microbial genomics, 5(2):.

'Candidatus Ornithobacterium hominis' represents a new member of the Flavobacteriaceae detected in 16S rRNA gene surveys of people from South-East Asia, Africa and Australia. It frequently colonizes the infant nasopharynx at high proportional abundance, and we demonstrate its presence in 42 % of nasopharyngeal swabs from 12-month-old children in the Maela refugee camp in Thailand. The species, a Gram-negative bacillus, has not yet been cultured, but the cells can be identified in mixed samples by fluorescent hybridization. Here, we report seven genomes assembled from metagenomic data, two to improved draft standard. The genomes are approximately 1.9 Mb, sharing 62 % average amino acid identity with the only other member of the genus, the bird pathogen Ornithobacterium rhinotracheale. The draft genomes encode multiple antibiotic-resistance genes, competition factors, Flavobacterium johnsoniae-like gliding motility genes and a homologue of the Pasteurella multocida mitogenic toxin. Intra- and inter-host genome comparison suggests that colonization with this bacterium is both persistent and strain exclusive.

RevDate: 2019-03-14

Metwaly A, D Haller (2019)

Strain-Level Diversity in the Gut: The P. copri Case.

Cell host & microbe, 25(3):349-350.

In this issue of Cell Host & Microbe, De Filippis et al. (2019) report that Prevotella copri strain-level diversity in the gut microbiome can be shaped by host diet. Individual signatures were analyzed by marker gene profiling in assembled pangenomes, providing a strong rationale for the functional adaptation of individual microbial ecosystems in response to diet.

RevDate: 2019-03-14

Martín-Núñez GM, Cornejo-Pareja I, Coin-Aragüez L, et al (2019)

H. pylori eradication with antibiotic treatment causes changes in glucose homeostasis related to modifications in the gut microbiota.

PloS one, 14(3):e0213548 pii:PONE-D-18-32759.

BACKGROUND: H. pylori infection and eradication cause perturbations of the gut microbiome. The gut microbiota has been identified as a potential contributor to metabolic diseases. We evaluate whether these alterations in intestinal microbiota composition produced by H. pylori infection and its posterior eradication with antibiotic treatment could be associated with glucose homeostasis in metabolically healthy subjects.

METHODS: Forty adult patients infected with H. pylori and 20 control subjects were recruited. The infected subjects were evaluated before and two months after eradication treatment (omeprazole, clarithromycin, amoxicillin). The microbiota composition in fecal samples was determined by 16S rRNA gene (V3-V4) sequencing using Illumina Miseq.

RESULTS: Patients (pre- and post-H. pylori eradication) showed a decreased bacterial richness and diversity with respect to controls. There was an improvement in glucose homeostasis in subjects two months after H. pylori eradication treatment. Changes in the amount of Rikenellaceae, Butyricimonas, E. biforme, B. fragilis, and Megamonas were inversely associated with changes in the glucose level or related parameters (Hb1ac) in H. pylori eradication subjects.

CONCLUSIONS: H. pylori infection and eradication with antibiotic treatment causes alteration of the human gut microbiome. The increase in SCFA-producing bacteria and glucose-removing bacteria, specifically members of Megamonas, Rikenellaceae and Butyricimonas, has been related with an improvement in glucose homeostasis after H. pylori eradication with antibiotic treatment.

RevDate: 2019-03-14

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

Detection of critical antibiotic resistance genes through routine microbiome surveillance.

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

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

RevDate: 2019-03-14

Knowles SCL, Eccles RM, L Baltrūnaitė (2019)

Species identity dominates over environment in shaping the microbiota of small mammals.

The mammalian gut microbiota is considered pivotal to host fitness, yet the determinants of community composition remain poorly understood. Laboratory studies show that environmental factors, particularly diet, are important, while comparative work emphasises host genetics. Here, we compare the influence of host genetics and the environment on the microbiota of sympatric small mammal species (mice, voles, shrews) across multiple habitats. While sharing a habitat caused some microbiota convergence, the influence of species identity dominated. In all three host genera examined, an individual's microbiota was more similar to conspecifics living elsewhere than to heterospecifics at the same site. Our results suggest this species-specificity arises in part through host-microbe codiversification. Stomach contents analysis suggested that diet also shapes the microbiota, but where diet is itself influenced by species identity. In this way, we can reconcile the importance of both diet and genetics, while showing that species identity is the strongest predictor of microbiota composition.

RevDate: 2019-03-14

Forssberg H (2019)

Microbiome programming of brain development: implications for neurodevelopmental disorders.

Developmental medicine and child neurology [Epub ahead of print].

During the last decade, research on germ-free mice has discovered that the gut microbiome (i.e. the normal bacteria colonizing the gastrointestinal tract) can programme brain function and behaviour during early development. At the same time a growing number of clinical studies have shown altered gut microflora in children with autism spectrum disorder (ASD), in combination with altered bacterial metabolites and inflammatory cytokines being part of the gut-brain axis. This review covers the concept of the microbiome; how it is established during childhood; how it is affected by malnutrition; how it can programme the development of the brain through epigenetic mechanisms; which pathways are used from the gut to the brain; and assesses findings that suggest the gut microbiome may be involved in ASD and other neurodevelopmental disorders. This is a new research field with a number of exciting, but so far fragmented, findings indicating the important role of the normal microbiome in shaping the brain. Research also suggests that disruptions of the microbiome may be involved in the aetiology of neurodevelopmental disorders. WHAT THIS PAPER ADDS: The gut microbiome shapes the brain via the gut-brain axis. The microbiome may play a role in neurodevelopmental disorders.

RevDate: 2019-03-14

Nayfach S, Shi ZJ, Seshadri R, et al (2019)

Novel insights from uncultivated genomes of the global human gut microbiome.

Nature pii:10.1038/s41586-019-1058-x [Epub ahead of print].

Largely due to challenges cultivating microbes under laboratory conditions, the genome sequence of many species in the human gut microbiome remains unknown. To address this problem, we reconstructed 60,664 prokaryotic draft genomes from 3,810 faecal metagenomes from geographically and phenotypically diverse human subjects. These genomes provide reference points for 2,058 previously unknown species-level operational taxonomic units (OTUs), representing a 50% increase in the phylogenetic diversity of sequenced gut bacteria. On average, new OTUs comprise 33% of richness and 28% of species abundance per individual and are enriched in humans from rural populations. A meta-analysis of clinical gut microbiome studies pinpointed numerous disease associations for new OTUs, which have the potential to improve predictive models. Finally, our analysis revealed that uncultured gut species have undergone genome reduction with loss of certain biosynthetic pathways, which may offer clues for improving cultivation strategies in the future.

RevDate: 2019-03-14

Tu P, Gao B, Chi L, et al (2019)

Subchronic low-dose 2,4-D exposure changed plasma acylcarnitine levels and induced gut microbiome perturbations in mice.

Scientific reports, 9(1):4363 pii:10.1038/s41598-019-40776-3.

The gut microbiota critically confers various health benefits, whereas environmental chemicals can affect its constitution and functionality thereby increasing disease risk. In the present study, we aim to evaluate the toxic effects of a wildly-used herbicide 2,4-D (2,4-dichlorophenoxyacetic acid) on the gut microbiome and host using an occupationally relevant dose. A mouse model was used combined with metagenomic sequencing and metabolomic profiling to examine the alterations induced by subchronic low-dose 2,4-D exposure in fecal and plasma samples. The metagenomics results revealed a distinct gut microbial community with profound changes in diverse microbial pathways including urea degradation, amino acid and carbohydrate metabolism in 2,4-D-treated mice. Moreover, the metabolomics results revealed that the metabolic profiles in treatment group were differentiated from control group in both fecal and plasma samples. Toxic effects on the host of 2,4-D at an occupationally relevant dose were observed indicated by decreased acylcarnitine levels in plasma. These findings indicated that 2,4-D can cause toxicity and substantially impact the gut microbiome in mice at occupationally relevant doses, inferring that the relationship between environmental contaminants and microbiota is largely underestimated calling for more comprehensive consideration of the toxicity of occupational exposures.

RevDate: 2019-03-14

Ridge EA, Pachhain S, Choudhury SR, et al (2019)

The influence of the host microbiome on 3,4-methylenedioxymethamphetamine (MDMA)-induced hyperthermia and vice versa.

Scientific reports, 9(1):4313 pii:10.1038/s41598-019-40803-3.

Hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) can be life-threatening. Here, we investigate the role of the gut microbiome and TGR5 bile acid receptors in MDMA-mediated hyperthermia. Fourteen days prior to treatment with MDMA, male Sprague-Dawley rats were provided water or water treated with antibiotics. Animals that had received antibiotics displayed a reduction in gut bacteria and an attenuated hyperthermic response to MDMA. MDMA treated animals showed increased uncoupling protein 1 (UCP1) and TGR5 expression levels in brown adipose tissue and skeletal muscle while increased expression of UCP3 was observed only in skeletal muscle. Antibiotics prior to MDMA administration significantly blunted these increases in gene expression. Furthermore, inhibition of the TGR5 receptor with triamterene or of deiodinase II downstream of the TGR5 receptor with iopanoic acid also resulted in the attenuation of MDMA-induced hyperthermia. MDMA-treatment enriched the relative proportion of a Proteus mirabilis strain in the ceca of animals not pre-treated with antibiotics. These findings suggest a contributing role for the gut microbiota in MDMA-mediated hyperthermia and that MDMA treatment can trigger a rapid remodeling of the composition of the gut microbiome.

RevDate: 2019-03-14

Tran TTT, Cousin FJ, Lynch DB, et al (2019)

Prebiotic supplementation in frail older people affects specific gut microbiota taxa but not global diversity.

Microbiome, 7(1):39 pii:10.1186/s40168-019-0654-1.

BACKGROUND: There are complex interactions between aging, frailty, diet, and the gut microbiota; modulation of the gut microbiota by diet could lead to healthier aging. The purpose of this study was to test the effect of diets differing in sugar, fat, and fiber content upon the gut microbiota of mice humanized with microbiota from healthy or frail older people. We also performed a 6-month dietary fiber supplementation in three human cohorts representing three distinct life-stages.

METHODS: Mice were colonized with human microbiota and then underwent an 8-week dietary intervention with either a high-fiber/low-fat diet typical of elderly community dwellers or a low-fiber/high-fat diet typical of long-stay residential care subjects. A cross-over design was used where the diets were switched after 4 weeks to the other diet type to identify responsive taxa and innate immunity changes. In the human intervention, the subjects supplemented their normal diet with a mix of five prebiotics (wheat dextrin, resistant starch, polydextrose, soluble corn fiber, and galactooligo-saccharide) at 10 g/day combined total, for healthy subjects and 20 g/day for frail subjects, or placebo (10 g/day maltodextrin) for 26 weeks. The gut microbiota was profiled and immune responses were assayed by T cell markers in mice, and serum cytokines in humans.

RESULTS: Humanized mice maintained gut microbiota types reflecting the respective healthy or frail human donor. Changes in abundance of specific taxa occurred with the diet switch. In mice with the community type microbiota, the observed differences reflected compositions previously associated with higher frailty. The dominance of Prevotella present initially in community inoculated mice was replaced by Bacteroides, Alistipes, and Oscillibacter. Frail type microbiota showed a differential effect on innate immune markers in both conventional and germ-free mice, but a moderate number of taxonomic changes occurring upon diet switch with an increase in abundance of Parabacteroides, Blautia, Clostridium cluster IV, and Phascolarctobacterium. In the human intervention, prebiotic supplementation did not drive any global changes in alpha- or beta-diversity, but the abundance of certain bacterial taxa, particularly Ruminococcaceae (Clostridium cluster IV), Parabacteroides, Phascolarctobacterium, increased, and levels of the chemokine CXCL11 were significantly lower in the frail elderly group, but increased during the wash-out period.

CONCLUSIONS: Switching to a nutritionally poorer diet has a profound effect on the microbiota in mouse models, with changes in the gut microbiota from healthy donors reflecting previously observed differences between elderly frail and non-frail individuals. However, the frailty-associated gut microbiota did not reciprocally switch to a younger healthy-subject like state, and supplementation with prebiotics was associated with fewer detected effects in humans than diet adjustment in animal models.

RevDate: 2019-03-14

Das P, Babaei P, J Nielsen (2019)

Metagenomic analysis of microbe-mediated vitamin metabolism in the human gut microbiome.

BMC genomics, 20(1):208 pii:10.1186/s12864-019-5591-7.

BACKGROUND: Human gut microbial communities have been known to produce vitamins, which are subsequently absorbed by the host in the large intestine. However, the relationship between species with vitamin pathway associated functional features or their gene abundance in different states of health and disease is lacking. Here, we analyzed shotgun fecal metagenomes of individuals from four different countries for genes that are involved in vitamin biosynthetic pathways and transport mechanisms and corresponding species' abundance.

RESULTS: We found that the prevalence of these genes were found to be distributed across the dominant phyla of gut species. The number of positive correlations were high between species harboring genes related to vitamin biosynthetic pathways and transporter mechanisms than that with either alone. Although, the range of total gene abundances remained constant across healthy populations at the global level, species composition and their presence for metabolic pathway related genes determine the abundance and functional genetic content of vitamin metabolism. Based on metatranscriptomics data, the equation between abundance of vitamin-biosynthetic enzymes and vitamin-dependent enzymes suggests that the production and utilization potential of these enzymes seems way more complex usage allocations than just mere direct linear associations.

CONCLUSIONS: Our findings provide a rationale to examine and disentangle the interrelationship between B-vitamin dosage (dietary or microbe-mediated) on gut microbial members and the host, in the gut microbiota of individuals with under- or overnutrition.

RevDate: 2019-03-14

Yang L, Hao Y, Hu J, et al (2019)

Differential effects of depot medroxyprogesterone acetate administration on vaginal microbiome in Hispanic White and Black women.

Emerging microbes & infections, 8(1):197-210.

The use of depot medroxyprogesterone acetate (DMPA), a 3-monthly injectable hormonal contraceptive, is associated with an increased risk of HIV acquisition possibly through alteration of the vaginal microbiome. In this longitudinal interventional study, we investigated the impact of DMPA administration on the vaginal microbiome in Hispanic White and Black women at the baseline (visit 1), 1 month (visit 2), and 3 months (visit 3) following DMPA treatment by using 16S rRNA gene sequencing. No significant changes in the vaginal microbiome were observed after DMPA treatment when Hispanic White and Black women were analysed as a combined group. However, DMPA treatment enriched total vaginosis-associated bacteria (VNAB) and Prevotella at visit 2, and simplified the correlational network in the vaginal microbiome in Black women, while increasing the network size in Hispanic White women. The microbiome in Black women became more diversified and contained more VNAB than Hispanic White women after DMPA treatment. While the Firmicutes to Bacteroidetes (F/B) ratio and Lactobacillus to Prevotella (L/P) ratio were comparable between Black and Hispanic White women at visit 1, both ratios were lower in Black women than in Hispanic White women at visit 2. In conclusion, DMPA treatment altered the community network and enriched VNAB in Black women but not in Hispanic White women. The Lactobacillus deficiency and enrichment of VNAB may contribute to the increased risk of HIV acquisition in Black women. Future studies on the impact of racial differences on the risk of HIV acquisition will offer insights into developing effective strategies for HIV prevention. Abbreviations: DMPA: depot medroxyprogesterone acetate; PCR: polymerase chain reaction; OTU: operational taxonomic unit; STI: sexually transmitted infections; VNAB: vaginosis-associated bacteria.

RevDate: 2019-03-14

Park H, Laffin MR, Jovel J, et al (2019)

The success of fecal microbial transplantation in Clostridium difficile infection correlates with bacteriophage relative abundance in the donor: a retrospective cohort study.

Gut microbes [Epub ahead of print].

BACKGROUND: Fecal microbial transplantation (FMT) is used in the treatment of relapsing Clostridium difficile infection (rCDI). Failure rate for FMT is as high as 10% but the mechanisms contributing to a failed FMT are not understood. We utilized metagenomic data to identify the role of bacteria and bacteriophages on FMT success.

RESULTS: Subjects with rCDI (n = 19) received FMT from volunteer donors (n = 7) via colonoscopy. Twelve patients fully recovered after a single FMT, while seven patients required a subsequent FMT. DNA was extracted from patient and donor stool samples for shotgun metagenomic analysis. Metagenomics libraries were analyzed focusing on bacterial taxonomy and bacteriophage sequences. Gammaproteobacteria were dominant in rCDI patients prior to FMT largely due to elevated levels of Klebsiella and Escherichia. A successful FMT led to increased levels of Clostridia and Bacteroidia and a reduction in Gammaproteobacteria. In contrast, a failed FMT led to no significant changes in bacterial composition. Bacteriophages were classified during whole metagenomic analysis of each sample and were markedly different between rCDI patients, donors, and a healthy control cohort (n = 96). Bacteriophage sequence reads were increased in CDI patients compared with donors and healthy controls. Successful FMT donors had higher bacteriophage α-diversity and lower relative abundance compared to the donors of a failed initial FMT.

CONCLUSIONS: In this retrospective analysis, FMTs with increased bacteriophage α-diversity were more likely to successfully treat rCDI. In addition, the relative number of bacteriophage reads was lower in donations leading to a successful FMT. These results suggest that bacteriophage abundance may have some role in determining the relative success of FMT.

RevDate: 2019-03-14

Miraglia F, E Colla (2019)

Microbiome, Parkinson's Disease and Molecular Mimicry.

Cells, 8(3): pii:cells8030222.

Parkinson's Disease (PD) is typically classified as a neurodegenerative disease affecting the motor system. Recent evidence, however, has uncovered the presence of Lewy bodies in locations outside the CNS, in direct contact with the external environment, including the olfactory bulbs and the enteric nervous system. This, combined with the ability of alpha-synuclein (αS) to propagate in a prion-like manner, has supported the hypothesis that the resident microbial community, commonly referred to as microbiota, might play a causative role in the development of PD. In this article, we will be reviewing current knowledge on the importance of the microbiota in PD pathology, concentrating our investigation on mechanisms of microbiota-host interactions that might become harmful and favor the onset of PD. Such processes, which include the secretion of bacterial amyloid proteins or other metabolites, may influence the aggregation propensity of αS directly or indirectly, for example by favoring a pro-inflammatory environment in the gut. Thus, while the development of PD has not yet being associated with a unique microbial species, more data will be necessary to examine potential harmful interactions between the microbiota and the host, and to understand their relevance in PD pathogenesis.

RevDate: 2019-03-13

Isolauri E, Rautava S, Salminen S, et al (2019)

Early-Life Nutrition and Microbiome Development.

Nestle Nutrition Institute workshop series, 90:151-162.

Recent demonstrations link clinical conditions, phenotypes alternating from inflammatory bowel disease, obesity, and allergic diseases to neurodevelopmental disorders, to aberrant gut microbiota composition. This has led to a growing interest in host-microbe crosstalk, characterizing the healthy microbiome and modifying its deviations at an early age. The rationale arises from the recognition of the intimate interrelationship between diet, immune system, and microbiome and the origins of human diseases. Before satisfactory preventive measures can be put in practice, important questions remain to be solved. First, we need more profound understanding of the complex mechanisms underlying these heterogeneous manifestations of immune-mediated and microbiome-associated chronic conditions. Second, long-term follow-up studies are required to determine whether the changes in the microbiome underlie the pathogenesis of noncommunicable diseases or are merely end results thereof, confronting the question of causality. This uncertainty notwithstanding, the complex and bidirectional interrelationship of the diet and the gut microbiota is becoming evident. Early exposures by the enteral route induce dynamic adaptive modifications in the microbiota composition and activity, which may carry long-term clinical impacts. Microbiota changes, again, control energy acquisition and storage and may contribute to gut immunological milieu; high-energy Western diets alter the microenvironment of the gut leading to propagation of the inflammatory tone and perturbation of gut barrier function and thereby to systemic low-grade inflammation. On this basis, rigorous clinical intervention studies, providing the ultimate answers to these questions, need accurate characterization of the immediate environment of the child, in particular the early nutrition. The model of early nutrition for future studies is the healthy breastfed infant that remains healthy in the long term. Scientific interest is currently extending from the duration of breastfeeding to the composition of breast milk, which shows marked variation according to the mother's immunological and metabolic health, antibiotic use, and mode of delivery. Human milk, rich in bioactive compounds, including health-promoting microbes and their optimal growth factors, human milk oligosaccharides, continues to afford tools to study diet-microbiota interactions for research aiming at reducing the risk of noncommunicable diseases.


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
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Papers in Classical Genetics

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

Digital Books

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


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 )