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Bibliography on: Microbiome

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ESP: PubMed Auto Bibliography 16 Jan 2019 at 01:40 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: 2019-01-14

Schnapp Z, Hartman C, Livnat G, et al (2018)

Decreased Fecal Calprotectin Levels in Cystic Fibrosis Patients After Antibiotic Treatment for Respiratory Exacerbation.

Journal of pediatric gastroenterology and nutrition [Epub ahead of print].

OBJECTIVES: In all patients with cystic fibrosis (CF), gastrointestinal (GI) tract cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction occurs early in life. .The identical pathophysiological triad of obstruction, infection and inflammation causes disease of the airways and in the intestinal tract (CF enteropathy). Mucus accumulation within GI tract is a niche for abnormal microbial colonization, leading to dysbiosis. Fecal calprotectin (FC) is a neutrophil cytosolic protein released during apoptosis and necrosis and reflects inflammatory status. Systemic antibiotic treatment for pulmonary exacerbations has been shown to improve systemic inflammatory markers as well as serum and sputum calprotectin. Antibiotic treatment aimed at pulmonary complaints may improve GI tract inflammatory status. We hypothesized that high levels of fecal calprotectin present during pulmonary exacerbation are due, in part, to multi-organ dysbiosis and thus should diminish with systemic antibiotic treatment.

METHODS: This prospective pilot study enrolled 14 patients with CF, with no current GI symptoms. FC levels and lung function were measured at the beginning and end of systemic antibiotic treatment.

RESULTS: Compared to pre-antibiotic treatment baseline values, end of treatment FC levels declined significantly after antibiotic treatment, P = 0.004 and similarly, there was significant improvement in FEV1.0, P = 0.002.

CONCLUSIONS: High levels of FC during respiratory exacerbation may reflect a systemic exacerbation rather than solely pulmonary. Antibiotic treatment lowered the FC levels possibly by its impact on the intestinal microbiome.

RevDate: 2019-01-14

Polsinelli VB, Marteau L, SJ Shah (2019)

The role of splanchnic congestion and the intestinal microenvironment in the pathogenesis of advanced heart failure.

Current opinion in supportive and palliative care [Epub ahead of print].

PURPOSE OF REVIEW: Right-sided heart failure, which is often present in the setting of advanced heart failure, is associated with cardiac cachexia, the cardiorenal syndrome, and adverse outcomes. Improved understanding of venous congestion of the splanchnic circulation, which may play a key role in the pathogenesis of right-sided heart failure, could lead to novel therapeutics to ameliorate heart failure. Here we provide an overview of right-sided heart failure, splanchnic hemodynamics, fluid homeostasis, and the intestinal microenvironment. We review recent literature to describe pathophysiologic mechanisms and possible therapeutics.

RECENT FINDINGS: Several possible mechanisms centered around upregulation of sodium-hydrogen exchanger-3 (NHE3) may form a causal link between right ventricular dysfunction, splanchnic congestion, and worsening heart failure. These include an anaerobic environment in enterocytes, resulting in reduced intracellular pH; increased sodium absorption by the gut via NHE3; decreased pH at the intestinal brush border thus altering the gut microbiome profile; increased bacterial synthesis of trimethylamine N-oxide; and decreased bacterial synthesis of short-chain fatty acids causing abnormal intestinal barrier function.

SUMMARY: Splanchnic congestion in the setting of right-sided heart failure may serve an important role in the pathogenesis of advanced heart failure, and further exploration of these mechanisms may lead to new therapeutic advances.

RevDate: 2019-01-14

Chao XP, Sun TT, Wang S, et al (2019)

Correlation between the diversity of vaginal microbiota and the risk of high-risk human papillomavirus infection.

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 29(1):28-34.

OBJECTIVES: Since other genital infections enhance HIV susceptibility by inducing inflammation and evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of high-risk human papillomavirus (HPV) infections, we investigated the relationship between the composition of the vaginal microbiota and the risk of high-risk HPV infection.

METHODS: The study included 151 healthy women (65 HPV-positive and 86 HPV-negative) aged 20-65 at enrollment. Total genome DNA from samples was extracted using the hexadecyltrimethylammonium bromide (CTAB) CTAB method. The vaginal microbiota composition was determined by sequencing barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500.

RESULTS: Of the 30 most abundant bacteria at the genus level, we found only six bacteria with a statistical difference between HPV-positive and HPV-negative women: Bacteroides, Acinetobacter, Faecalibacterium, Streptococcus, Finegoldia, and Moryella. Lactobacillus was the predominant genus and was detected in all women, but there was no significant difference between the two groups for L. iners, L. jensenii, and L. gasseri. Furthermore, we found 26 types of bacteria with a statistical difference at the species level between the two groups. Anaerobic bacteria such as Bacteroides plebeius, Acinetobacter lwoffii, and Prevotella buccae were found significantly more frequently in HPV-positive women, which is the most important finding of our study.

CONCLUSION: Our findings suggest a possible role for the composition of the vaginal microbiota as a modifier of high-risk HPV infection, and specific microbiota species may serve as sensors for changes in the cervical microenvironment associated with high-risk HPV infection. The exact molecular mechanism of the vaginal microbiota in the course of high-risk HPV infection and cervical neoplasia should be further explored. Future research should include intervention in the composition of the vaginal microbiota to reverse the course of high-risk HPV infection and the natural history of cervical neoplasia.

RevDate: 2019-01-14

Ozkan J, MD Willcox (2019)

The Ocular Microbiome: Molecular Characterization of a Unique and Low Microbial Environment.

Current eye research [Epub ahead of print].

The ocular surface is continually exposed to bacteria from the environment and traditional culture-based microbiological studies have isolated a low diversity of microorganisms from this region. The use of culture-independent methods to define the ocular microbiome, primarily involving 16S ribosomal RNA gene sequencing, has shown that the microbial communities present on the ocular surface have a greater diversity than previously reported and appear to have an immune modulating function. These molecular techniques have been used to investigate the effect of contact lens wear and disease on the microbiota of the ocular surface and eyelids and these studies have consistently identified bacteria not previously identified in normal eyes. Recent studies also suggest a role of the ocular and non-ocular microbiome in retinal disease including age-related macular degeneration, glaucoma, uveitis and diabetic retinopathy. However, issues remain regarding the impact of contamination in these culture-independent sequencing techniques, particularly when investigating low microbial biomass samples from the eye. Ocular microbiome studies need to recognise the potential for contamination to impact findings and carefully control each stage of the experimental procedure and to utilise statistical methods to identify contamination signals.

RevDate: 2019-01-14

Leung DYM (2019)

The Microbiome and Allergic Diseases: A struggle between good and bad microbes.

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology pii:S1081-1206(19)30003-1 [Epub ahead of print].

RevDate: 2019-01-14

Ferreira Felizardo RJ, Mizuno Watanabe IK, Dardi P, et al (2019)

The interplay among gut microbiota, hypertension and kidney diseases: the role of short-chain fatty acids.

Pharmacological research pii:S1043-6618(18)31684-0 [Epub ahead of print].

The bacteria community living in the gut maintains a symbiotic relationship with the host and its unbalance has been associated with progression of a wide range of intestinal and extra intestinal conditions. Hypertension and chronic kidney disease (CKD) are closely associated diseases with high incidence rates all over the world. Increasing data have supported the involvement of gut microbiome in the blood pressure regulation and the impairment of CKD prognosis. In hypertension, the reduced number of short-chain fatty acids (SCFAs) producing bacteria is associated with modifications in gut environment, involving reduction of the hypoxic gut profile and worsening of the microbial balance, leading to a loss of epithelial barrier integrity, development of gut inflammation and the reduction of SCFAs plasma levels. Those modifications compromise the blood pressure regulation and, as a consequence, favor the end organ damage, also affecting the kidneys. In CKD, impaired renal function leads to accumulation of high levels of uremic toxins that reach the intestine and cause alterations in bacteria composition and fecal metabolite profile, inducing a positive feedback that allows translocation of endotoxins into the bloodstream, which enhances local kidney inflammation and exacerbate kidney injury, compromising even more CKD prognosis. In line with these data, the use of prebiotics, probiotics and fecal microbiota transplantation are becoming efficient therapies to improve the gut dysbiosis aiming hypertension and CKD treatment. This review describes how changes in gut microbiota composition can affect the development of hypertension and the progression of kidney diseases, highlighting the importance of the gut microbial composition uncovering to improve human health maintenance and, especially, for the development of new alternative therapies.

RevDate: 2019-01-14

Davidson WF, Leung DYM, Beck LA, et al (2019)

Report from the National Institute of Allergy and Infectious Diseases Workshop on "Atopic Dermatitis and the Atopic March: Mechanisms and Interventions".

The Journal of allergy and clinical immunology pii:S0091-6749(19)30014-4 [Epub ahead of print].

Atopic dermatitis (AD) affects up to 20% of children world-wide and is an increasing public health problem particularly in developed countries. Although AD in infants and young children can resolve, there is a well-recognized, increased risk of sequential progression from AD to other atopic diseases including food allergy, allergic rhinitis, allergic asthma and allergic rhinoconjunctivitis; a process referred to as the "atopic march". The mechanisms underlying the development of AD and subsequent progression to other atopic comorbidities, particularly food allergy, are incompletely understood and the subject of intense investigation. Other major research objectives are the development of effective strategies to prevent AD and food allergy as well as therapeutic interventions to inhibit the atopic march. In 2017, the Division of Allergy, Immunology and Transplantation of the National Institute of Allergy and Infectious Diseases sponsored a workshop to discuss current understanding and important advances in these research areas and to identify gaps in knowledge and future research directions. International and national experts in the field were joined by representatives from several National Institutes of Health institutes. Summaries of workshop presentations, key conclusions and recommendations are presented herein.

RevDate: 2019-01-14

Langan D, Kim EY, KD Moudgil (2018)

Modulation of autoimmune arthritis by environmental 'hygiene' and commensal microbiota.

Cellular immunology pii:S0008-8749(18)30514-8 [Epub ahead of print].

Observations in patients with autoimmune diseases and studies in animal models of autoimmunity have revealed that external environmental factors including exposure to microbes and the state of the host gut microbiota can influence susceptibility to autoimmunity and subsequent disease development. Mechanisms underlying these outcomes continue to be elucidated. These include deviation of the cytokine response and imbalance between pathogenic versus regulatory T cell subsets. Furthermore, specific commensal organisms are associated with enhanced severity of arthritis in susceptible individuals, while exposure to certain microbes or helminths can afford protection against this disease. In addition, the role of metabolites (e.g., short-chain fatty acids, tryptophan catabolites), produced either by the microbes themselves or from their action on dietary products, in modulation of arthritis is increasingly being realized. In this context, re-setting of the microbial dysbiosis in RA using prebiotics, probiotics, or fecal microbial transplant is emerging as a promising approach for the prevention and treatment of arthritis. It is hoped that advances in defining the interplay between gut microbiota, dietary products, and bioactive metabolites would help in the development of therapeutic regimen customized for the needs of individual patients in the near future.

RevDate: 2019-01-14

Kara SS, Volkan B, I Erten (2019)

Lactobacillus rhamnosus GG can protect malnourished children.

Beneficial microbes [Epub ahead of print].

Malnutrition affects virtually all organ systems, and malnourished children are more prone to infections. These children have dysbiosis, but probiotics can restore the disrupted gut microbiome. We investigated the protective effects of Lactobacillus rhamnosus GG in malnourished children in terms of incidence of infection, and anthropometric and metabolic parameters. 50 intervention and 50 control patients, aged 6 months to 5 years, with body weight and height below -2 SD, were randomly and prospectively recruited. The controls received a calorie and protein-appropriate diet for 3 months, while the study group additionally received approximately 109 L. rhamnosus GG for 3 months. Infection episodes and nutritional status were compared between the groups. 38 intervention, 33 control patients completed the study and the two groups were similar at baseline. The study group had fewer upper respiratory tract infections and gastroenteritis episodes at each month and at the end of the study. Children in the study group experienced fewer total upper respiratory infections and urinary tract infections. Hospitalisation was more frequent in the control group during the third month and at the end of the study. Total infection numbers were higher in the control group at each month and at the end of the study (P<0.001 for each). Increments in body mass index (BMI) and BMI Z-scores were more pronounced in the study group (P=0.008 and P=0.02, respectively). Daily prophylactic use of L. rhamnosus GG at 109 bacteria in malnourished children prevents most infections and improves nutritional status when used together with appropriate diet.

RevDate: 2019-01-14

Asante J, J Osei Sekyere (2019)

Understanding antimicrobial discovery and resistance from a metagenomic and metatranscriptomic perspective: Advances and applications.

Environmental microbiology reports [Epub ahead of print].

Our inability to cultivate most micro-organisms, specifically bacteria, in the laboratory has for many years restricted our view and understanding of the bacterial meta-resistome in all living and non-living environments. As a result, reservoirs, sources, and distribution of antibiotic resistance genes (ARGS) and antibiotic-producers, as well as the effects of human activity and antibiotics on the selection and dissemination of ARGs were not well comprehended. With the advances made in the fields of metagenomics and metatranscriptomics, many of the hitherto little-understood concepts are becoming clearer. Further, the discovery of antibiotics such as lugdinin and lactocillin from the human microbiota, buttressed the importance of these new fields. Metagenomics and metatranscriptomics are becoming important clinical diagnostic tools for screening and detecting pathogens and ARGs, assessing the effects of antibiotics, other xenobiotics, and human activity on the environment, characterizing the microbiome and the environmental resistome with lesser turnaround time and decreasing cost, as well as discovering antibiotic-producers. However, challenges with accurate binning, skewed ARGs databases, detection of less abundant and allelic variants of ARGs, and efficient mobilome characterization remain. Ongoing efforts in long-read, phased- and single-cell sequencing, strain-resolved binning, chromosomal-conformation capture, DNA-methylation binning, and deep-learning bioinformatic approaches offer promising prospects in reconstructing complete strain-level genomes and mobilomes from metagenomes. This article is protected by copyright. All rights reserved.

RevDate: 2019-01-14

Gotoh A, Ojima MN, T Katayama (2019)

Minority species influences microbiota formation: the role of Bifidobacterium with extracellular glycosidases in bifidus flora formation in breastfed infant guts.

Microbial biotechnology [Epub ahead of print].

The human body houses a variety of microbial ecosystems, such as the microbiotas on the skin, in the oral cavity and in the digestive tract. The gut microbiota is one such ecosystem that contains trillions of bacteria, and it is well established that it can significantly influence host health and diseases. With the advancement in bioinformatics tools, numerous comparative studies based on 16S ribosomal RNA (rRNA) gene sequences, metabolomics, pathological and epidemical analyses have revealed the correlative relationship between the abundance of certain taxa and disease states or amount of certain causative bioactive compounds. However, the 16S rRNA-based taxonomic analyses using next-generation sequencing (NGS) technology essentially detect only the majority species. Although the entire gut microbiome consists of 1013 microbial cells, NGS read counts are given in multiples of 106 , making it difficult to determine the diversity of the entire microbiota. Some recent studies have reported instances where certain minority species play a critical role in creating locally stable conditions for other species by stabilizing the fundamental microbiota, despite their low abundance. These minority species act as 'keystone species', which is a species whose effect on the community is disproportionately large compared to its relative abundance. One of the attributes of keystone species within the gut microbiota is its extensive enzymatic capacity for substrates that are rare or difficult to degrade for other species, such as dietary fibres or host-derived complex glycans, like human milk oligosaccharides (HMOs). In this paper, we propose that more emphasis should be placed on minority taxa and their possible role as keystone species in gut microbiota studies by referring to our recent studies on HMO-mediated microbiota formation in the infant gut.

RevDate: 2019-01-14

Blaustein RA, McFarland AG, Ben Maamar S, et al (2019)

Pangenomic Approach To Understanding Microbial Adaptations within a Model Built Environment, the International Space Station, Relative to Human Hosts and Soil.

mSystems, 4(1): pii:mSystems00281-18.

Understanding underlying mechanisms involved in microbial persistence in the built environment (BE) is essential for strategically mitigating potential health risks. To test the hypothesis that BEs impose selective pressures resulting in characteristic adaptive responses, we performed a pangenomics meta-analysis leveraging 189 genomes (accessed from GenBank) of two epidemiologically important taxa, Bacillus cereus and Staphylococcus aureus, isolated from various origins: the International Space Station (ISS; a model BE), Earth-based BEs, soil, and humans. Our objectives were to (i) identify differences in the pangenomic composition of generalist and host-associated organisms, (ii) characterize genes and functions involved in BE-associated selection, and (iii) identify genomic signatures of ISS-derived strains of potential relevance for astronaut health. The pangenome of B. cereus was more expansive than that of S. aureus, which had a dominant core component. Genomic contents of both taxa significantly correlated with isolate origin, demonstrating an importance for biogeography and potential niche adaptations. ISS/BE-enriched functions were often involved in biosynthesis, catabolism, materials transport, metabolism, and stress response. Multiple origin-enriched functions also overlapped across taxa, suggesting conserved adaptive processes. We further characterized two mobile genetic elements with local neighborhood genes encoding biosynthesis and stress response functions that distinctively associated with B. cereus from the ISS. Although antibiotic resistance genes were present in ISS/BE isolates, they were also common in counterparts elsewhere. Overall, despite differences in microbial lifestyle, some functions appear common to remaining viable in the BE, and those functions are not typically associated with direct impacts on human health. IMPORTANCE The built environment contains a variety of microorganisms, some of which pose critical human health risks (e.g., hospital-acquired infection, antibiotic resistance dissemination). We uncovered a combination of complex biological functions that may play a role in bacterial survival under the presumed selective pressures in a model built environment-the International Space Station-by using an approach to compare pangenomes of bacterial strains from two clinically relevant species (B. cereus and S. aureus) isolated from both built environments and humans. Our findings suggest that the most crucial bacterial functions involved in this potential adaptive response are specific to bacterial lifestyle and do not appear to have direct impacts on human health.

RevDate: 2019-01-14

Bai Y, Tao J, Zhou J, et al (2018)

Fucosylated Human Milk Oligosaccharides and N-Glycans in the Milk of Chinese Mothers Regulate the Gut Microbiome of Their Breast-Fed Infants during Different Lactation Stages.

mSystems, 3(6): pii:mSystems00206-18.

The milk glycobiome has a significant impact on the gut microbiota of infants, which plays a pivotal role in health and development. Fucosylated human milk oligosaccharides (HMOs) and N-glycans on milk proteins are beneficial for the development of healthy gut microbiota, and the fucosylation levels of these glycans can be affected by the maternal fucosyltransferase 2 gene (FUT2). Here, we present results of longitudinal research on paired milk and stool samples from 56 Chinese mothers (CMs) and their breast-fed children. Changes of HMOs and fucosylated N-glycans in milk of CMs at different lactation stages were detected, which allowed characterization of the major differences in milk glycans and consequential effects on the gut microbiome of infants according to maternal FUT2 status. Significant differences in the abundance of total and fucosylated HMOs between secretor and nonsecretor CMs were noted, especially during early lactation. Despite a tendency toward decreasing milk protein concentrations, the fucosylation levels of milk N-glycans increased during late lactation. The changes in the levels of fucosylated HMOs and milk N-glycans were highly correlated with the growth of Bifidobacterium spp. and Lactobacillus spp. in the gut of infants during early and later lactation, respectively. Enriched expression of genes encoding glycoside hydrolases, glycosyl transferases, ATP-binding cassette (ABC) transporters, and permeases in infants fed by secretor CMs contributed to the promotion of these bacteria in infants. Our data highlight the important role of fucosylated milk glycans in shaping the gut microbiome of infants and provide a solid foundation for development of "personalized" nutrition for Chinese infants. IMPORTANCE Human milk glycans provide a broad range of carbon sources for gut microbes in infants. Levels of protein glycosylation in human milk vary during lactation and may also be affected by the stages of gestation and lactation and by the secretor status of the mother. This was the first study to evaluate systematically dynamic changes in human milk oligosaccharides and fucosylated N-glycans in the milk of Chinese mothers with different secretor statuses during 6 months of lactation. Given the unique single nucleotide polymorphism site (rs1047781, A385T) on the fucosyltransferase 2 gene among Chinese populations, our report provides a specific insight into the milk glycobiome of Chinese mothers, which may exert effects on the gut microbiota of infants that differ from findings from other study cohorts.

RevDate: 2019-01-14

Bayer K, Jahn MT, Slaby BM, et al (2018)

Marine Sponges as Chloroflexi Hot Spots: Genomic Insights and High-Resolution Visualization of an Abundant and Diverse Symbiotic Clade.

mSystems, 3(6): pii:mSystems00150-18.

Members of the widespread bacterial phylum Chloroflexi can dominate high-microbial-abundance (HMA) sponge microbiomes. In the Sponge Microbiome Project, Chloroflexi sequences amounted to 20 to 30% of the total microbiome of certain HMA sponge genera with the classes/clades SAR202, Caldilineae, and Anaerolineae being the most prominent. We performed metagenomic and single-cell genomic analyses to elucidate the functional gene repertoire of Chloroflexi symbionts of Aplysina aerophoba. Eighteen draft genomes were reconstructed and placed into phylogenetic context of which six were investigated in detail. Common genomic features of Chloroflexi sponge symbionts were related to central energy and carbon converting pathways, amino acid and fatty acid metabolism, and respiration. Clade-specific metabolic features included a massively expanded genomic repertoire for carbohydrate degradation in Anaerolineae and Caldilineae genomes, but only amino acid utilization by SAR202. While Anaerolineae and Caldilineae import cofactors and vitamins, SAR202 genomes harbor genes encoding components involved in cofactor biosynthesis. A number of features relevant to symbiosis were further identified, including CRISPR-Cas systems, eukaryote-like repeat proteins, and secondary metabolite gene clusters. Chloroflexi symbionts were visualized in the sponge extracellular matrix at ultrastructural resolution by the fluorescence in situ hybridization-correlative light and electron microscopy (FISH-CLEM) method. Carbohydrate degradation potential was reported previously for "Candidatus Poribacteria" and SAUL, typical symbionts of HMA sponges, and we propose here that HMA sponge symbionts collectively engage in degradation of dissolved organic matter, both labile and recalcitrant. Thus, sponge microbes may not only provide nutrients to the sponge host, but they may also contribute to dissolved organic matter (DOM) recycling and primary productivity in reef ecosystems via a pathway termed the sponge loop. IMPORTANCEChloroflexi represent a widespread, yet enigmatic bacterial phylum with few cultivated members. We used metagenomic and single-cell genomic approaches to characterize the functional gene repertoire of Chloroflexi symbionts in marine sponges. The results of this study suggest clade-specific metabolic specialization and that Chloroflexi symbionts have the genomic potential for dissolved organic matter (DOM) degradation from seawater. Considering the abundance and dominance of sponges in many benthic environments, we predict that the role of sponge symbionts in biogeochemical cycles is larger than previously thought.

RevDate: 2019-01-13

Kamińska E (2018)

[The role of emollients in atopic dermatitis in children].

Developmental period medicine, 22(4):396-403.

Atopic dermatitis is a chronic inflammatory disease characterized by recurrent flares, intense itching, erythema, dry skin resulting from skin barrier defects, and staphylococcal infections. Multiple factors may affect the skin`s normal barrier function, including filaggrin gene mutations, immune dysregulation, altered skin microbiome, altered lipids in stratum corneum, or deficiency of antimicrobial peptides AMPs. The disease mainly affects children, causing a considerable impact on the quality of their life; its first manifestations occur with up to 90% of cases before the age of 5. For years emollients have been known as oily substances used to treat rough, scaling, xerotic conditions to make skin flexible and soft. Recently, we have learned that emollients can also moisten and hydrate dry skin, so the terms "emollient" and "moisturizer" are often used interchangeably. According to current management guidelines on atopic dermatitis prepared by dermatological societies, long-term emollient application direct to the skin and as bath additives are the basic therapy of atopic dermatitis. Emollients may be used in monotherapy or - in the flares - in conjunction with topical corticosteroids or calcineurin inhibitors. Clinical trials proved that regular emollient application moistens and hydrates the skin and helps the skin maintain a defensive barrier effect as well as reduces the amount of topical corticosteroids needed for atopic eczema in infants, children and adult patients. The results of trials and long clinical experience proved that emollients are safe and effective in patients with atopic dermatitis. This paper presents information based on recent knowledge concerning emollients: an overview of emollient components, their properties, mechanism of action, and the role they play in atopic eczema, as well as the results of clinical trials performed in children with atopic dermatitis.

RevDate: 2019-01-12

Untersmayr E, Bax HJ, Bergmann C, et al (2019)

AllergoOncology: microbiota in allergy and cancer - an EAACI position paper.

Allergy [Epub ahead of print].

The microbiota can play important roles in the development of human immunity and the establishment of immune homeostasis. Lifestyle factors including diet, hygiene, and exposure to viruses or bacteria, and medical interventions with antibiotics or anti-ulcer medications, regulate phylogenetic variability and the quality of cross-talk between innate and adaptive immune cells via mucosal and skin epithelia. More recently, microbiota and their composition have been linked to protective effects for health. Imbalance, however, has been linked to immune-related diseases such as allergy and cancer, characterized by impaired, or exaggerated immune tolerance, respectively. In this AllergoOncology position paper, we focus on the increasing evidence defining the microbiota composition as a key determinant of immunity and immune tolerance, linked to the risk for development of allergic and malignant diseases. We discuss novel insights into the role of microbiota in disease and patient responses to treatments in cancer and in allergy. These may highlight opportunities to improve patient outcomes with medical interventions supported through a restored microbiome. This article is protected by copyright. All rights reserved.

RevDate: 2019-01-12

Pak HH, Cummings NE, Green CL, et al (2019)

The Metabolic Response to a Low Amino Acid Diet is Independent of Diet-Induced Shifts in the Composition of the Gut Microbiome.

Scientific reports, 9(1):67 pii:10.1038/s41598-018-37177-3.

Obesity and type 2 diabetes are increasing in prevalence around the world, and there is a clear need for new and effective strategies to promote metabolic health. A low protein (LP) diet improves metabolic health in both rodents and humans, but the mechanisms that underlie this effect remain unknown. The gut microbiome has recently emerged as a potent regulator of host metabolism and the response to diet. Here, we demonstrate that a LP diet significantly alters the taxonomic composition of the gut microbiome at the phylum level, altering the relative abundance of Actinobacteria, Bacteroidetes, and Firmicutes. Transcriptional profiling suggested that any impact of the microbiome on liver metabolism was likely independent of the microbiome-farnesoid X receptor (FXR) axis. We therefore tested the ability of a LP diet to improve metabolic health following antibiotic ablation of the gut microbiota. We found that a LP diet promotes leanness, increases energy expenditure, and improves glycemic control equally well in mice treated with antibiotics as in untreated control animals. Our results demonstrate that the beneficial effects of a LP diet on glucose homeostasis, energy balance, and body composition are unlikely to be mediated by diet-induced changes in the taxonomic composition of the gut microbiome.

RevDate: 2019-01-12

Chen YM, Chiang YC, Tseng TY, et al (2019)

Molecular and Functional Analysis of the Type IV Pilus Gene Cluster in Streptococcus sanguinis SK36.

Applied and environmental microbiology pii:AEM.02788-18 [Epub ahead of print].

Streptococcus sanguinis, dominant in the oral microbiome, is the only known streptococcal species possessing a pil gene cluster for the biosynthesis of type IV pili (Tfp). Although this cluster is commonly present in the genome of S. sanguinis, most of the strains do not express Tfp-mediated twitching motility. Thus, this study was designed to investigate the biological functions encoded by the cluster in the twitching-negative strain, S. sanguinis SK36. We found that the cluster was transcribed as an operon, with three promoters located 5' to the cluster, and one in the intergenic region between SSA_2307 and SSA_2305. Studies using promoter-cat fusion strains revealed that the transcription of the cluster was mainly driven by the distal 5' promoter, which is located more than 800 bases 5' to the first gene of the cluster, SSA_2318. Optimal expression of the cluster occurred at the early-stationary growth phase in a CcpA-dependent manner, although a CcpA-binding consensus is absent in the promoter region. Expression of the cluster resulted in a short hair-like surface structure under transmission electron microscopy. Deletion of the putative pilin genes (SSA_2313-2315) abolished the biosynthesis of this structure and significantly reduced the adherence of SK36 to HeLa and SCC-4 cells. Mutations in the pil genes down-regulated biofilm formation by S. sanguinis SK36. Taken together, the results demonstrate that Tfp of SK36 are important for host cell adherence, but not for motility, and that expression of the pil cluster is subject to complex regulation.IMPORTANCEThe proteins and assembly machinery of the type IV pili (Tfp) are conserved throughout bacteria and archaea, and yet, the function of this surface structure differs from species to species, and even strain to strain. As seen in Streptococcus sanguinis SK36, the expression of the Tfp gene cluster results in a hair-like surface structure that is much shorter than the typical Tfp. This pilus is essential for the adherence of SK36, but is not involved in motility. Being a member of the highly diverse dental biofilm, perhaps S. sanguinis could more effectively utilize this structure to adhere to host cells and to interact with other microbes within the same niche.

RevDate: 2019-01-12

Feng S, SL McLellan (2019)

Highly specific sewage-derived Bacteroides qPCR assays target sewage polluted waters.

Applied and environmental microbiology pii:AEM.02696-18 [Epub ahead of print].

The identification of sewage contamination in water has primarily relied on detection of the human Bacteroides using markers within the V2 region of the 16S ribosomal RNA (rRNA) gene. Despite establishment of multiple assays that target the HF183 cluster (i.e., Bacteroides dorei) and other Bacteroides organisms (e.g., Bacteroides thetaiotomicron), the potential for more human-associated markers in this genus has not been explored in depth. We examined Bacteroides population structure in sewage and animal hosts across the V4V5 and V6 hypervariable regions. Using near full-length cloned sequences, we identified the sequences in the V4V5 and V6 hypervariable regions that are linked to the HF183 marker in V2 region and found these sequences were present in multiple animals. In addition, the V4V5 and V6 regions contained human fecal marker sequences for organisms that were independent of HF183 cluster. The most abundant Bacteroides in untreated sewage was not human associated but pipe derived. Two TaqMan qPCR assays were developed targeting the V4V5 and V6 regions of this organism. Validation studies using fecal samples from seven animal hosts (n=76) and uncontaminated water samples (n=30) demonstrated their high specificity for sewage. Freshwater Bacteroides were also identified in uncontaminated water samples, demonstrating that measures of total Bacteroides do not reflect fecal pollution. Comparison of two previously described human Bacteroides assays (HB and HF183/BacR287) in municipal wastewater influent and sewage contaminated urban water samples produced identical results, illustrating they target the same organism. Detection of sewage-derived Bacteroides provided an independent measure of sewage-impacted waters.IMPORTANCEBacteroides are major member of the gut microbiota and host-specific organisms within this genus have been used extensively to gain information on pollution sources. This study provides a broad view of the population structure of Bacteroides within sewage to contextualize the well-studied HF183 marker for a human-associated Bacteroides The study also delineates host-specific sequence patterns across multiple hypervariable regions of the 16S rRNA gene to improve our ability to use sequence data to assess water quality. Here, we demonstrate that regions downstream of the HF183 marker are non-specific, but other potential human-associated markers are present. Further, we show the most abundant Bacteroides in sewage is free-living, rather than host associated, and specifically found in sewage. Quantitative PCR assays that target organism specific to sewer pipes offer measures that are independent of the human microbiome for identifying sewage pollution in water.

RevDate: 2019-01-12

Kromann S, Hvidtfeldt A, Boye M, et al (2019)

In vitro synergy of sertraline and tetracycline cannot be reproduced in pigs orally challenged with a tetracycline resistant Escherichia coli.

BMC microbiology, 19(1):12 pii:10.1186/s12866-018-1383-5.

BACKGROUND: Antimicrobial helper-compounds may reverse antimicrobial resistance. Sertraline, a antidepressant drug, has been suggested as a tetracycline helper-compound. Tetracycline is the preferred antimicrobial for treatment of enteric diseases in pigs. This study is the first to evaluate the potency of sertraline as a tetracycline adjuvant in pigs.

METHODS: Forty-eight nursery pigs were divided into four treatment groups: Tetracycline, sertraline, tetracycline/sertraline or un-medicated control. Fecal and ileal samples were obtained before treatment, 48 h and nine days after five days of treatment, respectively. Colony forming units (CFU) of tetracycline resistant coliforms in each sample (ileal or fecal) and CFU of an orally inoculated tetracycline-resistant strain of Escherichia coli were determined at each sampling point. The microbiome of fecal and ileal and samples was analyzed by sequencing of the 16S V3-V4 region.

RESULTS: The results did not provide evidence that sertraline in combination with tetracycline has any impact on tetracycline resistant bacteria in either fecal or ileum samples, while in the tetracycline treated group of pigs, an increase in the prevalence of a tetracycline resistant indicator strain of Escherichia coli shortly after ended five-day treatment was observed. The ileal samples obtained shortly after ended treatment showed treatment-associated changes in the composition of the microbiota in the groups of pigs treated with tetracycline (+/-) sertraline. While tetracycline treatment increased the abundance in the reads of E. coli, sertraline/tetracycline treatment led to increased abundances of Streptococcus spp. and decreased abundances of Lactobacillus spp. However, all observed differences (on CFU counts and microbiota composition) between groups shortly after treatment had diminished in less than two weeks after last treatment day.

CONCLUSIONS: Sertraline (+/-) tetracycline treatment did not reduce the long-term level of tetracycline-resistant bacteria in the feces or small intestine contents of piglets compared to the un-medicated control group of pigs. The result of this study reflects the importance of in vivo studies for confirmation of the antimicrobial helper-compound potential of an in vitro active compound.

RevDate: 2019-01-12

Tröscher-Mußotter J, Tilocca B, Stefanski V, et al (2019)

Analysis of the Bacterial and Host Proteins along and across the Porcine Gastrointestinal Tract.

Proteomes, 7(1): pii:proteomes7010004.

Pigs are among the most important farm animals worldwide and research to optimize their feed efficiency and improve their welfare is still in progress. The porcine intestinal microbiome is so far mainly known from sequencing-based studies. Digesta and mucosa samples from five different porcine gastrointestinal tract sections were analyzed by metaproteomics to obtain a deeper insight into the functions of bacterial groups with concomitant analyses of host proteins. Firmicutes (Prevotellaceae) dominated mucosa and digesta samples, followed by Bacteroidetes. Actinobacteria and Proteobacteria were much higher in abundance in mucosa compared to digesta samples. Functional profiling reveals the presence of core functions shared between digesta and mucosa samples. Protein abundances of energy production and conversion were higher in mucosa samples, whereas in digesta samples more proteins were involved in lipid transport and metabolism; short-chain fatty acids production were detected. Differences were also highlighted between sections, with the small intestine appearing more involved in carbohydrate transport and metabolism than the large intestine. Thus, this study produced the first functional analyses of the porcine GIT biology, discussing the findings in relation to expected bacterial and host functions.

RevDate: 2019-01-11

Nicholson SE, Burmeister DM, Johnson TR, et al (2019)


The journal of trauma and acute care surgery [Epub ahead of print].

BACKGROUND: Traumatic injury can lead to a compromised intestinal epithelial barrier and inflammation. While alterations in the gut microbiome of critically injured patients may influence clinical outcomes, the impact of trauma on gut microbial composition is unknown. Our objective was to determine if the gut microbiome is altered in severely injured patients and begin to characterize changes in the gut microbiome due to time and therapeutic intervention.

METHODS: We conducted a prospective, observational study in adult patients (n=72) sustaining severe injury admitted to a Level I Trauma Center. Healthy volunteers (n=13) were also examined. Fecal specimens were collected on admission to the Emergency Department (ED) and at 3, 7, 10, and 13 (±2) days following injury. Microbial DNA was isolated for 16s rRNA sequencing, and α- and β-diversity were estimated, according to taxonomic classification against the Greengenes database.

RESULTS: The gut microbiome of trauma patients was altered on admission (i.e., within 30 minutes following injury) compared to healthy volunteers. Patients with an unchanged gut microbiome on admission were transfused more RBCs than those with an altered gut microbiome (p<0.001). Although the gut microbiome started to return to a β-diversity profile similar to that of healthy volunteers over time, it remained different from healthy controls. Alternatively, α-diversity initially increased post-injury, but subsequently decreased during the hospitalization. Injured patients on admission had a decreased abundance of traditionally beneficial microbial phyla (e.g., Firmicutes) with a concomitant decrease in opportunistic phyla (e.g., Proteobacteria) compared to healthy controls (p< 0.05). Large amounts of blood products and RBCs were both associated with higher α-diversity (p<0.001) and a β-diversity clustering closer to healthy controls.

CONCLUSIONS: The human gut microbiome changes early after trauma and may be aided by early massive transfusion. Ultimately, the gut microbiome of trauma patients may provide valuable diagnostic and therapeutic insight for the improvement of outcomes post-injury.

LEVEL OF EVIDENCE: Level III STUDY TYPE: Prognostic and Epidemiological.

RevDate: 2019-01-11

Hamada T, Nowak JA, Milner DA, et al (2019)

Integration of microbiology, molecular pathology, and epidemiology: a new paradigm to explore the pathogenesis of microbiome-driven neoplasms.

The Journal of pathology [Epub ahead of print].

Molecular pathological epidemiology (MPE) is an integrative transdisciplinary field that addresses heterogeneous effects of exogenous and endogenous factors (collectively termed "exposures"), including microorganisms, on disease occurrence and consequence utilising molecular pathological signatures of the disease. In parallel with the paradigm of precision medicine, findings from MPE research can provide aetiological insights into tailored strategies of disease prevention and treatment. Due to the availability of molecular pathological tests on tumours, the MPE approach has been utilised predominantly in research on cancers including breast, lung, prostate, and colorectal carcinomas. Mounting evidence indicates that the microbiome (inclusive of viruses, bacteria, fungi, and parasites) plays an important role in a variety of human diseases including neoplasms. An alteration of the microbiome may be not only a cause of neoplasia but also an informative biomarker that indicates or mediates the association of an epidemiological exposure with health conditions and outcomes. To adequately educate and train investigators in this emerging area, we herein propose the integration of microbiology into the MPE model (termed "microbiology-MPE"), which can improve our understanding of the complex interactions of environment, tumour cells, the immune system, and microbes in the tumour microenvironment during the carcinogenic process. Using this approach, we can examine how lifestyle factors, dietary patterns, medications, environmental exposures, and germline genetics influence cancer development and progression through impacting the microbial communities in the human body. Further integration of other disciplines (e.g. pharmacology, immunology, nutrition) into microbiology-MPE would expand this developing research frontier. With the advent of high-throughput next-generation sequencing technologies, researchers now have increasing access to large-scale metagenomics as well as other omics data (e.g. genomics, epigenomics, proteomics, and metabolomics) in population-based research. The integrative field of microbiology-MPE will open new opportunities for personalised medicine and public health.

RevDate: 2019-01-11

Moutinho BD, Baima JP, Rigo FF, et al (2019)

Fecal microbiota transplantation in refractory ulcerative colitis - a case report.

The Journal of international medical research [Epub ahead of print].

Studies comparing gut microbiota profiles of inflammatory bowel disease (IBD) patients have shown several changes in microbiota composition, with marked reduction of local biodiversity relative to that of healthy controls. Modulation of the bacterial community is a promising strategy to reduce the proportion of harmful microorganisms and increase the proportion of beneficial bacteria; this is expected to prevent or treat IBD. The exact mechanism of fecal microbiota transplantation (FMT) remains unknown; however, replacing the host microbiota can reestablish gut microbial composition and function in IBD patients. The present report describes an ulcerative colitis patient who underwent FMT. A 17-year-old male with moderate to severe clinical activity, which was refractory to mesalazine, azathioprine, and infliximab, underwent FMT as alternative therapy. The patient exhibited clinical improvement after the procedure; however, the symptoms returned. A second FMT was performed 8 months after the first procedure, but the patient did not improve. In conclusion, despite the FMT failure observed in this patient, the procedure is a promising therapeutic option for IBD patients, and more in-depth studies of this method are needed.

RevDate: 2019-01-11

Kolilekas L, Papiris S, D Bouros (2019)

Existing and emerging treatments for idiopathic pulmonary fibrosis.

Expert review of respiratory medicine [Epub ahead of print].

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a progressive and invariable fatal interstitial lung disease. Current antifibrotic treatment halts disease progression but do not cure the disease itself. In the last decade, a substantial understanding in disease pathobiological mechanisms led to the development of numerous clinical trials testing promising pharmacologic agents. Areas covered: In this review, we summarize and discuss current and emerging pharmacological therapies for IPF and highlight the potential of different promising investigational compounds in phase II-IV trials with positive or pending results. Expert commentary: Existing therapies for IPF slow disease progression and recent advances in understanding IPF complex pathogenesis unfolded multiple new possible therapeutic targets. A relevant number of promising clinical trials targeted specific biologic pathways, are ongoing or upcoming, but we are far away from a definitive cure of IPF soon. An 'oncologic approach' via tailoring medicine could be a realistic therapeutic intervention that may improve expectancy and quality of life in IPF.

RevDate: 2019-01-11

Zhou YX, Fuentes-Creollo G, Ponce F, et al (2019)

No difference in 4-nitroquinoline induced tumorigenesis between germ-free and colonized mice.

Molecular carcinogenesis [Epub ahead of print].

Variations in oral bacterial communities have been linked to oral cancer suggesting that the oral microbiome is an etiological factor that can influence oral cancer development. The 4-nitroquinoline 1-oxide (4-NQO)-induced murine oral and esophageal cancer model is frequently used to assess the effects of preventive and/or therapeutic agents. We used this model to assess the impact of the microbiome on tumorigenesis using axenic (germ-free) and conventionally housed mice. Increased toxicity was observed in germ-free mice, however, no difference in tumor incidence, multiplicity and size was observed. Transcriptional profiling of liver tissue from germ-free and conventionally housed mice identified 254 differentially expressed genes including ten cytochrome p450 enzymes, the largest family of phase-1 drug metabolizing enzymes in the liver. Gene ontology revealed that differentially expressed genes were enriched for liver steatosis, inflammation and oxidative stress in livers of germ-free mice. Our observations emphasize the importance of the microbiome in mediating chemical toxicity at least in part by altering host gene expression. Studies on the role of the microbiome in chemical-induced cancer using germ-free animal models should consider the potential difference in dose due to the microbiome-mediated changes in host metabolizing capacity, which might influence the ability to draw conclusions especially for tumor induction models that are dose dependent. This article is protected by copyright. All rights reserved.

RevDate: 2019-01-11

Xu H, H Li (2019)

Acne, the Skin Microbiome, and Antibiotic Treatment.

American journal of clinical dermatology pii:10.1007/s40257-018-00417-3 [Epub ahead of print].

Acne vulgaris is a chronic skin disorder involving hair follicles and sebaceous glands. Multiple factors contribute to the disease, including skin microbes. The skin microbiome in the follicle is composed of a diverse group of microorganisms. Among them, Propionibacterium acnes and Malassezia spp. have been linked to acne development through their influence on sebum secretion, comedone formation, and inflammatory response. Antibiotics targeting P. acnes have been the mainstay in acne treatment for the past four decades. Among them, macrolides, clindamycin, and tetracyclines are the most widely prescribed. As antibiotic resistance becomes an increasing concern in clinical practice, understanding the skin microbiome associated with acne and the effects of antibiotic use on the skin commensals is highly relevant and critical to clinicians. In this review, we summarize recent studies of the composition and dynamics of the skin microbiome in acne and the effects of antibiotic treatment on skin microbes.

RevDate: 2019-01-11

Grainger J, Daw R, K Wemyss (2018)

Systemic instruction of cell-mediated immunity by the intestinal microbiome.

F1000Research, 7:.

Recent research has shed light on the plethora of mechanisms by which the gastrointestinal commensal microbiome can influence the local immune response in the gut (in particular, the impact of the immune system on epithelial barrier homeostasis and ensuring microbial diversity). However, an area that is much less well explored but of tremendous therapeutic interest is the impact the gut microbiome has on systemic cell-mediated immune responses. In this commentary, we highlight some key studies that are beginning to broadly examine the different mechanisms by which the gastrointestinal microbiome can impact the systemic immune compartment. Specifically, we discuss the effects of the gut microbiome on lymphocyte polarisation and trafficking, tailoring of resident immune cells in the liver, and output of circulating immune cells from the bone marrow. Finally, we explore contexts in which this new understanding of long-range effects of the gut microbiome can have implications, including cancer therapies and vaccination.

RevDate: 2019-01-11

Ghosh D, Bernstein JA, Khurana Hershey GK, et al (2018)

Leveraging Multilayered "Omics" Data for Atopic Dermatitis: A Road Map to Precision Medicine.

Frontiers in immunology, 9:2727.

Atopic dermatitis (AD) is a complex multifactorial inflammatory skin disease that affects ~280 million people worldwide. About 85% of AD cases begin in childhood, a significant portion of which can persist into adulthood. Moreover, a typical progression of children with AD to food allergy, asthma or allergic rhinitis has been reported ("allergic march" or "atopic march"). AD comprises highly heterogeneous sub-phenotypes/endotypes resulting from complex interplay between intrinsic and extrinsic factors, such as environmental stimuli, and genetic factors regulating cutaneous functions (impaired barrier function, epidermal lipid, and protease abnormalities), immune functions and the microbiome. Though the roles of high-throughput "omics" integrations in defining endotypes are recognized, current analyses are primarily based on individual omics data and using binary clinical outcomes. Although individual omics analysis, such as genome-wide association studies (GWAS), can effectively map variants correlated with AD, the majority of the heritability and the functional relevance of discovered variants are not explained or known by the identified variants. The limited success of singular approaches underscores the need for holistic and integrated approaches to investigate complex phenotypes using trans-omics data integration strategies. Integrating omics layers (e.g., genome, epigenome, transcriptome, proteome, metabolome, lipidome, exposome, microbiome), which often have complementary and synergistic effects, might provide the opportunity to capture the flow of information underlying AD disease manifestation. Overlapping genes/candidates derived from multiple omics types include FLG, SPINK5, S100A8, and SERPINB3 in AD pathogenesis. Overlapping pathways include macrophage, endothelial cell and fibroblast activation pathways, in addition to well-known Th1/Th2 and NFkB activation pathways. Interestingly, there was more multi-omics overlap at the pathway level than gene level. Further analysis of multi-omics overlap at the tissue level showed that among 30 tissue types from the GTEx database, skin and esophagus were significantly enriched, indicating the biological interconnection between AD and food allergy. The present work explores multi-omics integration and provides new biological insights to better define the biological basis of AD etiology and confirm previously reported AD genes/pathways. In this context, we also discuss opportunities and challenges introduced by "big omics data" and their integration.

RevDate: 2019-01-11

Shao L, Ling Z, Chen D, et al (2018)

Disorganized Gut Microbiome Contributed to Liver Cirrhosis Progression: A Meta-Omics-Based Study.

Frontiers in microbiology, 9:3166.

Early detection and effective interventions for liver cirrhosis (LC) remain an urgent unmet clinical need. Inspired from intestinal disorders in LC patients, we investigated the associations between gut microbiome and disease progression based on a raw metagenomic dataset of 47 healthy controls, 49 compensated, and 46 decompensated LC patients from our previous study, and a metabolomic dataset of urine samples from the same controls/patients using ultra-performance liquid chromatography/mass spectrophotometry system. It was found that the combination and relative abundance of gut microbiome, the inter-microbiome regulatory networks, and the microbiome-host correlation patterns varied during disease progression. The significant reduction of bacteria involved in fermentation of plant cell wall polysaccharides and resistant starch (such as Alistipes sp. HG5, Clostridium thermocellum) contributed to the reduced supply of energy sources, the disorganized self-feeding and cross-feeding networks and the thriving of some opportunistic pathogens in genus Veillonella. The marked decrease of butyrate-producing bacteria and increase of Ruminococcus gnavus implicated in degradation of elements from the mucus layer provided an explanation for the impaired intestinal barrier function and systematic inflammation in LC patients. Our results pave the way for further developments in early detection and intervention of LC targeting on gut microbiome.

RevDate: 2019-01-11

Ho TTB, Groer MW, Kane B, et al (2018)

Enteric dysbiosis and fecal calprotectin expression in premature infants.

Pediatric research pii:10.1038/s41390-018-0254-y [Epub ahead of print].

BACKGROUND: Premature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC).

METHODS: Stool samples were collected from very-low-birth weight (VLBW) infants at ≤2, 3, and 4 weeks' postnatal age. Fecal microbiome was surveyed using polymerase chain reaction amplification of the V4 region of 16S ribosomal RNA, and FC was measured by enzyme immunoassay.

RESULTS: We enrolled 45 VLBW infants (gestation 27.9 ± 2.2 weeks, birth weight 1126 ± 208 g) and obtained stool samples at 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. FC was positively correlated with the genus Klebsiella (r = 0.207, p = 0.034) and its dominant amplicon sequence variant (r = 0.290, p = 0.003), but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance.

CONCLUSION: In premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella, and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution.

RevDate: 2019-01-11

Bergelson J, Mittelstrass J, MW Horton (2019)

Characterizing both bacteria and fungi improves understanding of the Arabidopsis root microbiome.

Scientific reports, 9(1):24 pii:10.1038/s41598-018-37208-z.

Roots provide plants mineral nutrients and stability in soil; while doing so, they come into contact with diverse soil microbes that affect plant health and productivity. Despite their ecological and agricultural relevance, the factors that shape the root microbiome remain poorly understood. We grew a worldwide panel of replicated Arabidopsis thaliana accessions outdoors and over winter to characterize their root-microbial communities. Although studies of the root microbiome tend to focus on bacteria, we found evidence that fungi have a strong influence on the structure of the root microbiome. Moreover, host effects appear to have a stronger influence on plant-fungal communities than plant-bacterial communities. Mapping the host genes that affect microbiome traits identified a priori candidate genes with roles in plant immunity; the root microbiome also appears to be strongly affected by genes that impact root and root hair development. Our results suggest that future analyses of the root microbiome should focus on multiple kingdoms, and that the root microbiome is shaped not only by genes involved in defense, but also by genes involved in plant form and physiology.

RevDate: 2019-01-11

Kenyon CR, Delva W, RM Brotman (2019)

Differential sexual network connectivity offers a parsimonious explanation for population-level variations in the prevalence of bacterial vaginosis: a data-driven, model-supported hypothesis.

BMC women's health, 19(1):8 pii:10.1186/s12905-018-0703-0.

BACKGROUND: The prevalence of bacterial vaginosis (BV) and vaginal microbiota types varies dramatically between different populations around the world. Understanding what underpins these differences is important, as high-diversity microbiotas associated with BV are implicated in adverse pregnancy outcomes and enhanced susceptibility to and transmission of sexually transmitted infections.

MAIN TEXT: We hypothesize that these variations in the vaginal microbiota can, in part, be explained by variations in the connectivity of sexual networks. We argue: 1) Couple-level data suggest that BV-associated bacteria can be sexually transmitted and hence high sexual network connectivity would be expected to promote the spread of BV-associated bacteria. Epidemiological studies have found positive associations between indicators of network connectivity and the prevalence of BV; 2) The relationship between BV prevalence and STI incidence/prevalence can be parsimoniously explained by differential network connectivity; 3) Studies from other mammals are generally supportive of the association between network connectivity and high-diversity vaginal microbiota.

CONCLUSION: To test this hypothesis, we propose a combination of empirical and simulation-based study designs.

RevDate: 2019-01-11

Dudík B, Sepová HK, A Bilková (2018)

Inflammatory bowel disease: factors involved in pathogenesis.

Ceska a Slovenska farmacie : casopis Ceske farmaceuticke spolecnosti a Slovenske farmaceuticke spolecnosti, 67(3):95-100.

The incidence of inflammatory bowel disease (IBD) in developed countries increases every year. The aetiology is still not completely understood and its clarification is a key prerequisite for effective prophylaxis and therapy. IBD is most-likely caused by a combination of several factors: environmental, genetic, immunological, and disruption of intestinal microbiota composition - dysbiosis. "Westernization" of lifestyle and urbanization seem to be among the most serious environmental factors. The pathogenesis is also influenced by the imbalance between the TH1 and TH2 cellular response and the expression of genes involved in T cell response and immunodeficiency. Last but not least, the worldwide overuse of antimicrobial drugs depletes the microbiome, which has a direct impact on the development of the dysbiosis. The subject of this review is a detailed characterization of the above-mentioned factors involved in the onset and development of IBD. Key words: gut microbiota inflammatory bowel disease immunopathogenesis dysbiosis.

RevDate: 2019-01-11

Kim K, Castro EJT, Shim H, et al (2018)

Differences Regarding the Molecular Features and Gut Microbiota Between Right and Left Colon Cancer.

Annals of coloproctology, 34(6):280-285.

For many years, developmental and physiological differences have been known to exist between anatomic segments of the colorectum. Because of different outcomes, prognoses, and clinical responses to chemotherapy, the distinction between right colon cancer (RCC) and left colon cancer (LCC) has gained attention. Furthermore, variations in the molecular features and gut microbiota between right and LCCs have recently been a hot research topic. CpG island methylator phenotype-high, microsatellite instability-high colorectal cancers are more likely to occur on the right side whereas tumors with chromosomal instability have been detected in approximately 75% of LCC patients and 30% of RCC patients. The mutation rates of oncogenes and tumor suppressor genes also differ between RCC and LCC patients. Biofilm is more abundant in RCC patients than LLC patients, as are Prevotella, Selenomonas, and Peptostreptococcus. Conversely, Fusobacterium, Escherichia/Shigella, and Leptotrichia are more abundant in LCC patients compared to RCC patients. Distinctive characteristics are apparent in terms of molecular features and gut microbiota between right and LCC. However, how or to what extent these differences influence diverging oncologic outcomes remains unclear. Further clinical and translational studies are needed to elucidate the causative relationship between primary tumor location and prognosis.

RevDate: 2019-01-10

Balasubramanian S, Osburne MS, BrinJones H, et al (2019)

Prophage induction, but not production of phage particles, is required for lethal disease in a microbiome-replete murine model of enterohemorrhagic E. coli infection.

PLoS pathogens, 15(1):e1007494 pii:PPATHOGENS-D-18-01242.

Enterohemorrhagic Escherichia coli (EHEC) colonize intestinal epithelium by generating characteristic attaching and effacing (AE) lesions. They are lysogenized by prophage that encode Shiga toxin 2 (Stx2), which is responsible for severe clinical manifestations. As a lysogen, prophage genes leading to lytic growth and stx2 expression are repressed, whereas induction of the bacterial SOS response in response to DNA damage leads to lytic phage growth and Stx2 production both in vitro and in germ-free or streptomycin-treated mice. Some commensal bacteria diminish prophage induction and concomitant Stx2 production in vitro, whereas it has been proposed that phage-susceptible commensals may amplify Stx2 production by facilitating successive cycles of infection in vivo. We tested the role of phage induction in both Stx production and lethal disease in microbiome-replete mice, using our mouse model encompassing the murine pathogen Citrobacter rodentium lysogenized with the Stx2-encoding phage Φstx2dact. This strain generates EHEC-like AE lesions on the murine intestine and causes lethal Stx-mediated disease. We found that lethal mouse infection did not require that Φstx2dact infect or lysogenize commensal bacteria. In addition, we detected circularized phage genomes, potentially in the early stage of replication, in feces of infected mice, confirming that prophage induction occurs during infection of microbiota-replete mice. Further, C. rodentium (Φstx2dact) mutants that do not respond to DNA damage or express stx produced neither high levels of Stx2 in vitro or lethal infection in vivo, confirming that SOS induction and concomitant expression of phage-encoded stx genes are required for disease. In contrast, C. rodentium (Φstx2dact) mutants incapable of prophage genome excision or of packaging phage genomes retained the ability to produce Stx in vitro, as well as to cause lethal disease in mice. Thus, in a microbiome-replete EHEC infection model, lytic induction of Stx-encoding prophage is essential for lethal disease, but actual phage production is not.

RevDate: 2019-01-10

Miranda-CasoLuengo R, Lu J, Williams EJ, et al (2019)

Delayed differentiation of vaginal and uterine microbiomes in dairy cows developing postpartum endometritis.

PloS one, 14(1):e0200974 pii:PONE-D-18-19761.

Bacterial overgrowth in the uterus is a normal event after parturition. In contrast to the healthy cow, animals unable to control the infection within 21 days after calving develop postpartum endometritis. Studies on the Microbial Ecology of the bovine reproductive tract have focused on either vaginal or uterine microbiomes. This is the first study that compares both microbiomes in the same animals. Terminal Restriction Fragment Length Polymorphism of the 16S rRNA gene showed that despite large differences associated to individuals, a shared community exist in vagina and uterus during the postpartum period. The largest changes associated with development of endometritis were observed at 7 days postpartum, a time when vaginal and uterine microbiomes were most similar. 16S rRNA pyrosequencing of the vaginal microbiome at 7 days postpartum showed at least three different microbiome types that were associated with later development of postpartum endometritis. All three microbiome types featured reduced bacterial diversity. Taken together, the above findings support a scenario where disruption of the compartmentalization of the reproductive tract during parturition results in the dispersal and mixing of the vaginal and uterine microbiomes, which subsequently are subject to differentiation. This differentiation was observed early postpartum in the healthy cow. In contrast, loss of bacterial diversity and dominance of the microbiome by few bacterial taxa were related to a delayed succession at 7DPP in cows that at 21 DPP or later were diagnosed with endometritis.

RevDate: 2019-01-10

Marcial-Coba MS, Knøchel S, DS Nielsen (2019)

Low-moisture food matrices as probiotic carriers.

FEMS microbiology letters pii:5281433 [Epub ahead of print].

To exert a beneficial effect on the host, adequate doses of probiotics must be administered and maintaining their viability until consumption is thus essential. Dehydrated probiotics exhibit enhanced long-term viability and can be incorporated into low-moisture food matrices which also possess high stability at refrigeration and ambient temperature. However, several factors associated with the desiccation process, the physicochemical properties of the matrix and the storage conditions can affect probiotic survival. In the near future, an increased demand for probiotics based on functionally dominant members of the gut microbiome ('next-generation probiotics', NGP) is expected. NGPs are very sensitive to oxygen and efficient encapsulation protocols are needed. Strategies to improve the viability of traditional probiotics and particularly of NGPs involve the selection of a suitable carrier as well as proper desiccation and protection techniques. Dried probiotic microcapsules may constitute an alternative to improve the microbial viability not only during storage but also upper gastrointestinal tract passage. Here we review the main dehydration techniques that are applied in the industry as well as the potential stresses associated with the desiccation process and storage. Finally, low- or intermediate-moisture food matrices suitable as carriers of traditional as well as NGPs will be discussed.

RevDate: 2019-01-10

Stewart CJ, Mansbach JM, Ajami NJ, et al (2019)

Serum metabolome is associated with nasopharyngeal microbiota and disease severity among infants with bronchiolitis.

The Journal of infectious diseases pii:5285940 [Epub ahead of print].

Background: Emerging evidence suggests relations of nasopharyngeal metabolome and microbiota with bronchiolitis severity. However, the influence of host systemic metabolism on disease pathobiology remains unclear. We aimed to examine metabolome profiles and their association with higher severity, defined by use of positive pressure ventilation (PPV), in infants hospitalized for bronchiolitis.

Methods: In 140 infants with bronchiolitis, metabolomic profiling was performed on serum: n=70 in the training dataset and n=70 independent samples in the test dataset. We also profiled the nasopharyngeal airway microbiota and examined its association with the serum metabolites.

Results: Serum metabolome profiles differed by bronchiolitis severity (P<0.001). In total, 20 metabolites in the training dataset were significantly associated with the risk of PPV and 18 metabolites remained significant following adjustment for confounders (FDR<0.10). Phosphatidylcholine metabolites were associated with higher risks of PPV use, while metabolites from the plasmalogen sub-pathway were associated with lower risks. The test dataset validated these findings (FDR<0.05). Streptococcus abundance was positively associated with metabolites that are associated with higher risks of PPV.

Conclusions: Serum metabolomic signatures were associated with both the nasopharyngeal microbiota and bronchiolitis severity. Our findings advance research into the complex interrelations between airway microbiome, host systemic response, and pathobiology of bronchiolitis.

RevDate: 2019-01-10

Vick AD, Hery DN, Markowiak SF, et al (2019)

Closing the Disparity in Pancreatic Cancer Outcomes: A Closer Look at Nonmodifiable Factors and Their Potential Use in Treatment.

Pancreas [Epub ahead of print].

OBJECTIVES: African Americans (AAs) have disproportionately higher incidence and lower survival rates from pancreatic cancer compared with whites. Historically, this disparity has been attributed to modifiable risk factors. Recent studies suggest that nonmodifiable aspects may also play an important role. We review these new contributions as potential targets for closing the disparity.

METHODS: A PubMed search was conducted to review studies of nonmodifiable elements contributing to pancreatic cancer disparities in AAs.

RESULTS: Several nonmodifiable risks are associated with the racial disparity in pancreatic cancer. SSTR5 P335L, Kaiso, and KDM4/JMJD2A demonstrate differential racial expression, increasing their potential as therapeutic targets. Many social determinants of health and their associations with diabetes, obesity, and the microbiome are partially modifiable risk factors that significantly contribute to outcomes in minorities. Barriers to progress include the low minority inclusion in research studies.

CONCLUSIONS: Genomics, epigenetics, the microbiome, and social determinants of health are components that contribute to the pancreatic cancer disparity in AAs. These factors can be researched, targeted, and modified to improve mortality rates. Closing the disparity in pancreatic cancer will require an integrated approach of personalized medicine, increased minority recruitment to studies, and advanced health care/education access.

RevDate: 2019-01-10

Xue J, Lai Y, Chi L, et al (2019)

Serum metabolomics reveals that gut microbiome perturbation mediates metabolic disruption induced by arsenic exposure in mice.

Journal of proteome research [Epub ahead of print].

Arsenic contamination in drinking water has been a worldwide health concern for decades. Except for being a well-recognized carcinogen, arsenic exposure has also been linked with diabetes, neurological effects, and cardiovascular diseases. Recently, increasing evidence have indicated that gut microbiome is an important risk factor in modulating the development of diseases. In the present study, we aim to investigate the role of gut microbiome perturbation in arsenic-induced diseases by coupling a mass spectrometry-based metabolomics approach and an animal model with altered gut microbiome induced by bacterial infection. Serum metabolic profiling has revealed that gut microbiome perturbation and arsenic exposure induced the dramatic changes of numerous metabolite pathways, including fatty acid metabolism, phospholipids, sphingolipids, cholesterols, and tryptophan metabolism, which were not or less disrupted when gut microbiome stays normal. In summary, this study suggested that gut microbiome perturbation can exacerbate or cause the metabolic disorders induced by arsenic exposure.

RevDate: 2019-01-10

Wang Q, Wang K, Wu W, et al (2019)

Host and microbiome multi-omics integration: applications and methodologies.

Biophysical reviews pii:10.1007/s12551-018-0491-7 [Epub ahead of print].

The study of the microbial community-the microbiome-associated with a human host is a maturing research field. It is increasingly clear that the composition of the human's microbiome is associated with various diseases such as gastrointestinal diseases, liver diseases and metabolic diseases. Using high-throughput technologies such as next-generation sequencing and mass spectrometry-based metabolomics, we are able to comprehensively sequence the microbiome-the metagenome-and associate these data with the genomic, epigenomics, transcriptomic and metabolic profile of the host. Our review summarises the application of integrating host omics with microbiome as well as the analytical methods and related tools applied in these studies. In addition, potential future directions are discussed.

RevDate: 2019-01-10

Brandstetter S, Toncheva AA, Niggel J, et al (2019)

KUNO-Kids birth cohort study: rationale, design, and cohort description.

Molecular and cellular pediatrics, 6(1):1 pii:10.1186/s40348-018-0088-z.

BACKGROUND: Birth cohort studies can contribute substantially to the understanding of health and disease - in childhood and over the life course. The KUNO-Kids birth cohort study was established to investigate various aspects of child health, using novel omics technologies in a systems medicine approach.

RESULTS: After 3 years of recruitment, 2515 infants and their families have joined the study. Parents with higher education are overrepresented as in many other birth cohorts and are more likely to complete follow-up assessments via self-report questionnaires. The vast majority of participants consented to clinical examinations of their child and to the non-invasive collection of diverse biosamples, which were processed specifically for their integrated use in omics technology covering genomics, epigenomics, transcriptomics, metabolomics, and microbiome analyses of the skin, oral cavity, and stool.

CONCLUSIONS: The data and diverse biomaterial collected in the KUNO-Kids birth cohort study will provide extensive opportunities for investigating child health and its determinants in a holistic approach. The combination of a broad range of research questions in one study will allow for a cost-effective use of biomaterial and omics results and for a comprehensive analysis of biological and social determinants of health and disease. Aiming for low attrition and ensuring participants' long-term commitment will be crucial to fully exploit the potential of the study.

RevDate: 2019-01-10

Treichel NS, Prevoršek Z, Mrak V, et al (2019)

Effect of the Nursing Mother on the Gut Microbiome of the Offspring During Early Mouse Development.

Microbial ecology pii:10.1007/s00248-019-01317-7 [Epub ahead of print].

The development of the gut microbiome is influenced by several factors. It is acquired during and after birth and involves both maternal and environmental factors as well as the genetic disposition of the offspring. However, it is unclear if the microbiome development is directly triggered by the mode of delivery and very early contact with the mother or mostly at later stages of initial development mainly by breast milk provided by the mother. To investigate to what extent the gut microbiome composition of the offspring is determined by the nursing mother, providing breast milk, compared to the birth mother during early development, a cross-fostering experiment involving two genetically different mouse lines was developed, being prone to be obese or lean, respectively. The microbiome of the colon was analyzed by high-throughput 16S rRNA gene sequencing, when the mice were 3 weeks old. The nursing mother affected both α- and β-diversity of the offspring's gut microbiome and shaped its composition. Especially bacterial families directly transferred by breast milk, like Streptococcaceae, or families which are strongly influenced by the quality of the breast milk like Rikenellaceae, showed a strong response. The core microbiome transferred from the obese nursing mother showed a higher robustness in comparison to the microbiome transferred from the lean nursing mother. Overall, the nursing mother impacts the gut microbial composition of the offspring during early development and might play an important role for health and disease of the animals at later stages of life.

RevDate: 2019-01-10

Fenker DE, McDaniel CT, Panmanee W, et al (2018)

A Comparison between Two Pathophysiologically Different yet Microbiologically Similar Lung Diseases: Cystic Fibrosis and Chronic Obstructive Pulmonary Disease.

International journal of respiratory and pulmonary medicine, 5(2):.

Cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are chronic pulmonary diseases that affect ~70,000 and 251 million individuals worldwide, respectively. Although these two diseases have distinctly different pathophysiologies, both cause chronic respiratory insufficiency that erodes quality of life and causes significant morbidity and eventually death. In both CF and COPD, the respiratory microbiome plays a major contributing role in disease progression and morbidity. Pulmonary pathogens can differ dramatically during various stages of each disease and frequently cause acute worsening of lung function due to disease exacerbation. Despite some similarities, outcome and timing/type of exacerbation can also be quite different between CF and COPD. Given these clinical distinctions, both patients and physicians should be aware of emerging therapeutic options currently being offered or in development for the treatment of lung infections in individuals with CF and COPD. Although interventions are available that prolong life and mitigate morbidity, neither disorder is curable. Both acute and chronic pulmonary infections contribute to an inexorable downward course and may trigger exacerbations, culminating in loss of lung function or respiratory failure. Knowledge of the pulmonary pathogens causing these infections, their clinical presentation, consequences, and management are, therefore, critical. In this review, we compare and contrast CF and COPD, including underlying causes, general outcomes, features of the lung microbiome, and potential treatment strategies.

RevDate: 2019-01-10

Pugazhendhi A, Kumar G, P Sivagurunathan (2019)

Microbiome involved in anaerobic hydrogen producing granules: A mini review.

Biotechnology reports (Amsterdam, Netherlands), 21:e00301 pii:e00301.

This mini review overviewed the latest updates on the anaerobic hydrogen fermentation using the granulation technology and the microbiome involved in the process. Additionally, the implication of various reactor design and their microbial changes were compared and provided the new insights on the role of microbiomes for rapid granules formation and long term stable operation in a continuous mode operation. The information provided in this communication would help to understand the key role of microbiomes and their importance in anaerobic hydrogen producing granular systems.

RevDate: 2019-01-10

Rowan-Nash AD, Korry BJ, Mylonakis E, et al (2019)

Cross-Domain and Viral Interactions in the Microbiome.

Microbiology and molecular biology reviews : MMBR, 83(1): pii:83/1/e00044-18.

SUMMARYThe importance of the microbiome to human health is increasingly recognized and has become a major focus of recent research. However, much of the work has focused on a few aspects, particularly the bacterial component of the microbiome, most frequently in the gastrointestinal tract. Yet humans and other animals can be colonized by a wide array of organisms spanning all domains of life, including bacteria and archaea, unicellular eukaryotes such as fungi, multicellular eukaryotes such as helminths, and viruses. As they share the same host niches, they can compete with, synergize with, and antagonize each other, with potential impacts on their host. Here, we discuss these major groups making up the human microbiome, with a focus on how they interact with each other and their multicellular host.

RevDate: 2019-01-10

Rechenberger J, Samaras P, Jarzab A, et al (2019)

Challenges in Clinical Metaproteomics Highlighted by the Analysis of Acute Leukemia Patients with Gut Colonization by Multidrug-Resistant Enterobacteriaceae.

Proteomes, 7(1): pii:proteomes7010002.

The microbiome has a strong impact on human health and disease and is, therefore, increasingly studied in a clinical context. Metaproteomics is also attracting considerable attention, and such data can be efficiently generated today owing to improvements in mass spectrometry-based proteomics. As we will discuss in this study, there are still major challenges notably in data analysis that need to be overcome. Here, we analyzed 212 fecal samples from 56 hospitalized acute leukemia patients with multidrug-resistant Enterobactericeae (MRE) gut colonization using metagenomics and metaproteomics. This is one of the largest clinical metaproteomic studies to date, and the first metaproteomic study addressing the gut microbiome in MRE colonized acute leukemia patients. Based on this substantial data set, we discuss major current limitations in clinical metaproteomic data analysis to provide guidance to researchers in the field. Notably, the results show that public metagenome databases are incomplete and that sample-specific metagenomes improve results. Furthermore, biological variation is tremendous which challenges clinical study designs and argues that longitudinal measurements of individual patients are a valuable future addition to the analysis of patient cohorts.

RevDate: 2019-01-09

Sanctuary MR, Kain JN, Chen SY, et al (2019)

Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms.

PloS one, 14(1):e0210064 pii:PONE-D-18-06023.

Over half of all children with autism spectrum disorders (ASD) have gastrointestinal (GI) co-morbidities including chronic constipation, diarrhea, and irritable bowel syndrome. The severity of these symptoms has been correlated with the degree of GI microbial dysbiosis. The study objective was to assess tolerability of a probiotic (Bifidobacterium infantis) in combination with a bovine colostrum product (BCP) as a source of prebiotic oligosaccharides and to evaluate GI, microbiome and immune factors in children with ASD and GI co-morbidities. This pilot study is a randomized, double blind, controlled trial of combination treatment (BCP + B. infantis) vs. BCP alone in a cross-over study in children ages 2-11 with ASD and GI co-morbidities (n = 8). This 12-week study included 5 weeks of probiotic-prebiotic supplementation, followed by a two-week washout period, and 5 weeks of prebiotic only supplementation. The primary outcome of tolerability was assessed using validated questionnaires of GI function and atypical behaviors, along with side effects. Results suggest that the combination treatment is well-tolerated in this cohort. The most common side effect was mild gassiness. Some participants on both treatments saw a reduction in the frequency of certain GI symptoms, as well as reduced occurrence of particular aberrant behaviors. Improvement may be explained by a reduction in IL-13 and TNF-α production in some participants. Although limited conclusions can be drawn from this small pilot study, the results support the need for further research into the efficacy of these treatments.

RevDate: 2019-01-09

Lee KH, Gordon A, Shedden K, et al (2019)

The respiratory microbiome and susceptibility to influenza virus infection.

PloS one, 14(1):e0207898 pii:PONE-D-18-31833.

Influenza is a major cause of morbidity and mortality worldwide. However, vaccine effectiveness has been low to moderate in recent years and vaccine coverage remains low, especially in low- and middle-income countries. Supplementary methods of prevention should be explored to reduce the high burden of influenza. A potential target is the respiratory tract microbiome, complex microbial communities which envelop the respiratory epithelium and play an important role in shaping host immunity. Using a household transmission study, we examined whether the nose/throat microbiota was associated with influenza susceptibility among participants exposed to influenza virus in the household. Further, we characterized changes in the nose/throat microbiota to explore whether community stability was influenced by influenza virus infection. Using a generalized linear mixed effects model, we found a nasal/oropharyngeal community state type (CST) associated with decreased susceptibility to influenza. The CST was rare and transitory among young children but a prevalent and stable CST among adults. Using boosting and linear mixed effects models, we found associations between the nose/throat microbiota and influenza also existed at the taxa level, specifically with the relative abundance of Alloprevotella, Prevotella, and Bacteroides oligotypes. We found high rates of change between bacterial community states among both secondary cases and household contacts who were not infected during follow up. Further work is needed to separate the effect of influenza virus infection from the considerable short-term changes that occur even in the absence of virus. Lastly, age was strongly associated with susceptibility to influenza and the nose/throat bacterial community structure. Although additional studies are needed to determine causality, our results suggest the nose/throat microbiome may be a potential target for reducing the burden of influenza.

RevDate: 2019-01-09

Doonan J, Denman S, Pachebat JA, et al (2019)

Genomic analysis of bacteria in the Acute Oak Decline pathobiome.

Microbial genomics [Epub ahead of print].

The UK's native oak is under serious threat from Acute Oak Decline (AOD). Stem tissue necrosis is a primary symptom of AOD and several bacteria are associated with necrotic lesions. Two members of the lesion pathobiome, Brenneria goodwinii and Gibbsiella quercinecans, have been identified as causative agents of tissue necrosis. However, additional bacteria including Lonsdalea britannica and Rahnella species have been detected in the lesion microbiome, but their role in tissue degradation is unclear. Consequently, information on potential genome-encoded mechanisms for tissue necrosis is critical to understand the role and mechanisms used by bacterial members of the lesion pathobiome in the aetiology of AOD. Here, the whole genomes of bacteria isolated from AOD-affected trees were sequenced, annotated and compared against canonical bacterial phytopathogens and non-pathogenic symbionts. Using orthologous gene inference methods, shared virulence genes that retain the same function were identified. Furthermore, functional annotation of phytopathogenic virulence genes demonstrated that all studied members of the AOD lesion microbiota possessed genes associated with phytopathogens. However, the genome of B. goodwinii was the most characteristic of a necrogenic phytopathogen, corroborating previous pathological and metatranscriptomic studies that implicate it as the key causal agent of AOD lesions. Furthermore, we investigated the genome sequences of other AOD lesion microbiota to understand the potential ability of microbes to cause disease or contribute to pathogenic potential of organisms isolated from this complex pathobiome. The role of these members remains uncertain but some such as G. quercinecans may contribute to tissue necrosis through the release of necrotizing enzymes and may help more dangerous pathogens activate and realize their pathogenic potential or they may contribute as secondary/opportunistic pathogens with the potential to act as accessory species for B. goodwinii. We demonstrate that in combination with ecological data, whole genome sequencing provides key insights into the pathogenic potential of bacterial species whether they be phytopathogens, part-contributors or stimulators of the pathobiome.

RevDate: 2019-01-09

Yadav D, Dutta A, SS Mande (2019)

OTUX: V-region specific OTU database for improved 16S rRNA OTU picking and efficient cross-study taxonomic comparison of microbiomes.

DNA research : an international journal for rapid publication of reports on genes and genomes pii:5280828 [Epub ahead of print].

Many microbiome studies employ reference-based operational taxonomic unit (OTU)-picking methods, which in general, rely on databases cataloguing reference OTUs identified through clustering full-length 16S rRNA genes. Given that the rate of accumulation of mutations are not uniform throughout the length of a 16S rRNA gene across different taxonomic clades, results of OTU identification or taxonomic classification obtained using 'short-read' sequence queries (as generated by next-generation sequencing platforms) can be inconsistent and of suboptimal accuracy. De novo OTU clustering results too can significantly vary depending upon the hypervariable region (V-region) targeted for sequencing. As a consequence, comparison of microbiomes profiled in different scientific studies becomes difficult and often poses a challenge in analysing new findings in context of prior knowledge. The OTUX approach of reference-based OTU-picking proposes to overcome these limitations by using 'customized' OTU reference databases, which can cater to different sets of short-read sequences corresponding to different 16S V-regions. The results obtained with OTUX-approach (which are in terms of OTUX-OTU identifiers) can also be 'mapped back' or represented in terms of other OTU database identifiers/taxonomy, e.g. Greengenes, thus allowing for easy cross-study comparisons. Validation with simulated datasets indicates more efficient, accurate, and consistent taxonomic classifications obtained using OTUX-approach, as compared with conventional methods.

RevDate: 2019-01-09

Dehner C, Fine R, MA Kriegel (2019)

The microbiome in systemic autoimmune disease: mechanistic insights from recent studies.

Current opinion in rheumatology [Epub ahead of print].

PURPOSE OF REVIEW: The resident bacterial communities and the host immune system have coevolved for millennia. However, recent changes in modern societies have disrupted this coevolutionary homeostasis and contributed to a rise in immune-mediated conditions. The purpose of this review is to provide an overview of recently elucidated mechanisms of how certain taxa within the bacterial microbiome propagate autoimmunity.

RECENT FINDINGS: Interactions between the bacterial microbiome with innate and adaptive immune cells propagate autoreactivity, chronic inflammation, and tissue damage in susceptible hosts. These interactions contribute to autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus, which are the focus of this review. Recent findings suggest that autoimmune manifestations in genetically susceptible individuals can arise through cross-reactivity with commensal orthologs of autoantigens or commensal-mediated posttranslational modification of autoantigens. Physiologic responses to gut, oral, or skin commensal bacteria can thus be misdirected toward such autoantigens in susceptible hosts. In addition, recent studies highlight that a breach of the gut barrier and translocation of commensal bacteria to non-gut organs can trigger several autoimmune pathways that can be prevented by commensal vaccination or dietary interventions.

SUMMARY: Complex host-microbiota interactions contribute to systemic autoimmunity outside the gut. On a molecular level, posttranslational modification of, and cross-reactivity with, autoantigens represent mechanisms of how the microbiota mediates autoimmunity. On a cellular level, translocation of live gut bacteria across a dysfunctional gut barrier allows for direct interactions with immune and tissue cells, instigating autoimmunity systemically.

RevDate: 2019-01-09

Sloan TJ, Turton JC, Tyson J, et al (2019)

Examining diabetic heel ulcers through an ecological lens: microbial community dynamics associated with healing and infection.

Journal of medical microbiology [Epub ahead of print].

PURPOSE: While some micro-organisms, such as Staphylococcus aureus, are clearly implicated in causing tissue damage in diabetic foot ulcers (DFUs), our knowledge of the contribution of the entire microbiome to clinical outcomes is limited. We profiled the microbiome of a longitudinal sample series of 28 people with diabetes and DFUs of the heel in an attempt to better characterize the relationship between healing, infection and the microbiome.

METHODOLOGY: In total, 237 samples were analysed from 28 DFUs, collected at fortnightly intervals for 6 months or until healing. Microbiome profiles were generated by 16S rRNA gene sequence analysis, supplemented by targeted nanopore sequencing.Result/Key findings. DFUs which failed to heal during the study period (20/28, 71.4 %) were more likely to be persistently colonized with a heterogeneous community of micro-organisms including anaerobes and Enterobacteriaceae (log-likelihood ratio 9.56, P=0.008). During clinically apparent infection, a reduction in the diversity of micro-organisms in a DFU was often observed due to expansion of one or two taxa, with recovery in diversity at resolution. Modelling of the predicted species interactions in a single DFU with high diversity indicated that networks of metabolic interactions may exist that contribute to the formation of stable communities.

CONCLUSION: Longitudinal profiling is an essential tool for improving our understanding of the microbiology of chronic wounds, as community dynamics associated with clinical events can only be identified by examining changes over multiple time points. The development of complex communities, particularly involving Enterobacteriaceae and strict anaerobes, may be contributing to poor outcomes in DFUs and requires further investigation.

RevDate: 2019-01-09

Jung C, L Brubaker (2019)

The etiology and management of recurrent urinary tract infections in postmenopausal women.

Climacteric : the journal of the International Menopause Society [Epub ahead of print].

Urinary tract infections (UTIs) are one of the most common infections and affect up to 50% of women in their lifetime, with almost half of these women experiencing a recurrence in 6-12 months. Menopause predisposes women to recurrent UTI (rUTI), as normally lower levels of estrogen lead to changes in the urogenital epithelium and subsequently urogenital microbiome. The recently discovered urobiome is now known to have different compositions in both healthy and unhealthy bladders, including a role in the pathophysiology of rUTI, and may be a therapeutic target for prevention and treatment options for rUTI. In postmenopausal women with frequent UTI, the diagnosis of acute UTI should be made using a combination of the symptom assessment and urine diagnostic studies. The choice of UTI antibiotic should include consideration of efficacy, collateral effects, and side-effects. Some women may be candidates for self-start therapy, in which the patient accurately recognizes her UTI symptoms and then starts previously prescribed antibiotics. A large component of the management of women with rUTI is prevention. Urobiome research for bladder health and disease is a young field of investigation with significant potential to improve care for postmenopausal women affected by rUTI through novel, evidence-based prevention and treatment strategies.

RevDate: 2019-01-09

Zhai J, Knox K, Twigg HL, et al (2019)

Exact variance component tests for longitudinal microbiome studies.

Genetic epidemiology [Epub ahead of print].

In metagenomic studies, testing the association between microbiome composition and clinical outcomes translates to testing the nullity of variance components. Motivated by a lung human immunodeficiency virus (HIV) microbiome project, we study longitudinal microbiome data by using variance component models with more than two variance components. Current testing strategies only apply to models with exactly two variance components and when sample sizes are large. Therefore, they are not applicable to longitudinal microbiome studies. In this paper, we propose exact tests (score test, likelihood ratio test, and restricted likelihood ratio test) to (a) test the association of the overall microbiome composition in a longitudinal design and (b) detect the association of one specific microbiome cluster while adjusting for the effects from related clusters. Our approach combines the exact tests for null hypothesis with a single variance component with a strategy of reducing multiple variance components to a single one. Simulation studies demonstrate that our method has a correct type I error rate and superior power compared to existing methods at small sample sizes and weak signals. Finally, we apply our method to a longitudinal pulmonary microbiome study of HIV-infected patients and reveal two interesting genera Prevotella and Veillonella associated with forced vital capacity. Our findings shed light on the impact of the lung microbiome on HIV complexities. The method is implemented in the open-source, high-performance computing language Julia and is freely available at

RevDate: 2019-01-09

Friedrich AW (2019)

Control of hospital acquired infections and antimicrobial resistance in Europe: the way to go.

Wiener medizinische Wochenschrift (1946) pii:10.1007/s10354-018-0676-5 [Epub ahead of print].

One of the major challenges for modern medicine is our ageing society and an increased level of immunocompromised hosts. More invasive and intensive medical interventions will increase the number of healthcare-associated infections (HCAI), which means infection that occur because of or in concomitance, but in any case, during or after healthcare interventions. Such infections are caused usually endogenously from microbial components of the patient's own microbiome. Usually, the microorganisms of the microbiome show a natural resistance against a few antibiotics. Due to selection processes and epidemic transmission of specific clones, microorganisms that have become resistant to multiple antibiotics become part of the patient's microbiome and can subsequently cause infections that are difficult or even impossible to treat. The kind of infections that will occur depends on diverse factors. Already today, according to Cassini et al., 2,609,911 new cases of HCAI occur every year in the European Union and European Economic Area (EU/EEA). The cumulative burden of the six HAIs was estimated at 501 disability-adjusted life years (DALYs) per 100,000 general population each year in the EU/EEA. In a recent publication, 426,277 healthcare-associated infections caused by antimicrobial resistant microorganisms were calculated to occur in the EU every year. Attributable deaths in the EU due to antimicrobial resistant microorganisms were estimated to be 33,110 per year. We know that we cannot prevent all HCAI. Because medical innovations will allow for an increased number of novel treatments that will comprise abiotic materials, microorganisms will adapt to this environment and enhance the risk for new HCAI. The challenge for the future will not be to try to prevent all infections, as some of them will remain unavoidable, but to prevent the occurrence of non-treatable microorganisms that would make unavoidable infections additionally untreatable. That means that we need to reflect on how we organize infection prevention, diagnostics and control. While patients with classical infectious diseases present with infectious diseases (ID)-specific symptoms, patients with HCAI present usually with another underlying disease. HCAI are therefore perceived as a secondary damage not following classical clinical and epidemiological rules. However, more recently we have to consider how we should react to HCAI and antimicrobial resistance (AMR) as they are quite different in epidemiology and transmission behavior than classical infectious diseases. Today, the prevalence of AMR is rising all over Europe. Although good success has been seen in many countries, methicillin-resistant Staphylococcus aureus (MRSA) remains an important challenge for many countries. In addition to MRSA, multidrug-resistant Escherichia coli and carbapenem-resistant Enterobacteriaceae are becoming a problem of public health importance. Furthermore, we need to focus more on implementation of known infection prevention measures than trying to solve the problem by observing and describing it. However, in addition to medical factors such as antibiotic use, hand hygiene etc., we tend to forget that there are factors behind these factors that have a major influence and are found in the structures of our different healthcare systems. We need to look more at the context before we try to implement prevention measures and need to learn from each other. A common goal to tackle carbapenem-resistant Enterobacteriaceae (CRE) by 2030 would be an important step to foster collaboration across Europe. As the current funding and remmuneration system does not sufficiently support prevention of HCAI and AMR, it is time for the development of a less production- but more prevention-economic financing system for clinical microbiology and infection control.

RevDate: 2019-01-09

Kim JY, Kim EM, Yi MH, et al (2019)

Chinese liver fluke Clonorchis sinensis infection changes the gut microbiome and increases probiotic Lactobacillus in mice.

Parasitology research pii:10.1007/s00436-018-6179-x [Epub ahead of print].

Chinese liver fluke Clonorchis sinensis changes the host's immune system. Recently, it has been reported that helminths including C. sinensis can ameliorate immune-related diseases such as allergy. In addition, recent studies showed that helminth infection can alleviate immune-mediated disorders by altering the gut microbiome. However, changes in the gut microbiome due to C. sinensis have not been reported yet. In this study, changes in the gut microbiome of C57BL/6 mice infected with C. sinensis metacercariae were evaluated over time. Stool was analyzed by 16S rRNA amplicon analysis using high-throughput sequencing technology. There was no apparent difference in species richness and diversity between the infected and control groups. However, the composition of the microbiome was different between the infected and control groups at 20 days and 30 days post-infection, and the difference disappeared at 50 days post-infection. In particular, this microbiome alteration was associated with a change in the relative abundance of genus Lactobacillus and the probiotic Lactobacillus species that are known to have an immune-modulation role in immune-mediated diseases.

RevDate: 2019-01-09

Borges LGDA, Giongo A, Pereira LM, et al (2018)

Comparison of the nasopharynx microbiome between influenza and non-influenza cases of severe acute respiratory infections: A pilot study.

Health science reports, 1(6):e47 pii:HSR247.

Aims: Influenza A virus (IAV) can cause severe acute respiratory infection (SARI), and disease outcome may be associated with changes in the microbiome of the nasopharynx. This is a pilot study to characterize the microbiome of the nasopharynx in patients hospitalized with SARI, infected and not infected by IAV.

Methods and Results: Using target sequencing of the 16S rRNA gene, we assessed the bacterial community of nasopharyngeal aspirate samples and compared the microbiome of patients infected with IAV with the microbiome of patients who were negative for IAV. We observed differences in the relative abundance of Proteobacteria and Firmicutes between SARI patients, with Streptococcus being enriched and Pseudomonas underrepresented in IAV patients compared with patients who were not infected with IAV.

Conclusion: Pseudomonas taxon seems to be in high frequency on the nasopharynx of SARI patients with non-IAV infection and might present a negative association with Streptococcus taxon. Microbial profile appears to be different between SARI patients infected or not infected with IAV.

RevDate: 2019-01-09

Lee SH, Joo NS, Kim KM, et al (2018)

The Therapeutic Effect of a Multistrain Probiotic on Diarrhea-Predominant Irritable Bowel Syndrome: A Pilot Study.

Gastroenterology research and practice, 2018:8791916.

Backgrounds: Recent studies suggest that diarrhea-predominant irritable bowel syndrome (IBS) is associated with intestinal bacterial microflora, colonic inflammation, and small intestinal bacterial overgrowth (SIBO). The purpose of this study was to evaluate the effect of a multistrain probiotic intake on these associated factors in patients with diarrhea-predominant IBS.

Methods: The recruited volunteers were adults who were diagnosed with diarrhea-predominant IBS according to the Rome III criteria. After 8 weeks of probiotic ingestion, changes in gastrointestinal symptoms, fecal microbiome, SIBO, and fecal calprotectin were determined.

Results: There was an increase in beneficial bacteria (41.2 ± 16.8% vs. 53.7 ± 15.3%, P = 0.018) and a decrease in harmful bacteria (13.0 ± 13.9% vs. 4.7 ± 4.0%, P = 0.010) in the microbial stool analysis. The SIBO prevalence also decreased at the end of treatment. However, the average levels of fecal calprotectin showed a decreasing tendency, without reaching statistical significance (364.4 ± 729.1 mg/kg vs. 200.9 ± 347.6 mg/kg, P = 0.375).

Conclusion: Treatment with a multistrain probiotic for 8 weeks led to significant increases in beneficial bacteria in the gut as well as the improvement of gastrointestinal symptoms. This study is registered at the Clinical Research Information Service (KCT0002906).

RevDate: 2019-01-09

Belizário JE, Faintuch J, M Garay-Malpartida (2018)

Gut Microbiome Dysbiosis and Immunometabolism: New Frontiers for Treatment of Metabolic Diseases.

Mediators of inflammation, 2018:2037838.

Maintenance of healthy human metabolism depends on a symbiotic consortium among bacteria, archaea, viruses, fungi, and host eukaryotic cells throughout the human gastrointestinal tract. Microbial communities provide the enzymatic machinery and the metabolic pathways that contribute to food digestion, xenobiotic metabolism, and production of a variety of bioactive molecules. These include vitamins, amino acids, short-chain fatty acids (SCFAs), and metabolites, which are essential for the interconnected pathways of glycolysis, the tricarboxylic acid/Krebs cycle, oxidative phosphorylation (OXPHOS), and amino acid and fatty acid metabolism. Recent studies have been elucidating how nutrients that fuel the metabolic processes impact on the ways immune cells, in particular, macrophages, respond to different stimuli under physiological and pathological conditions and become activated and acquire a specialized function. The two major inflammatory phenotypes of macrophages are controlled through differential consumption of glucose, glutamine, and oxygen. M1 phenotype is triggered by polarization signal from bacterial lipopolysaccharide (LPS) and Th1 proinflammatory cytokines such as interferon-γ, TNF-α, and IL-1β, or both, whereas M2 phenotype is triggered by Th2 cytokines such as interleukin-4 and interleukin-13 as well as anti-inflammatory cytokines, IL-10 and TGFβ, or glucocorticoids. Glucose utilization and production of chemical mediators including ATP, reactive oxygen species (ROS), nitric oxide (NO), and NADPH support effector activities of M1 macrophages. Dysbiosis is an imbalance of commensal and pathogenic bacteria and the production of microbial antigens and metabolites. It is now known that the gut microbiota-derived products induce low-grade inflammatory activation of tissue-resident macrophages and contribute to metabolic and degenerative diseases, including diabetes, obesity, metabolic syndrome, and cancer. Here, we update the potential interplay of host gut microbiome dysbiosis and metabolic diseases. We also summarize on advances on fecal therapy, probiotics, prebiotics, symbiotics, and nutrients and small molecule inhibitors of metabolic pathway enzymes as prophylactic and therapeutic agents for metabolic diseases.

RevDate: 2019-01-09

Nishida AH, H Ochman (2019)

A great-ape view of the gut microbiome.

Nature reviews. Genetics pii:10.1038/s41576-018-0085-z [Epub ahead of print].

Humans assemble a specialized microbiome from a world teeming with diverse microorganisms. Comparison to the microbiomes of great apes provides a dimension that is indispensable to understanding how these microbial communities form, function and change. This evolutionary perspective exposes not only how human gut microbiomes have been shaped by our great-ape heritage but also the features that make humans unique, as exemplified by an expansive loss of bacterial and archaeal diversity and the identification of microbial lineages that have co-diversified with their hosts.

RevDate: 2019-01-09

Bernard NJ (2019)

Dietary modulation of the microbiome as therapy.

Nature reviews. Rheumatology pii:10.1038/s41584-019-0165-2 [Epub ahead of print].

RevDate: 2019-01-09

Maseda D, Zackular JP, Trindade B, et al (2019)

Nonsteroidal Anti-inflammatory Drugs Alter the Microbiota and Exacerbate Clostridium difficile Colitis while Dysregulating the Inflammatory Response.

mBio, 10(1): pii:mBio.02282-18.

Clostridium difficile infection (CDI) is a major public health threat worldwide. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with enhanced susceptibility to and severity of CDI; however, the mechanisms driving this phenomenon have not been elucidated. NSAIDs alter prostaglandin (PG) metabolism by inhibiting cyclooxygenase (COX) enzymes. Here, we found that treatment with the NSAID indomethacin prior to infection altered the microbiota and dramatically increased mortality and the intestinal pathology associated with CDI in mice. We demonstrated that in C. difficile-infected animals, indomethacin treatment led to PG deregulation, an altered proinflammatory transcriptional and protein profile, and perturbed epithelial cell junctions. These effects were paralleled by increased recruitment of intestinal neutrophils and CD4+ cells and also by a perturbation of the gut microbiota. Together, these data implicate NSAIDs in the disruption of protective COX-mediated PG production during CDI, resulting in altered epithelial integrity and associated immune responses.IMPORTANCEClostridium difficile infection (CDI) is a spore-forming anaerobic bacterium and leading cause of antibiotic-associated colitis. Epidemiological data suggest that use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk for CDI in humans, a potentially important observation given the widespread use of NSAIDs. Prior studies in rodent models of CDI found that NSAID exposure following infection increases the severity of CDI, but mechanisms to explain this are lacking. Here we present new data from a mouse model of antibiotic-associated CDI suggesting that brief NSAID exposure prior to CDI increases the severity of the infectious colitis. These data shed new light on potential mechanisms linking NSAID use to worsened CDI, including drug-induced disturbances to the gut microbiome and colonic epithelial integrity. Studies were limited to a single NSAID (indomethacin), so future studies are needed to assess the generalizability of our findings and to establish a direct link to the human condition.

RevDate: 2019-01-09

Gerner SM, Rattei T, AB Graf (2018)

Assessment of urban microbiome assemblies with the help of targeted in silico gold standards.

Biology direct, 13(1):22 pii:10.1186/s13062-018-0225-6.

BACKGROUND: Microbial communities play a crucial role in our environment and may influence human health tremendously. Despite being the place where human interaction is most abundant we still know little about the urban microbiome. This is highlighted by the large amount of unclassified DNA reads found in urban metagenome samples. The only in silico approach that allows us to find unknown species, is the assembly and classification of draft genomes from a metagenomic dataset. In this study we (1) investigate the applicability of an assembly and binning approach for urban metagenome datasets, and (2) develop a new method for the generation of in silico gold standards to better understand the specific challenges of such datasets and provide a guide in the selection of available software.

RESULTS: We applied combinations of three assembly (Megahit, SPAdes and MetaSPAdes) and three binning tools (MaxBin, MetaBAT and CONCOCT) to whole genome shotgun datasets from the CAMDA 2017 Challenge. Complex in silico gold standards with a simulated bacterial fraction were generated for representative samples of each surface type and city. Using these gold standards, we found the combination of SPAdes and MetaBAT to be optimal for urban metagenome datasets by providing the best trade-off between the number of high-quality genome draft bins (MIMAG standards) retrieved, the least amount of misassemblies and contamination. The assembled draft genomes included known species like Propionibacterium acnes but also novel species according to respective ANI values.

CONCLUSIONS: In our work, we showed that, even for datasets with high diversity and low sequencing depth from urban environments, assembly and binning-based methods can provide high-quality genome drafts. Of vital importance to retrieve high-quality genome drafts is sequence depth but even more so a high proportion of the bacterial sequence fraction too achieve high coverage for bacterial genomes. In contrast to read-based methods relying on database knowledge, genome-centric methods as applied in this study can provide valuable information about unknown species and strains as well as functional contributions of single community members within a sample. Furthermore, we present a method for the generation of sample-specific highly complex in silico gold standards.

REVIEWERS: This article was reviewed by Craig Herbold, Serghei Mangul and Yana Bromberg.

RevDate: 2019-01-09

Osmanovic D, Kessler DA, Rabin Y, et al (2018)

Darwinian selection of host and bacteria supports emergence of Lamarckian-like adaptation of the system as a whole.

Biology direct, 13(1):24 pii:10.1186/s13062-018-0224-7.

BACKGROUND: The relatively fast selection of symbiotic bacteria within hosts and the potential transmission of these bacteria across generations of hosts raise the question of whether interactions between host and bacteria support emergent adaptive capabilities beyond those of germ-free hosts.

RESULTS: To investigate possibilities for emergent adaptations that may distinguish composite host-microbiome systems from germ-free hosts, we introduce a population genetics model of a host-microbiome system with vertical transmission of bacteria. The host and its bacteria are jointly exposed to a toxic agent, creating a toxic stress that can be alleviated by selection of resistant individuals and by secretion of a detoxification agent ("detox"). We show that toxic exposure in one generation of hosts leads to selection of resistant bacteria, which in turn, increases the toxic tolerance of the host's offspring. Prolonged exposure to toxin over many host generations promotes anadditional form of emergent adaptation due to selection of hosts based on detox produced by their bacterial community as a whole (as opposed to properties of individual bacteria).

CONCLUSIONS: These findings show that interactions between pure Darwinian selections of host and its bacteria can give rise to emergent adaptive capabilities, including Lamarckian-like adaptation of the host-microbiome system.

REVIEWERS: This article was reviewed by Eugene Koonin, Yuri Wolf and Philippe Huneman.

RevDate: 2019-01-09

Imhann F, Van der Velde KJ, Barbieri R, et al (2019)

The 1000IBD project: multi-omics data of 1000 inflammatory bowel disease patients; data release 1.

BMC gastroenterology, 19(1):5 pii:10.1186/s12876-018-0917-5.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic complex disease of the gastrointestinal tract. Patients with IBD can experience a wide range of symptoms, but the pathophysiological mechanisms that cause these individual differences in clinical presentation remain largely unknown. In consequence, IBD is currently classified into subtypes using clinical characteristics. If we are to develop a more targeted treatment approach, molecular subtypes of IBD need to be discovered that can be used as new drug targets. To achieve this, we need multiple layers of molecular data generated from the same IBD patients.

CONSTRUCTION AND CONTENT: We initiated the 1000IBD project ( to prospectively follow more than 1000 IBD patients from the Northern provinces of the Netherlands. For these patients, we have collected a uniquely large number of phenotypes and generated multi-omics profiles. To date, 1215 participants have been enrolled in the project and enrolment is on-going. Phenotype data collected for these participants includes information on dietary and environmental factors, drug responses and adverse drug events. Genome information has been generated using genotyping (ImmunoChip, Global Screening Array and HumanExomeChip) and sequencing (whole exome sequencing and targeted resequencing of IBD susceptibility loci), transcriptome information generated using RNA-sequencing of intestinal biopsies and microbiome information generated using both sequencing of the 16S rRNA gene and whole genome shotgun metagenomic sequencing.

UTILITY AND DISCUSSION: All molecular data generated within the 1000IBD project will be shared on the European Genome-Phenome Archive ( , accession no: EGAS00001002702). The first data release, detailed in this announcement and released simultaneously with this publication, will contain basic phenotypes for 1215 participants, genotypes of 314 participants and gut microbiome data from stool samples (315 participants) and biopsies (107 participants) generated by tag sequencing the 16S gene. Future releases will comprise many more additional phenotypes and -omics data layers. 1000IBD data can be used by other researchers as a replication cohort, a dataset to test new software tools, or a dataset for applying new statistical models.

CONCLUSIONS: We report on the establishment and future development of the 1000IBD project: the first comprehensive multi-omics dataset aimed at discovering IBD biomarker profiles and treatment targets.

RevDate: 2019-01-08

Vaziri ND, Suematsu Y, Shimomura A, et al (2017)

[Uremic toxins and gut micro biome].

Nihon Jinzo Gakkai shi, 59(4):535-544.

In the past, little attention had been paid to the intestine and its microbial flora as a potential source of systemic inflammation in chronic kidney disease(CKD). Systemic inflammation plays a central role in progression of CKD and its cardiovascular and various other complications. The gastrointestinal tract houses a large community of microbes that have a symbiotic relationship with the host. The normal microbial flora protects the host against pathogenic microorganisms. It also contributes to the energy metabolism, micronutrient homeostasis and nitrogen bal- ance. Recent studies have revealed significant changes in the composition and function of the microbial flora in CKD patients and animals. These changes are driven by altered intestinal bio- chemical environment caused by: I-heavy influx of urea and uric acid from body fluids into the gastrointestinal tract, II- restrictions of potassium-rich food including fruits and vegetables which as the main source of indigestible complex carbohydrates are the essential nutrients for the guts' symbiotic microbial com- munity, and III- various medications such as phosphate binders, antibiotics etc. Together the changes in intestinal milieu and the resultant microbial dysbiosis play a major role in systemic inflammation and uremic toxicity by several mechanisms : I-generation of several microbial derived uremic toxins such as indoxyl sulfate, p-cresol sulfate and trimethylamine-N-oxide etc. II-reduction of microbial derived micronutrients such a short chain fatty acids (SCFA) which are the main source of nutrients for colonocytes. This is caused by diminished substrates (indigestible complex carbohydrates) which leads to depletion of SCFA-making bacteria. In addition, III-Disruption of the intestinal epithelial barrier by ammonia and ammonium hydroxide generated from hydrolysis of urea by urease-possessing microbial species which are common complications of CKD, and bowel ischemia caused by excessive use of diuretics (in CKD patients) and aggressive ultrafiltration by hemodialysis (in ESRD patients) can impair gastrointestinal epithelial barrier. The resulting breakdown of the gut epithelial barrier (tight junction complex) leads to influx of endotoxin, microbial fragments, and other noxious luminal products in the sub-epithelial tissue and systemic circulation leading to local and systemic inflammation and oxidative stress which are the major cause of morbidity and mortality in CKD population. This review is intended to provide an overview of the effects of CKD on the gut microbiome and intestinal epithelial barrier structure and the potential interventions aimed at mitigating these abnormalities.

RevDate: 2019-01-08

Flowers SA, Baxter NT, Ward KM, et al (2019)

Effects of Atypical Antipsychotic Treatment and Resistant Starch Supplementation on Gut Microbiome Composition in a Cohort of Patients with Bipolar Disorder or Schizophrenia.

Pharmacotherapy [Epub ahead of print].

STUDY OBJECTIVE: Previous studies have identified shifts in gut microbiota associated with atypical antipsychotic (AAP) treatment, which may link AAPs to metabolic burden. Dietary prebiotics such as resistant starch may be beneficial in obesity and glucose regulation, but little is known mechanistically about its ability to modify gut microbiota in AAP-treated individuals. This investigation was undertaken to mechanistically delineate the effects of AAP treatment and resistant starch supplementation on gut microbiota in a psychiatric population.

DESIGN: Cross-sectional cohort study.

SETTING: The study was performed in an outpatient setting.

PATIENTS: Thirty-seven adults with a diagnosis of bipolar disorder or schizophrenia who were treated with an AAP (clozapine, olanzapine, risperidone, quetiapine, or ziprasidone [21 patients]) or lithium and/or lamotrigine (16 patients) for at least 6 months.

INTERVENTION: Patients in the AAP group received raw unmodified potato starch (resistant starch) daily for 14 days.

MEASUREMENTS AND MAIN RESULTS: Of the 37 patients, the mean ± SD age was 52.2 ± 12.5 years, and 57% were male. The primary outcome was gut microbiome DNA composition. Microbiome DNA obtained from stool samples from all patients was subject to 16S rRNA gene sequencing before and during resistant starch supplementation. Inter- and Intragroup microbial diversity measures were performed by permutational multivariate analysis of variance and Inverse Simpson Diversity Index, respectively. Differentially abundant organisms were detected by using linear discriminant analysis effect size. Although no significant difference in overall microbiota composition was detected at baseline between AAP users and nonusers, non-AAP users showed increased fractional representation of Alistipes. AAP-treated females exhibited decreased diversity compared with non-AAP-treated females. Although the microbiome of AAP-treated patients varied with resistant starch administration, an increased abundance of the Actinobacteria phylum was observed.

CONCLUSION: These data suggest that AAP treatment is associated with measurable differences in gut microbiota, particularly in female AAP-treated patients in whom reduced species richness was observed. Additionally, variable microbiome responses to resistant starch supplementation were seen, with a significant increase in starch degraders. This article is protected by copyright. All rights reserved.

RevDate: 2019-01-08

Huang SF, Yang YY, Chou KT, et al (2019)

Systemic proinflammation after Mycobacterium tuberculosis infection was correlated to the gut microbiome in HIV-uninfected humans.

European journal of clinical investigation [Epub ahead of print].

BACKGROUND: The dysbiosis of gut microbiome and interaction with host immunity after Mycobacterium tuberculosis (MTB) infection are under-investigation. We had found fatigue symptom concurrent with dysbiosis by decreasing the ratio of Firmicutes to Bacteroidetes (F/B ratio) in active tuberculosis (TB). The study aims to assess the inflammatory biomarkers and their interaction with gut microbiome in active TB and latent TB infection before starting anti-TB regimens.

MATERIALS AND METHOD: Interleukin-1 beta (IL-1B), IL-4, IL-6, IL-10, CD3+, CD4+, CD8+ T cells, and interferon-gamma (IFN-γ) releasing assay (IGRA) were measured in 25 active TB patients, 32 LTBI subjects, and 23 healthy controls (HC). Gut microbiome profiles were obtained using 16S rRNA MiSeq sequencing method.

RESULTS: The leukocytosis (7008±383 cell/cum, p<0.05), increase in IL-6 (229.7±104μg/dL, p<0.05), and decrease in IL-4 (0.27μg/dL±0.1, p<0.05) were presented in active TB. The proportion of polymorphic neutrophil (PMN) in peripheral blood was positively related to the relative abundance of Bacteroidetes in LTBI and active TB (R2 =0.23, p<0.05). The F/B ratio was positively related to the detectable IL-1B in TB (R2 =0.97, p<0.01) and to the IL-4 in LTBI (R2 =0.27, p<0.05). In LTBI, the relative abundances of Coriobacteriales was positively related to the secretion of IFN-gamma against TB antigens more likely associated with of CD4+ T cell (R2 =0.42, p<0.05).

CONCLUSION: In active TB, dysbiosis with higher relative abundances of Bacteroidetes in stool and low F/B ratio was related to systemic proinflammation. In LTBI, dose-response relationship between peripheral PMN and relative abundances of Bacteroidetes was remained but not lead to systemic inflammation. This article is protected by copyright. All rights reserved.

RevDate: 2019-01-08

Rossi GA, Morelli P, Galietta LJ, et al (2019)

Airway microenvironment alterations and pathogen growth in cystic fibrosis.

Pediatric pulmonology [Epub ahead of print].

Cystic Fibrosis Transmembrane Regulator (CFTR) dysfunction is associated with epithelial cell vulnerability and with dysregulation of the local inflammatory responses resulting in excessive airway neutrophilic inflammation and pathogen growth. In combination with impaired mucociliary clearance, and dysregulation of defense function, bacterial infection follows with eventual airway damage and remodeling. Because of these inherent vulnerabilities, viral infections are also more severe and prolonged and appear to render the airway even more prone to bacterial infection. Airway acidity, deficient nitric oxide production and increased iron concentrations, further enhance the airway milieu's susceptibility to infection. Novel diagnostic techniques of the airway microbiome elucidate the coexistence of an array of non-virulent taxa beyond the recognized virulent organisms, predominantly Pseudomonas aeruginosa. The complex interplay between these two bacterial populations, including upregulation of virulence genes and utilization of mucin as a nutrient source, modulates the action of pathogens, modifies the CF airway milieu and contributes to the processes leading to airway derangement. The review provides an update on recent advances of the complex mechanisms that render the CF airway vulnerable to inflammation, infection and ultimately structural damage, the key pathogenetic elements of CF. The recent contributions on CF pathogenesis will hopefully help in identifying new prophylactic measures and therapeutic targets for this highly destructive disorder.

RevDate: 2019-01-08

Sharpton SR, Yong GJM, Terrault NA, et al (2019)

Gut Microbial Metabolism and Nonalcoholic Fatty Liver Disease.

Hepatology communications, 3(1):29-43 pii:HEP41284.

The gut microbiome, the multispecies community of microbes that exists in the gastrointestinal tract, encodes several orders of magnitude more functional genes than the human genome. It also plays a pivotal role in human health, in part due to metabolism of environmental, dietary, and host-derived substrates, which produce bioactive metabolites. Perturbations to the composition and associated metabolic output of the gut microbiome have been associated with a number of chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD). Here, we review the rapidly evolving suite of next-generation techniques used for studying gut microbiome composition, functional gene content, and bioactive products and discuss relationships with the pathogenesis of NAFLD.

RevDate: 2019-01-08

Ried K, Travica N, A Sali (2018)

The Effect of Kyolic Aged Garlic Extract on Gut Microbiota, Inflammation, and Cardiovascular Markers in Hypertensives: The GarGIC Trial.

Frontiers in nutrition, 5:122.

Background: Previous research suggests Kyolic-aged-garlic-extract to be effective in reducing blood pressure in a large proportion of hypertensive patients similar to first-line standard antihypertensive medication. High blood pressure has been linked to gut dysbiosis, with a significant decrease in microbial richness and diversity in hypertensives compared to normotensives. Furthermore, gut dysbiosis has been associated with increased inflammatory status and risk of cardiovascular events. Objective: To assess the effect of Kyolic aged GARlic extract on Gut microbiota, Inflammation, and Cardiovascular markers, including blood pressure, pulse wave velocity and arterial stiffness. Methods: A total of 49 participants with uncontrolled hypertension completed a double-blind randomized placebo-controlled trial of 12-weeks, investigating the effect of daily intake of aged-garlic-extract (1.2 g containing 1.2 mg S-allylcysteine) or placebo on blood pressure, pulse wave velocity and arterial stiffness, inflammatory markers, and gut microbiota. Results: Mean blood pressure was significantly reduced by 10 ± 3.6 mmHg systolic and 5.4 ± 2.3 mmHg diastolic compared to placebo. Vitamin B12 status played a role in responsiveness to garlic on blood pressure in 17% of patients. Garlic significantly lowered central blood pressure, pulse pressure and arterial stiffness (p < 0.05). Trends observed in inflammatory markers TNF-α and IL-6 need to be confirmed in larger trials. Furthermore, aged-garlic-extract improved gut microbiota, evident by higher microbial richness and diversity with a marked increase in Lactobacillus and Clostridia species after 3 months of supplementation. Conclusions: Kyolic-aged-garlic-extract is effective in reducing blood pressure in patients with uncontrolled hypertension, and has the potential to improve arterial stiffness, inflammation, and gut microbial profile. Aged-garlic-extract is highly tolerable with a high safety profile as a stand-alone or adjunctive antihypertensive treatment, with multiple benefits for cardiovascular health. Trial Registration: Australian New Zealand Clinical Trial Registry ACTRN12616000185460 (

RevDate: 2019-01-08

Guerreiro CS, Calado Â, Sousa J, et al (2018)

Diet, Microbiota, and Gut Permeability-The Unknown Triad in Rheumatoid Arthritis.

Frontiers in medicine, 5:349.

Growing experimental and clinical evidence suggests that a chronic inflammatory response induced by gut dysbiosis can critically contribute to the development of rheumatic diseases, including rheumatoid arthritis (RA). Of interest, an adherence to a Mediterranean diet has been linked to a reduction in mortality and morbidity in patients with inflammatory diseases. Diet and intestinal microbiota are modifying factors that may influence intestinal barrier strength, functional integrity, and permeability regulation. Intestinal microbiota may play a crucial role in RA pathogenesis, but up to now no solid data has clarified a mechanistic relationship between gut microbiota and the development of RA. Nonetheless, microbiota composition in subjects with RA differs from that of controls and this altered microbiome can be partially restored after prescribing disease modifying antirheumatic drugs. High levels of Prevotella copri and similar species are correlated with low levels of microbiota previously associated with immune regulating properties. In addition, some nutrients can alter intestinal permeability and thereby influence the immune response without a known impact on the microbiota. However, critical questions remain to be elucidated, such as the way microbiome fluctuates in relation to diet, and how disease activity may be influenced by changes in diet, microbiota or diet-intestinal microbiota equilibrium.

RevDate: 2019-01-08

Torsten M, L Aaron (2018)

Microbial Transglutaminase Is Immunogenic and Potentially Pathogenic in Pediatric Celiac Disease.

Frontiers in pediatrics, 6:389.

The enzyme microbial transglutaminase is heavily used in the food processing industries to ameliorate food qualities and elongate the products' shelf life. As a protein's glue, it cross-links gliadin peptides, creating neo-complexes that are immunogenic and potentially pathogenic to celiac disease communities. Even lacking sequence identity, it imitates functionally the endogenous tissue transglutaminase, known to be the autoantigen of celiac disease and representing an undisputable key player in celiac disease initiation and progress. The present review expend on the enzyme characteristics, exogenous intestinal sources, its cross-linking avidity to gluten or gliadin, turning naïve protein to immunogenic ones. Several observation on microbial transglutaminase cross linked complexes immunogenicity in celiac patients are reviewed and its pathogenicity is summarized. Warnings on its potential risks for the gluten dependent conditions are highlighted. When substantiated, it might represent a new environmental factor of celiac disease genesis. It is hoped that the presented knowledge will encourage further research to explore the mechanism and the pathogenic pathways taken by the gliadin cross linked enzyme in driving celiac disease.

RevDate: 2019-01-08

Hu YL, Pang W, Huang Y, et al (2018)

The Gastric Microbiome Is Perturbed in Advanced Gastric Adenocarcinoma Identified Through Shotgun Metagenomics.

Frontiers in cellular and infection microbiology, 8:433.

Objective: Dysbiosis of gastric microbiota such as Helicobacter pylori plays a significant role in pathogenesis and progression of gastric cancer. Our aim was to evaluate the composition and functional effects of gastric microbiota in superficial gastritis (SG) and advanced gastric adenocarcinoma (GC). Methods: We carried out shotgun metagenomic sequencing on gastric wash samples from 6 patients with GC and 5 patients with SG. The taxonomic composition was profiled using MetaPhlAn2 and functional gene pathway was profiled using HUMAnN2. Differences in microbial composition and pathways between the two patient groups were assessed via LEfSe. Results: The gastric microbiota in GC patients was characterized by reduced species richness, enrichment of 13 bacterial taxa and depletion of 31 taxa (q < 0.05). The most representative taxa which were abundant in GC corresponded to the commensals or opportunistic pathogens that usually colonize the oral cavity, including genera Neisseria, Alloprevotella, and Aggregatibacter, species Streptococcus_mitis_oralis_pneumoniae and strain Porphyromonas_endodontalis.t_GCF_000174815. Each of the three GC-associated genera could separate GC from SG completely. In particular, Sphingobium yanoikuyae, a bacterium capable of degrading carcinogenic compounds, was depleted in GC. Functionally, pathways associated with the biosynthesis of lipopolysaccharide (LPS) and L-arginine were enriched in GC, whereas pathways involved in the fermentation of short chain fatty acids (SCFAs) and branched amino acid metabolism were more abundant in SG. Conclusions: Our results present new alterations in the gastric microbiome in patients with GC from a whole-genome perspective, suggesting that microbiome composition and function can be used for prognosis and diagnosis of GC.

RevDate: 2019-01-08

Drall KM, Tun HM, AL Kozyrskyj (2018)

Commentary: The Influence of Proton Pump Inhibitors on the Fecal Microbiome of Infants with Gastroesophageal Reflux-A Prospective Longitudinal Interventional Study.

Frontiers in cellular and infection microbiology, 8:430.

RevDate: 2019-01-08

Zhu C, Yuan C, Ao S, et al (2018)

The Predictive Potentiality of Salivary Microbiome for the Recurrence of Early Childhood Caries.

Frontiers in cellular and infection microbiology, 8:423.

The aim of this study was to investigate the variation of the salivary microbiota in the recurrence of early childhood caries (ECC), and to explore and verify the potential microbial indicators of ECC recurrence. Saliva samples from kindergarten children were tracked every 6 months for 1 year. Finally, in total 28 children and 84 samples were placed on the analysis phase: 7 children with ECC recurrence made up the ECC-recurrence (ER) group, 6 children without ECC recurrence constituted the non-ECC-recurrence (NER) group, and 15 children who kept ECC-free were set as the ECC-free (EF) group. DNA amplicons of the V3-V4 hypervariable region of the bacterial 16S rDNA were generated and sequencing was performed using Illumina MiSeq PE250 platform. No statistically significant differences of the Shannon indices were found in both cross-sectional and longitudinal comparisons. Furthermore, both principal coordinates analysis (PCoA) and heatmap plots demonstrated that the salivary microbial community structure might have potentiality to predict ECC recurrence at an early phase. The relative abundance of Fusobacterium, Prevotella, Leptotrichia, and Capnocytophaga differed significantly between the ER and NER groups at baseline. The values of area under the curve (AUC) of the four genera and their combined synthesis in the prediction for ECC recurrence were 0.857, 0.833, 0.786, 0.833, and 0.952, respectively. The relative abundance of Fusobacterium, Prevotella, Leptotrichia, and Capnocytophaga and their combination showed satisfactory accuracy in the prediction for ECC recurrence, indicating that salivary microbiome had predictive potentiality for recurrence of this disease. These findings might facilitate more effective strategy to be taken in the management of the recurrence of ECC.

RevDate: 2019-01-08

Yu P, F Hochholdinger (2018)

The Role of Host Genetic Signatures on Root-Microbe Interactions in the Rhizosphere and Endosphere.

Frontiers in plant science, 9:1896.

Microbiomes inhabiting plants are crucial for plant productivity and well-being. A plethora of interactions between roots, microbiomes, and soil shapes the self-organization of the microbial community associated with the root system. The rhizosphere (i.e., the soil close to the root surface) and endosphere (i.e., all inner root tissues) are critical interfaces for the exchange of resources between roots and the soil environment. In recent years, next-generation sequencing technologies have enabled systemic studies of root-associated microbiomes in the endosphere and interactions between roots and microbes at the root-soil interfaces. Genetic factors such as species and genotype of host plants are the driving force of microbial community differentiation and composition. In this mini-review, we will survey the role of these factors on plant-microbe interactions by highlighting the results of next-generation genomic and transcriptomic studies in the rhizosphere and endosphere of land plants. Moreover, environmental factors such as geography and soil type shape the microbiome. Relationships between the root-associated microbiome, architectural variations and functional switches within the root system determine the health and fitness of the whole plant system. A detailed understanding of plant-microbe interactions is of fundamental agricultural importance and significance for crop improvement by plant breeding.

RevDate: 2019-01-08

Vossen ARJV, van der Zee HH, EP Prens (2018)

Hidradenitis Suppurativa: A Systematic Review Integrating Inflammatory Pathways Into a Cohesive Pathogenic Model.

Frontiers in immunology, 9:2965.

Background: The pathogenesis of hidradenitis suppurativa (HS) is not fully understood. This systematic review examined the latest evidence for molecular inflammatory pathways involved in HS as a chronic inflammatory skin disease. Methods: A systematic literature search was performed in PubMed/Medline and EMBASE from January 2013 through September 2017, according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Findings on HS pathogenesis were also compared with those of other immune-mediated inflammatory diseases (IMIDs) in a non-systematic review. In addition, current therapeutic options for HS are briefly discussed on the basis of the findings for the inflammatory pathways involved in HS. Results: A total of 32 eligible publications were identified by the systematic search; these were supplemented with three additional publications. The extracted data indicated that four key themes underlie the pathogenesis of HS and related syndromic conditions. First, nicastrin (NCSTN) and PSTPIP1 mutations are directly associated with auto-inflammatory disease. Secondly, the up-regulation of several cytokines including tumor necrosis factor-α and T helper-17/interleukin-23 are connected to auto-inflammatory mechanisms in the pathogenesis of HS. Thirdly, the microbiome of lesional skin differs significantly vs. normal-appearing skin. Fourthly, HS risk is enhanced through physiological and environmental factors such as smoking, obesity, and mechanical friction. There is significant overlap between the pathogenesis of HS, its syndromic forms and other IMIDs, particularly with respect to aberrations in the innate immune response. Conclusions: The evidence presented in this review supports HS as an auto-inflammatory skin disorder associated with alterations in the innate immune system. Based on these most recent data, an integrative viewpoint is presented on the pathogenesis of HS. Current management strategies on HS consist of anti-inflammatory therapies, surgical removal of chronic lesions, and lifestyle changes such as smoking cessation and weight loss. As large gaps remain in the understanding of the pathogenesis of HS, further research is warranted to ultimately improve the management and treatment of patients with HS and related syndromic conditions.

RevDate: 2019-01-08

Satitsuksanoa P, Jansen K, Głobińska A, et al (2018)

Regulatory Immune Mechanisms in Tolerance to Food Allergy.

Frontiers in immunology, 9:2939.

Oral tolerance can develop after frequent exposure to food allergens. Upon ingestion, food is digested into small protein fragments in the gastrointestinal tract. Small food particles are later absorbed into the human body. Interestingly, some of these ingested food proteins can cause allergic immune responses, which can lead to food allergy. So far it has not been completely elucidated how these proteins become immunogenic and cause food allergies. In contrast, oral tolerance helps to prevent the pathologic reactions against different types of food antigens from animal or plant origin. Tolerance to food is mainly acquired by dendritic cells, epithelial cells in the gut, and the gut microbiome. A subset of CD103+ DCs is capable of inducing T regulatory cells (Treg cells) that express anti-inflammatory cytokines. Anergic T cells also contribute to oral tolerance, by reducing the number of effector cells. Similar to Treg cells, B regulatory cells (Breg cells) suppress effector T cells and contribute to the immune tolerance to food allergens. Furthermore, the human microbiome is an essential mediator in the induction of oral tolerance or food allergy. In this review, we outline the current understanding of regulatory immune mechanisms in oral tolerance. The biological changes reflecting early consequences of immune stimulation with food allergens should provide useful information for the development of novel therapeutic treatments.

RevDate: 2019-01-08

Thofte O, Su YC, Brant M, et al (2018)

EF-Tu From Non-typeable Haemophilus influenzae Is an Immunogenic Surface-Exposed Protein Targeted by Bactericidal Antibodies.

Frontiers in immunology, 9:2910.

Non-typeable Haemophilus influenzae (NTHi), a commensal organism in pre-school children, is an opportunistic pathogen causing respiratory tract infections including acute otitis media. Adults suffering from chronic obstructive pulmonary disease (COPD) are persistently colonized by NTHi. Previous research has suggested that, in some bacterial species, the intracellular elongation factor thermo-unstable (EF-Tu) can moonlight as a surface protein upon host encounter. The aim of this study was to determine whether EF-Tu localizes to the surface of H. influenzae, and if such surface-associated EF-Tu is a target for bactericidal antibodies. Using flow cytometry, transmission immunoelectron microscopy, and epitope mapping, we demonstrated that EF-Tu is exposed at the surface of NTHi, and identified immunodominant epitopes of this protein. Rabbits immunized with whole-cell NTHi produced significantly more immunoglobulin G (IgG) directed against EF-Tu than against the NTHi outer membrane proteins D and F as revealed by enzyme-linked immunosorbent assays. Chemical cleavage of NTHi EF-Tu by cyanogen bromide (CNBr) followed by immunoblotting showed that the immunodominant epitopes were located within the central and C-terminal regions of the protein. Peptide epitope mapping by dot blot analysis further revealed four different immunodominant peptide sequences; EF-Tu41-65, EF-Tu161-185, EF-Tu221-245, and EF-Tu281-305. These epitopes were confirmed to be surface-exposed and accessible by peptide-specific antibodies in flow cytometry. We also analyzed whether antibodies raised against NTHi EF-Tu cross-react with other respiratory tract pathogens. Anti-EF-Tu IgG significantly detected EF-Tu on unencapsulated bacteria, including the Gram-negative H. parainfluenzae, H. haemolyticus, Moraxella catarrhalis and various Gram-positive Streptococci of the oral microbiome. In contrast, considerably less EF-Tu was observed at the surface of encapsulated bacteria including H. influenzae serotype b (Hib) and Streptococcus pneumoniae (e.g., serotype 3 and 4). Removal of the capsule, as exemplified by Hib RM804, resulted in increased EF-Tu surface density. Finally, anti-NTHi EF-Tu IgG promoted complement-dependent bacterial killing of NTHi and other unencapsulated Gram-negative bacteria as well as opsonophagocytosis of Gram-positive bacteria. In conclusion, our data demonstrate that NTHi EF-Tu is surface-exposed and recognized by antibodies mediating host innate immunity against NTHi in addition to other unencapsulated respiratory tract bacteria.

RevDate: 2019-01-08

Dahl Å (2018)

Pollen Lipids Can Play a Role in Allergic Airway Inflammation.

Frontiers in immunology, 9:2816.

In seed plants, pollen grains carry the male gametes to female structures. They are frequent in the ambient air, and cause airway inflammation in one out of four persons in the population. This was traditionally attributed to soluble glycoproteins, leaking into the nasal mucosa or the conjunctiva, and able to bind antibodies. It is now more and more recognized that also other immunomodulating compounds are present. Lipids bind to Toll-like and PPARγ receptors belonging to antigen-presenting cells in the mammal immune system, activate invariant Natural Killer T-cells, and are able to induce a Type 2 reaction in effector cells. They may also mimic lipid mediators from mammal mast cells. Pollen grains have a rich lipodome of their own. Among the lipids that have been associated with an atopic reaction are saturated and unsaturated fatty acids, glycophospholipids, sphingolipids, sterols, and oxylipids, as well as lipopolysaccharides from the microbiome on the pollen surface. Lipids can be ligands to allergenic proteins.

RevDate: 2019-01-08

Han M, Yang P, Zhong C, et al (2018)

The Human Gut Virome in Hypertension.

Frontiers in microbiology, 9:3150.

Objectives: Previous studies have reported that the gut microbiome has an important link with the development of hypertension. Though previous researches have focused on the links of gut bacteria with hypertension, little has been known about the linkage of gut viruses to hypertension and the development of hypertension, largely due to the lack of data mining tools for such investigation. In this work, we have analyzed 196 fecal metagenomic data related to hypertension aiming to profile the gut virome and link the gut virome to pre-hypertension and hypertension. Design: Here, we have applied a statistically sound method for mining of gut virome data and linking gut virome to hypertension. We characterized the viral composition and bacterial composition of 196 samples, identified the viral-type of each sample and linked gut virome to hypertension. Results: We stratified these 196 fecal samples into two viral-types and selected 32 viruses as the biomarkers for these groups. We found that viruses could have a superior resolution and discrimination power than bacteria for differentiation of healthy samples and pre-hypertension samples, as well as hypertension samples. Moreover, as to the co-occurrence networks linking viruses and bacteria, we found increasingly pervasive virus-bacteria linkages from healthy people to pre-hypertension people to hypertension patients. Conclusion: Overall, our results have shown ample indications of the link between human gut virome and hypertension, and could help provide microbial solutions toward early diagnoses of hypertension.

RevDate: 2019-01-08

Coretti L, Paparo L, Riccio MP, et al (2018)

Gut Microbiota Features in Young Children With Autism Spectrum Disorders.

Frontiers in microbiology, 9:3146.

Proliferation and/or depletion of clusters of specific bacteria regulate intestinal functions and may interfere with neuro-immune communication and behavior in patients with autism spectrum disorder (ASD). Consistently, qualitative and quantitative alteration of bacterial metabolites may functionally affect ASD pathophysiology. Up to date, age-restricted cohort studies, that may potentially help to identify specific microbial signatures in ASD, are lacking. We investigated the gut microbiota (GM) structure and fecal short chain fatty acids (SCFAs) levels in a cohort of young children (2-4 years of age) with ASD, with respect to age-matched neurotypical healthy controls. Strong increase of Bacteroidetes and Proteobacteria and decrease of Actinobacteria was observed in these patients. Among the 91 OTUs whose relative abundance was altered in ASD patients, we observed a striking depletion of Bifidobacterium longum, one of the dominant bacteria in infant GM and, conversely, an increase of Faecalibacterium prausnitzii, a late colonizer of healthy human gut and a major butyrate producer. High levels of F. prausnitzii were associated to increase of fecal butyrate levels within normal range, and over representation of KEGG functions related to butyrate production in ASD patients. Here we report unbalance of GM structure with a shift in colonization by gut beneficial bacterial species in ASD patients as off early childhood.

RevDate: 2019-01-08

Guo M, Chen J, Li Q, et al (2018)

Dynamics of Gut Microbiome in Giant Panda Cubs Reveal Transitional Microbes and Pathways in Early Life.

Frontiers in microbiology, 9:3138.

Adult giant pandas (Ailuropoda melanoleuca) express transitional characteristics in that they consume bamboos, despite their carnivore-like digestive tracts. Their genome contains no cellulolytic enzymes; therefore, understanding the development of the giant panda gut microbiome, especially in early life, is important for decoding the rules underlying gut microbial formation, inheritance and dietary transitions. With deep metagenomic sequencing, we investigated the gut microbiomes of two newborn giant panda brothers and their parents living in Macao, China, from 2016 to 2017. Both giant panda cubs exhibited progressive increases in gut microbial richness during growth, particularly from the 6th month after birth. Enterobacteriaceae dominated the gut microbial compositions in both adult giant pandas and cubs. A total of 583 co-abundance genes (CAGs) and about 79 metagenomic species (MGS) from bacteria or viruses displayed significant changes with age. Seven genera (Shewanella, Oblitimonas, Helicobacter, Haemophilus, Aeromonas, Listeria, and Fusobacterium) showed great importance with respect to gut microbial structural determination in the nursing stage of giant panda cubs. Furthermore, 10 orthologous gene functions and 44 pathways showed significant changes with age. Of the significant pathways, 16 from Escherichia, Klebsiella, Propionibacterium, Lactobacillus, and Lactococcus displayed marked differences between parents and their cubs at birth, while 29 pathways from Escherichia, Campylobacter and Lactobacillus exhibited significant increase in cubs from 6 to 9 months of age. In addition, oxidoreductases, transferases, and hydrolases dominated the significantly changed gut microbial enzymes during the growth of giant panda cubs, while few of them were involved in cellulose degradation. The findings indicated diet-stimulated gut microbiome transitions and the important role of Enterobacteriaceae in the guts of giant panda in early life.

RevDate: 2019-01-08

Yan Q, Li X, Ma B, et al (2018)

Different Concentrations of Doxycycline in Swine Manure Affect the Microbiome and Degradation of Doxycycline Residue in Soil.

Frontiers in microbiology, 9:3129.

Antibiotic residues that enter the soil through swine manure could disturb the number, community structure and functions of microbiota which could also degrade antibiotics in soil. Five different concentrations of doxycycline (DOX) incorporated into swine manure were added to soil to explore the effects of DOX on microbiota in soil and degradation itself. The results showed that the soil microbiome evolved an adaptation to the soil containing DOX by generating resistance genes. Moreover, some of the organisms within the soil microbiome played crucial roles in the degradation of DOX. The average degradation half-life of DOX in non-sterile groups was 13.85 ± 0.45 days, which was significantly shorter than the 29.26 ± 0.98 days in the group with sterilized soil (P < 0.01), indicating that the soil microbiome promoted DOX degradation. DOX addition affected the number of tetracycline resistance genes, depending on the type of gene and the DOX concentration. Among these genes, tetA, tetM, tetW, and tetX had significantly higher copy numbers when the concentration of DOX was higher. In contrast, a lower concentration of DOX had an inhibitory effect on tetG. At the same time, the microbial compositions were affected by the initial concentration of DOX and the different experimental periods. The soil chemical indicators also affected the microbial diversity changes, mainly because some microorganisms could survive in adversity and become dominant bacterial groups, such as the genera Vagococcus and Enterococcus (which were associated with electrical conductivity) and Caldicoprobacter spp. (which were positively correlated with pH). Our study mainly revealed soil microbiota and DOX degradation answered differently under variable concentrations of DOX mixed with swine manure in soil.

RevDate: 2019-01-08

Xiao J, Chen L, Yu Y, et al (2018)

A Phylogeny-Regularized Sparse Regression Model for Predictive Modeling of Microbial Community Data.

Frontiers in microbiology, 9:3112.

Fueled by technological advancement, there has been a surge of human microbiome studies surveying the microbial communities associated with the human body and their links with health and disease. As a complement to the human genome, the human microbiome holds great potential for precision medicine. Efficient predictive models based on microbiome data could be potentially used in various clinical applications such as disease diagnosis, patient stratification and drug response prediction. One important characteristic of the microbial community data is the phylogenetic tree that relates all the microbial taxa based on their evolutionary history. The phylogenetic tree is an informative prior for more efficient prediction since the microbial community changes are usually not randomly distributed on the tree but tend to occur in clades at varying phylogenetic depths (clustered signal). Although community-wide changes are possible for some conditions, it is also likely that the community changes are only associated with a small subset of "marker" taxa (sparse signal). Unfortunately, predictive models of microbial community data taking into account both the sparsity and the tree structure remain under-developed. In this paper, we propose a predictive framework to exploit sparse and clustered microbiome signals using a phylogeny-regularized sparse regression model. Our approach is motivated by evolutionary theory, where a natural correlation structure among microbial taxa exists according to the phylogenetic relationship. A novel phylogeny-based smoothness penalty is proposed to smooth the coefficients of the microbial taxa with respect to the phylogenetic tree. Using simulated and real datasets, we show that our method achieves better prediction performance than competing sparse regression methods for sparse and clustered microbiome signals.

RevDate: 2019-01-08

Regier Y, Komma K, Weigel M, et al (2018)

Microbiome Analysis Reveals the Presence of Bartonella spp. and Acinetobacter spp. in Deer Keds (Lipoptena cervi).

Frontiers in microbiology, 9:3100.

The deer ked (Lipoptena cervi) is distributed in Europe, North America, and Siberia and mainly infests cervids as roe deer, fallow deer, and moose. From a one health perspective, deer keds occasionally bite other animals or humans and are a potential vector for Bartonella schoenbuchensis. This bacterium belongs to a lineage of ruminant-associated Bartonella spp. and is suspected to cause dermatitis and febrile diseases in humans. In this study, we analyzed the microbiome from 130 deer keds collected from roe deer, fallow deer and humans in the federal states of Hesse, Baden-Wuerttemberg, and Brandenburg, Germany. Endosymbiontic Arsenophonus spp. and Bartonella spp. represented the biggest portion (~90%) of the microbiome. Most Bartonella spp. (n = 93) were confirmed to represent B. schoenbuchensis. In deer keds collected from humans, no Bartonella spp. were detected. Furthermore, Acinetobacter spp. were present in four samples, one of those was confirmed to represent A. baumannii. These data suggest that deer keds harbor only a very narrow spectrum of bacteria which are potentially pathogenic for animals of humans.

RevDate: 2019-01-08

Zhang H, Hua R, Zhang B, et al (2018)

Serine Alleviates Dextran Sulfate Sodium-Induced Colitis and Regulates the Gut Microbiota in Mice.

Frontiers in microbiology, 9:3062.

Serine alleviates inflammatory responses and is beneficial for gut health; however, whether it exerts any effects on ulcerative colitis or regulates intestinal microbiota remains unknown. We investigated the effects of serine supplementation on colonic morphology, inflammation, and microbiota composition in dextran sulfate sodium (DSS)-induced colitis model in mice. Acute colitis was induced through the oral intake of 3.5% DSS in water for 7 days. Mice with acute colitis were divided into two groups; The DSS and Ser-treated groups were rectally administrated with PBS or 1% (w/v) serine (40 mg/kg body weight) for 7 days. The results showed that serine decreased the disease activity index, as well as myeloperoxidase, eosinophil peroxidase, and proinflammatory cytokine concentrations in colonic tissue, while serine improved colonic morphology and inhibited cell apoptosis in colitis mice. In addition, 16S rRNA phylogenetic sequencing revealed a shift in bacterial community composition, and changes in microbiota functional profiles following serine supplementation, although no significant difference in α-diversity analysis was observed. The effects of serine supplementation helped on the recovery of major perturbations to macrobiotic functions, such as amino acids metabolism; tissue replication and repair; and cell growth and death. Serine might have great potential for the renewal of colonic tissue in DSS-induced colitis.

RevDate: 2019-01-08

Mavrodi OV, Jung CM, Eberly JO, et al (2018)

Rhizosphere Microbial Communities of Spartina alterniflora and Juncus roemerianus From Restored and Natural Tidal Marshes on Deer Island, Mississippi.

Frontiers in microbiology, 9:3049.

The U. S. Gulf of Mexico is experiencing a dramatic increase in tidal marsh restoration actions, which involves planting coastal areas with smooth cordgrass (Spartina alterniflora) and black needlerush (Juncus roemerianus) for erosion control and to provide habitat for fish and wildlife. It can take decades for sedimentary cycles in restored marshes to approach reference conditions, and the contribution of the sediment microbial communities to these processes is poorly elucidated. In this study, we addressed this gap by comparing rhizosphere microbiomes of S. alterniflora and J. roemerianus from two restored marshes and a natural reference marsh located at Deer Island, MS. Our results revealed that plants from the restored and reference areas supported similar microbial diversity indicating the rapid colonization of planted grasses with indigenous soil microbiota. Although close in composition, the microbial communities from the three studied sites differed significantly in the relative abundance of specific taxa. The observed differences are likely driven by the host plant identity and properties of sediment material used for the creation of restored marshes. Some of the differentially distributed groups of bacteria include taxa involved in the cycling of carbon, nitrogen, and sulfur, and may influence the succession of vegetation at the restored sites to climax condition. We also demonstrated that plants from the restored and reference sites vary in the frequency of culturable rhizobacteria that exhibit traits commonly associated with the promotion of plant growth and suppression of phytopathogenic fungi. Our findings will contribute to the establishment of benchmarks for the assessment of the outcome of coastal restoration projects in the Gulf of Mexico and better define factors that affect the long-term resiliency of tidal marshes and their vulnerability to climate change.

RevDate: 2019-01-08

Porcar M, Louie KB, Kosina SM, et al (2018)

Microbial Ecology on Solar Panels in Berkeley, CA, United States.

Frontiers in microbiology, 9:3043.

Solar panels can be found practically all over the world and represent a standard surface that can be colonized by microbial communities that are resistant to harsh environmental conditions, including high irradiation, temperature fluctuations and desiccation. These properties make them not only ideal sources of stress-resistant bacteria, but also standard devices to study the microbial communities and their colonization process from different areas of Earth. We report here a comprehensive description of the microbial communities associated with solar panels in Berkeley, CA, United States. Cultivable bacteria were isolated to characterize their adhesive capabilities, and UV- and desiccation-resistance properties. Furthermore, a parallel culture-independent metagenomic and metabolomic approach has allowed us to gain insight on the taxonomic and functional nature of these communities. Metagenomic analysis was performed using the Illumina HiSeq2500 sequencing platform, revealing that the bacterial population of the Berkeley solar panels is composed mainly of Actinobacteria, Bacteroidetes and Proteobacteria, as well as lower amounts of Deinococcus-Thermus and Firmicutes. Furthermore, a clear predominance of Hymenobacter sp. was also observed. A functional analysis revealed that pathways involved in the persistence of microbes on solar panels (i.e., stress response, capsule development, and metabolite repair) and genes assigned to carotenoid biosynthesis were common to all metagenomes. On the other hand, genes involved in photosynthetic pathways and general autotrophic subsystems were rare, suggesting that these pathways are not critical for persistence on solar panels. Metabolomics was performed using a liquid chromatography tandem mass spectrometry (LC-MS/MS) approach. When comparing the metabolome of the solar panels from Berkeley and from Valencia (Spain), a very similar composition in polar metabolites could be observed, although some metabolites appeared to be differentially represented (for example, trigonelline, pantolactone and 5-valerolactone were more abundant in the samples from Valencia than in the ones from Berkeley). Furthermore, triglyceride metabolites were highly abundant in all the solar panel samples, and both locations displayed similar profiles. The comparison of the taxonomic profile of the Californian solar panels with those previously described in Spain revealed striking similarities, highlighting the central role of both selective pressures and the ubiquity of microbial populations in the colonization and establishment of microbial communities.

RevDate: 2019-01-08

López-García A, Pineda-Quiroga C, Atxaerandio R, et al (2018)

Comparison of Mothur and QIIME for the Analysis of Rumen Microbiota Composition Based on 16S rRNA Amplicon Sequences.

Frontiers in microbiology, 9:3010.

Background: Microbiome studies need to analyze massive sequencing data, which requires the use of sophisticated bioinformatics pipelines. Up to date, several tools are available, although the literature is scarce on studies that compare the performance of different bioinformatics pipelines on rumen microbiota when 16S rRNA amplicons are analyzed. The impact of the pipeline on the outcome of the results is also unknown, mainly in terms of the output from studies using these tools as an intermediate phenotype (pseudophenotypes). This study compares two commonly used software (Quantitative Insights Into Microbial Ecology) (QIIME) and mothur, and two microbial gene data bases (GreenGenes and SILVA) for 16S rRNA gene analysis, using metagenome read data collected from rumen content of a cohort of dairy cows. Results: We compared the relative abundance (RA) of the identified OTUs at the genus level. Both tools presented a high degree of agreement at identifying the most abundant genera: Bifidobacterium, Butyrivibrio, Methanobrevibacter, Prevotella, and Succiniclasticum (RA > 1%), regardless the database. There were no statistical differences between mothur and QIIME (P > 0.05) at estimating the overall RA of the most abundant (RA > 10%) genera, either using SILVA or GreenGenes. However, differences were found at RA < 10% (P < 0.05) when using GreenGenes as database, with mothur assigning OTUs to a larger number of genera and in larger RA for these less frequent microorganisms. With this database mothur resulted in larger richness (P < 0.05), more favorable rarefaction curves and a larger analytic sensitivity. These differences caused significant and relevant differences between tools at identifying the dissimilarity of microbiotas between pairs of animals. However, these differences were attenuated, but not erased, when SILVA was used as the reference database. Conclusion: The findings showed that the SILVA database seemed a preferred reference dataset for classifying OTUs from rumen microbiota. If this database was used, both QIIME and mothur produced comparable richness and diversity, and also in the RA of most common rumen microbes. However, important differences were found for less common microorganisms which impacted on the beta diversity calculated between pipelines. This may have relevant implications at studying global rumen microbiota.

RevDate: 2019-01-08

Deng H, Yang S, Zhang Y, et al (2018)

Bacteroides fragilis Prevents Clostridium difficile Infection in a Mouse Model by Restoring Gut Barrier and Microbiome Regulation.

Frontiers in microbiology, 9:2976.

Clostridium difficile is currently the leading cause of nosocomial infection. Antibiotics remain the first-line therapy for C. difficile-associated diseases (CDAD), despite the risks of resistance promotion and further gut microbiota perturbation. Notably, the abundance of Bacteroides fragilis was reported to be significantly decreased in CDAD patients. This study aimed to clarify the prophylactic effects of B. fragilis strain ZY-312 in a mouse model of C. difficile infection (CDI). The CDI mouse model was successfully created using C. difficile strain VPI 10463 spores, as confirmed by lethal diarrhea (12.5% survival rate), serious gut barrier disruption, and microbiota disruption. CDI model mice prophylactically treated with B. fragilis exhibited significantly higher survival rates (100% in low dosage group, 87.5% in high dosage group) and improved clinical manifestations. Histopathological analysis of colon and cecum tissue samples revealed an intact gut barrier with strong ZO-1 and Muc-2 expression. The bacterial diversity and relative abundance of gut microbiota were significantly improved. Interestingly, the relative abundance of Akkermansia muciniphila was positively correlated with B. fragilis treatment. In vitro experiments showed that B. fragilis inhibited C. difficile adherence, and attenuated the decrease in CDI-induced transepithelial electrical resistance, ZO-1 and MUC-2 loss, and apoptosis, suggesting that B. fragilis protected against CDI possibly by resisting pathogen colonization and improving gut barrier integrity and functions. In summary, B. fragilis exerted protective effects on a CDI mouse model by modulating gut microbiota and alleviating barrier destruction, thereby relieving epithelial stress and pathogenic colitis triggered by C. difficile. This study provides an alternative preventative measure for CDI and lays the foundations for further investigations of the relationships among opportunistic pathogens, commensal microbiota, and the gut barrier.

RevDate: 2019-01-08

Gannesen AV, Lesouhaitier O, Racine PJ, et al (2018)

Regulation of Monospecies and Mixed Biofilms Formation of Skin Staphylococcus aureus and Cutibacterium acnes by Human Natriuretic Peptides.

Frontiers in microbiology, 9:2912.

Staphylococcus aureus and Cutibacterium acnes are common representatives of the human skin microbiome. However, when these bacteria are organized in biofilm, they could be involved in several skin disorders such as acne or psoriasis. They inhabit in hollows of hair follicles and skin glands, where they form biofilms. There, they are continuously exposed to human hormones, including human natriuretic peptides (NUPs). We first observed that the atrial natriuretic peptide (ANP) and the C-type natriuretic peptide (CNP) have a strong effect S. aureus and C. acnes biofilm formation on the skin. These effects are significantly dependent on the aero-anaerobic conditions and temperature. We also show that both ANP and CNP increased competitive advantages of C. acnes toward S. aureus in mixed biofilm. Because of their temperature-dependent effects, NUPs appear to act as a thermostat, allowing the skin to modulate bacterial development in normal and inflammatory conditions. This is an important step toward understanding how human neuroendocrine systems can regulate the cutaneous microbial community and should be important for applications in fundamental sciences, medicine, dermatology, and cosmetology.

RevDate: 2019-01-08

Huitzil S, Sandoval-Motta S, Frank A, et al (2018)

Modeling the Role of the Microbiome in Evolution.

Frontiers in physiology, 9:1836.

There is undeniable evidence showing that bacteria have strongly influenced the evolution and biological functions of multicellular organisms. It has been hypothesized that many host-microbial interactions have emerged so as to increase the adaptive fitness of the holobiont (the host plus its microbiota). Although this association has been corroborated for many specific cases, general mechanisms explaining the role of the microbiota in the evolution of the host are yet to be understood. Here we present an evolutionary model in which a network representing the host adapts in order to perform a predefined function. During its adaptation, the host network (HN) can interact with other networks representing its microbiota. We show that this interaction greatly accelerates and improves the adaptability of the HN without decreasing the adaptation of the microbial networks. Furthermore, the adaptation of the HN to perform several functions is possible only when it interacts with many different bacterial networks in a specialized way (each bacterial network participating in the adaptation of one function). Disrupting these interactions often leads to non-adaptive states, reminiscent of dysbiosis, where none of the networks the holobiont consists of can perform their respective functions. By considering the holobiont as a unit of selection and focusing on the adaptation of the host to predefined but arbitrary functions, our model predicts the need for specialized diversity in the microbiota. This structural and dynamical complexity in the holobiont facilitates its adaptation, whereas a homogeneous (non-specialized) microbiota is inconsequential or even detrimental to the holobiont's evolution. To our knowledge, this is the first model in which symbiotic interactions, diversity, specialization and dysbiosis in an ecosystem emerge as a result of coevolution. It also helps us understand the emergence of complex organisms, as they adapt more easily to perform multiple tasks than non-complex ones.

RevDate: 2019-01-08

Van Dyken P, B Lacoste (2018)

Impact of Metabolic Syndrome on Neuroinflammation and the Blood-Brain Barrier.

Frontiers in neuroscience, 12:930.

Metabolic syndrome, which includes diabetes and obesity, is one of the most widespread medical conditions. It induces systemic inflammation, causing far reaching effects on the body that are still being uncovered. Neuropathologies triggered by metabolic syndrome often result from increased permeability of the blood-brain-barrier (BBB). The BBB, a system designed to restrict entry of toxins, immune cells, and pathogens to the brain, is vital for proper neuronal function. Local and systemic inflammation induced by obesity or type 2 diabetes mellitus can cause BBB breakdown, decreased removal of waste, and increased infiltration of immune cells. This leads to disruption of glial and neuronal cells, causing hormonal dysregulation, increased immune sensitivity, or cognitive impairment depending on the affected brain region. Inflammatory effects of metabolic syndrome have been linked to neurodegenerative diseases. In this review, we discuss the effects of obesity and diabetes-induced inflammation on the BBB, the roles played by leptin and insulin resistance, as well as BBB changes occurring at the molecular level. We explore signaling pathways including VEGF, HIFs, PKC, Rho/ROCK, eNOS, and miRNAs. Finally, we discuss the broader implications of neural inflammation, including its connection to Alzheimer's disease, multiple sclerosis, and the gut microbiome.

RevDate: 2019-01-08

Christensen E (2019)

[The gut microbiome is important in chronic liver disease].

Ugeskrift for laeger, 181(2):.

There is increasing evidence of gut dysbiosis being a significant factor in the development and progression of important chronic liver diseases including non-alcoholic steatohepatitis (NASH), alcoholic liver disease, primary sclerosing cholangitis and cirrhosis. Dysbiotic microbiota and their toxic metabolites translocate across the gut epithelium via the portal vein and cause damage to the liver. In NASH, alcohol-producing gut bacteria may be critical for its development. Therapeutic measures to normalise the gut microbiota with diet, probiotics or transplantation of normal microbiota seem to have a beneficial effect.

RevDate: 2019-01-08

Williams B, Weber KM, Chlipala G, et al (2019)

HIV status does not affect rectal microbiome composition, diversity or stability over time: A Chicago Women's Interagency HIV Study (WIHS).

AIDS research and human retroviruses [Epub ahead of print].

It remains unclear whether differences in gut microbiota noted between HIV infected and uninfected individuals are driven by HIV or sexual behavior. We evaluated rectal swab microbiota of HIV-infected and uninfected women with similar demographic, neighborhood and diet characteristics enrolled in the Chicago Women's Interagency HIV Study (WIHS). DNA was amplified for sequencing of fragments of bacterial small subunit (SSU or 16S) ribosomal RNA (rRNA) genes. HIV infected and uninfected women did not differ by Shannon diversity index (p=0.14), NMDS plot of Bray-Curtis indices (p=0.488, r=0.0027) or copy number of individual taxa. Both groups demonstrated marked microbiome stability over time (p=0.889).

RevDate: 2019-01-08

Kan JM, Cowan CSM, Ooi CY, et al (2019)

What can the gut microbiome teach us about the connections between child physical and mental health? A systematic review.

Developmental psychobiology [Epub ahead of print].

A deeper understanding of the gut-brain axis is of significance in pediatrics, given the influential role of early childhood experiences and exposures in shaping the microbiome, and health, across the life course. This systematic review synthesized evidence on the connection between the gut microbiome and mental health in children with physical illness. Six electronic databases were systematically searched and data extracted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Of 1,476 identified articles, 11 articles reporting on nine unique studies (all randomized controlled trials) were included. Most studies examined the gut microbiome in infants with colic, while the remaining studies investigated outcomes in children aged 1 day to 18 years at risk for atopic dermatitis or irritable bowel syndrome. Baseline and postintervention gut microbiome differences varied across studies. Findings on psychological functioning also varied, with only half of the captured studies showing a positive effect of intervention on psychological well-being. Only two studies analyzed the association between the gut microbiome and psychological outcomes, each with a different pattern of results. As the field moves forward, it will be critical to gain a better understanding of the microbiome characteristics that influence mental health outcomes in pediatric populations.


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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Woodinville, WA 98077

E-mail: RJR8222 @

Papers in Classical Genetics

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

Digital Books

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


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


Biographical information about many key scientists.

Selected Bibliographies

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

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