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Bibliography on: Microbiome

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ESP: PubMed Auto Bibliography 15 Sep 2019 at 01:41 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: 2019-09-14

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

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

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

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

RevDate: 2019-09-14

Ito Y, Ito T, Yamashiro K, et al (2019)

Antimicrobial and antibiofilm effects of abietic acid on cariogenic Streptococcus mutans.

Odontology pii:10.1007/s10266-019-00456-0 [Epub ahead of print].

Dental caries is a type of oral microbiome dysbiosis and biofilm infection that affects oral and systemic conditions. For healthy life expectancy, natural bacteriostatic products are ideal for daily and lifetime use as anti-oral infection agents. This study aimed to evaluate the inhibitory effects of abietic acid, a diterpene derived from pine rosin, on the in vitro growth of cariogenic bacterial species, Streptococcus mutans. The effective minimum inhibitory concentration of abietic acid was determined through observation of S. mutans growth, acidification, and biofilm formation. The inhibitory effects of abietic acid on the bacterial membrane were investigated through the use of in situ viability analysis and scanning electron microscopic analysis. Cytotoxicity of abietic acid was also examined in the context of several human cell lines using tetrazolium reduction assay. Abietic acid was found to inhibit key bacterial growth hallmarks such as colony forming ability, adenosine triphosphate activity (both planktonic and biofilm), acid production, and biofilm formation. Abietic acid was identified as bacteriostatic, and this compound caused minimal damage to the bacterial membrane. This action was different from that of povidone-iodine or cetylpyridinium chloride. Additionally, abietic acid was significantly less cytotoxic compared to povidone-iodine, and it exerted lower toxicity towards epithelial cells and fibroblasts compared to that against monocytic cells. These data suggest that abietic acid may prove useful as an antibacterial and antibiofilm agent for controlling S. mutans infection.

RevDate: 2019-09-14

Kalantar-Zadeh K, Berean KJ, Burgell RE, et al (2019)

Intestinal gases: influence on gut disorders and the role of dietary manipulations.

Nature reviews. Gastroenterology & hepatology pii:10.1038/s41575-019-0193-z [Epub ahead of print].

The inner workings of the intestines, in which the body and microbiome intersect to influence gut function and systemic health, remain elusive. Carbon dioxide, hydrogen, methane and hydrogen sulfide, as well as a variety of trace gases, are generated by the chemical interactions and microbiota within the gut. Profiling of these intestinal gases and their responses to dietary changes can reveal the products and functions of the gut microbiota and their influence on human health. Indeed, different tools for measuring these intestinal gases have been developed, including newly developed gas-sensing capsule technology. Gases can, according to their type, concentration and volume, induce or relieve abdominal symptoms, and might also have physiological, pathogenic and therapeutic effects. Thus, profiling and modulating intestinal gases could be powerful tools for disease prevention and/or therapy. As the interactions between the microbiota, chemical constituents and fermentative substrates of the gut are principally influenced by dietary intake, altering the diet, which, in turn, changes gas profiles, is the main therapeutic approach for gastrointestinal disorders. An improved understanding of the complex interactions within the intestines that generate gases will enhance our ability to prevent, diagnose, treat and monitor many gastrointestinal disorders.

RevDate: 2019-09-14

Salli K, Anglenius H, Hirvonen J, et al (2019)

The effect of 2'-fucosyllactose on simulated infant gut microbiome and metabolites; a pilot study in comparison to GOS and lactose.

Scientific reports, 9(1):13232 pii:10.1038/s41598-019-49497-z.

Human milk oligosaccharides (HMOs) shape gut microbiota during infancy by acting as fermentable energy source. Using a semi-continuous colon simulator, effect of an HMO, 2'-fucosyllactose (2'-FL), on composition of the infant microbiota and microbial metabolites was evaluated in comparison to galacto-oligosaccharide (GOS) and lactose and control without additional carbon source. Data was analysed according to faecal sample donor feeding type: breast-fed (BF) or formula-fed (FF), and to rate of 2'-FL fermentation: fast or slow. Variation was found between the simulations in the ability to utilise 2'-FL. The predominant phyla regulated by 2'-FL, GOS and lactose were significant increase in Firmicutes, numerical in Actinobacteria, and numerical decrease in Proteobacteria compared to control. Verrucomicrobia increased in FF accounted for Akkermansia, whereas in fast-fermenting simulations Actinobacteria increased with trend for higher Bifidobacterium, and Proteobacteria decrease accounted for Enterobacteriaceae. Short-chain fatty acids and lactic acid with 2'-FL were produced in intermediate levels being between ones generated by the control and GOS or lactose. In 2'-FL fast-fermenting group, acetic acid specifically increased with 2'-FL, whereas lactose and GOS also increased lactic acid. The results highlight specificity of 2'-FL as energy source for only certain microbes over GOS and lactose in the simulated gut model.

RevDate: 2019-09-14

Schmidtner AK, Slattery DA, Gläsner J, et al (2019)

Minocycline alters behavior, microglia and the gut microbiome in a trait-anxiety-dependent manner.

Translational psychiatry, 9(1):223 pii:10.1038/s41398-019-0556-9.

Major depressive disorder is the main cause of disability worldwide with imperfect treatment options. However, novel therapeutic approaches are currently discussed, from augmentation strategies to novel treatments targeting the immune system or the microbiome-gut-brain axis. Therefore, we examined the potential beneficial effects of minocycline, a tetracycline antibiotic with pleiotropic, immunomodulatory action, alone or as augmentation of escitalopram on behavior, prefrontal microglial density, and the gut microbiome in rats selectively bred for high anxiety-like behavior (HAB). We show that concomitant with their high innate anxiety and depression, HABs have lower microglial numbers in the infralimbic and prelimbic prefrontal cortex and an altered gut microbiota composition compared with controls. Three weeks of minocycline treatment alleviated the depressive-like phenotype, further reduced microglial density, exclusively in male HAB rats, and reduced plasma concentrations of pro-inflammatory cytokines. However, coadministration of escitalopram, which had no effect alone, prevented these minocycline-induced effects. Moreover, minocycline led to a robust shift in cecal microbial composition in both HABs and rats non-selected for anxiety-like behavior. Minocycline markedly increased relative abundance of Lachnospiraceae and Clostridiales Family XIII, families known for their butyrate production, with a corresponding increase and positive correlation in plasma 3-OH-butyrate levels in a trait-dependent manner. Thus, our data suggest that the antidepressant effect of minocycline is sex- and trait-dependent, associated with a reduced microglial number in the prefrontal cortex, and with changes in microbial composition and their metabolites. These results further support the microbiome-gut-brain axis as potential target in the treatment of depression.

RevDate: 2019-09-14

McCormack UM, Curião T, Metzler-Zebeli BU, et al (2019)

Seeking to improve feed efficiency in pigs through microbial modulation via fecal microbiota transplantation in sows and dietary supplementation of offspring with inulin.

Applied and environmental microbiology pii:AEM.01255-19 [Epub ahead of print].

As previous studies have demonstrated a link between the porcine intestinal microbiome and feed efficiency (FE), microbiota manipulation may offer a means of improving FE in pigs. A fecal microbiota transplantation procedure (FMTp), using fecal extracts from highly feed efficient pigs, was performed in pregnant sows (n=11), with a control group (n=11) receiving no FMTp. At weaning, offspring were allocated, within sow treatment, to 1) control (n=67; no dietary supplement) or 2) inulin (n=65; 6-week dietary inulin supplementation) treatments. The sow FMTp, alone or in combination with offspring inulin supplementation, reduced offspring body weight by 8.1-10.6 Kg at ∼140 days of age, but there was no effect on feed intake. It resulted in better FE, higher bacterial diversity and higher relative abundances of potentially beneficial bacterial taxa (Fibrobacter, Prevotella) in offspring. Due to FMTp and/or inulin supplementation, relative abundance of potential pathogens (Chlamydia, Treponema) in the ileum, and cecal concentrations of butyric acid were significantly lower. Maternal FMTp led to a greater number of jejunal goblet cells in offspring. Inulin supplementation alone did not affect growth or FE, but up-regulated duodenal genes linked to glucose and volatile fatty acid homeostasis and increased mean platelet volume, but reduced ileal propionic acid, granulocyte counts, and serum urea. Overall, FMTp in pregnant sows, with/without offspring dietary inulin supplementation, beneficially modulated offspring intestinal microbiota (albeit mostly low relative abundance taxa) and associated physiological parameters. Although FE was improved, the detrimental effect on growth limits the application of this FMTp/inulin strategy in commercial pig production.IMPORTANCE As previous research suggests a link between microbiota and FE, modulation of the intestinal microbiome may be effective in improving FE in pigs. The FMTp in gestating sows, alone/in combination with offspring post-weaning dietary inulin supplementation, achieved improvements in FE, and resulted in higher relative abundance of intestinal bacteria associated with fiber degradation, and lower relative abundance of potential pathogens. However, there was a detrimental effect on growth, although this may not be wholly attributable to microbiota transplantation, as antibiotic and other interventions were also part of the FMT regime. Therefore, further work with additional control groups is needed to disentangle the effects of each component of the FMTp in order to develop a regime with practical applications in pig production. Additional research based on findings from this study may also identify specific dietary supplements for promotion/maintenance of the microbiota transferred via maternal FMTp, thereby optimizing pig growth and FE.

RevDate: 2019-09-14

Scepanovic P, Hodel F, Mondot S, et al (2019)

A comprehensive assessment of demographic, environmental, and host genetic associations with gut microbiome diversity in healthy individuals.

Microbiome, 7(1):130 pii:10.1186/s40168-019-0747-x.

BACKGROUND: The gut microbiome is an important determinant of human health. Its composition has been shown to be influenced by multiple environmental factors and likely by host genetic variation. In the framework of the Milieu Intérieur Consortium, a total of 1000 healthy individuals of western European ancestry, with a 1:1 sex ratio and evenly stratified across five decades of life (age 20-69), were recruited. We generated 16S ribosomal RNA profiles from stool samples for 858 participants. We investigated genetic and non-genetic factors that contribute to individual differences in fecal microbiome composition.

RESULTS: Among 110 demographic, clinical, and environmental factors, 11 were identified as significantly correlated with α-diversity, ß-diversity, or abundance of specific microbial communities in multivariable models. Age and blood alanine aminotransferase levels showed the strongest associations with microbiome diversity. In total, all non-genetic factors explained 16.4% of the variance. We then searched for associations between > 5 million single nucleotide polymorphisms and the same indicators of fecal microbiome diversity, including the significant non-genetic factors as covariates. No genome-wide significant associations were identified after correction for multiple testing. A small fraction of previously reported associations between human genetic variants and specific taxa could be replicated in our cohort, while no replication was observed for any of the diversity metrics.

CONCLUSION: In a well-characterized cohort of healthy individuals, we identified several non-genetic variables associated with fecal microbiome diversity. In contrast, host genetics only had a negligible influence. Demographic and environmental factors are thus the main contributors to fecal microbiome composition in healthy individuals.

TRIAL REGISTRATION: identifier NCT01699893.

RevDate: 2019-09-14

Wheat W, Chow L, Kuzmik A, et al (2019)

Local immune and microbiological responses to mucosal administration of a Liposome-TLR agonist immunotherapeutic in dogs.

BMC veterinary research, 15(1):330 pii:10.1186/s12917-019-2073-8.

BACKGROUND: Non-specific immunotherapeutics have been evaluated previously in dogs, primarily for cancer treatment. However, there remains a need for a more broadly targeted, general purpose immunotherapeutic capable of activating innate immune defenses for non-specific protection or early treatment of viral and bacterial infections. To address need, our group has developed a liposomal immune stimulant (liposome-TLR complexes, LTC) containing TLR 3 and 9 agonists specifically designed to activate mucosal immune defenses in sites such as nasal cavity and oropharynx, following topical delivery. In this study, we evaluated the local immune stimulatory properties of LTC in vitro and in healthy purpose-bred dogs, including activation of cellular recruitment and cytokine production. The ability of LTC treatment to elicit effective antiviral immunity was assessed in dogs following a canine herpesvirus outbreak, and the impact of LTC treatment on the local microbiome of the oropharynx was also investigated.

RESULTS: These studies revealed that LTC potently activated innate immune responses in vitro and triggered significant recruitment of inflammatory monocytes and T cells into the nasal cavity and oropharynx of healthy dogs. Administration of LTC to dogs shortly after an outbreak of canine herpesvirus infection resulted in significant reduction in clinical signs of infection. Interestingly, administration of LTC to healthy dogs did not disrupt the microbiome in the oropharynx, suggesting resiliency of the microflora to transient immune activation.

CONCLUSIONS: Taken together, these results indicate that LTC administration mucosally to dogs can trigger local innate immune activation and activation of antiviral immunity, without significantly disrupting the composition of the local microbiome. Thus, the LTC immune stimulant has potential for use as a non-specific immunotherapy for prevention or early treatment of viral and bacterial infections in dogs.

RevDate: 2019-09-14

Ingham AC, Kielsen K, Cilieborg MS, et al (2019)

Specific gut microbiome members are associated with distinct immune markers in pediatric allogeneic hematopoietic stem cell transplantation.

Microbiome, 7(1):131 pii:10.1186/s40168-019-0745-z.

BACKGROUND: Increasing evidence reveals the importance of the microbiome in health and disease and inseparable host-microbial dependencies. Host-microbe interactions are highly relevant in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT), i.e., a replacement of the cellular components of the patients' immune system with that of a foreign donor. HSCT is employed as curative immunotherapy for a number of non-malignant and malignant hematologic conditions, including cancers such as acute lymphoblastic leukemia. The procedure can be accompanied by severe side effects such as infections, acute graft-versus-host disease (aGvHD), and death. Here, we performed a longitudinal analysis of immunological markers, immune reconstitution and gut microbiota composition in relation to clinical outcomes in children undergoing HSCT. Such an analysis could reveal biomarkers, e.g., at the time point prior to HSCT, that in the future could be used to predict which patients are of high risk in relation to side effects and clinical outcomes and guide treatment strategies accordingly.

RESULTS: In two multivariate analyses (sparse partial least squares regression and canonical correspondence analysis), we identified three consistent clusters: (1) high concentrations of the antimicrobial peptide human beta-defensin 2 (hBD2) prior to the transplantation in patients with high abundances of Lactobacillaceae, who later developed moderate or severe aGvHD and exhibited high mortality. (2) Rapid reconstitution of NK and B cells in patients with high abundances of obligate anaerobes such as Ruminococcaceae, who developed no or mild aGvHD and exhibited low mortality. (3) High inflammation, indicated by high levels of C-reactive protein, in patients with high abundances of facultative anaerobic bacteria such as Enterobacteriaceae. Furthermore, we observed that antibiotic treatment influenced the bacterial community state.

CONCLUSIONS: We identify multivariate associations between specific microbial taxa, host immune markers, immune cell reconstitution, and clinical outcomes in relation to HSCT. Our findings encourage further investigations into establishing longitudinal surveillance of the intestinal microbiome and relevant immune markers, such as hBD2, in HSCT patients. Profiling of the microbiome may prove useful as a prognostic tool that could help identify patients at risk of poor immune reconstitution and adverse outcomes, such as aGvHD and death, upon HSCT, providing actionable information in guiding precision medicine.

RevDate: 2019-09-14

Brown GC (2019)

The endotoxin hypothesis of neurodegeneration.

Journal of neuroinflammation, 16(1):180 pii:10.1186/s12974-019-1564-7.

The endotoxin hypothesis of neurodegeneration is the hypothesis that endotoxin causes or contributes to neurodegeneration. Endotoxin is a lipopolysaccharide (LPS), constituting much of the outer membrane of gram-negative bacteria, present at high concentrations in gut, gums and skin and in other tissue during bacterial infection. Blood plasma levels of endotoxin are normally low, but are elevated during infections, gut inflammation, gum disease and neurodegenerative disease. Adding endotoxin at such levels to blood of healthy humans induces systemic inflammation and brain microglial activation. Adding high levels of endotoxin to the blood or body of rodents induces microglial activation, priming and/or tolerance, memory deficits and loss of brain synapses and neurons. Endotoxin promotes amyloid β and tau aggregation and neuropathology, suggesting the possibility that endotoxin synergises with different aggregable proteins to give different neurodegenerative diseases. Blood and brain endotoxin levels are elevated in Alzheimer's disease, which is accelerated by systemic infections, including gum disease. Endotoxin binds directly to APOE, and the APOE4 variant both sensitises to endotoxin and predisposes to Alzheimer's disease. Intestinal permeability increases early in Parkinson's disease, and injection of endotoxin into mice induces α-synuclein production and aggregation, as well as loss of dopaminergic neurons in the substantia nigra. The gut microbiome changes in Parkinson's disease, and changing the endotoxin-producing bacterial species can affect the disease in patients and mouse models. Blood endotoxin is elevated in amyotrophic lateral sclerosis, and endotoxin promotes TDP-43 aggregation and neuropathology. Peripheral diseases that elevate blood endotoxin, such as sepsis, AIDS and liver failure, also result in neurodegeneration. Endotoxin directly and indirectly activates microglia that damage neurons via nitric oxide, oxidants and cytokines, and by phagocytosis of synapses and neurons. The endotoxin hypothesis is unproven, but if correct, then neurodegeneration may be reduced by decreasing endotoxin levels or endotoxin-induced neuroinflammation.

RevDate: 2019-09-13

Jørgensen AR, Thomsen SF, Karmisholt KE, et al (2019)

Clinical, microbiological, immunological and imaging characteristics of tunnels and fistulas in hidradenitis suppurativa and Crohn's disease.

Experimental dermatology [Epub ahead of print].

Hidradenitis suppurativa (HS) tunnels and Crohn's disease (CD) fistulas are a challenge to treat. Although pathogenic similarities have been described between HS and CD, recent studies indicate that clinical, microbiological, immunological and imaging characteristics differ between these diseases. This review highlights the differences between HS tunnels and CD fistulas. Next generation sequencing studies demonstrate a microbiome in HS tunnels dominated by Porphyromonas spp., Prevotella spp. whereas no specific bacteria have been associated with cutaneous CD. Immunologically, TNF has been found upregulated in HS tunnels along with various interleukins (IL-8, IL-16, IL-1α, IL-1β). In CD fistulas, Th1, Th17, IL-17, IFN-ɤ, TNF and IL-23 are increased. US imaging is an important tool in HS. US of HS tunnels depict hypoechoic band-like structure across skin layers in the dermis and/or hypodermis connected to the base of a widened hair follicle. In CD, MR imaging of simple perianal fistulas illustrates a linear, nonbranching inflammatory tract relating to an internal opening in the anus or low rectum and an external opening to the skin surface. An increased awareness of the immediate potential differences between HS tunnels and CD fistulas may optimize treatment regimens of these intractable skin manifestations.

RevDate: 2019-09-13

Kim R, Attayek P, Wang Y, et al (2019)

An in vitro intestinal platform with a self-sustaining oxygen gradient to study the human gut/microbiome interface.

Biofabrication [Epub ahead of print].

An oxygen gradient formed along the length of colonic crypts supports stem-cell proliferation at the normoxic crypt base while supporting obligate anaerobe growth in the anoxic colonic lumen. Primary human colonic epithelial cells derived from human gastrointestinal stem cells were cultured within a device possessing materials of tailored oxygen permeability to produce an oxygen-depleted luminal (0.8±0.1% O2) and oxygen-rich basal (11.1±0.5% O2) compartment. This oxygen difference created a stable oxygen gradient across the colonic epithelial cells which remained viable and properly polarized. Facultative and obligate anaerobes Lactobacillus rhamnosus, Bifidobacterium adolescentis, and Clostridium difficile grew readily within the luminal reservoir. When formed along the length of an in vitro crypt, the oxygen gradient facilitated cell compartmentalization within the crypt by enhancing confinement of the proliferative cells to the crypt base. This platform provides a simple system to create a physiological oxygen gradient across an intestinal mimic while simultaneously supporting anaerobe co-culture.

RevDate: 2019-09-13

Eggers S, Safdar N, Sethi AK, et al (2019)

Urinary lead concentration and composition of the adult gut microbiota in a cross-sectional population-based sample.

Environment international, 133(Pt A):105122 pii:S0160-4120(19)31817-3 [Epub ahead of print].

BACKGROUND: Lead (Pb) is a ubiquitous environmental contaminant with an array of detrimental health effects in children and adults, including neurological and immune dysfunction. Emerging evidence suggests that Pb exposure may alter the composition of the gut microbiota, however few studies have examined this association in human populations. The purpose of this study was to examine the association between urinary Pb concentration and the composition of the adult gut microbiota in a population-based sample of adults.

METHODS: Data used in this study were collected as part of the Survey of the Health of Wisconsin (SHOW) and its ancillary microbiome study. The SHOW is a household-based health examination survey of Wisconsin residents, collecting a variety of survey data on health determinants and outcomes, as well as objective measurements of body habitus, and biological specimens including urine. The ancillary microbiome study added additional questions and biological specimen collection, including stool, from participants age 18+. Pb concentration was analyzed in urine samples, and gut microbiota composition was assessed using DNA sequencing of the 16S rRNA V4 region, extracted from stool samples. Data processing and statistical analyses were performed in mothur, Python, R, and SAS.

RESULTS: Of 696 participants, urinary Pb concentration was highest in those age 70+, females, those with a high school diploma or lower, current and former smokers, and those without indoor pets. In adjusted models, increasing urinary Pb levels were associated with increases in microbial α-diversity (p = 0.071) and richness (p = 0.005). Differences in microbial β-diversity were significantly associated (p = 0.003) with differences in urinary Pb level. Presence of Proteobacteria, including members of the Burkholderiales, was significantly associated with increased urinary Pb.

CONCLUSION: These results suggest that Pb exposure is associated with differences in the composition of the adult gut microbiota in a population-based human sample. Further investigation of this association is warranted.

RevDate: 2019-09-13

Mohan V, Das A, I Sagi (2019)

Emerging roles of ECM remodeling processes in cancer.

Seminars in cancer biology pii:S1044-579X(19)30268-8 [Epub ahead of print].

Extracellular matrix (ECM) plays a central and dynamic role in the creation of tumor microenvironment. Herein we discuss the emerging biophysical and biochemical aspects of ECM buildup and proteolysis in cancer niche formation. Dysregulated ECM remodeling by cancer cells facilitate irreversible proteolysis and crosslinking, which in turn influence cell signaling, micro environmental cues, angiogenesis and tissue biomechanics. Further, we introduce the emerging roles of cancer microbiome in aberrant tumor ECM remodeling and membrane bound nano-sized vesicles called exosomes in creation of distant pre-metastatic niches. A detailed molecular and biophysical understanding of the ECM morphologies and its components such as key enzymes, structural and signaling molecules is critical in successfully finding the next generation of therapeutic and diagnostic targets in cancer.

RevDate: 2019-09-13

Mozaffarian D (2019)

Dairy Foods, Obesity, and Metabolic Health: The Role of the Food Matrix Compared with Single Nutrients.

Advances in nutrition (Bethesda, Md.), 10(5):917S-923S.

In the 20th century, scientific and geopolitical events led to the concept of food as a delivery system for calories and specific isolated nutrients. As a result, conventional dietary guidelines have focused on individual nutrients to maintain health and prevent disease. For dairy foods, this has led to general dietary recommendations to consume 2-3 daily servings of reduced-fat dairy foods, without regard to type (e.g., yogurt, cheese, milk), largely based on theorized benefits of isolated nutrients for bone health (e.g., calcium, vitamin D) and theorized harms of isolated nutrients for cardiovascular diseases (CVDs) and obesity (e.g., total fat, saturated fat, total calories). However, advances in nutrition science have demonstrated that foods represent complex matrices of nutrients, minerals, bioactives, food structures, and other factors (e.g., phoshopholipids, prebiotics, probiotics) with correspondingly complex effects on health and disease. The present evidence suggests that whole-fat dairy foods do not cause weight gain, that overall dairy consumption increases lean body mass and reduces body fat, that yogurt consumption and probiotics reduce weight gain, that fermented dairy consumption including cheese is linked to lower CVD risk, and that yogurt, cheese, and even dairy fat may protect against type 2 diabetes. Based on the current science, dairy consumption is part of a healthy diet, without strong evidence to favor reduced-fat products; while intakes of probiotic-containing unsweetened and fermented dairy products such as yogurt and cheese appear especially beneficial.

RevDate: 2019-09-13

McCann A, Jeffery IB, Ouliass B, et al (2019)

Exploratory analysis of covariation of microbiota-derived vitamin K and cognition in older adults.

The American journal of clinical nutrition pii:5569648 [Epub ahead of print].

BACKGROUND: Vitamin K has multiple important physiological roles, including blood coagulation and beneficial effects on myelin integrity in the brain. Some intestinal microbes possess the genes to produce vitamin K in the form of menaquinone (MK). MK appears in higher concentration in tissues, such as the brain, particularly MK4, than the dietary form of phylloquinone (PK). Lower PK concentrations have been reported in patients with Alzheimer disease while higher serum PK concentrations have been positively associated with verbal episodic memory. Despite knowledge of the importance of vitamin K for various health parameters, few studies have measured MK concentration and biosynthesis by gut commensals.

OBJECTIVE: The aim of the current study was to investigate the relation between genes involved in gut-microbiota derived MK, concentrations of MK isoforms, and cognitive function.

METHODS: Shotgun metagenomic sequencing of the gut microbiome of 74 elderly individuals with different cognitive ability levels was performed. From this, gene counts for microbial MK biosynthesis were determined. Associations between clusters of individuals, grouped based on a similar presence and prevalence of MK biosynthesis genes, and cognitive ability were investigated. Fecal MK concentrations were quantified by HPLC to investigate correlations with subject clusters.

RESULTS: Separation of subject groups defined by banded quantification of the genetic potential of their microbiome to biosynthesize MK was associated with significant differences in cognitive ability [assessed using the Mini-Mental State Examination (MMSE)]. Three MK isoforms were found to be positively associated with MMSE, along with the identification of key components of the MK pathway that drive this association. Although the causality and direction of these associations remain unknown, these findings justify further studies.

CONCLUSIONS: This study provides evidence that although total concentrations of MK did not covary with cognition, certain MK isoforms synthesized by the gut microbiome, particularly the longer chains, are positively associated with cognition.

RevDate: 2019-09-13

Belanche A, Yáñez-Ruiz DR, Detheridge AP, et al (2019)

Maternal vs artificial rearing shapes the rumen microbiome having minor long-term physiological implications.

Environmental microbiology [Epub ahead of print].

Increasing productivity is a key target in ruminant science which requires better understanding of the rumen microbiota. This study investigated how maternal vs artificial rearing shapes the rumen microbiota using 24 sets of triplet lambs. Lambs within each sibling set were randomly assigned to: natural rearing on the ewe (NN); ewe colostrum for 24h followed by artificial milk feeding (NA); and colostrum alternative and artificial milk feeding (AA). Maternal colostrum feeding enhanced VFA production at weaning but not thereafter. At weaning, lambs reared on milk replacer had no rumen protozoa and lower microbial diversity, whereas natural rearing accelerated the rumen microbial development and facilitated the transition to solid diet. Differences in the rumen prokaryotic communities disappear later in life when all lambs were grouped on the same pasture up to 23 weeks of age. However, NN animals retained higher fungal diversity and abundances of Piromyces, Feramyces and Diplodiniinae protozoa as well as higher feed digestibility (+4%) and animal growth (+6.5%) during the grazing period. Nevertheless, no correlations were found between rumen microbiota and productive outcomes. These findings suggest that the early-life nutritional intervention determine the initial rumen microbial community but the persistence of these effects later in life is weak. This article is protected by copyright. All rights reserved.

RevDate: 2019-09-13

Ticinesi A, Nouvenne A, Corrente V, et al (2019)

Diverticular Disease: a Gut Microbiota Perspective.

Journal of gastrointestinal and liver diseases : JGLD, 28(3):327-337.

Gut microbiota composition and functionality are involved in the pathophysiology of several intestinal and extraintestinal diseases, and are increasingly considered a modulator of local and systemic inflammation. However, the involvement of gut microbiota in diverticulosis and in diverticular disease is still poorly investigated. In this review, we critically analyze the existing evidence on the fecal and mucosa-associated microbiota composition and functionality across different stages of diverticular disease. We also explore the influence of risk factors for diverticulosis on gut microbiota composition, and speculate on the possible relevance of these associations for the pathogenesis of diverticula. We overview the current treatments of diverticular disease targeting the intestinal microbiome, highlighting the current areas of uncertainty and the need for future studies. Although no conclusive remarks on the relationship between microbiota and diverticular disease can be made, preliminary data suggest that abdominal symptoms are associated with reduced representation of taxa with a possible anti-inflammatory effect, such as Clostridium cluster IV, and overgrowth of Enterobacteriaceae, Bifidobacteria and Akkermansia. The role of the microbiota in the early stages of the disease is still very uncertain. Future studies should help to disentangle the role of the microbiome in the pathogenesis of diverticular disease and its progression towards more severe forms.

RevDate: 2019-09-13

Duysburgh C, Van den Abbeele P, Krishnan K, et al (2019)

A synbiotic concept containing spore-forming Bacillus strains and a prebiotic fiber blend consistently enhanced metabolic activity by modulation of the gut microbiome in vitro.

International journal of pharmaceutics: X, 1:100021 pii:100021.

A standardized in vitro simulation of the human gastrointestinal tract (M-SHIME®) was used to assess the effect of repeated daily administration of a synbiotic formulation, containing five spore-forming Bacillus strains and a prebiotic fiber blend, on the microbial activity and composition of three simulated human subjects. Firstly, while confirming recent findings, deeper phylogenetic insight was obtained in the resident M-SHIME® microbiota, demonstrating that the model maintains a diverse and representative, colon region-specific luminal and mucosal microbial community. Supplementation of the synbiotic concept increased microbial diversity in the distal colon areas, whereas specific enhancement of Bacillaceae levels was observed in the ascending colon suggesting a successful engraftment of the Bacillus spores, which probably resulted in a stimulatory effect on, among others, Bifidobacteriaceae, Lactobacillaceae, Prevotellaceae, Tannerellaceae and Faecalibacterium prausnitzii contributing directly or indirectly to stimulation of acetate, propionate and butyrate production. When compared with a previous study investigating the Bacillus strains, the generated data suggest a synergistic effect on the intestinal microbiota for the synbiotic formulation. Given the fact that the probiotic strains have been shown to impact post-prandial metabolic endotoxemia in human individuals, it might be interesting to further investigate the efficacy of the synbiotic concept in protecting against obesity-related disorders.

RevDate: 2019-09-13

Koradia P, Kapadia S, Trivedi Y, et al (2019)

Probiotic and cranberry supplementation for preventing recurrent uncomplicated urinary tract infections in premenopausal women: a controlled pilot study.

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

Objectives: To assess efficacy and safety of Bio-Kult Pro-Cyan (BKPro-Cyan), a product containing two strains of Lactobacilli plus cranberry extract, for preventing recurrent UTIs in pre-menopausal adult women.Methods: This was a randomized, double-blind, placebo-controlled pilot study. Subjects received BKPro-Cyan or placebo twice-daily for 26 weeks. The primary endpoint was the proportion of subjects with recurrent UTI at the end of the study.Results: 115 subjects were screened; 90 were enrolled; 81 completed the study. After 26 weeks, a significantly lower number of women experienced recurrent UTIs with BKPro-Cyan compared to placebo (9.1 vs 33.3%; P = 0.0053). BKPro-Cyan produced statistically significant improvements compared to placebo for multiple secondary endpoints, including: greater number of subjects who experienced no UTIs (90 vs 67%; P < 0.05); longer time to first UTI (174 vs 90 days; P = 0.001); shorter duration of active UTI (5 vs 12 days; P = 0.009); Fewer subjects requiring antibiotics (3 vs 11; P < 0.05); and shorter median duration of antibiotic treatment (4 vs 7 days; P = 0.09).Conclusions: BKPro-Cyan was safe and effective for preventing recurrent UTI in pre-menopausal adult women. These findings support the need for further well-designed trials to clarify the benefits that may be achieved.

RevDate: 2019-09-13

Rodriguez AE, MI Restrepo (2019)

New perspectives in Aspiration Community Acquired Pneumonia.

Expert review of clinical pharmacology [Epub ahead of print].

INTRODUCTION: Aspiration pneumonia is a subclass of community-acquired pneumonia that is expected to have an increasing contribution in mortality and morbidity, particularly in the elderly population over the next coming decades. While studies have revealed significant progress in identifying risk factors for aspiration pneumonia, the clinical presentation and diagnosis remains challenging to healthcare providers. Areas Covered: We conducted a broad literature review using the MeSH heading in PubMed/MEDLINE of "aspiration pneumonia" from January 1970 to July 2019. The understanding of the microbiology of aspiration pneumonia has evolved from a possible shift in the causative organisms away from anaerobes to traditional community-acquired pneumonia organisms. The importance of this shift is not yet known, but it has questioned the pathogenic role of anaerobes, appropriate anaerobic testing and the role of these pathogens in the pulmonary microbiome in patients with pneumonia. The identification of risk factors led to strategies to prevent or minimize the risk of aspiration pneumonia with moderate success. Expert Opinion: Our expert opinion is that further research is needed to determine the role of the microbiome with aspiration pneumonia and patient risk factors. There is also a great need to develop clinical tools to help providers diagnose, treat, and prevent aspiration pneumonia.

RevDate: 2019-09-13

El Aidy S, Bolsius YG, Raven F, et al (2019)

A brief period of sleep deprivation leads to subtle changes in mouse gut microbiota.

Journal of sleep research [Epub ahead of print].

Not getting enough sleep is a common problem in our society and contributes to numerous health problems, including high blood pressure, diabetes and obesity. Related to these observations, a wealth of studies has underscored the negative impact of both acute and chronic sleep deprivation on cognitive function. More recently it has become apparent that the gut microbiota composition can be rapidly altered, modulates brain function and is affected by the aforementioned health problems. As such, changes in the microbiota composition may contribute to the behavioural and physiological phenotypes associated with sleep deprivation. It is unclear, however, whether a brief period of sleep deprivation can also negatively impact the gut microbiota. Here, we examined the impact of 5 hr of sleep deprivation on gut microbiota composition of male C57Bl6/J mice. Despite the fact that the overall microbial composition did not change between the control- and sleep-deprived groups, the relative abundance of the Clostridiaceae and Lachnospiraceae were slightly altered in sleep-deprived animals compared to controls. Together, these data suggest that depriving mice of sleep for 5 hr leads to subtle changes in the gut microbiota composition.

RevDate: 2019-09-13

Grady KL, Sorensen JW, Stopnisek N, et al (2019)

Assembly and seasonality of core phyllosphere microbiota on perennial biofuel crops.

Nature communications, 10(1):4135 pii:10.1038/s41467-019-11974-4.

Perennial grasses are promising feedstocks for biofuel production, with potential for leveraging their native microbiomes to increase their productivity and resilience to environmental stress. Here, we characterize the 16S rRNA gene diversity and seasonal assembly of bacterial and archaeal microbiomes of two perennial cellulosic feedstocks, switchgrass (Panicum virgatum L.) and miscanthus (Miscanthus x giganteus). We sample leaves and soil every three weeks from pre-emergence through senescence for two consecutive switchgrass growing seasons and one miscanthus season, and identify core leaf taxa based on occupancy. Virtually all leaf taxa are also detected in soil; source-sink modeling shows non-random, ecological filtering by the leaf, suggesting that soil is an important reservoir of phyllosphere diversity. Core leaf taxa include early, mid, and late season groups that were consistent across years and crops. This consistency in leaf microbiome dynamics and core members is promising for microbiome manipulation or management to support crop production.

RevDate: 2019-09-13

Botté ES, Nielsen S, Abdul Wahab MA, et al (2019)

Changes in the metabolic potential of the sponge microbiome under ocean acidification.

Nature communications, 10(1):4134 pii:10.1038/s41467-019-12156-y.

Anthropogenic CO2 emissions are causing ocean acidification, which can affect the physiology of marine organisms. Here we assess the possible effects of ocean acidification on the metabolic potential of sponge symbionts, inferred by metagenomic analyses of the microbiomes of two sponge species sampled at a shallow volcanic CO2 seep and a nearby control reef. When comparing microbial functions between the seep and control sites, the microbiome of the sponge Stylissa flabelliformis (which is more abundant at the control site) exhibits at the seep reduced potential for uptake of exogenous carbohydrates and amino acids, and for degradation of host-derived creatine, creatinine and taurine. The microbiome of Coelocarteria singaporensis (which is more abundant at the seep) exhibits reduced potential for carbohydrate import at the seep, but greater capacity for archaeal carbon fixation via the 3-hydroxypropionate/4-hydroxybutyrate pathway, as well as archaeal and bacterial urea production and ammonia assimilation from arginine and creatine catabolism. Together these metabolic features might contribute to enhanced tolerance of the sponge symbionts, and possibly their host, to ocean acidification.

RevDate: 2019-09-13

Li L, Abou-Samra E, Ning Z, et al (2019)

An in vitro model maintaining taxon-specific functional activities of the gut microbiome.

Nature communications, 10(1):4146 pii:10.1038/s41467-019-12087-8.

In vitro gut microbiome models could provide timely and cost-efficient solutions to study microbiome responses to drugs. For this purpose, in vitro models that maintain the functional and compositional profiles of in vivo gut microbiomes would be extremely valuable. Here, we present a 96-deep well plate-based culturing model (MiPro) that maintains the functional and compositional profiles of individual gut microbiomes, as assessed by metaproteomics, while allowing a four-fold increase in viable bacteria counts. Comparison of taxon-specific functions between pre- and post-culture microbiomes shows a Pearson's correlation coefficient r of 0.83 ± 0.03. In addition, we show a high degree of correlation between gut microbiome responses to metformin in the MiPro model and those in mice fed a high-fat diet. We propose MiPro as an in vitro gut microbiome model for scalable investigation of drug-microbiome interactions such as during high-throughput drug screening.

RevDate: 2019-09-13

Medawar E, Huhn S, Villringer A, et al (2019)

The effects of plant-based diets on the body and the brain: a systematic review.

Translational psychiatry, 9(1):226 pii:10.1038/s41398-019-0552-0.

Western societies notice an increasing interest in plant-based eating patterns such as vegetarian and vegan, yet potential effects on the body and brain are a matter of debate. Therefore, we systematically reviewed existing human interventional studies on putative effects of a plant-based diet on the metabolism and cognition, and what is known about the underlying mechanisms. Using the search terms "plant-based OR vegan OR vegetarian AND diet AND intervention" in PubMed filtered for clinical trials in humans retrieved 205 studies out of which 27, plus an additional search extending the selection to another five studies, were eligible for inclusion based on three independent ratings. We found robust evidence for short- to moderate-term beneficial effects of plant-based diets versus conventional diets (duration ≤ 24 months) on weight status, energy metabolism and systemic inflammation in healthy participants, obese and type-2 diabetes patients. Initial experimental studies proposed novel microbiome-related pathways, by which plant-based diets modulate the gut microbiome towards a favorable diversity of bacteria species, yet a functional "bottom up" signaling of plant-based diet-induced microbial changes remains highly speculative. In addition, little is known, based on interventional studies about cognitive effects linked to plant-based diets. Thus, a causal impact of plant-based diets on cognitive functions, mental and neurological health and respective underlying mechanisms has yet to be demonstrated. In sum, the increasing interest for plant-based diets raises the opportunity for developing novel preventive and therapeutic strategies against obesity, eating disorders and related comorbidities. Still, putative effects of plant-based diets on brain health and cognitive functions as well as the underlying mechanisms remain largely unexplored and new studies need to address these questions.

RevDate: 2019-09-13

Langley S, Eng T, Wan KH, et al (2019)

Complete Genome Sequence of Agrobacterium sp. Strain 33MFTa1.1, Isolated from Thlaspi arvense Roots.

Microbiology resource announcements, 8(37): pii:8/37/e00432-19.

Agrobacterium sp. strain 33MFTa1.1 was isolated for functional host-microbe interaction studies from the Thlaspi arvense root-associated microbiome. The complete genome is comprised of a circular chromosome of 2,771,937 bp, a linear chromosome of 2,068,443 bp, and a plasmid of 496,948 bp, with G+C contents of 59%, 59%, and 58%, respectively.

RevDate: 2019-09-13

Allen-Vercoe E, Carmical JR, Forry SP, et al (2019)

Perspectives for Consideration in the Development of Microbial Cell Reference Materials.

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology pii:1055-9965.EPI-19-0557 [Epub ahead of print].

Microbiome measurement and analyses benefit greatly from incorporation of reference materials as controls. However, there are many points to consider in defining an ideal whole cell reference material standard. Such a standard would embody all the diversity and measurement challenges present in real samples, would be completely characterized to provide 'ground truth' data, and would be inexpensive and widely available. This ideal is, unfortunately, not readily attainable because of the diverse nature of different sequencing projects. Some applications may benefit most from highly complex reference materials, while others will value characterization or low expense more highly. The selection of appropriate microbial whole cell reference materials to benchmark and validate microbial measurements should be considered carefully and may vary among specific applications. In this commentary, we describe a perspective on the development of whole cell microbial reference materials for use in metagenomics analyses.

RevDate: 2019-09-13

Naghibi MM, Day R, Stone S, et al (2019)

Probiotics for the Prophylaxis of Migraine: A Systematic Review of Randomized Placebo Controlled Trials.

Journal of clinical medicine, 8(9): pii:jcm8091441.

Migraine is a common and disabling neurological condition with a complex etiology. Recent advances in the understanding of the gut microbiome have shown the role of gut micro-organisms in disease outcomes for distant organs-including the brain. Interventions targeting the gut microbiome have been shown to be effective in multiple neurological diagnoses, but there is little research into the role of the microbiome in migraine. This systematic review seeks to assess the current research landscape of randomized placebo controlled trials utilizing probiotic interventions as migraine prophylaxis. Searches were conducted of scientific databases including PubMed, MEDLINE, and the Cochrane Library, following PRISMA guidelines. Of 68 screened studies, 2 were eligible for analysis. Due to methodological differences, meta-analysis was not possible. Qualitative comparison of the studies demonstrated a dichotomy of results-one trial reported no significant change in migraine frequency and intensity, while the second trial reported highly significant improvements. No clear 'gold standard' currently exists for microbiome research, let alone for migraine-related microbiome research. The heterogeneity of outcome measures used in the two trials included in this systematic review shows the need for a standardization of outcome measures, therefore a series of recommendations for future probiotic-migraine research are included.

RevDate: 2019-09-13

Heidari M, Noorizadeh F, Wu K, et al (2019)

Dry Eye Disease: Emerging Approaches to Disease Analysis and Therapy.

Journal of clinical medicine, 8(9): pii:jcm8091439.

Dry eye disease (DED) is among the most common ocular disorders affecting tens of millions of individuals worldwide; however, the condition remains incompletely understood and treated. Valuable insights have emerged from multidisciplinary approaches, including immunometabolic analyses, microbiome analyses, and bioengineering. Furthermore, we have seen new developments in clinical assessment approaches and treatment strategies in the recent past. Here, we review the emerging frontiers in the pathobiology and clinical management of DED.

RevDate: 2019-09-12

Sharma D, Sandhya P, Vellarikkal SK, et al (2019)

Saliva microbiome in primary Sjogren's syndrome reveals distinct set of disease associated microbes.

Oral diseases [Epub ahead of print].

OBJECTIVE: This study systematically aims to evaluate the salivary microbiome in patients with primary Sjögren's syndrome(pSS) using 16S rRNA sequencing approach.

METHODS: DNA isolation and 16S rRNA sequencing was performed on saliva of 37 pSS and 35 control (CC) samples on HiSeq 2500 platform. 16S rRNA sequence analysis was performed independently using two popular computational pipelines, QIIME and LoTuS.

RESULTS: There were no significant changes in the alpha diversity between saliva of patients and controls. However, four genera including Bifidobacterium, Lactobacillus, Dialister and Leptotrichia were found to be differential between the two sets, and common between both QIIME and LoTuS analysis pipelines (Fold change of 2 and p < 0.05). Bifidobacterium, Dialister and Lactobacillus were found to be enriched, while Leptotrichia was significantly depleted in pSS compared to the controls. Exploration of microbial diversity measures (Chao, Observed Species and Shannon Index) revealed a significant increase in the diversity in patients with renal tubular acidosis. An opposite trend was noted, with depletion of diversity in patients with steroids.

CONCLUSION: Our analysis suggests that while no significant changes in the diversity of the salivary microbiome could be observed in Sjogren's syndrome compared to the controls, a set of four genera were significantly and consistently differential in the saliva of patients with pSS. Additionally, a difference in alpha diversity in patients with renal tubular acidosis and those on steroids was observed.

RevDate: 2019-09-12

Gabay O, Vicenty J, Zack-Taylor A, et al (2019)

Exposure to TNF Antagonist Therapies Induces Variations of the Gut Microbiota in an in vivo Model Using Healthy Mice.

RevDate: 2019-09-12

Getachew B, Y Tizabi (2019)

Antidepressant Effects of Moxidectin, an Antiparasitic Drug, in a Rat Model of Depression.

Behavioural brain research pii:S0166-4328(19)31059-9 [Epub ahead of print].

Substantial data indicate that an imbalance in gut microbiome (GM), also referred to as dysbiosis, may play an important role in depression. Moreover, drugs that normalize GM can result in an antidepressant-like effect. It was reported recently that moxidectin (MOX), an antiparasitic drug commonly used in veterinary medicine, has a positive influence on microbiota implicated in mood regulation. We undertook this study to determine whether MOX would actually show antidepressant-like properties in an animal model of depression and whether it would affect the hippocampal and frontal cortex levels of brain-derived neurotrophic factor (BDNF) or tumor necrosis factor (TNF)-alpha, peptides that have been implicated in pathogenesis of depression and effectiveness of various antidepressants. Adult male Wistar-Kyoto rats, a putative animal model of depression, were treated with a single dose of MOX (2.5 mg/kg, i.p.) and their performance in the open field locomotor activity (OFLA) as well as in the forced swim test (FST) was evaluated at 24 h, one week and two weeks after the single injection. A separate group of rats were injected with 2.5 mg/kg MOX and sacrificed 24 h later for neurochemical evaluations. MOX resulted in a decrease in immobility score after 24 h, whereas OFLA was not affected. Concomitant with the 24 h behavioral effects, the levels of hippocampal and frontal cortical BDNF were significantly increased, whereas the levels of TNF-alpha in both these areas were significantly decreased. The decrease in immobility scores was still evident after one week, but not 2 weeks of rest. These results indicate long lasting antidepressant effects of a single MOX dose and suggest potential utility of this drug in treatment-resistant depression.

RevDate: 2019-09-12

Martinez-Guryn K, Leone V, EB Chang (2019)

Regional Diversity of the Gastrointestinal Microbiome.

Cell host & microbe, 26(3):314-324.

The role of gut microbes in health and disease has often been surmised from stool, which is easily sampled and rich in microbial diversity, density, and abundance. Microbial analyses of stool have been accepted as measures to determine the relationship of gut microbiomes with host health and disease, based on the belief that it represents all microbial populations throughout the gut. However, functional heterogeneity of each gastrointestinal tract (GIT) segment gives rise to regional differences in gut microbial populations. Herein, we summarize the literature regarding the microbial landscape along the rostral to caudal, i.e., horizontal mouth to anus, axis of the GIT. We aim to identify gaps in the literature, particularly regarding small intestinal microbiota abundance and diversity, highlight the importance of regional microbiota on host health and disease, as well as discuss opportunities to advance this line of research.

RevDate: 2019-09-12

Neu J (2019)

Fueling the Optimal Microbiome: Interventions for Severe Acute Malnutrition.

Cell host & microbe, 26(3):307-308.

Studies of the intestinal microbial environment largely focus on microbial taxonomy, without clarifying their health benefits. Two recent studies (Raman et al. and Gehrig et al.) classify microbial environments into "ecogroups" that provide insight into their metabolic and/or nutritional pathways and how this can be used for interventions in malnourished children.

RevDate: 2019-09-12

Yurtdaş G, Y Akdevelioğlu (2019)

A New Approach to Polycystic Ovary Syndrome: The Gut Microbiota.

Journal of the American College of Nutrition [Epub ahead of print].

Polycystic ovary syndrome (PCOS) is a widespread endocrine disease that affects 6% to 20% of women of reproductive age and is associated with high risk of infertility, obesity, and insulin resistance. Although genetic, neuroendocrine, and metabolic causes have been stated to lead to PCOS, the etiology of PCOS remains unclear. Recent studies in humans and rodent models have shown an association between changes in the gut microbiome and the metabolic and clinical parameters of PCOS. In addition, it has been proposed that dysbiosis of gut microbiota may be a potential pathogenetic factor in the development of PCOS. In this context, modification of gut microbiota with probiotic, prebiotic, and synbiotic agents suggests that these products may serve as new treatment options for PCOS. In this review, it is aimed to explain the relationship between PCOS and gut microbiota with possible mechanisms and to examine the new treatment approaches that can be developed in this direction. Key teaching points Studies have shown that gut microbiota may be a potential pathogenetic factor in the development of PCOS. Dysbiosis of gut microbiota in women with PCOS appears to be associated with PCOS phenotypes. Studies suggest that insulin resistance, sex hormone concentrations, and obesity may affect the diversity and composition of gut microbiota in women with PCOS. With better understanding of the role of intestinal microbiota in PCOS, interventions including prebiotics, probiotics, and synbiotics can be considered as future treatment options.

RevDate: 2019-09-12

Subirats J, Domingues A, E Topp (2019)

Does Dietary Consumption of Antibiotics by Humans Promote Antibiotic Resistance in the Gut Microbiome?.

Journal of food protection [Epub ahead of print].

Mandated authorities have developed principles for evaluating the safety of antimicrobial residues in food and have established microbiological acceptable daily intakes (ADIs) and recommended maximum residue limits (MRLs) for antibiotic residues in food products. The evaluation of the ADI is based in relevant scientific information such as MIC data of predominant human intestinal bacteria. However, it does not include data derived from minimal selective concentration (MSC) predictions that estimate the lowest concentration of an antibiotic that will provide resistant bacteria an advantage over susceptible bacteria. Based on these insights, we sought to determine whether human exposure to selected antibiotics through ingestion of foodstuffs could result in colon concentrations exceeding apparent MSCs. Nine antibiotics-tetracycline, oxytetracycline, ciprofloxacin, sarafloxacin, erythromycin, spiramycin, tilmicosin, tylosin, and lincomycin-were selected for analysis. Dietary exposure was estimated either using published measured antibiotic concentrations in foodstuffs or using ADI values or food MRLs and a conservative diet. Using the ADI, the estimated antibiotic residue concentrations in the human colon of all antibiotics assessed may be up to a 1,000-fold greater than the predicted MSCs. When the dietary exposure assessment used MRLs or measured concentration in foodstuffs, the estimated concentrations were considerably lower but still within the MSC range for most of the foodstuffs assessed. These results suggest that the ingestion of antibiotic residues through food consumption may expose intestinal microbiota to antibiotic concentrations exceeding the MSC boundaries, thus favoring the growth of potential resistant bacteria. We suggest that MRL and ADI values be revisited in light of the recognition that antibiotic concentrations significantly below the MIC may select for resistance.

RevDate: 2019-09-12

Xu Z, Liu X, Niu Y, et al (2019)

Skin benefits of moisturising body wash formulas for children with atopic dermatitis: A randomised controlled clinical study in China.

The Australasian journal of dermatology [Epub ahead of print].

BACKGROUND: It acknowledged that skin care is an important part of atopic dermatitis therapy. However, clinical evidences are limited for the best bathing practices, especially the skin health performance of cleansing products on children's atopic dermatitis skin.

METHODS: A randomised controlled clinical study was conducted in China among 4- to 18-year-old children with mild-to-moderate atopic dermatitis to evaluate the skin health effect of three cleansing systems (a mild synthetic bar, an ultra-mild body wash with lipids, and an ultra-mild body wash with lipids and zinc pyrithione) by measuring SCORing of Atopic Dermatitis (SCORAD), consumption of topical corticosteroid and the characteristics of microbiome.

RESULTS: Increased Staphylococcus aureus abundance and decreased microbial diversity were observed in atopic dermatitis lesion sites compared with healthy control sites. After 4 weeks of treatment, all three treatments showed clinically important improvement from baseline in SCORAD. Four-week corticosteroid consumption was significantly lower for the two body wash groups than the bar group. A significant decrease in S. aureus abundance and increase in microbial diversity were observed in the lesion sites for the two body wash formulas, while the microbial diversity was statistically insignificant for the mild cleansing bar group. However, there were no incremental benefits provided by the body wash formulas based on the assessment of SCORAD.

CONCLUSIONS: These results demonstrated the safety and efficacy of using the investigational body wash formulas with lipids in reducing the needs for corticosteroid and improving the healthy composition of skin microbiome vs. the mild synthetic bar soap.

RevDate: 2019-09-12

Wang S, Peng R, Qin S, et al (2019)

Effects of oligosaccharide-sialic acid (OS) compound on maternal-newborn gut microbiome, glucose metabolism and systematic immunity in pregnancy: protocol for a randomised controlled study.

BMJ open, 9(9):e026583 pii:bmjopen-2018-026583.

INTRODUCTION: The gut microbiota participates in multiple human biological processes, including metabolism and immune responses. During pregnancy, the dynamics of gut microbiota is involved in physiological adaptation. The disturbed profile of microbiome is associated with maternal complications, such as gestational diabetes mellitus (GDM), which further transfers to the offspring and influence their metabolic and immunological functions in the long term. Prebiotics targeting the gut microbiota and modulating metabolic and immune functions have been shown to be effective in non-pregnant populations with metabolic syndrome. Hence, we propose the use of a prebiotic supplement, oligosaccharide-sialic acid (OS) from the first trimester until delivery in pregnant women, can benefit maternal/new-born gut microbiome, glucose metabolism and innate immunity.

METHODS AND ANALYSIS: In this prospective double-blinded randomised clinical trial, recruited singleton pregnancies will be stratified by body mass index (BMI) and randomly assigned to consume the OS preparation or placebo daily from the first trimester. At seven later time points (before and after recruitment in the first trimester, in the middle and third trimesters, before delivery, at birth and 42 days postpartum), compliance will be evaluated and/or biological samples will be collected. Along with maternal clinical information, questionnaires on lifestyle and infant development will be recorded. The primary outcomes are the effect of OS on the maternal-offspring gut microbiome and GDM incidence. The secondary outcomes are maternal glycolipid biochemical parameters, cytokine profiles, weight gain during pregnancy and infant morbidities, growth and development. The study aims to validate the effects of OS on reducing maternal morbidity within different BMI groups. The multiple dimensional dataset generated from the study includes clinical and lifestyle-related information, various biological markers and associated protective or risk factors for morbidity and prognosis. An extended follow-up through 42 days after birth could further explore the intrauterine influence on the long-term health of offspring.

ETHICS AND DISSEMINATION: This protocol has been approved by Peking University First Hospital, National Unit of Clinical Trial Ethics Committee (reference number: 164). The results are expected to be published in scientific manuscripts by 2021.


RevDate: 2019-09-12

Zemouri C, Jakubovics NS, Crielaard W, et al (2019)

Resistance and resilience to experimental gingivitis: a systematic scoping review.

BMC oral health, 19(1):212 pii:10.1186/s12903-019-0889-z.

BACKGROUND: This systematic scoping review aimed to identify changes in biomarkers of microbiological, immunological and biochemical origin during experimental gingivitis (EG) studies that might indicate resistance and resilience.

METHODS: The term 'experimental gingivitis' was run in PubMed from inception to April 11th, 2018. From the 411 studies retrieved, 22 studies were included for this review.

RESULTS: Studies reporting data on biomarker changes during and after full mouth EG trial were included. Two studies reported findings on changes in biomarkers of microbiological, 12 on immunological and eight on biochemical origin. Changes were reported in the induction phase, and occasionally in the resolution phase. The microbiological composition of both supragingival and subgingival dental plaque changed over the course of EG to a more pathogenic direction, but showed a shift back to a more normal composition. This indicates resilience of the oral microbiome. For immunological biomarkers, it was challenging to retrieve a robust pattern of changes across multiple studies. IL-1β and IL-6 in saliva and in gingival crevicular fluid increased during induction phase and returned in the resolution phase below baseline values. The biochemical parameters cystatin-SN, cystatin-S and lactoferrin in saliva were increased at the end of induction phase, however also here no clear pattern emerged based on all available studies.

CONCLUSIONS: More research is needed to investigate which microbiological, immunological, and biochemical biomarkers can be useful for future investigations into the resistance and resilience of the oral cavity to experimental gingivitis.

RevDate: 2019-09-12

Tavakoli S, S Yooseph (2019)

Learning a mixture of microbial networks using minorization-maximization.

Bioinformatics (Oxford, England), 35(14):i23-i30.

MOTIVATION: The interactions among the constituent members of a microbial community play a major role in determining the overall behavior of the community and the abundance levels of its members. These interactions can be modeled using a network whose nodes represent microbial taxa and edges represent pairwise interactions. A microbial network is typically constructed from a sample-taxa count matrix that is obtained by sequencing multiple biological samples and identifying taxa counts. From large-scale microbiome studies, it is evident that microbial community compositions and interactions are impacted by environmental and/or host factors. Thus, it is not unreasonable to expect that a sample-taxa matrix generated as part of a large study involving multiple environmental or clinical parameters can be associated with more than one microbial network. However, to our knowledge, microbial network inference methods proposed thus far assume that the sample-taxa matrix is associated with a single network.

RESULTS: We present a mixture model framework to address the scenario when the sample-taxa matrix is associated with K microbial networks. This count matrix is modeled using a mixture of K Multivariate Poisson Log-Normal distributions and parameters are estimated using a maximum likelihood framework. Our parameter estimation algorithm is based on the minorization-maximization principle combined with gradient ascent and block updates. Synthetic datasets were generated to assess the performance of our approach on absolute count data, compositional data and normalized data. We also addressed the recovery of sparse networks based on an l1-penalty model.

MixMPLN is implemented in R and is freely available at

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RevDate: 2019-09-12

Sayyari E, Kawas B, S Mirarab (2019)

TADA: phylogenetic augmentation of microbiome samples enhances phenotype classification.

Bioinformatics (Oxford, England), 35(14):i31-i40.

MOTIVATION: Learning associations of traits with the microbial composition of a set of samples is a fundamental goal in microbiome studies. Recently, machine learning methods have been explored for this goal, with some promise. However, in comparison to other fields, microbiome data are high-dimensional and not abundant; leading to a high-dimensional low-sample-size under-determined system. Moreover, microbiome data are often unbalanced and biased. Given such training data, machine learning methods often fail to perform a classification task with sufficient accuracy. Lack of signal is especially problematic when classes are represented in an unbalanced way in the training data; with some classes under-represented. The presence of inter-correlations among subsets of observations further compounds these issues. As a result, machine learning methods have had only limited success in predicting many traits from microbiome. Data augmentation consists of building synthetic samples and adding them to the training data and is a technique that has proved helpful for many machine learning tasks.

RESULTS: In this paper, we propose a new data augmentation technique for classifying phenotypes based on the microbiome. Our algorithm, called TADA, uses available data and a statistical generative model to create new samples augmenting existing ones, addressing issues of low-sample-size. In generating new samples, TADA takes into account phylogenetic relationships between microbial species. On two real datasets, we show that adding these synthetic samples to the training set improves the accuracy of downstream classification, especially when the training data have an unbalanced representation of classes.

TADA is available at

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RevDate: 2019-09-12

Valdes C, Stebliankin V, G Narasimhan (2019)

Large scale microbiome profiling in the cloud.

Bioinformatics (Oxford, England), 35(14):i13-i22.

MOTIVATION: Bacterial metagenomics profiling for metagenomic whole sequencing (mWGS) usually starts by aligning sequencing reads to a collection of reference genomes. Current profiling tools are designed to work against a small representative collection of genomes, and do not scale very well to larger reference genome collections. However, large reference genome collections are capable of providing a more complete and accurate profile of the bacterial population in a metagenomics dataset. In this paper, we discuss a scalable, efficient and affordable approach to this problem, bringing big data solutions within the reach of laboratories with modest resources.

RESULTS: We developed Flint, a metagenomics profiling pipeline that is built on top of the Apache Spark framework, and is designed for fast real-time profiling of metagenomic samples against a large collection of reference genomes. Flint takes advantage of Spark's built-in parallelism and streaming engine architecture to quickly map reads against a large (170 GB) reference collection of 43 552 bacterial genomes from Ensembl. Flint runs on Amazon's Elastic MapReduce service, and is able to profile 1 million Illumina paired-end reads against over 40 K genomes on 64 machines in 67 s-an order of magnitude faster than the state of the art, while using a much larger reference collection. Streaming the sequencing reads allows this approach to sustain mapping rates of 55 million reads per hour, at an hourly cluster cost of $8.00 USD, while avoiding the necessity of storing large quantities of intermediate alignments.

Flint is open source software, available under the MIT License (MIT). Source code is available at

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RevDate: 2019-09-12

Prochazkova P, Roubalova R, Dvorak J, et al (2019)

Microbiota, Microbial Metabolites, and Barrier Function in A Patient with Anorexia Nervosa after Fecal Microbiota Transplantation.

Microorganisms, 7(9): pii:microorganisms7090338.

The change in the gut microbiome and microbial metabolites in a patient suffering from severe and enduring anorexia nervosa (AN) and diagnosed with small intestinal bacterial overgrowth syndrome (SIBO) was investigated. Microbial gut dysbiosis is associated with both AN and SIBO, and therefore gut microbiome changes by serial fecal microbiota transplantation (FMT) is a possible therapeutic modality. This study assessed the effects of FMT on gut barrier function, microbiota composition, and the levels of bacterial metabolic products. The patient treatment with FMT led to the improvement of gut barrier function, which was altered prior to FMT. Very low bacterial alpha diversity, a lack of beneficial bacteria, together with a great abundance of fungal species were observed in the patient stool sample before FMT. After FMT, both bacterial species richness and gut microbiome evenness increased in the patient, while the fungal alpha diversity decreased. The total short-chain fatty acids (SCFAs) levels (molecules presenting an important source of energy for epithelial gut cells) gradually increased after FMT. Contrarily, one of the most abundant intestinal neurotransmitters, serotonin, tended to decrease throughout the observation period. Overall, gut microbial dysbiosis improvement after FMT was considered. However, there were no signs of patient clinical improvement. The need for an in-depth analysis of the donor´s stool and correct selection pre-FMT is evident.

RevDate: 2019-09-12

Di Iorio BR, Rocchetti MT, De Angelis M, et al (2019)

Nutritional Therapy Modulates Intestinal Microbiota and Reduces Serum Levels of Total and Free Indoxyl Sulfate and P-Cresyl Sulfate in Chronic Kidney Disease (Medika Study).

Journal of clinical medicine, 8(9): pii:jcm8091424.

In chronic kidney disease (CKD), the gut-microbiota metabolites indoxyl sulfate (IS) and p-cresyl sulfate (PCS) progressively accumulate due to their high albumin-binding capacity, leading to clinical complications. In a prospective crossover controlled trial, 60 patients with CKD grades 3B-4 (GFR = 21.6 ± 13.2 mL/min) were randomly assigned to two dietary regimens: (i) 3 months of free diet (FD) (FD is the diet usually used by the patient before being enrolled in the Medika study), 6 months of very low protein diet (VLPD), 3 months of FD and 6 months of Mediterranean diet (MD); (ii) 3 months of FD, 6 months of MD, 3 months of FD, and 6 months of VLPD. VLPD reduced inflammatory Proteobacteria and increased Actinobacteria phyla. MD and VLPD increased some butyrate-forming species of Lachnospiraceae, Ruminococcaceae, Prevotellaceae, Bifidobacteriaceae, and decrease the pathobionts Enterobacteriaceae. The increased level of potential anti-inflammatory Blautia and Faecalibacterium, as well as butyrate-forming Coprococcus and Roseburia species in VLPD was positively associated with dietary intakes and it was negatively correlated with IS and PCS. Compared to FD and MD, VLPD showed a lower amount of some Lactobacillus, Akkermansia, Streptococcus, and Escherichia species. MD and VLPD reduced both the total and free serum IS (MD -36%, -40% and VLPD -69%, -73%, respectively) and PCS (MD -38%, -44% and VLPD -58%, -71%, respectively) compared to FD. VLPD reduced serum D-lactate compared to MD and FD. MD and, to a greater extent, VLPD are effective in the beneficial modulation of gut microbiota, reducing IS and PCS serum levels, and restoring intestinal permeability in CKD patients.

RevDate: 2019-09-12

Yasukawa Z, Inoue R, Ozeki M, et al (2019)

Effect of Repeated Consumption of Partially Hydrolyzed Guar Gum on Fecal Characteristics and Gut Microbiota: A Randomized, Double-Blind, Placebo-Controlled, and Parallel-Group Clinical Trial.

Nutrients, 11(9): pii:nu11092170.

Partially hydrolyzed guar gum (PHGG) is a water-soluble dietary fiber and is used in solid and liquid food to regulate gut function. The aim of this study was to investigate effects of PHGG on bowel movements (stool form and frequency), plasma bile acids, quality of life, and gut microbiota of healthy volunteers with a tendency toward diarrhea, i.e., irritable bowel syndrome diarrhea (IBS-D)-like symptoms. A randomized, double-blind, placebo-controlled, and parallel trial was performed on 44 healthy volunteers (22 males, 22 females, 41.9 ± 6.3 years old (average ± SD)) with minimum 7 bowel movements every week, wherein above 50% of their stool was between the Bristol stool scale (BSS) value of 5 and 6. Intake of the PHGG for 3 months significantly improved stool form, evaluated using BSS, and had no effects on stool frequency. BSS was significantly normalized in the group consuming the PHGG compared with the placebo. Comprehensive fecal microbiome analysis by the 16S rRNA-sequence method detected significant changes in the ratio of some bacteria, such as an increase of Bifidobacterium (p < 0.05) in the PHGG group. Our results suggest that intake of PHGG improves human stool form via regulating intestinal microbiota.

RevDate: 2019-09-11

Nie J, Zhang L, Zhao G, et al (2019)

Quercetin reduces atherosclerotic lesions by altering the gut microbiota and reducing atherogenic lipid metabolites.

Journal of applied microbiology [Epub ahead of print].

AIMS: Epidemiological studies have correlated cardiovascular disease (CVD) and atherosclerosis with lifestyle factors such as sedentary behavior and a high-calorie diet. Recent studies of pathogenesis have highlighted the significance of the intestinal microbiota and chronic inflammation with respect to both the onset and development of atherosclerosis. This study examined the hypothesis that the oral administration of quercetin to low-density lipoprotein receptor-null (Ldlr-/-) mice would improve gut health by altering the gut microbiota and controlling the levels of atherogenic lipid metabolites and pro-inflammatory mediators in the intestine and serum.

METHODS AND RESULTS: Mice were maintained on a high-fat diet with or without oral quercetin administration for 12 weeks. Quercetin treatment suppressed body weight gains and reduced the extent of atherosclerotic lesions in the aortic sinus. Reduced malondialdehyde (MDA) and increased interleukin 6 (IL-6) levels further indicated the protective effect of quercetin against immune/inflammatory responses and oxidative stress. Furthermore, quercetin led to decreased intestinal levels of cholesterol, lysophosphatidic acids (LPAs) and atherogenic lysophosphatidylcholine (LPC 18:1) and an increased level of coprostanol. A phylum-level microbial analysis revealed that quercetin treatment reduced the abundance of Verrocomicrobia and increased microbiome diversity and the abundances of Actinobacteria, Cyanobacteria and Firmicutes. A Spearman analysis revealed negative correlations of Actinobacteria with intestinal and plasma LPC 18:1 and cecal cholesterol levels and of Firmicutes and Cyanobacteria with the plasma LPC 18:1 level.

CONCLUSIONS: This study demonstrated the ability of quercetin treatment to reduce lipid levels, as well as the areas of atherosclerotic lesions and sizes of plaques. This treatment also altered the composition of the gut microbiota and decreased the levels of atherogenic lipid metabolites.

Oral quercetin treatment may represent a new approach to mitigating the onset and development of atherosclerosis.

RevDate: 2019-09-11

King CH, Desai H, Sylvetsky AC, et al (2019)

Baseline human gut microbiota profile in healthy people and standard reporting template.

PloS one, 14(9):e0206484 pii:PONE-D-18-29457.

A comprehensive knowledge of the types and ratios of microbes that inhabit the healthy human gut is necessary before any kind of pre-clinical or clinical study can be performed that attempts to alter the microbiome to treat a condition or improve therapy outcome. To address this need we present an innovative scalable comprehensive analysis workflow, a healthy human reference microbiome list and abundance profile (GutFeelingKB), and a novel Fecal Biome Population Report (FecalBiome) with clinical applicability. GutFeelingKB provides a list of 157 organisms (8 phyla, 18 classes, 23 orders, 38 families, 59 genera and 109 species) that forms the baseline biome and therefore can be used as healthy controls for studies related to dysbiosis. This list can be expanded to 863 organisms if closely related proteomes are considered. The incorporation of microbiome science into routine clinical practice necessitates a standard report for comparison of an individual's microbiome to the growing knowledgebase of "normal" microbiome data. The FecalBiome and the underlying technology of GutFeelingKB address this need. The knowledgebase can be useful to regulatory agencies for the assessment of fecal transplant and other microbiome products, as it contains a list of organisms from healthy individuals. In addition to the list of organisms and their abundances, this study also generated a collection of assembled contiguous sequences (contigs) of metagenomics dark matter. In this study, metagenomic dark matter represents sequences that cannot be mapped to any known sequence but can be assembled into contigs of 10,000 nucleotides or higher. These sequences can be used to create primers to study potential novel organisms. All data is freely available from and NCBI's Short Read Archive.

RevDate: 2019-09-11

Berlin P, Reiner J, Witte M, et al (2019)

Nod2 deficiency functionally impairs adaptation to short bowel syndrome via alterations of the epithelial barrier function.

American journal of physiology. Gastrointestinal and liver physiology [Epub ahead of print].

Nucleotide-binding oligomerization domain-containing protein 2 (Nod2) gene mutations are a risk factor for Crohn´s disease and also associated with worse outcome in short bowel syndrome (SBS) patients, independent of the underlying disease. The aim of the study was to analyze the effect of Nod2 deficiency on barrier function and stool microbiome after extensive ileocecal resection in mice. Male C57BL6/J wild-type and Nod2 knock-out mice underwent 40% ileocecal resection. Sham control mice received simple transection of the ileum. Clinical outcome was monitored daily. Barrier function was measured with Ussing chambers using FITC-4-kDa-Dextran flux, transmucosal electrical resistance and dilution potentials. Immunofluorescence of claudin-2 was studied. Composition of the stool microbiome was assessed by 16S rRNA gene sequencing. Resected Nod2 KO mice had impaired clinical outcome compared to resected WT mice. This was accompanied by increased stool water contents and increased plasma aldosterone. Histomorphological adaptation was independent of Nod2. Barrier function studies revealed impaired sodium to chloride permeability and altered claudin-2 localization in the absence of Nod2. Resection induced decreases of bacterial diversity and a shift of Bacteriodetes/Firmicutes ratios. ICR-induced increase in Proteobacteria was absent in Nod2-deficient mice. Verrucomicrobia temporarilly increased in Nod2 KO mice. Nod2 deficiency functionally impairs adaptation to short bowel syndrome via a lesser increase of epithelial sodium pore permeability, altered epithelial barrier function and the microbiome.

RevDate: 2019-09-11

Tiffany CR, AJ Baumler (2019)

Dysbiosis: from fiction to function.

American journal of physiology. Gastrointestinal and liver physiology [Epub ahead of print].

Advances in data collection technologies reveal that an imbalance (dysbiosis) in the composition of host-associated microbial communities (microbiota) is linked to many human illnesses. This association makes dysbiosis a central concept for understanding how the human microbiota contributes to health and disease. However, it remains problematic to define the term dysbiosis by cataloguing microbial species names. Here we discuss how incorporating the germ-organ concept, ecological assumptions and immunological principles into a theoretical framework for microbiota research provides a functional definition for dysbiosis. The generation of such a framework suggests that the next logical step in microbiota research will be to illuminate the mechanistic underpinnings of dysbiosis, which often involves a weakening of immune mechanisms that balance our microbial communities.

RevDate: 2019-09-11

Zhou F, Paz HA, Sadri M, et al (2019)

Dietary Bovine Milk Exosomes Elicit Changes in Bacterial Communities in C57BL/6 Mice.

American journal of physiology. Gastrointestinal and liver physiology [Epub ahead of print].

Exosomes and exosome-like vesicles participate in cell-to-cell communication in animals, plant and bacteria. Dietary exosomes in bovine milk are bioavailable in non-bovine species, but a fraction of milk exosomes reaches the large intestine. We hypothesized that milk exosomes alter the composition of the gut microbiome in mice. C57BL/6 mice were fed AIN-93G diets, defined by their content of bovine milk exosomes and RNA cargos: exosome/RNA-depleted (ERD) versus exosome/RNA-sufficient (ERS) diets. Feeding was initiated at age three weeks and cecum content was collected at ages 7, 15 and 47 weeks. Microbial communities were identified by 16S rRNA gene sequencing. Milk exosomes altered bacterial communities in the murine cecum. The abundance of three phyla, seven families and 52 operational taxonomic units (OTUs) was different in the ceca from mice fed ERD and ERS (P < 0.05). For example, at the phylum level, Tenericutes were more than three-fold abundance in ERS mice at ages 15 and 47 weeks compared with ERD mice (P < 0.05). At the family level, Verrucomicrobiaceae were much less abundant in ERS mice compared with ERD mice age 47 weeks (P < 0.05). At the OTU level, four OTUs from the family of Lachnospiraceae were more than 2 times more abundant in ERS mice compared with ERD at age 7 and 47 weeks (P < 0.05). We conclude that exosomes in bovine milk alter microbial communities in non-bovine species, suggesting that exosomes and their cargos participate in the crosstalk between bacterial and animal kingdoms.

RevDate: 2019-09-11

van Mierlo MMF, Totté JEE, Fieten KB, et al (2019)

The influence of treatment in alpine and moderate maritime climate on the composition of the skin microbiome in patients with difficult to treat atopic dermatitis.

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology [Epub ahead of print].

BACKGROUND: The skin microbiome, characterized by an overgrowth of Staphylococcus aureus, plays an important role in the pathogenesis of atopic dermatitis (AD). Multidisciplinary treatment in alpine climate is known for its positive effect on disease severity in children with AD and can result in a different immune response compared to moderate maritime climate. However, the effect on the composition of the skin microbiome in AD is unknown.

OBJECTIVE: To determine the effect of treatment in alpine climate and moderate maritime climate on the microbiome for lesional and non-lesional skin in children with difficult to treat AD.

METHODS: This study is part of the DAVOS trial (ISRCTN88136485), a pragmatic randomized controlled trial in which 84 children with difficult to treat AD were randomized to a six week personalized integrative multidisciplinary treatment in either alpine climate (intervention) or moderate maritime climate (control). Before and directly after treatment, swabs were collected from lesional and non-lesional skin and analyzed using 16S rRNA sequencing. Additional quantitative (q)PCR for Staphylococcus aureus and Staphylococcus epidermidis was performed.

RESULTS: Alpine climate treatment led to a significant change in the microbiota on lesional skin, whereas no significant change was found after moderate maritime climate. On both lesional and non-lesional skin we observed a significant increase in Shannon diversity and a significant decrease in both Staphylococcus abundance and S. aureus load after alpine climate treatment. The decrease in S. aureus was significantly larger on lesional skin following alpine climate treatment compared to moderate maritime climate treatment. S. epidermidis load was stable over time.

Alpine climate treatment leads to significant changes in the composition of the skin microbiome in children with AD, mainly caused by a reduction in the Staphylococcus genus. This study shows new perspectives in the potential mode of action for therapies in AD. This article is protected by copyright. All rights reserved.

RevDate: 2019-09-11

Araujo R, Dunlap C, Barnett S, et al (2019)

Decoding Wheat Endosphere-Rhizosphere Microbiomes in Rhizoctonia solani-Infested Soils Challenged by Streptomyces Biocontrol Agents.

Frontiers in plant science, 10:1038.

The endosphere and the rhizosphere are pertinent milieus with microbial communities that perturb the agronomic traits of crop plants through beneficial or detrimental interactions. In this study, we challenged these communities by adding Streptomyces biocontrol strains to wheat seeds in soils with severe Rhizoctonia solani infestation. Wheat plants were grown in a glasshouse standardized system, and the bacterial and fungal microbiomes of 233 samples of wheat roots (endosphere) and rhizosphere soils were monitored for 20 weeks, from seed to mature plant stage. The results showed highly dynamic and diverse microbial communities that changed over time, with Sphingomonas bacteria and Aspergillus, Dipodascus, and Trichoderma fungi increasing over time. Application of biocontrol Streptomyces strains promoted plant growth and maturation of wheat heads and modulated the root microbiome, decreasing Paenibacillus and increasing other bacterial and fungal OTUs. The soils with the highest levels of R. solani had increased reads of Thanatephorus (Rhizoctonia anamorph) and increased root disease levels and increased Balneimonas, Massilia, Pseudomonas, and unclassified Micrococcaceae. As we enter the era of biologically sustainable agriculture, it may be possible to reduce and limit the effects of serious fungal infestations by promoting a beneficial microbiome through the application of biocontrol agents during different periods of plant development.

RevDate: 2019-09-11

Turon M, Cáliz J, Triadó-Margarit X, et al (2019)

Sponges and Their Microbiomes Show Similar Community Metrics Across Impacted and Well-Preserved Reefs.

Frontiers in microbiology, 10:1961.

Sponge diversity has been reported to decrease from well-preserved to polluted environments, but whether diversity and intra-species variation of their associated microbiomes also change as function of environmental quality remains unknown. Our study aimed to assess whether microbiome composition and structure are related to the proliferation of some sponges and not others under degraded conditions. We characterized the most frequent sponges and their associated bacteria in two close areas (impacted and well-preserved) of Nha Trang Bay (Indo-Pacific). Sponge assemblages were richer and more diverse in the well-preserved reefs, but more abundant (individuals/m. transect) in the impacted environments, where two species (Clathria reinwardti and Amphimedon paraviridis) dominated. Sponge microbiomes from the polluted zones had, in general, lower bacterial diversity and core size and consequently, higher intra-species dispersion than microbiomes of sponges from the well-preserved environments. Microbial communities reflect the reduction of diversity and richness shown by their host sponges. In this sense, sponges with less complex and more variable microbiomes proliferate under degraded environmental conditions, following the ecological paradigm that negatively correlates community diversity and environmental degradation. Thereby, the diversity and structure of sponge microbiomes might indirectly determine the presence and proliferation of sponge species in certain habitats.

RevDate: 2019-09-11

Garcia-Lemos AM, Großkinsky DK, Stokholm MS, et al (2019)

Root-Associated Microbial Communities of Abies nordmanniana: Insights Into Interactions of Microbial Communities With Antioxidative Enzymes and Plant Growth.

Frontiers in microbiology, 10:1937.

Abies nordmanniana is a major Christmas tree species in Europe, but their uneven and prolonged growth slows down their production. By a 16S and 18S rRNA gene amplicon sequencing approach, we performed a characterization of root-associated bacterial and fungal communities for three-year-old A. nordmanniana plants collected from two nurseries in Denmark and Germany and displaying different growth patterns (small versus tall plants). Proteobacteria had the highest relative abundance at both sampling sites and plant sizes, and Ascomycota was the most abundant fungal phylum. At the order level, Acidobacteriales, Actinomycetales, Burkholderiales, Rhizobiales, and Xanthomonadales represented the bacterial core microbiome of A. nordmanniana, independently of the sampling site or plant size, while the fungal core microbiome included members of the Agaricales, Hypocreales, and Pezizales. Principal Coordinate Analysis indicated that both bacterial and fungal communities clustered according to the sampling site pointing to the significance of soil characteristics and climatic conditions for the composition of root-associated microbial communities. Major differences between communities from tall and small plants were a dominance of the potential pathogen Fusarium (Hypocreales) in the small plants from Germany, while Agaricales, that includes reported beneficial ectomycorrhizal fungi, dominated in the tall plants. An evaluation of plant root antioxidative enzyme profiles showed higher levels of the antioxidative enzymes ascorbate peroxidase, peroxidase, and superoxide dismutase in small plants compared to tall plants. We suggest that the higher antioxidative enzyme activities combined with the growth arrest phenotype indicate higher oxidative stress levels in the small plants. Additionally, the correlations between the relative abundances of specific taxa of the microbiome with the plant antioxidative enzyme profiles were established. The main result was that many more bacterial taxa correlated positively than negatively with one or more antioxidative enzyme activity. This may suggest that the ability of bacteria to increase plant antioxidative enzyme defenses is widespread.

RevDate: 2019-09-11

Olekhnovich EI, Manolov AI, Samoilov AE, et al (2019)

Shifts in the Human Gut Microbiota Structure Caused by Quadruple Helicobacter pylori Eradication Therapy.

Frontiers in microbiology, 10:1902.

The human gut microbiome plays an important role both in health and disease. Use of antibiotics can alter gut microbiota composition, which can lead to various deleterious events. Here we report a whole genome sequencing metagenomic/genomic study of the intestinal microbiota changes caused by Helicobacter pylori (HP) eradication therapy. Using approaches for metagenomic data analysis we revealed a statistically significant decrease in alpha-diversity and relative abundance of Bifidobacterium adolescentis due to HP eradication therapy, while the relative abundance of Enterococcus faecium increased. We have detected changes in general metagenome resistome profiles as well: after HP eradication therapy, the ermB, CFX group, and tetQ genes were overrepresented, while tetO and tetW genes were underrepresented. We have confirmed these results with genome-resolved metagenomic approaches. MAG (metagenome-assembled genomes) abundance profiles have changed dramatically after HP eradication therapy. Focusing on ermB gene conferring resistance to macrolides, which were included in the HP eradication therapy scheme, we have shown a connection between antibiotic resistance genes (ARGs) and some overrepresented MAGs. Moreover, some E. faecium strains isolated from stool samples obtained after HP eradication have manifested greater antibiotic resistance in vitro in comparison to other isolates, as well as the higher number of ARGs conferring resistance to macrolides and tetracyclines.

RevDate: 2019-09-11

Bates KA, Shelton JMG, Mercier VL, et al (2019)

Captivity and Infection by the Fungal Pathogen Batrachochytrium salamandrivorans Perturb the Amphibian Skin Microbiome.

Frontiers in microbiology, 10:1834.

The emerging fungal pathogen, Batrachochytrium salamandrivorans (Bsal) is responsible for the catastrophic decline of European salamanders and poses a threat to amphibians globally. The amphibian skin microbiome can influence disease outcome for several host-pathogen systems, yet little is known of its role in Bsal infection. In addition, many experimental in-vivo amphibian disease studies to date have relied on specimens that have been kept in captivity for long periods without considering the influence of environment on the microbiome and how this may impact the host response to pathogen exposure. We characterized the impact of captivity and exposure to Bsal on the skin bacterial and fungal communities of two co-occurring European newt species, the smooth newt, Lissotriton vulgaris and the great-crested newt, Triturus cristatus. We show that captivity led to significant losses in bacterial and fungal diversity of amphibian skin, which may be indicative of a decline in microbe-mediated protection. We further demonstrate that in both L. vulgaris and T. cristatus, Bsal infection was associated with changes in the composition of skin bacterial communities with possible negative consequences to host health. Our findings advance current understanding of the role of host-associated microbiota in Bsal infection and highlight important considerations for ex-situ amphibian conservation programmes.

RevDate: 2019-09-11

Li YF, Xu JK, Chen YW, et al (2019)

Characterization of Gut Microbiome in the Mussel Mytilus galloprovincialis in Response to Thermal Stress.

Frontiers in physiology, 10:1086.

The gut microbiota is essential for utilization of energy and nutrition and may have a role in host immunity in response to environmental shifts. The present study evaluated the temperature stress (increasing from 21 to 27°C) on gut microbiome and dynamics of the mussel Mytilus galloprovincialis by 16S rRNA gene sequencing with the aim of discovering the gut microbiome resilience to warming. Exposure to high temperature of 27°C significantly reduced the survival of M. galloprovincialis associated with increased microbial diversity of gut. The microbial communities were shifted with elevated temperature (from 21 to 27°C) and different exposure time (from day 0 to day 7) by principal coordinate analysis (PCoA). Linear discriminant analysis effect size (LEfSe) revealed that the relative abundance of Vibrio and Arcobacter presented in live animals as the top genus-level biomarkers during the initial exposure to 27°C and followed by microbiomes fluctuation with increasing exposure time at day 4 and day 7. The proliferation of opportunistic pathogens such as genus Vibrio and Arcobacter might increase host susceptibility to disease and contributed greatly to mortality. The results obtained in this study provide the knowledge on ecological adaptation for south domestication of M. galloprovincialis and host-bacteria interaction during temperature stress (27°C).

RevDate: 2019-09-11

Mohan A, Grace J, Wang BR, et al (2019)

The Effects of Obesity in Asthma.

Current allergy and asthma reports, 19(10):49 pii:10.1007/s11882-019-0877-z.

PURPOSE OF REVIEW: Rising costs and increasing morbidity makes the identification and treatment of high-risk asthma phenotypes important. In this review, we outline the complex relationship between obesity and asthma.

RECENT FINDINGS: Studies have confirmed a bi-directional relationship between obesity and asthma. Pathophysiological factors implicated include genetic risk, the effect of diet and microbiome, and obesity-related cytokines. There have been robust, albeit derived, efforts to phenotype this group with distinct clinical presentations based on age of onset of asthma. Unfortunately, the poor performance of biomarkers and traditional lung function testing has impeded diagnosis, phenotyping, and management of the obese asthma patient. There is also a lack of targeted interventions with weight loss showing some benefits. Obesity increases the prevalence of asthma and is associated with worse outcomes. There are unique research and clinical challenges while managing this group of patients.

RevDate: 2019-09-11

Lamei S, Stephan JG, Nilson B, et al (2019)

Feeding Honeybee Colonies with Honeybee-Specific Lactic Acid Bacteria (Hbs-LAB) Does Not Affect Colony-Level Hbs-LAB Composition or Paenibacillus larvae Spore Levels, Although American Foulbrood Affected Colonies Harbor a More Diverse Hbs-LAB Community.

Microbial ecology pii:10.1007/s00248-019-01434-3 [Epub ahead of print].

The main current methods for controlling American Foulbrood (AFB) in honeybees, caused by the bacterial pathogen Paenibacillus larvae, are enforced incineration or prophylactic antibiotic treatment, neither of which is fully satisfactory. This has led to an increased interest in the natural relationships between the pathogenic and mutualistic microorganisms of the honeybee microbiome, in particular, the antagonistic effects of Honeybee-Specific Lactic Acid Bacteria (hbs-LAB) against P. larvae. We investigated whether supplemental administration of these bacteria affected P. larvae infection at colony level over an entire flowering season. Over the season, the supplements affected neither colony-level hbs-LAB composition nor naturally subclinical or clinical P. larvae spore levels. The composition of hbs-LAB in colonies was, however, more diverse in apiaries with a history of clinical AFB, although this was also unrelated to P. larvae spore levels. During the experiments, we also showed that qPCR could detect a wider range of hbs-LAB, with higher specificity and sensitivity than mass spectrometry. Honeybee colonies are complex super-organisms where social immune defenses, natural homeostatic mechanisms, and microbiome diversity and function play a major role in disease resistance. This means that observations made at the individual bee level cannot be simply extrapolated to infer similar effects at colony level. Although individual laboratory larval assays have clearly demonstrated the antagonistic effects of hbs-LAB on P. larvae infection, the results from the experiments presented here indicate that direct conversion of such practice to colony-level administration of live hbs-LAB is not effective.

RevDate: 2019-09-11

Zhao ZH, Xin FZ, Xue Y, et al (2019)

Indole-3-propionic acid inhibits gut dysbiosis and endotoxin leakage to attenuate steatohepatitis in rats.

Experimental & molecular medicine, 51(9):103 pii:10.1038/s12276-019-0304-5.

Microbial metabolites have emerged as critical components that mediate the metabolic effects of the gut microbiota. Here, we show that indole-3-propionic acid (IPA), a tryptophan metabolite produced by gut bacteria, is a potent anti-non-alcoholic steatohepatitis (NASH) microbial metabolite. Here, we demonstrate that administration of IPA modulates the microbiota composition in the gut and inhibits microbial dysbiosis in rats fed a high-fat diet. IPA induces the expression of tight junction proteins, such as ZO-1 and Occludin, and maintains intestinal epithelium homeostasis, leading to a reduction in plasma endotoxin levels. Interestingly, IPA inhibits NF-κB signaling and reduces the levels of proinflammatory cytokines, such as TNFα, IL-1β, and IL-6, in response to endotoxin in macrophages to repress hepatic inflammation and liver injury. Moreover, IPA is sufficient to inhibit the expression of fibrogenic and collagen genes and attenuate diet-induced NASH phenotypes. The beneficial effects of IPA on the liver are likely mediated through inhibiting the production of endotoxin in the gut. These findings suggest a protective role of IPA in the control of metabolism and uncover the gut microbiome and liver cross-talk in regulating the intestinal microenvironment and liver pathology via a novel dietary nutrient metabolite. IPA may provide a new therapeutic strategy for treating NASH.

RevDate: 2019-09-11

Zhang CJ, Pan J, Duan CH, et al (2019)

Prokaryotic Diversity in Mangrove Sediments across Southeastern China Fundamentally Differs from That in Other Biomes.

mSystems, 4(5): pii:4/5/e00442-19.

Mangroves, as a blue carbon reservoir, provide an environment for a variety of microorganisms. Mangroves lie in special locations connecting coastal and estuarine areas and experience fluctuating conditions, which are expected to intensify with climate change, creating a need to better understand the relative roles of stochastic and deterministic processes in shaping microbial community assembly. Here, a study of microbial communities inhabiting mangrove sediments across southeastern China, spanning mangroves in six nature reserves, was conducted. We performed high-throughput DNA sequencing of these samples and compared them with data of 1,370 sediment samples collected from the Earth Microbiome Project (EMP) to compare the microbial diversity of mangroves with that of other biomes. Our results showed that prokaryotic alpha diversity in mangroves was significantly higher than that in other biomes and that microbial beta diversity generally clustered according to biome types. The core operational taxonomic units (OTUs) in mangroves were mostly assigned to Gammaproteobacteria, Deltaproteobacteria, Chloroflexi, and Euryarchaeota The majority of beta nearest-taxon index values were higher than 2, indicating that community assembly in mangroves was better explained through a deterministic process than through a stochastic process. Mean annual precipitation (MAP) and total organic carbon (TOC) were main deterministic factors explaining variation in the microbial community. This study fills a gap in addressing the unique microbial diversity of mangrove ecosystems and their microbial community assembly mechanisms.IMPORTANCE Understanding the underlying mechanisms of microbial community assembly patterns is a vital issue in microbial ecology. Mangroves, as an important and special ecosystem, provide a unique environment for examining the relative importance of stochastic and deterministic processes. We made the first global-scale comparison and found that microbial diversity was significantly different in mangrove sediments compared to that of other biomes. Furthermore, our results suggest that a deterministic process is more important in shaping microbial community assembly in mangroves.

RevDate: 2019-09-11

Moore RE, SD Townsend (2019)

Temporal development of the infant gut microbiome.

Open biology, 9(9):190128.

The majority of organisms that inhabit the human body reside in the gut. Since babies are born with an immature immune system, they depend on a highly synchronized microbial colonization process to ensure the correct microbes are present for optimal immune function and development. In a balanced microbiome, symbiotic and commensal species outcompete pathogens for resources. They also provide a protective barrier against chemical signals and toxic metabolites. In this targeted review we will describe factors that influence the temporal development of the infant microbiome, including the mode of delivery and gestational age at birth, maternal and infant perinatal antibiotic infusions, and feeding method-breastfeeding versus formula feeding. We will close by discussing wider environmental pressures and early intimate contact, particularly between mother and child, as they play a pivotal role in early microbial acquisition and community succession in the infant.

RevDate: 2019-09-10

Paz A, Salinas N, V Matamoros (2019)

Unravelling the role of vegetation in the attenuation of contaminants of emerging concern from wetland systems: Preliminary results from column studies.

Water research, 166:115031 pii:S0043-1354(19)30805-X [Epub ahead of print].

Water pollution with contaminants of emerging concern (CECs) is widespread in water bodies due to the low effectiveness of industrial and urban wastewater treatment systems. In recent decades, the implementation of vegetation-based wastewater treatment systems such as wetlands has been observed to help solve this issue. However, there is a lack of knowledge regarding the removal percentage attributable to plants and how plants affect this removal improvement. In this study, we monitored planted (Phragmites australis) and unplanted sand columns to assess the effect of vegetation on the attenuation of 5 well-known CECs (benzotriazole, sulfamethoxazole, carbamazepine, bisphenol A, and diclofenac) and link it to the presence of different root exudates. The columns were operated in a continuous feeding mode for more than 6 months at 3 hydraulic loading rates (HLRs) (70, 140, and 280 mm d-1). We found that the presence of vegetation increased CEC attenuation from no effect to more than 200% compared to the unplanted columns. The highest effect was observed for carbamazepine (94-200%), followed by diclofenac (22-171%), benzotriazole (48-127%), and sulfamethoxazole (no effect to 43%), depending on the tested HLR. Furthermore, the greater CEC attenuation in planted columns was linked to the release of certain root exudates that may shape the root microbiome. We expect our assay to be a starting point for exploring the role of root exudates in enhancing CEC removal efficiency in wastewater.

RevDate: 2019-09-10

Ghaisas S, Langley MR, Palanisamy BN, et al (2019)

MitoPark Transgenic Mouse Model Recapitulates the Gastrointestinal Dysfunction and Gut-Microbiome Changes of Parkinson's Disease.

Neurotoxicology pii:S0161-813X(19)30088-9 [Epub ahead of print].

Gastrointestinal (GI) disturbances are one of the earliest symptoms affecting most patients with Parkinson's disease (PD). In many cases, these symptoms are observed years before motor impairments become apparent. Hence, the molecular and cellular underpinnings that contribute to this early GI dysfunction in PD using a relevant animal model has actively been explored. The MitoPark model is a chronic, progressive mouse model recapitulating several key pathophysiological aspects of PD. However, GI dysfunction and gut microbiome changes have not been categorized in this model. Herein, we show that decreased GI motility was one of the first non-motor symptoms to develop, evident as early as 8 weeks with significantly different transit times from 12 weeks onwards. These symptoms were observed well before motor symptoms developed, thereby paralleling PD progression in humans. At age 24 weeks, we observed increased colon transit time and reduced fecal water content, indicative of constipation. Intestinal inflammation was evidenced with increased expression of iNOS and TNFα in the small and large intestine. Specifically, iNOS was observed mainly in the enteric plexi, indicating enteric glial cell activation. A pronounced loss of tyrosine hydroxylase-positive neurons occurred at 24 weeks both in the mid-brain region as well as the gut, leading to a corresponding decrease in dopamine (DA) production. We also observed decreased DARPP-32 expression in the colon, validating the loss of DAergic neurons in the gut. However, the total number of enteric neurons did not significantly differ between the two groups. Metabolomic gas chromatography-mass spectrometry analysis of fecal samples showed increased sterol, glycerol, and tocopherol production in MitoPark mice compared to age-matched littermate controls at 20 weeks of age while 16 s microbiome sequencing showed a transient temporal increase in the genus Prevotella. Together, the data shed more light on the role of the gut dopaminergic system in maintaining intestinal health. Importantly, this model recapitulates the chronology and development of GI dysfunction along with other non-motor symptoms and can become an attractive translational animal model for pre-clinical assessment of the efficacy of new anti-Parkinsonian drugs that can alleviate GI dysfunction in PD.

RevDate: 2019-09-10

Tardelli M, Bruschi FV, Fuchs CD, et al (2019)

Monoacylglycerol lipase inhibition protects from liver injury in mouse models of sclerosing cholangitis.

Hepatology (Baltimore, Md.) [Epub ahead of print].

Monoacylglycerol lipase (MGL) is the last enzymatic step in triglyceride degradation, hydrolyzing monoglycerides into glycerol and fatty acids (FA) and converting 2-arachidonoylglycerol into arachidonic acid (AA), thus providing ligands for nuclear receptors (NRs) as key regulators of hepatic bile acid (BA)/lipid metabolism and inflammation. We aimed to explore the role of MGL in the development of cholestatic liver and bile duct injury in mouse models of sclerosing cholangitis (SC), a disease so far lacking effective pharmacological therapy. To this aim we analyzed the effects of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding to induce SC in wild type (WT) and knockout (MGL-/-) mice and tested pharmacological inhibition with JZL184 in the Mdr2-/- mouse model of SC. Cholestatic liver injury and fibrosis were assessed by serum biochemistry, liver histology, gene expression and western blot characterization of BA and FA synthesis/transport. Moreover, intestinal FAs and fecal microbiome were analyzed. Transfection and silencing were performed in Caco2 cells. MGL-/- mice were protected from DDC-induced biliary fibrosis and inflammation with reduced serum liver enzymes, increased FA/BA metabolism and β-oxidation. Notably, pharmacological (JZL184) inhibition of MGL ameliorated cholestatic injury in DDC-fed WT mice and protected Mdr2-/- from spontaneous liver injury, with improved liver enzymes, inflammation and biliary fibrosis. In vitro experiments confirmed that silencing of MGL decreases prostaglandin E2 accumulation in the intestine upregulating peroxisome proliferator activated receptor (PPAR) -α and -γ activity, thus reducing inflammation. Conclusions: Collectively, our study unravels MGL as a novel metabolic target, demonstrating that MGL inhibition may be considered as potential therapy for SC.

RevDate: 2019-09-10

Weitekamp CA, Phelps D, Swank A, et al (2019)

Triclosan-selected host-associated microbiota perform xenobiotic biotransformations in larval zebrafish.

Toxicological sciences : an official journal of the Society of Toxicology pii:5560334 [Epub ahead of print].

Microbiota regulate important physiologic processes during early host development. They also biotransform xenobiotics and serve as key intermediaries for chemical exposure. Antimicrobial agents in the environment may disrupt these complex interactions and alter key metabolic functions provided by host-associated microbiota. To examine the role of microbiota in xenobiotic metabolism, we exposed zebrafish larvae to the antimicrobial agent triclosan. Conventionally colonized (CC), microbe-free axenic (AX), or axenic colonized on day 1 (AC1) zebrafish were exposed to 0.16-0.30 uM triclosan or vehicle on days 1, 6, 7, 8, and 9 days post fertilization (dpf). After 6 dpf and 10 dpf, host-associated microbial community structure and putative function were assessed by 16S rRNA gene sequencing. At 10 dpf, triclosan exposure selected for bacterial taxa, including Rheinheimera. Triclosan-selected microbes were predicted to be enriched in pathways related to mechanisms of antibiotic resistance, sulfonation, oxidative stress, and drug metabolism. Furthermore, at 10 dpf, colonized zebrafish contained 2.5-3 times more triclosan relative to AX larvae. Non-targeted chemical analysis revealed that, relative to AX larvae, both cohorts of colonized larvae showed elevations in 23 chemical features, including parent triclosan and putative triclosan sulfate. Taken together, these data suggest that triclosan exposure selects for microbes that harbor the capacity to biotransform triclosan into chemical metabolites with unknown toxicity profiles. More broadly, these data support the concept that microbiota modify the toxicokinetics of xenobiotic exposure.

RevDate: 2019-09-10

Douglas GM, MGI Langille (2019)

Current and Promising Approaches to Identify Horizontal Gene Transfer Events in Metagenomes.

Genome biology and evolution pii:5554466 [Epub ahead of print].

High-throughput shotgun metagenomics sequencing has enabled the profiling of myriad natural communities. This data is commonly used to identify gene families and pathways that were potentially gained or lost in an environment and which may be involved in microbial adaptation. Despite the widespread interest in these events, there are no established best-practices for identifying gene gain and loss in metagenomics data. Horizontal gene transfer (HGT) represents several mechanisms of gene gain that are especially of interest in clinical microbiology, due to the rapid spread of antibiotic resistance genes in natural communities. Several additional mechanisms of gene gain and loss, including gene duplication, gene loss-of-function events, and de novo gene birth are also important to consider in the context of metagenomes, but have been less studied. This review is largely focused on detecting HGT in prokaryotic metagenomes, but methods for detecting these other mechanisms are first discussed. For this article to be self-contained we provide a general background on HGT and the different possible signatures of this process. Lastly, we discuss how improved assembly of genomes from metagenomes would be the most straight-forward approach for improving the inference of gene gain and loss events. Several recent technological advances could help improve metagenome assemblies: long-read sequencing, determining the physical proximity of contigs, optical mapping of short sequences along chromosomes, and single-cell metagenomics. The benefits and limitations of these advances are discussed and open-questions in this area are highlighted.

RevDate: 2019-09-10

Freed LL, Easson C, Baker LJ, et al (2019)

Characterization of the microbiome and bioluminescent symbionts across life stages of ceratioid anglerfishes of the gulf of mexico.

FEMS microbiology ecology pii:5567176 [Epub ahead of print].

The interdependence of diverse organisms through symbiosis reaches even the deepest parts of the oceans. As part of the DEEPEND project ( research on deep Gulf of Mexico biodiversity, we profiled the bacterial communities ('microbiomes') and luminous symbionts of 36 specimens of adult and larval deep-sea anglerfishes of the suborder Ceratioidei using 16S rDNA. Transmission Electron Microscopy was used to characterize the location of symbionts in adult light organs (esca). Whole larval microbiomes, and adult skin and gut microbiomes, were dominated by bacteria in the genera Moritella and Pseudoalteromonas genera. 16S rDNA sequencing results from adult fishes corroborate the previously published identity of ceratioid bioluminescent symbionts and support findings that these symbionts do not consistently exhibit host specificity at the host family level. Bioluminescent symbiont amplicon sequence variants (ASVs) were absent from larval ceratioid samples, but were found at all depths in the seawater, with a highest abundance found at mesopelagic depths. As adults spend the majority of their lives in the meso and bathypelagic, the trend in symbiont abundance is consistent with their life history. These findings support the hypothesis that bioluminescent symbionts are not present throughout host development, and that ceratioids acquire their bioluminescent symbionts from the environment.

RevDate: 2019-09-10

Zhao M, Yuan J, Dong M, et al (2019)

Predominance of soil vs root effect in rhizosphere microbiota reassembly.

FEMS microbiology ecology pii:5558233 [Epub ahead of print].

Rhizosphere community assembly is simultaneously affected by both plants and bulk soils and is vital for plant health. However, it is still unclear how and to what extent disease-suppressive rhizosphere microbiota can be constructed from bulk soil, and the underlying agents involved in the process that render the rhizosphere suppressive against pathogenic microbes remain elusive. In this study, the evolutionary processes of the rhizosphere microbiome were explored based on transplanting plants previously growing in distinct disease-incidence soils to one disease suppressive soil. Our results showed that distinct rhizoplane bacterial communities were assembled on account of the original bulk soil communities with different disease incidences. Furthermore, the bacterial communities in the transplanted rhizosphere were noticeably influenced by the second disease-suppressive microbial pool, rather than that of original formed rhizoplane microbiota and homogenous non-transplanted rhizosphere microbiome, contributing to a significant decrease in the pathogen population. In addition, Spearman correlations between relative abundances of bacterial taxa and the abundance of Ralstonia solanacearum indicated Anoxybacillus, Flavobacterium, Permianibacter and Pseudomonas were predicted to be associated with disease-suppressive function formation. Altogether, our results showed that bulk soil played an important role in the process of assembling and reassembling the rhizosphere microbiome of plants.

RevDate: 2019-09-10

Hata T, Miyata N, Takakura S, et al (2019)

The gut microbiome derived from anorexia nervosa patients impairs weight gain and behavioral performance in female mice.

Endocrinology pii:5554100 [Epub ahead of print].

Anorexia nervosa (AN) results in gut dysbiosis, but whether the dysbiosis contributes to AN-specific pathologies such as poor weight gain and neuropsychiatric abnormalities remains unclear. To address this, germ-free mice were reconstituted with the microbiota of four AN restricting-type patients (gAN mice) and four healthy control individuals (gHC mice). The effects of gut microbes on weight gain and behavioral characteristics were examined. Fecal microbial profiles in recipient gnotobiotic mice were clustered with those of the human donors. Compared with gHC mice, gAN mice showed a decrease in body weight gain, concomitant with reduced food intake. Food efficiency ratio (body weight gain/food intake) was also significantly lower in gAN mice than in gHC mice, suggesting that decreased appetite as well as the capacity to convert ingested food to unit of body substance may contribute to poor weight gain. Both anxiety-related behavior measured by open-field tests and compulsive behavior measured by marble-burying test were increased only in gAN mice but not in gHC mice. Serotonin levels in the brain stem of gAN mice were lower than those in the brain stem of gHC mice. Moreover, the genus Bacteroides showed the highest correlation with the number of buried marbles among all genera identified. Administration of Bacteroides vulgatus reversed compulsive behavior but failed to exert any significant effect on body weight. Collectively, these results indicate that AN-specific dysbiosis may contribute to both poor weight gain and mental disorders in AN patients.

RevDate: 2019-09-10

Jaworska K, Bielinska K, Gawrys-Kopczynska M, et al (2019)

TMA (trimethylamine), but not its oxide TMAO (trimethylamine-oxide), exerts hemodynamic effects - implications for interpretation of cardiovascular actions of gut microbiome.

Cardiovascular research pii:5555292 [Epub ahead of print].

RevDate: 2019-09-10

Kim KJ, Park J, Park SC, et al (2019)

Phylogenetic Tree-based Microbiome Association Test.

Bioinformatics (Oxford, England) pii:5559486 [Epub ahead of print].

MOTIVATION: Ecological patterns of the human microbiota exhibit high inter-subject variation, with few operational taxonomic units (OTUs) shared across individuals. To overcome these issues, non-parametric approaches, such as the Mann-Whitney U-test and Wilcoxon rank-sum test, have often been used to identify OTUs associated with host diseases. However, these approaches only use the ranks of observed relative abundances, leading to information loss, and are associated with high false-negative rates. In this study, we propose a phylogenetic tree-based microbiome association test (TMAT) to analyze the associations between microbiome OTU abundances and disease phenotypes. Phylogenetic trees illustrate patterns of similarity among different OTUs, and TMAT provides an efficient method for utilizing such information for association analyses. The proposed TMAT provides test statistics for each node, which are combined to identify mutations associated with host diseases.

RESULTS: Power estimates of TMAT were compared with existing methods using extensive simulations based on real absolute abundances. Simulation studies showed that TMAT preserves the nominal type-1 error rate, and estimates of its statistical power generally outperformed existing methods in the considered scenarios. Furthermore, TMAT can be used to detect phylogenetic mutations associated with host diseases, providing more in-depth insight into bacterial pathology.

AVAILABILITY: The 16S rRNA amplicon sequencing metagenomics datasets for colorectal carcinoma and myalgic encephalomyelitis/chronic fatigue syndrome are available from the European Nucleotide Archive (ENA) database under project accession number PRJEB6070 and PRJEB13092, respectively. TMAT was implemented in the R package. Detailed information is available at

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RevDate: 2019-09-10

Adams SH, Anthony JC, Carvajal R, et al (2019)

Perspective: Guiding Principles for the Implementation of Personalized Nutrition Approaches That Benefit Health and Function.

Advances in nutrition (Bethesda, Md.) pii:5556010 [Epub ahead of print].

Personalized nutrition (PN) approaches have been shown to help drive behavior change and positively influence health outcomes. This has led to an increase in the development of commercially available PN programs, which utilize various forms of individual-level information to provide services and products for consumers. The lack of a well-accepted definition of PN or an established set of guiding principles for the implementation of PN creates barriers for establishing credibility and efficacy. To address these points, the North American Branch of the International Life Sciences Institute convened a multidisciplinary panel. In this article, a definition for PN is proposed: "Personalized nutrition uses individual-specific information, founded in evidence-based science, to promote dietary behavior change that may result in measurable health benefits." In addition, 10 guiding principles for PN approaches are proposed: 1) define potential users and beneficiaries; 2) use validated diagnostic methods and measures; 3) maintain data quality and relevance; 4) derive data-driven recommendations from validated models and algorithms; 5) design PN studies around validated individual health or function needs and outcomes; 6) provide rigorous scientific evidence for an effect on health or function; 7) deliver user-friendly tools; 8) for healthy individuals, align with population-based recommendations; 9) communicate transparently about potential effects; and 10) protect individual data privacy and act responsibly. These principles are intended to establish a basis for responsible approaches to the evidence-based research and practice of PN and serve as an invitation for further public dialog. Several challenges were identified for PN to continue gaining acceptance, including defining the health-disease continuum, identification of biomarkers, changing regulatory landscapes, accessibility, and measuring success. Although PN approaches hold promise for public health in the future, further research is needed on the accuracy of dietary intake measurement, utilization and standardization of systems approaches, and application and communication of evidence.

RevDate: 2019-09-10

Soh M, Miyake S, Lim A, et al (2019)

Schaedlerella arabinosiphila gen. nov., sp. nov., a D-arabinose-utilizing bacterium isolated from faeces of C57BL/6J mice that is a close relative of Clostridium species ASF 502.

International journal of systematic and evolutionary microbiology [Epub ahead of print].

The use of gnotobiotics has attracted wide interest in recent years due to technological advances that have revealed the importance of host-associated microbiomes for host physiology and health. One of the oldest and most important gnotobiotic mouse model, the altered Schaedler flora (ASF) has been used for several decades. ASF comprises eight different bacterial strains, which have been characterized to different extent, but only a few are available through public strain collections. Here, the isolation of a close relative of one of the less-studied ASF strains, Clostridium species ASF 502, from faeces of C57BL/6J mice is reported. Isolate TLL-A1T shares 99.5 % 16S rRNA gene sequence identity with Clostridium species ASF 502 and phylogenetic analyses indicate that both strains belong to the uncultured so-called 'Lachnospiraceae UCG 006' clade. The rare sugar d-arabinose was used as a sole carbon source in the anaerobic isolation medium. Results of growth experiments with TLL-A1T on different carbon sources and analysis of its ~6.5 Gb indicate that TLL-A1T harbours a large gene repertoire that enables it to utilize a variety of carbohydrates for growth. Comparative genome analyses of TLL-A1T and Clostridium species ASF 502 reveal differences in genome content between the two strains, in particular with regards to carbohydrate-activating enzymes. Based on genomic, molecular and phenotypic differences, we propose to classify strain TLL-A1T (DSM 106076T=KCTC 15657T) as a representative of a new genus and a new species, for which we propose the name Schaedlerella arabinosiphila gen. nov., sp. nov.

RevDate: 2019-09-10

Westblade LF, Satlin MJ, Albakry S, et al (2019)

Gastrointestinal Pathogen Colonization and the Microbiome in Asymptomatic Kidney Transplant Recipients.

Transplant infectious disease : an official journal of the Transplantation Society [Epub ahead of print].

BACKGROUND: In kidney transplant recipients, gastrointestinal (GI) pathogens in feces are only evaluated during diarrheal episodes. Little is known about the prevalence of GI pathogens in asymptomatic individuals in this population.

METHODS: We recruited 142 kidney transplant recipients who provided a non-diarrheal fecal sample within the first 10 days after transplantation. The specimens were evaluated for GI pathogens using the BioFire® FilmArray® GI Panel (BioFire® Diagnostics, LLC; Salt Lake City, UT), which tests for 22 pathogens. The fecal microbiome was also characterized using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We evaluated whether detection of Clostridioides difficile and other GI pathogens was associated with post-transplant diarrhea within the first 3 months after transplantation.

RESULTS: Among the 142 subjects, a potential pathogen was detected in 43 (30%) using the GI Panel. The most common organisms detected were C. difficile (n=24, 17%), enteropathogenic Escherichia coli (n=8, 6%), and norovirus (n=5, 4%). Detection of a pathogen on the GI panel or detection of C. difficile alone was not associated with future post-transplant diarrhea (P > 0.05). The estimated number of gut bacterial species was significantly lower in subjects colonized with C. difficile than those not colonized with C. difficile (P = 0.01).

CONCLUSION: Colonization with GI pathogens, particularly C. difficile, is common at the time of kidney transplantation but does not predict subsequent diarrhea. Detection of C. difficile carriage was associated with decreased microbial diversity and may be a biomarker of gut dysbiosis.

RevDate: 2019-09-10

McLaren MR, Willis AD, BJ Callahan (2019)

Consistent and correctable bias in metagenomic sequencing experiments.

eLife, 8: pii:46923.

Marker-gene and metagenomic sequencing have profoundly expanded our ability to measure biological communities. But the measurements they provide differ from the truth, often dramatically, because these experiments are biased toward detecting some taxa over others. This experimental bias makes the taxon or gene abundances measured by different protocols quantitatively incomparable and can lead to spurious biological conclusions. We propose a mathematical model for how bias distorts community measurements based on the properties of real experiments. We validate this model with 16S rRNA gene and shotgun metagenomics data from defined bacterial communities. Our model better fits the experimental data despite being simpler than previous models. We illustrate how our model can be used to evaluate protocols, to understand the effect of bias on downstream statistical analyses, and to measure and correct bias given suitable calibration controls. These results illuminate new avenues toward truly quantitative and reproducible metagenomics measurements.

RevDate: 2019-09-10

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

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

eLife, 8: pii:46540.

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

RevDate: 2019-09-10

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

Microbiome as an Immunological Modifier.

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

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

RevDate: 2019-09-10

Ikeda E, Shiba T, Ikeda Y, et al (2019)

Japanese subgingival microbiota in health vs disease and their roles in predicted functions associated with periodontitis.

Odontology pii:10.1007/s10266-019-00452-4 [Epub ahead of print].

The present study aimed to identify and compare the microbial signatures between periodontally healthy and periodontitis subjects using 454 sequences of 16S rRNA genes. Subgingival plaque samples were collected from ten periodontally healthy subjects and ten matched chronic periodontitis patients. Bacterial DNA was extracted and next-generation sequencing of 16S rRNA genes was performed. The microbial composition differed between healthy subjects and periodontitis patients at all phylogenetic levels. Particularly, 16 species, including Lautropia mirabilis and Neisseria subflava predominated in healthy subjects, whereas nine species, including Porphyromonas gingivalis and Filifactor alocis predominated in periodontitis. UniFrac, a principal coordinate and network analysis, confirmed distinct community profiles in healthy subjects and periodontitis patients. Using predicted function profiling, pathways involved in phenylpropanoid, GPI-anchor biosynthesis, and metabolism of alanine, arginine, aspartate, butanoate, cyanoamino acid, fatty acid, glutamate, methane, proline, and vitamin B6 were significantly over-represented in periodontitis patients. These results highlight the oral microbiota alterations in microbial composition in periodontitis and suggest the genes and metabolic pathways associated with health and periodontitis. Our findings help to further elucidate microbial composition and interactions in health and periodontitis.

RevDate: 2019-09-10

Praus F, M Schönthaler (2019)

[Modifiable and non-modifiable risk factors for urolithiasis].

Der Urologe. Ausg. A pii:10.1007/s00120-019-01031-9 [Epub ahead of print].

Knowledge of the risk factors for urolithiasis is the key for sufficient metaphylaxis and reduction of recurrence events. Modifiable risk factors include diet, drink quantity, occupation, environmental factors, number of pregnancies and the intestinal microbiome. The treatment of associated diseases, such as the various manifestations of metabolic syndrome can reduce the risk for urolithiasis and recurrences. Knowledge of non-modifiable risk factors, such as gender, ethnicity, positive family history as well as specific genetic defects and polymorphisms of the calcium and phosphate balance enables personalized counselling and follow-up of affected patients.

RevDate: 2019-09-10

Culbertson EJ, Felder-Scott C, Deva AK, et al (2019)

Optimizing Breast Pocket Irrigation: The Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) Era.

Aesthetic surgery journal pii:5566480 [Epub ahead of print].

BACKGROUND: Specific antimicrobial breast pocket irrigations have been proven to reduce capsular contracture by 10x over the past 20 years, and with the emergence of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and its link to bacteria/technique there has been a renewed interest in different ant-microbial breast pocket preparation agents. Our previous studies have identified both Betadine containing and non-Betadine containing antimicrobial irrigations that provide excellent broad-spectrum bacterial coverage. The current science of BIA-ALCL has implicated the gram-negative microbiome as a key in pathogenesis.

OBJECTIVES: The purpose of this study is to revisit the antimicrobial effectiveness of clinically utilized Betadine and non-Betadine solutions, along with other antimicrobial agents that have not yet been tested, against multiple organisms, including additional common gram-negative bacteria associated with chronic breast implant infections/inflammation.

METHODS: Using standardized technique current and new anti-microbial breast irrigations were tested for bactericidal activity vs. multiple gram-positive and gram-negative strains. Test results are detailed and clinical recommendation for current anti-microbial irrigations are provided.

RESULTS: Betadine containing irrigations performed superior in the testing.

CONCLUSION: There are quite few misnomers with regard to anti-microbial breast pocket irrigation. These are discussed and final evidence-based recommendation for practice are given.

RevDate: 2019-09-10

Stower H (2019)

Predicting pancreatic cancer survival via the tumor microbiome.

Nature medicine, 25(9):1330.

RevDate: 2019-09-10

Wypych TP, Wickramasinghe LC, BJ Marsland (2019)

The influence of the microbiome on respiratory health.

Nature immunology pii:10.1038/s41590-019-0451-9 [Epub ahead of print].

The revolution in microbiota research over the past decade has provided invaluable knowledge about the function of the microbial species that inhabit the human body. It has become widely accepted that these microorganisms, collectively called 'the microbiota', engage in networks of interactions with each other and with the host that aim to benefit both the microbial members and the mammalian members of this unique ecosystem. The lungs, previously thought to be sterile, are now known to harbor a unique microbiota and, additionally, to be influenced by microbial signals from distal body sites, such as the intestine. Here we review the role of the lung and gut microbiotas in respiratory health and disease and highlight the main pathways of communication that underlie the gut-lung axis.

RevDate: 2019-09-10

Wilkins LJ, Monga M, AW Miller (2019)

Defining Dysbiosis for a Cluster of Chronic Diseases.

Scientific reports, 9(1):12918 pii:10.1038/s41598-019-49452-y.

The prevalence of many chronic diseases has increased over the last decades. It has been postulated that dysbiosis driven by environmental factors such as antibiotic use is shifting the microbiome in ways that increase inflammation and the onset of chronic disease. Dysbiosis can be defined through the loss or gain of bacteria that either promote health or disease, respectively. Here we use multiple independent datasets to determine the nature of dysbiosis for a cluster of chronic diseases that includes urinary stone disease (USD), obesity, diabetes, cardiovascular disease, and kidney disease, which often exist as co-morbidities. For all disease states, individuals exhibited a statistically significant association with antibiotics in the last year compared to healthy counterparts. There was also a statistically significant association between antibiotic use and gut microbiota composition. Furthermore, each disease state was associated with a loss of microbial diversity in the gut. Three genera, Bacteroides, Prevotella, and Ruminococcus, were the most common dysbiotic taxa in terms of being enriched or depleted in disease populations and was driven in part by the diversity of operational taxonomic units (OTUs) within these genera. Results of the cross-sectional analysis suggest that antibiotic-driven loss of microbial diversity may increase the risk for chronic disease. However, longitudinal studies are needed to confirm the causative effect of diversity loss for chronic disease risk.

RevDate: 2019-09-10

Kaklamanos EG, Nassar R, Kalfas S, et al (2019)

A single-centre investigator-blinded randomised parallel group clinical trial to investigate the effect of probiotic strains Streptococcus salivarius M18 and Lactobacillus acidophilus on gingival health of paediatric patients undergoing treatment with fixed orthodontic appliances: study protocol.

BMJ open, 9(9):e030638 pii:bmjopen-2019-030638.

BACKGROUND: There is limited data on the beneficial effects of probiotics on the gingival health of patients undergoing treatment with fixed orthodontic appliances. This study aims to compare the effect of probiotic tablets combined with regular oral hygiene versus regular oral hygiene alone on gingival status in these patients. The effect of probiotic intake on plaque formation and salivary microbiome composition will be also assessed.

METHODS AND ANALYSIS: This is a 3 month single-centre, single blind (clinical and laboratory examiners), parallel group randomised controlled two arm superiority trial. Fifty paediatric patients attending the Postgraduate Orthodontic Clinic at the Hamdan Bin Mohammed College of Dental Medicine (HBMCDM), Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai, United Arab Emirates, who meet the eligibility criteria will be recruited. Block randomisation with 1:1 allocation and concealment of allocation will be carried out. The treatment group will receive probiotic tablets containing Streptococcus salivarius M18 and Lactobacillus acidophilus together with regular oral hygiene versus the control group on regular oral hygiene alone. Clinical examination and collection of saliva for microbiome assay will be carried out at baseline and end of study. Self-reporting by patients will be used to document acceptability and adverse effects. Statistically significant decrease in gingival bleeding on probing in the treatment group will be classified as primary outcome of treatment success. Statistically significant reduction in Plaque Index, Gingival Index and shift in the composition of the oral microbiome in favour of beneficial bacteria are secondary outcomes indicative of efficacy of probiotic intake.

ETHICS AND DISSEMINATION: Ethical approval for the study has been granted by the HBMCDM, MBRU, Institutional Review Board (Reference #: MBRU-IRB-2018-015). Study findings will be disseminated via publication in peer-reviewed journal.


RevDate: 2019-09-10

Sims TT, Colbert LE, Zheng J, et al (2019)

Gut microbial diversity and genus-level differences identified in cervical cancer patients versus healthy controls.

Gynecologic oncology pii:S0090-8258(19)31489-1 [Epub ahead of print].

OBJECTIVES: The aim of this study was to characterize variation in the gut microbiome of women with locally advanced cervical cancer and compare it to healthy controls.

METHODS: We characterized the 16S rDNA fecal microbiome in 42 cervical cancer patients and 46 healthy female controls. Shannon diversity index (SDI) was used to evaluate alpha (within sample) diversity. Beta (between sample) diversity was examined using principle coordinate analysis (PCoA) of unweighted Unifrac distances. Relative abundance of microbial taxa was compared between samples using Linear Discriminant Analysis Effect Size (LEfSe).

RESULTS: Within cervical cancer patients, bacterial alpha diversity was positively correlated with age (p = 0.22) but exhibited an inverse relationship in control subjects (p < 0.01). Alpha diversity was significantly higher in cervical cancer patients as compared to controls (p < 0.05), though stratification by age suggested this relationship was restricted to older women (>50 years; p < 0.01). Beta diversity (unweighted Unifrac; p < 0.01) also significantly differed between cervical cancer patients and controls. Based on age- and race-adjusted LEfSe analysis, multiple taxa significantly differed between cervical cancer patients and controls. Prevotella, Porphyromonas, and Dialister were significantly enriched in cervical cancer patients, while Bacteroides, Alistipes and members of the Lachnospiracea family were significantly enriched in healthy subjects.

CONCLUSION: Our study suggests differences in gut microbiota diversity and composition between cervical cancer patients and controls. Associations within the gut microbiome by age may reflect etiologic/clinical differences. These findings provide rationale for further study of the gut microbiome in cervical cancer.

RevDate: 2019-09-10

McPherson AS, Dhungyel OP, RJ Whittington (2019)

The microbiome of the footrot lesion in Merino sheep is characterized by a persistent bacterial dysbiosis.

Veterinary microbiology, 236:108378.

Footrot is prevalent in most sheep-producing countries; the disease compromises sheep health and welfare and has a considerable economic impact. The disease is the result of interactions between the essential causative agent, Dichelobacter nodosus, and the bacterial community of the foot, with the pasture environment and host resistance influencing disease expression. The Merino, which is the main wool sheep breed in Australia, is particularly susceptible to footrot. We characterised the bacterial communities on the feet of healthy and footrot-affected Merino sheep across a 10-month period via sequencing and analysis of the V3-V4 regions of the bacterial 16S ribosomal RNA gene. Distinct bacterial communities were associated with the feet of healthy and footrot-affected sheep. Infection with D. nodosus appeared to trigger a shift in the composition of the bacterial community from predominantly Gram-positive, aerobic taxa to predominantly Gram-negative, anaerobic taxa. A total of 15 bacterial genera were preferentially abundant on the feet of footrot-affected sheep, several of which have previously been implicated in footrot and other mixed bacterial diseases of the epidermis of ruminants. Some, including Porphyromonas, can trigger a shift in the composition of bacterial communities and may therefore be of significance to the expression of footrot. A comparison of the communities in footrot lesions of different scores and at different times revealed that this state of dysbiosis is persistent at the active margins of lesions, irrespective of their severity.

RevDate: 2019-09-10

Hauptmann AL, Paulová P, Castro-Mejía JL, et al (2020)

The microbial composition of dried fish prepared according to Greenlandic Inuit traditions and industrial counterparts.

Food microbiology, 85:103305.

The practices of preparing traditional foods in the Arctic are rapidly disappearing. Traditional foods of the Arctic represent a rarity among food studies in that they are meat-sourced and prepared in non-industrial settings. These foods, generally consumed without any heating step prior to consumption, harbor an insofar undescribed microbiome. The food-associated microbiomes have implications not only with respect to disease risk, but might also positively influence host health by transferring a yet unknown diversity of live microbes to the human gastrointestinal tract. Here we report the first study of the microbial composition of traditionally dried fish prepared according to Greenlandic traditions and their industrial counterparts. We show that dried capelin prepared according to traditional methods have microbiomes clearly different from industrially prepared capelin, which also have more homogenous microbiomes than traditionally prepared capelin. Interestingly, the locally preferred type of traditionally dried capelin, described to be tastier than other traditionally dried capelin, contains bacteria that potentially confer distinct taste. Finally, we show that dried cod have comparably more homogenous microbiomes when compared to capelin and that in general, the environment of drying is a major determinant of the microbial composition of these indigenous food products.

RevDate: 2019-09-10

Szafranek-Nakonieczna A, Pytlak A, Grządziel J, et al (2019)

Changes in the Substrate Source Reveal Novel Interactions in the Sediment-Derived Methanogenic Microbial Community.

International journal of molecular sciences, 20(18): pii:ijms20184415.

Methanogenesis occurs in many natural environments and is used in biotechnology for biogas production. The efficiency of methane production depends on the microbiome structure that determines interspecies electron transfer. In this research, the microbial community retrieved from mining subsidence reservoir sediment was used to establish enrichment cultures on media containing different carbon sources (tryptone, yeast extract, acetate, CO2/H2). The microbiome composition and methane production rate of the cultures were screened as a function of the substrate and transition stage. The relationships between the microorganisms involved in methane formation were the major focus of this study. Methanogenic consortia were identified by next generation sequencing (NGS) and functional genes connected with organic matter transformation were predicted using the PICRUSt approach and annotated in the KEGG. The methane production rate (exceeding 12.8 mg CH4 L-1 d-1) was highest in the culture grown with tryptone, yeast extract, and CO2/H2. The analysis of communities that developed on various carbon sources casts new light on the ecophysiology of the recently described bacterial phylum Caldiserica and methanogenic Archaea representing the genera Methanomassiliicoccus and Methanothrix. Furthermore, it is hypothesized that representatives of Caldiserica may support hydrogenotrophic methanogenesis.

RevDate: 2019-09-09

Woo TE, CD Sibley (2019)

The emerging utility of the cutaneous microbiome in the treatment of acne and atopic dermatitis.

Journal of the American Academy of Dermatology pii:S0190-9622(19)32686-6 [Epub ahead of print].

The cutaneous microbiome has potential for therapeutic intervention in inflammatory-driven skin disease. Research into atopic dermatitis and acne vulgaris has highlighted the importance of the skin microbiota in disease pathogenesis, prognostication and targets for therapeutic intervention. Current management of these conditions aims to control the inflammatory response thought to be associated with specific pathogens using both topical and systemic antimicrobials. However, commensal microbiota found naturally on the skin have been shown to play an important role in the resolution of disease flares. While often efficacious, the mainstay treatments are not without side effects and raise concerns regarding the development of antimicrobial resistance. Augmentation of microbial communities with targeted biotherapy could revolutionize the way inflammatory conditions of the skin are treated. Herein, we review evidence for the role of the cutaneous microbiome in atopic dermatitis and acne vulgaris and suggest that these conditions highlight the potential for microbiome-directed therapeutics.

RevDate: 2019-09-09

Lu A, Petrullo L, Carrera S, et al (2019)

Developmental responses to early-life adversity: Evolutionary and mechanistic perspectives.

Evolutionary anthropology [Epub ahead of print].

Adverse ecological and social conditions during early life are known to influence development, with rippling effects that may explain variation in adult health and fitness. The adaptive function of such developmental plasticity, however, remains relatively untested in long-lived animals, resulting in much debate over which evolutionary models are most applicable. Furthermore, despite the promise of clinical interventions that might alleviate the health consequences of early-life adversity, research on the proximate mechanisms governing phenotypic responses to adversity have been largely limited to studies on glucocorticoids. Here, we synthesize the current state of research on developmental plasticity, discussing both ultimate and proximate mechanisms. First, we evaluate the utility of adaptive models proposed to explain developmental responses to early-life adversity, particularly for long-lived mammals such as humans. In doing so, we highlight how parent-offspring conflict complicates our understanding of whether mothers or offspring benefit from these responses. Second, we discuss the role of glucocorticoids and a second physiological system-the gut microbiome-that has emerged as an additional, clinically relevant mechanism by which early-life adversity can influence development. Finally, we suggest ways in which nonhuman primates can serve as models to study the effects of early-life adversity, both from evolutionary and clinical perspectives.

RevDate: 2019-09-09

Ville A, Levine E, Zhi D, et al (2019)

Alterations in the Gut Microbiome at 6 Months of Age in Obese Latino Infants.

Journal of the American College of Nutrition [Epub ahead of print].

Objective: To investigate gut microbial composition in Latino infants in relation to breastfeeding, obesity, and antibiotic exposure. Method: We analyzed the gut microbiome in 6-month-old Latino infants from an ongoing urban mother-child cohort. Alpha and beta diversity were assessed in relation to infants' early dietary exposure and anthropometrics including obesity. Results: Infants exclusively breastfed at 4 to 6 weeks had lower alpha diversity and less bacterial abundance compared with those who did not. Breastfeeding status at 4 to 6 weeks and 6 months of age accounted for differences in alpha and beta diversity. Infants who were obese at 6 months of age had higher levels of alpha diversity compared with non-obese infants. Conclusions: Early exclusive breastfeeding and obesity impacts microbial diversity by 6 months of age in Latino infants, a group at high risk for future obesity.

RevDate: 2019-09-09

Elwood C, Albert AYK, McClymont E, et al (2019)

Different and diverse anaerobic microbiota were seen in women living with HIV with unsuppressed HIV viral load and in women with recurrent bacterial vaginosis: a cohort study.

BJOG : an international journal of obstetrics and gynaecology [Epub ahead of print].

OBJECTIVE: To compare the vaginal microbiota of women living with HIV (WLWH) to the vaginal microbiota of women with recurrent bacterial vaginosis (BV) and healthy women without HIV to determine if there are differences in the vaginal microbiome, what factors influence these differences, and to characterize HIV clinical parameters including viral load and CD4 count in relation to the vaginal microbiome.

DESIGN: Observational cohort study.

SETTING: Canada.

POPULATION: Women aged 18-49 years who were premenopausal and not pregnant were recruited into three cohorts: healthy women, WLWH, and women with recurrent BV.

METHODS: Demographic and clinical data were collected via interviews and medical chart reviews. Vaginal swabs were collected for Gram stain assessment and microbiome profiling utilizing the cpn60 barcode sequence.

MAIN OUTCOME MEASURES: To compare overall community composition differences, we used compositional data analysis methods, hierarchical clustering, and Kruskal-Wallis tests where appropriate.

RESULTS: Clinical markers such as odour and abnormal discharge, but not irritation, were associated with higher microbial diversity. WLWH with unsuppressed HIV viral loads were more likely than other groups to have non-Gardnerella dominated microbiomes. HIV was associated with higher vaginal microbial diversity and this was related to HIV viral load, with unsuppressed women demonstrating significantly higher relative abundance of Megasphaera genomosp. 1, Atopobium vaginae, and Clostridiales sp. (all p<0.05) compared to all other groups.

CONCLUSIONS: In WLWH, unsuppressed HIV viral loads were associated with a distinct dysbiotic profile consisting of very low levels of Lactobacillus and high levels of anaerobes.

RevDate: 2019-09-09

Boertien JM, Pereira PAB, Aho VTE, et al (2019)

Increasing Comparability and Utility of Gut Microbiome Studies in Parkinson's Disease: A Systematic Review.

Journal of Parkinson's disease pii:JPD191711 [Epub ahead of print].

Gut microbiota have been studied in relation to the pathophysiology of Parkinson's disease (PD) due to the early gastrointestinal symptomatology and presence of alpha-synuclein pathology in the enteric nervous system, hypothesized to ascend via the vagal nerve to the central nervous system. Accordingly, sixteen human case-control studies have published gut microbiome composition changes in PD and reported over 100 differentially abundant taxa covering all taxonomic levels from phylum to genus or species, depending on methodology. While certain findings were replicated across several studies, various contradictory findings were reported. Here, differences in methodologies and the presence of possible confounders in the study populations are assessed for their potential to confound the results of gut microbiome studies in PD. Gut microbiome studies in PD exhibited considerable variability with respect to the study population, sample transport conditions, laboratory protocols and sequencing, bioinformatics pipelines, and biostatistical methods. To move from the current heterogeneous dataset towards clinically relevant biomarkers and the identification of putative therapeutic targets, recommendations are derived from the limitations of the available studies to increase the future comparability of microbiome studies in PD. In addition, integration of currently available data on the gut microbiome in PD is proposed to identify robust gut microbiome profiles in PD. Furthermore, expansion of the current dataset to atypical parkinsonism cohorts, prodromal and treatment-naïve de novo PD subjects, measurements of fecal microbial concentrations and a multi-omics assessment are required to provide clinically relevant biomarkers and reveal therapeutic targets within the gut microbiome of PD.

RevDate: 2019-09-09

Baird PN, P Hysi (2019)

Twin Registries Moving Forward and Meeting the Future: A Review.

Twin research and human genetics : the official journal of the International Society for Twin Studies, 22(4):201-209.

Twin registries have developed as a valuable resource for the study of many aspects of disease and society over the years in many different countries. A number of these registries include large numbers of twins with data collected at varying information levels for twin cohorts over the past several decades. More recent expansion of twin datasets has allowed for the collection of genetic data, together with many other levels of 'omic' information along with multiple demographic, physiological, health outcomes and other measures typically used in epidemiologic research. Other twin data sources outside these registries reflect research interests in particular aspects of disease or specific phenotypic assessment. Twin registries have the potential to play a key role in many aspects of the artificial intelligence/machine learning-driven projects of the future and will continue to keep adapting to the changing research landscape.

RevDate: 2019-09-09

Rabe A, Gesell Salazar M, Michalik S, et al (2019)

Metaproteomics analysis of microbial diversity of human saliva and tongue dorsum in young healthy individuals.

Journal of oral microbiology, 11(1):1654786 pii:1654786.

Background: The human oral microbiome influences initiation or progression of diseases like caries or periodontitis. Metaproteomics approaches enable the simultaneous investigation of microbial and host proteins and their interactions to improve understanding of oral diseases. Objective: In this study, we provide a detailed metaproteomics perspective of the composition of salivary and tongue microbial communities of young healthy subjects. Design: Stimulated saliva and tongue samples were collected from 24 healthy volunteers, subjected to shotgun nLC-MS/MS and analyzed by the Trans-Proteomic Pipeline and the Prophane tool. Results: 3,969 bacterial and 1,857 human proteins could be identified from saliva and tongue, respectively. In total, 1,971 bacterial metaproteins and 1,154 human proteins were shared in both sample types. Twice the amount of bacterial metaproteins were uniquely identified for the tongue dorsum compared to saliva. Overall, 107 bacterial genera of seven phyla formed the microbiome. Comparative analysis identified significant functional differences between the microbial biofilm on the tongue and the microbiome of saliva. Conclusion: Even if the microbial communities of saliva and tongue dorsum showed a strong similarity based on identified protein functions and deduced bacterial composition, certain specific characteristics were observed. Both microbiomes exhibit a great diversity with seven genera being most abundant.

RevDate: 2019-09-09

Ortiz S, Herrman E, Lyashenko C, et al (2019)

Sex-specific differences in the salivary microbiome of caries-active children.

Journal of oral microbiology, 11(1):1653124 pii:1653124.

Background and Objectives: Dental caries is a chronic disease affecting young children and has multi-factorial risk factors. The purpose of this work was to identify sex-specific differences in the salivary microbiota within caries-active children. Design: Saliva specimens were collected from 85 children (boys: 41; girls: 44) between the ages of 2-12 years. Salivary microbial DNA was subjected to PCR amplification using V3-V4 16S rDNA-specific primers and next-generation sequencing. Results: Significant sex differences in salivary microbiota were found between caries-active boys versus caries-active girls. Neisseria flavescens, Rothia aeria, and Haemophilus pittmaniae were found at significantly higher levels in caries-active boys. In contrast, Lactococcus lactis, Selenomonas species HOT 126, Actinobaculum species HOT 183, Veillonella parvula, and Alloprevotella species HOT 473 were found at significantly higher levels in caries-active girls. Conclusion: We have found the acid-generating, cariogenic Lactococcus lactis to be much more abundant in caries-active girls than caries-active boys, indicating that this microorganism may play a more significant role in shaping the cariogenic microbiome in girls. In addition, in caries-active girls, Alloprevotella species HOT 473 was the only species that exhibited both significant sex differences (4.4-fold difference; p=0.0003) as well as high abundance in numbers (1.85% of the total microbial population).

RevDate: 2019-09-09

Rawson T, Dawkins MS, MB Bonsall (2019)

A Mathematical Model of Campylobacter Dynamics Within a Broiler Flock.

Frontiers in microbiology, 10:1940.

Globally, the bacterial genus Campylobacter is one of the leading causes of human gastroenteritis, with its primary route of infection being through poultry meat. The application of biosecurity measures is currently limited by a lack of understanding of the transmission dynamics within a flock. Our work is the first to undertake a mathematical modeling approach to Campylobacter population dynamics within a flock of broilers (chickens bred specifically for meat). A system of stochastic differential equations is used to model the routes of infection between co-housed birds. The presented model displays the strong correlation between housing density and Campylobacter prevalence, and shows how stochastic variation is the driving factor determining which strains of Campylobacter will emerge first within a flock. The model also shows how the system will rapidly select for phenotypic advantages, to quickly eliminate demographically-weaker strains. A global sensitivity analysis is performed, highlighting that the growth and death rate of other native bacterial species likely contributes the greatest to preventing flock outbreaks, presenting a promising approach to hypothesizing new methods of combatting disease transmission.

RevDate: 2019-09-09

Philips CA, Augustine P, Yerol PK, et al (2019)

Severe alcoholic hepatitis: current perspectives.

Hepatic medicine : evidence and research, 11:97-108 pii:197933.

Severe acute alcoholic hepatitis (AH) is a catastrophic disease in the natural history of alcoholic liver disease with a very high 180-day mortality. It can present as acute on chronic liver failure with worse prognosis in the presence of infections and higher grades of liver disease severity. The clinical scenario involves a patient with a recent history of heavy alcohol consumption within three months of presentation with jaundice and characteristic liver enzyme elevation pattern with coagulopathy, hepatic encephalopathy, variceal bleeding and sepsis that results in extrahepatic organ failures. Several liver disease severities and therapy response indicators are in clinical use. Even though not approved, the only recommended treatment option for patients with severe AH is corticosteroids, which is without long term survival benefit. Novel efficacious treatment options awaiting high-quality multi-center studies include liver transplantation (involves strict selection criteria), growth factor therapy and fecal microbiota transplantation. In this exhaustive review, we discuss the definitions, disease severity, histopathology, and treatment options - past, present, and future, in patients with severe alcoholic hepatitis.


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
961 Red Tail Lane
Bellingham, WA 98226

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 )