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Bibliography on: Human Microbiome

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ESP: PubMed Auto Bibliography 08 Jul 2020 at 01:46 Created: 

Human Microbiome

The human microbiome is the set of all microbes that live on or in humans. Together, a human body and its associated microbiomes constitute a human holobiont. Although a human holobiont is mostly mammal by weight, by cell count it is mostly microbial. The number of microbial genes in the associated microbiomes far outnumber the number of human genes in the human genome. Just as humans (and other multicellular eukaryotes) evolved in the constant presence of gravity, so they also evolved in the constant presence of microbes. Consequently, nearly every aspect of human biology has evolved to deal with, and to take advantage of, the existence of associated microbiota. In some cases, the absence of a "normal microbiome" can cause disease, which can be treated by the transplant of a correct microbiome from a healthy donor. For example, fecal transplants are an effective treatment for chronic diarrhea from over abundant Clostridium difficile bacteria in the gut.

Created with PubMed® Query: "human microbiome" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2020-07-07

Yang Y, Liu S, Wang Y, et al (2020)

Changes of saliva microbiota in the onset and after the treatment of diabetes in patients with periodontitis.

Aging, 12: pii:103399 [Epub ahead of print].

The relationship between type 2 diabetes mellitus (T2DM) and oral microbiota is still insufficiently recognized. In the present study, we compared the salivary microbiome of nondiabetic individuals, treatment-naïve diabetic patients, and diabetic patients treated with metformin or a combination of insulin and other drugs. The α- and β-diversity demonstrated significant differences in the salivary microbiome between the nondiabetic people and patients with a history of diabetes, while little divergence was found among individuals with a history of diabetes. After characterizing the effects of periodontitis on the microbial composition of each group, the salivary microbiome of the treatment-naïve diabetic patient group was compared with that of nondiabetic people and the metformin/combined treatment groups. The results revealed changes in the contents of certain bacteria after both the onset and the treatment of diabetes; among these differential bacteria, Blautia_wexlerae, Lactobacillus_fermentum, Nocardia_coeliaca and Selenomonas_artemidis varied in all processes. A subsequent correlational analysis of the differential bacteria and clinical characteristics demonstrated that salivary microbes were related to drug treatment and certain pathological changes. Finally, the four common differential bacteria were employed for distinguishing the treatment-naïve diabetic patients from the nondiabetic people and the treated patients, with prediction accuracies of 83.3%, 75% and 75%, respectively.

RevDate: 2020-07-04

Ianiro G, Mullish BH, Kelly CR, et al (2020)

Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic.

Gut pii:gutjnl-2020-321829 [Epub ahead of print].

The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.

RevDate: 2020-07-04

Creswell R, Tan J, Leff JW, et al (2020)

High-resolution temporal profiling of the human gut microbiome reveals consistent and cascading alterations in response to dietary glycans.

Genome medicine, 12(1):59 pii:10.1186/s13073-020-00758-x.

BACKGROUND: Dietary glycans, widely used as food ingredients and not directly digested by humans, are of intense interest for their beneficial roles in human health through shaping the microbiome. Characterizing the consistency and temporal responses of the gut microbiome to glycans is critical for rationally developing and deploying these compounds as therapeutics.

METHODS: We investigated the effect of two chemically distinct glycans (fructooligosaccharides and polydextrose) through three clinical studies conducted with 80 healthy volunteers. Stool samples, collected at dense temporal resolution (~ 4 times per week over 10 weeks) and analyzed using shotgun metagenomic sequencing, enabled detailed characterization of participants' microbiomes. For analyzing the microbiome time-series data, we developed MC-TIMME2 (Microbial Counts Trajectories Infinite Mixture Model Engine 2.0), a purpose-built computational tool based on nonparametric Bayesian methods that infer temporal patterns induced by perturbations and groups of microbes sharing these patterns.

RESULTS: Overall microbiome structure as well as individual taxa showed rapid, consistent, and durable alterations across participants, regardless of compound dose or the order in which glycans were consumed. Significant changes also occurred in the abundances of microbial carbohydrate utilization genes in response to polydextrose, but not in response to fructooligosaccharides. Using MC-TIMME2, we produced detailed, high-resolution temporal maps of the microbiota in response to glycans within and across microbiomes.

CONCLUSIONS: Our findings indicate that dietary glycans cause reproducible, dynamic, and differential alterations to the community structure of the human microbiome.

RevDate: 2020-07-03

Ames NJ, Barb JJ, Schuebel K, et al (2020)

Longitudinal gut microbiome changes in alcohol use disorder are influenced by abstinence and drinking quantity.

Gut microbes, 11(6):1608-1631.

Many patients with alcohol use disorder (AUD) consume alcohol chronically and in large amounts that alter intestinal microbiota, damage the gastrointestinal tract, and thereby injure other organs via malabsorption and intestinal inflammation. We hypothesized that alcohol consumption and subsequent abstinence would change the gut microbiome in adults admitted to a treatment program. Stool and oral specimens, diet data, gastrointestinal assessment scores, anxiety, depression measures and drinking amounts were collected longitudinally for up to 4 weeks in 22 newly abstinent inpatients with AUD who were dichotomized as less heavy drinkers (LHD, <10 drinks/d) and very heavy drinkers (VHD, 10 or more drinks/d). Next-generation 16 S rRNA gene sequencing was performed to measure the gut and oral microbiome at up to ten time points/subject and LHD and VHD were compared for change in principal components, Shannon diversity index and specific genera. The first three principal components explained 46.7% of the variance in gut microbiome diversity across time and all study subjects, indicating the change in gut microbiome following abstinence. The first time point was an outlier in three-dimensional principal component space versus all other time points. The gut microbiota in LHD and VHD were significantly dissimilar in change from day 1 to day 5 (p = .03) and from day 1 to week 3 (p = .02). The VHD drinking group displayed greater change from baseline. The Shannon diversity index of the gut microbiome changed significantly during abstinence in five participants. In both groups, the Shannon diversity was lower in the oral microbiome than gut. Ten total genera were shared between oral and stool in the AUD participants. These data were compared with healthy controls from the Human Microbiome Project to investigate the concept of a core microbiome. Rapid changes in gut microbiome following abstinence from alcohol suggest resilience of the gut microbiome in AUD and reflects the benefits of refraining from the highest levels of alcohol and potential benefits of abstinence.

RevDate: 2020-07-02

Ogunrinola GA, Oyewale JO, Oshamika OO, et al (2020)

The Human Microbiome and Its Impacts on Health.

International journal of microbiology, 2020:8045646.

The human microbiome comprises bacteria, archaea, viruses, and eukaryotes which reside within and outside our bodies. These organisms impact human physiology, both in health and in disease, contributing to the enhancement or impairment of metabolic and immune functions. Micro-organisms colonise various sites on and in the human body, where they adapt to specific features of each niche. Facultative anaerobes are more dominant in the gastrointestinal tract, whereas strict aerobes inhabit the respiratory tract, nasal cavity, and skin surface. The indigenous organisms in the human body are well adapted to the immune system, due to the biological interaction of the organisms with the immune system over time. An alteration in the intestinal microbial community plays a major role in human health and disease pathogenesis. These alterations result from lifestyle and the presence of an underlying disease. Dysbiosis increases host susceptibility to infection, and the nature of which depends on the anatomical site involved. The unique diversity of the human microbiota accounts for the specific metabolic activities and functions of these micro-organisms within each body site. It is therefore important to understand the microbial composition and activities of the human microbiome as they contribute to health and disease.

RevDate: 2020-07-01

Ohadian Moghadam S, SA Momeni (2020)

Human microbiome and prostate cancer development: current insights into the prevention and treatment.

Frontiers of medicine pii:10.1007/s11684-019-0731-7 [Epub ahead of print].

The huge communities of microorganisms that symbiotically colonize humans are recognized as significant players in health and disease. The human microbiome may influence prostate cancer development. To date, several studies have focused on the effect of prostate infections as well as the composition of the human microbiome in relation to prostate cancer risk. Current studies suggest that the microbiota of men with prostate cancer significantly differs from that of healthy men, demonstrating that certain bacteria could be associated with cancer development as well as altered responses to treatment. In healthy individuals, the microbiome plays a crucial role in the maintenance of homeostasis of body metabolism. Dysbiosis may contribute to the emergence of health problems, including malignancy through affecting systemic immune responses and creating systemic inflammation, and changing serum hormone levels. In this review, we discuss recent data about how the microbes colonizing different parts of the human body including urinary tract, gastrointestinal tract, oral cavity, and skin might affect the risk of developing prostate cancer. Furthermore, we discuss strategies to target the microbiome for risk assessment, prevention, and treatment of prostate cancer.

RevDate: 2020-07-01

Rees J, Christophersen CC, Lewis JR, et al (2020)

The study protocol for a pseudo-randomised pre-post designed controlled intervention trial to study the effects of a 7-week cooking program on self-efficacy and biomarkers of health: the ECU lifestyle and biomarkers get connected study (ECULABJMOF) including the Jamie's Ministry of Food WA participant experience.

BMC public health, 20(1):1037 pii:10.1186/s12889-020-09124-3.

BACKGROUND: Australia, like other nations, has experienced a shift in dietary patterns away from home cooking of nutritious foods, towards a reliance on pre-prepared convenience meals. These are typically energy-dense, nutrient-poor and contribute to the rising prevalence of obesity and chronic disease burden. The aims of this study were to evaluate whether a community-based cooking program instigated a change to participants' skills, attitudes, knowledge, enjoyment and satisfaction of cooking and cooking confidence (self-efficacy).

METHODS: The pseudo-random, pre-post study design consisted of an intervention and a control group. Participant recruitment and group allocation was based on their program start dates. Intervention participants were surveyed three times (baseline, 7 weeks and 6 months) and the control group were surveyed at baseline and 5 weeks. All participants were registered via an online website and were 18 years or over. Upon consent, participants were offered four levels of commitment, defined by different assessments. The minimum participation level included an online survey and levels 2, 3 and 4 involved attendance at a clinic with increasing functional, anthropometric and biomarker measurements. Primary endpoints were participants' cooking confidence as a proxy for self-efficacy. Secondary endpoints were dietary intake, physical activity levels, body composition, anthropometry, blood, urine and faecal biomarkers of systemic, physical and mental health.

DISCUSSION: The community cooking program provided participants with information and advice on food sourcing, preparation and nutrition to improve home cooking skills. The study was designed to explore whether food literacy programs are efficacious in improving participant physical health and well-being in order to combat the rise in obesity and diet-related disease. It will support future use of public health cooking program initiatives aimed at improving food literacy, self-efficacy and physical and mental health. The extensive data collected will inform future research into the relationship between diet, the gut-microbiota and human health.

TRIAL REGISTRATION: Retrospectively registered on 16.08.2019 with the Australian New Zealand Clinical Trials Registry (ANZCTR). ACTRN12619001144101 . Protocol version 4.

RevDate: 2020-07-01

Roder T, Wüthrich D, Bär C, et al (2020)

In Silico Comparison Shows that the Pan-Genome of a Dairy-Related Bacterial Culture Collection Covers Most Reactions Annotated to Human Microbiomes.

Microorganisms, 8(7): pii:microorganisms8070966.

The diversity of the human microbiome is positively associated with human health. However, this diversity is endangered by Westernized dietary patterns that are characterized by a decreased nutrient variety. Diversity might potentially be improved by promoting dietary patterns rich in microbial strains. Various collections of bacterial cultures resulting from a century of dairy research are readily available worldwide, and could be exploited to contribute towards this end. We have conducted a functional in silico analysis of the metagenome of 24 strains, each representing one of the species in a bacterial culture collection composed of 626 sequenced strains, and compared the pathways potentially covered by this metagenome to the intestinal metagenome of four healthy, although overweight, humans. Remarkably, the pan-genome of the 24 strains covers 89% of the human gut microbiome's annotated enzymatic reactions. Furthermore, the dairy microbial collection covers biological pathways, such as methylglyoxal degradation, sulfate reduction, g-aminobutyric (GABA) acid degradation and salicylate degradation, which are differently covered among the four subjects and are involved in a range of cardiometabolic, intestinal, and neurological disorders. We conclude that microbial culture collections derived from dairy research have the genomic potential to complement and restore functional redundancy in human microbiomes.

RevDate: 2020-06-30

Qian XB, Chen T, Xu YP, et al (2020)

A guide to human microbiome research: study design, sample collection, and bioinformatics analysis.

Chinese medical journal [Epub ahead of print].

The purpose of this review is to provide medical researchers, especially those without a bioinformatics background, with an easy-to-understand summary of the concepts and technologies used in microbiome research. First, we define primary concepts such as microbiota, microbiome, and metagenome. Then, we discuss study design schemes, the methods of sample size calculation, and the methods for improving the reliability of research. We emphasize the importance of negative and positive controls in this section. Next, we discuss statistical analysis methods used in microbiome research, focusing on problems with multiple comparisons and ways to compare β-diversity between groups. Finally, we provide step-by-step pipelines for bioinformatics analysis. In summary, the meticulous study design is a key step to obtaining meaningful results, and appropriate statistical methods are important for accurate interpretation of microbiome data. The step-by-step pipelines provide researchers with insights into newly developed bioinformatics analysis methods.

RevDate: 2020-06-30

Delbeke H, Younas S, Casteels I, et al (2020)

Current knowledge on the human eye microbiome: a systematic review of available amplicon and metagenomic sequencing data.

Acta ophthalmologica [Epub ahead of print].

Insights in the ocular surface microbiome are still at an early stage and many more questions remain unanswered compared with other human-associated microbial communities. The current knowledge on the human microbiome changed our viewpoint on bacteria and human health and significantly enhanced our understanding of human pathophysiology. Also in ocular medicine, microbiome research might impact treatment. Here, we summarize the current knowledge on ocular microbiome research with a particular focus on potential confounding factors and their effects on microbiome composition. Moreover, we present the ocular surface core microbiome based on current available data and defined it as genera present in almost half of the published control cohorts with a relative abundance of at least 1%.

RevDate: 2020-06-30

Simões da Silva TM, Piazentin ACM, Mendonça CMN, et al (2020)

Buffalo milk increases viability and resistance of probiotic bacteria in dairy beverages under in vitro simulated gastrointestinal conditions.

Journal of dairy science pii:S0022-0302(20)30479-3 [Epub ahead of print].

Probiotic dairy beverages prepared from buffalo and cow milks with different levels of whey (0, 25, and 50%) were evaluated for kinetic fermentation parameters, protein and fat contents, post-acidification profile, viability of Streptococcus thermophilus, Lactobacillus bulgaricus, and Lactobacillus acidophilus during 21 d of refrigerated storage, and resistance to in vitro gastrointestinal conditions. Progressive acidification that occurred during storage of all dairy products was reduced in the presence of whey. Lactic acid bacteria showed viable cell counts at the end of shelf life, with the highest values (7.33 to 8.83 log cfu/mL) detected in buffalo dairy products. Compared with fermented cow milk products, those made with buffalo milk showed better bacterial viability during in vitro simulated gastrointestinal digestion, which suggests a beneficial protective effect on human microbiome.

RevDate: 2020-06-30

Marzano V, Pane S, Foglietta G, et al (2020)

Mass Spectrometry Based-Proteomic Analysis of Anisakis spp.: A Preliminary Study towards a New Diagnostic Tool.

Genes, 11(6): pii:genes11060693.

Anisakiasis is nowadays a well-known infection, mainly caused by the accidental ingestion of Anisakis larvae, following the consumption of raw or undercooked fishes and cephalopods. Due to the similarity of symptoms with those of common gastrointestinal disorders, this infection is often underestimated, and the need for new specific diagnostic tools is becoming crucial. Given the remarkable impact that MALDI-TOF MS biotyping had in the last decade in clinical routine practice for the recognition of bacterial and fungi strains, a similar scenario could be foreseen for the identification of parasites, such as nematodes. In this work, a MALDI-TOF MS profiling of Anisakis proteome was pursued with a view to constructing a first spectral library for the diagnosis of Anisakis infections. At the same time, a shotgun proteomics approach by LC-ESI-MS/MS was performed on the two main fractions obtained from protein extraction, to evaluate the protein species enriched by the protocol. A set of MALDI-TOF MS signals associated with proteins originating in the ribosomal fraction of the nematode extract was selected as a potential diagnostic tool for the identification of Anisakis spp.

RevDate: 2020-06-27

Ouabbou S, He Y, Butler K, et al (2020)

Inflammation in Mental Disorders: Is the Microbiota the Missing Link?.

Neuroscience bulletin pii:10.1007/s12264-020-00535-1 [Epub ahead of print].

Research suggests that inflammation is important in the pathophysiology of mental disorders. In addition, a growing body of evidence has led to the concept of the microbiota-gut-brain axis. To understand the potential interactions, we begin by exploring the liaison between the immune system and mental disorders, then we describe the evidence that the microbiota impact the immune response in the developing brain. Next, we review the literature that has documented microbiome alterations in major mental disorders. We end with a summary of therapeutic applications, ranging from psycho-biotics to immunomodulatory drugs that could affect the microbiota-gut-brain axis, and potential treatments to alleviate the adverse effects of antipsychotics. We conclude that there is promising evidence to support the position that the microbiota plays an important role in the immunological pathophysiology of mental disorders with an emphasis on psychotic disorders and mood disorders. However, more research is needed to elucidate the mechanisms.

RevDate: 2020-06-26

Xue AJ, Miao SJ, Sun H, et al (2020)

Intestinal dysbiosis in pediatric Crohn's disease patients with IL10RA mutations.

World journal of gastroenterology, 26(22):3098-3109.

BACKGROUND: Several studies have employed animal models to explore the association between microbiota and interleukin (IL) 10 signaling; however, limited information is available about the human microbiome.

AIM: To characterize the microbiome in patients with IL10RA mutations and to explore the association between gut dysbiosis and disease severity.

METHODS: Fecal samples were collected from patients who were diagnosed with loss-of-function mutations in the IL10RA gene between January 2017 and July 2018 at the Children's Hospital of Fudan University. Age-matched volunteer children were recruited as healthy controls. Patients with Crohn's disease (CD) were used as disease controls to standardize the antibiotic exposure. Microbial DNA was extracted from the fecal samples. All analyses were based on the 16S rRNA gene sequencing data.

RESULTS: Seventeen patients with IL10RA mutations (IL10RA group), 17 patients with pediatric CD, and 26 healthy children were included. Both patients with IL10RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability. The relative abundance of Firmicutes was substantially increased in the IL10RA group (P = 0.02). On further comparison of the relative abundance of taxa between patients with IL10RA mutations and healthy children, 13 taxa showed significant differences. The IL10RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD.

CONCLUSION: In patients with IL10RA mutations and early onset inflammatory bowel disease, gut dysbiosis shows a moderate association with disease severity.

RevDate: 2020-06-25

Jiang S, Xiao G, Koh AY, et al (2020)

HARMONIES: A Hybrid Approach for Microbiome Networks Inference via Exploiting Sparsity.

Frontiers in genetics, 11:445.

The human microbiome is a collection of microorganisms. They form complex communities and collectively affect host health. Recently, the advances in next-generation sequencing technology enable the high-throughput profiling of the human microbiome. This calls for a statistical model to construct microbial networks from the microbiome sequencing count data. As microbiome count data are high-dimensional and suffer from uneven sampling depth, over-dispersion, and zero-inflation, these characteristics can bias the network estimation and require specialized analytical tools. Here we propose a general framework, HARMONIES, Hybrid Approach foR MicrobiOme Network Inferences via Exploiting Sparsity, to infer a sparse microbiome network. HARMONIES first utilizes a zero-inflated negative binomial (ZINB) distribution to model the skewness and excess zeros in the microbiome data, as well as incorporates a stochastic process prior for sample-wise normalization. This approach infers a sparse and stable network by imposing non-trivial regularizations based on the Gaussian graphical model. In comprehensive simulation studies, HARMONIES outperformed four other commonly used methods. When using published microbiome data from a colorectal cancer study, it discovered a novel community with disease-enriched bacteria. In summary, HARMONIES is a novel and useful statistical framework for microbiome network inference, and it is available at

RevDate: 2020-06-25

Hermes GDA, Eckermann HA, de Vos WM, et al (2020)

Does entry to center-based childcare affect gut microbial colonization in young infants?.

Scientific reports, 10(1):10235 pii:10.1038/s41598-020-66404-z.

Entry to center-based childcare (CC) at three months of life can be an important challenge for infants as it includes major stressors such as long maternal separations and frequently changing caregivers. Stress and the new environment may in turn alter the composition of the gut microbiota with possible implications for future health outcomes. As part of an ongoing longitudinal study, we investigated whether CC, as compared to being cared for by the parents at home, alters the composition of the gut microbiota, while accounting for known covariates of the infant gut microbiota. Stool samples of infants who entered CC (n = 49) and control infants (n = 49) were obtained before and four weeks after CC entrance. Using Redundancy analysis, Random Forests and Bayesian linear models we found that infant gut microbiota was not affected in a uniform way by entry to CC. In line with the literature, breastfeeding, birth mode, age, and the presence of siblings were shown to significantly impact the microbial composition.

RevDate: 2020-06-24

López-Laguna H, Sánchez-García L, Serna N, et al (2020)

Engineering Protein Nanoparticles Out from Components of the Human Microbiome.

Small (Weinheim an der Bergstrasse, Germany) [Epub ahead of print].

Nanoscale protein materials are highly convenient as vehicles for targeted drug delivery because of their structural and functional versatility. Selective binding to specific cell surface receptors and penetration into target cells require the use of targeting peptides. Such homing stretches should be incorporated to larger proteins that do not interact with body components, to prevent undesired drug release into nontarget organs. Because of their low interactivity with human body components and their tolerated immunogenicity, proteins derived from the human microbiome are appealing and fully biocompatible building blocks for the biofabrication of nonreactive, inert protein materials within the nanoscale. Several phage and phage-like bacterial proteins with natural structural roles are produced in Escherichia coli as polyhistidine-tagged recombinant proteins, looking for their organization as discrete, nanoscale particulate materials. While all of them self-assemble in a variety of sizes, the stability of the resulting constructs at 37 °C is found to be severely compromised. However, the fine adjustment of temperature and Zn2+ concentration allows the formation of robust nanomaterials, fully stable in complex media and under physiological conditions. Then, microbiome-derived proteins show promise for the regulatable construction of scaffold protein nanomaterials, which can be tailored and strengthened by simple physicochemical approaches.

RevDate: 2020-06-23

Chauhan V, SS Kanwar (2020)

Lipopeptide(s) associated with human microbiome as potent cancer drug.

Seminars in cancer biology pii:S1044-579X(20)30148-6 [Epub ahead of print].

Human microbiota comprises of trillions of microbes which have evolved with and continued to live on/ within their human hosts. Different environmental factors and diet have a large impact upon human microbiota population. These microorganisms live in synergy with their hosts and are beneficial to the host in many different ways. Many microorganisms help to fight against human diseases. Cancer is one such diseases which effects a large human population often leading to death. Cancer is also one of the most fatal human diseases killing millions of people world-wide every year. Though many treatment procedures are available but none is 100 % effective in curing cancer. In this review, we seek to understand the role of human microbiota in cancer treatment. Lipopeptide(s) (LPs) produced by different microorganisms can act as efficient drug(s) against cancer. LPs are low molecular weight lipo-proteins that are also known for their anti-cancer activities. As human microbiota belongs to an environment within the host body, a drug prepared using these microorganisms will be easily accepted by the body. This novel approach of using LPs produced by human microbiota can be considered for the much needed change in cancer treatment. Therefore, it is proposed that research should focus on the host-microbe interaction which could pave the way in understanding role played by these microorganisms in cancer treatment.

RevDate: 2020-06-23

Baud D, Dimopoulou Agri V, Gibson GR, et al (2020)

Using Probiotics to Flatten the Curve of Coronavirus Disease COVID-2019 Pandemic.

Frontiers in public health, 8:186.

RevDate: 2020-06-23

Alverdy JC, Keskey R, R Thewissen (2020)

Can the cecal ligation and puncture model be repurposed to better inform therapy in human sepsis?.

Infection and immunity pii:IAI.00942-19 [Epub ahead of print].

A recent report by the National Institutes of Health on sepsis research has implied that there is a trend to move away from mouse models of sepsis. The most commonly used animal model to study the pathogenesis of human sepsis is cecal ligation and puncture (CLP) in mice. The model has been the mainstay of sepsis research for decades and continues to be considered the gold standard to inform novel pathways of sepsis physiology and its therapeutic direction. Although there have been many criticism of the model, particularly regarding its relevance to human disease, how this model might be repurposed to be more reflective of the human condition begs discussion. In this piece, we compare and contrast the mouse microbiome of the CLP model to the emerging science of the microbiome of human sepsis and discuss the relevance for mice to harbor the very pathogens present in the human microbiome during sepsis as well as an underlying disease process to mimic the characteristics of those patients with undesirable outcomes. How to repurpose this model to incorporate these "human factors" is discussed in detail and suggestions offered.

RevDate: 2020-06-21

Rattan P, Minacapelli CD, V Rustgi (2020)

The Microbiome and Hepatocellular Carcinoma.

Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society [Epub ahead of print].

The human microbiome is a vast and complex system encompassing all the microbes and their genes that occupy the environmentally exposed surfaces of the human body. The gut microbiota and its associated microbiome play an integral role in mammalian metabolism, immune tolerance as well as immunocompetence. Disruptions in the human gut microbiome are associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease (CLD). The persistence of this inflammation has been shown to induce the accumulation of genetic and epigenetic changes leading to hepatocellular carcinoma (HCC). Therefore, the importance and prognostic influence of the gut microbiome on hepatocarcinogenesis has been increasingly studied in recent years. This review discusses the mechanisms by which imbalances in the gut microbiome disturb the gut-liver axis to impact hepatocarcinogenesis, including disruption of the intestinal barrier, changes in bile acid metabolism and reduction in tumor-suppressing miRNA. Furthermore, this review summarizes recent advances in potential microbiome-based therapeutic opportunities in HCC.

RevDate: 2020-06-20

Hu Y, Fang L, Nicholson C, et al (2020)

Implications of Error-Prone Long-Read Whole-Genome Shotgun Sequencing on Characterizing Reference Microbiomes.

iScience, 23(6):101223 pii:S2589-0042(20)30408-9 [Epub ahead of print].

Long-read sequencing techniques, such as the Oxford Nanopore Technology, can generate reads that are tens of kilobases in length and are therefore particularly relevant for microbiome studies. However, owing to the higher per-base error rates than typical short-read sequencing, the application of long-read sequencing on microbiomes remains largely unexplored. Here we deeply sequenced two human microbiota mock community samples (HM-276D and HM-277D) from the Human Microbiome Project. We showed that assembly programs consistently achieved high accuracy (∼99%) and completeness (∼99%) for bacterial strains with adequate coverage. We also found that long-read sequencing provides accurate estimates of species-level abundance (R = 0.94 for 20 bacteria with abundance ranging from 0.005% to 64%). Our results not only demonstrate the feasibility of characterizing complete microbial genomes and populations from error-prone Nanopore sequencing data but also highlight necessary bioinformatics improvements for future metagenomics tool development.

RevDate: 2020-06-19

Ma ZS (2020)

Critical Network Structures and Medical Ecology Mechanisms Underlying Human Microbiome-Associated Diseases.

iScience, 23(6):101195 pii:S2589-0042(20)30380-1 [Epub ahead of print].

A fundamental problem in studies on human microbiome-associated diseases (MADs) is to understand the relationships between microbiome structures and health status of hosts. For example, species diversity metrics have been routinely evaluated in virtually all studies on MADs, yet a recent meta-analysis revealed that, in only approximately one-third of the cases, diversity and diseases were related. In this study, we ask whether Hubbell's neutral theory (supplemented with the normalized stochasticity ratio [NSR]) or critical microbiome network structures may offer better alternatives. Whereas neutral theory and NSR focus on stochastic processes, we use core/periphery and high-salience skeleton networks to evaluate deterministic, asymmetrical niche effects, assuming that all species or their interactions were not "born" equal and focusing on non-neutral, critical network structures. We found that properties of critical network structures are more indicative of disease effects. Finally, seven findings (mechanisms, interpretations, and postulations) regarding medical ecology mechanisms underlying MADs were summarized.

RevDate: 2020-06-19

Hampton-Marcell JT, Larsen P, Anton T, et al (2020)

Detecting personal microbiota signatures at artificial crime scenes.

Forensic science international, 313:110351 pii:S0379-0738(20)30213-9 [Epub ahead of print].

When mapped to the environments we interact with on a daily basis, the 36 million microbial cells per hour that humans emit leave a trail of evidence that can be leveraged for forensic analysis. We employed 16S rRNA amplicon sequencing to map unique microbial sequence variants between human skin and building surfaces in three experimental conditions: over time during controlled and uncontrolled incidental interactions with a door handle, and during multiple mock burglaries in ten real residences. We demonstrate that humans (n = 30) leave behind microbial signatures that can be used to track interaction with various surfaces within a building, but the likelihood of accurately detecting the specific burglar for a given home was between 20-25%. Also, the human microbiome contains rare microbial taxa that can be combined to create a unique microbial profile, which when compared to 600 other individuals can improve our ability to link an individual 'burglar' to a residence. In total, 5512 discriminating, non-singleton unique exact sequence variants (uESVs) were identified as unique to an individual, with a minimum of 1 and a maximum of 568, suggesting some people maintain a greater degree of unique taxa compared to our population of 600. Approximate 60-77% of the unique exact sequence variants originated from the hands of participants, and these microbial discriminators spanned 36 phyla but were dominated by the Proteobacteria (34%). A fitted regression generated to determine whether an intruder's uESVs found on door handles in an office decayed over time in the presence or absence of office workers, found no significant shift in proportion of uESVs over time irrespective of the presence of office workers. While it was possible to detect the correct burglars' microbiota as having contributed to the invaded space, the predictions were very weak in comparison to accepted forensic standards. This suggests that at this time 16S rRNA amplicon sequencing of the built environment microbiota cannot be used as a reliable trace evidence standard for criminal investigations.

RevDate: 2020-06-19

De Filippis F, Pasolli E, D Ercolini (2020)

The food-gut axis: lactic acid bacteria and their link to food, the gut microbiome and human health.

FEMS microbiology reviews pii:5859486 [Epub ahead of print].

Lactic acid bacteria (LAB) are present in foods, the environment and the animal gut, although fermented foods (FFs) are recognized as the primary niche of LAB activity. Several LAB strains have been studied for their health-promoting properties and are employed as probiotics. FFs are recognized for their potential beneficial effects, which we review in this article. They are also an important source of LAB, which are ingested daily upon FF consumption. In this review, we describe the diversity of LAB and their occurrence in food as well as the gut microbiome. We discuss the opportunities to study LAB diversity and functional properties by considering the availability of both genomic and metagenomic data in public repositories, as well as the different latest computational tools for data analysis. In addition, we discuss the role of LAB as potential probiotics by reporting the prevalence of key genomic features in public genomes and by surveying the outcomes of LAB use in clinical trials involving human subjects. Finally, we highlight the need for further studies aimed at improving our knowledge of the link between LAB-fermented foods and the human gut from the perspective of health promotion.

RevDate: 2020-06-20

Coil DA, Neches RY, Lang JM, et al (2020)

Bacterial communities associated with cell phones and shoes.

PeerJ, 8:e9235.

Background: Every human being carries with them a collection of microbes, a collection that is likely both unique to that person, but also dynamic as a result of significant flux with the surrounding environment. The interaction of the human microbiome (i.e., the microbes that are found directly in contact with a person in places such as the gut, mouth, and skin) and the microbiome of accessory objects (e.g., shoes, clothing, phones, jewelry) is of potential interest to both epidemiology and the developing field of microbial forensics. Therefore, the microbiome of personal accessories are of interest because they serve as both a microbial source and sink for an individual, they may provide information about the microbial exposure experienced by an individual, and they can be sampled non-invasively.

Findings: We report here a large-scale study of the microbiome found on cell phones and shoes. Cell phones serve as a potential source and sink for skin and oral microbiome, while shoes can act as sampling devices for microbial environmental experience. Using 16S rRNA gene sequencing, we characterized the microbiome of thousands of paired sets of cell phones and shoes from individuals at sporting events, museums, and other venues around the United States.

Conclusions: We place this data in the context of previous studies and demonstrate that the microbiome of phones and shoes are different. This difference is driven largely by the presence of "environmental" taxa (taxa from groups that tend to be found in places like soil) on shoes and human-associated taxa (taxa from groups that are abundant in the human microbiome) on phones. This large dataset also contains many novel taxa, highlighting the fact that much of microbial diversity remains uncharacterized, even on commonplace objects.

RevDate: 2020-06-19

Puebla-Barragan S, Renaud J, Sumarah M, et al (2020)

Malodorous biogenic amines in Escherichia coli-caused urinary tract infections in women-a metabolomics approach.

Scientific reports, 10(1):9703.

Many women suffer from urinary tract infections (UTIs). In addition to pain and increased urgency to urinate, malodour is a significant issue for these patients. The specific factors causing this malodour are unclear, and there are no targeted treatment options to counteract it effectively. We used a metabolomics approach to compare the chemical composition of metabolites in the urine of women with E. coli UTIs (n = 15) and those who are healthy (n = 10). The biogenic amines trimethylamine and putrescine, which cause malodour in other urogenital conditions, were significantly increased in UTI patients. Conversely, the precursor of trimethylamine, trimethylamine N-oxide, was lower. To further confirm the source of the malodorous compounds, in vitro experiments were conducted by incubating strains of uropathogenic E. coli in sterilized urine from healthy women. All tested strains accumulated trimethylamine and putrescine. Notably, cadaverine was also produced by E. coli strains in vitro; however, it was not significantly different between both groups. We confirmed that the malodorous amines TMA and putrescine are found in higher concentrations in the urine of patients with an E.coli-caused UTI.

RevDate: 2020-06-16

Kenny DJ, Plichta DR, Shungin D, et al (2020)

Cholesterol Metabolism by Uncultured Human Gut Bacteria Influences Host Cholesterol Level.

Cell host & microbe pii:S1931-3128(20)30295-X [Epub ahead of print].

The human microbiome encodes extensive metabolic capabilities, but our understanding of the mechanisms linking gut microbes to human metabolism remains limited. Here, we focus on the conversion of cholesterol to the poorly absorbed sterol coprostanol by the gut microbiota to develop a framework for the identification of functional enzymes and microbes. By integrating paired metagenomics and metabolomics data from existing cohorts with biochemical knowledge and experimentation, we predict and validate a group of microbial cholesterol dehydrogenases that contribute to coprostanol formation. These enzymes are encoded by ismA genes in a clade of uncultured microorganisms, which are prevalent in geographically diverse human cohorts. Individuals harboring coprostanol-forming microbes have significantly lower fecal cholesterol levels and lower serum total cholesterol with effects comparable to those attributed to variations in lipid homeostasis genes. Thus, cholesterol metabolism by these microbes may play important roles in reducing intestinal and serum cholesterol concentrations, directly impacting human health.

RevDate: 2020-06-19

Diakite A, Dubourg G, Dione N, et al (2020)

Optimization and standardization of the culturomics technique for human microbiome exploration.

Scientific reports, 10(1):9674.

Culturomics is a high-throughput culture approach that has dramatically contributed to the recent renewal of culture. While metagenomics enabled substantial advances in exploring the microbiota, culturomics significantly expanded our knowledge regarding the bacterial gut repertoire through the discovery and the description of hundreds of new taxa. While this approach relies on the variation of culture conditions and media, we have tested so far more than 300 conditions since the beginning of culturomics studies. In this context, we aimed herein to identify the most profitable conditions for optimizing culturomics approach. For this purpose, we have analysed a set of 58 culturomics conditions that were previously applied to 8 faecal specimens, enabling the isolation of 497 bacterial species. As a result, we were able to reduce the number of conditions used to isolate these 497 of more than a half (i.e. to 25 culture conditions). We have also established a list of the 16 conditions that allowed to capture 98% of the total number of species previously isolated. These data constitute a methodological starting point for culture-based microbiota studies by improving the culturomics workflow without any loss of captured bacterial diversity.

RevDate: 2020-06-19

Philips A, Stolarek I, Handschuh L, et al (2020)

Analysis of oral microbiome from fossil human remains revealed the significant differences in virulence factors of modern and ancient Tannerella forsythia.

BMC genomics, 21(1):402.

BACKGROUND: Recent advances in the next-generation sequencing (NGS) allowed the metagenomic analyses of DNA from many different environments and sources, including thousands of years old skeletal remains. It has been shown that most of the DNA extracted from ancient samples is microbial. There are several reports demonstrating that the considerable fraction of extracted DNA belonged to the bacteria accompanying the studied individuals before their death.

RESULTS: In this study we scanned 344 microbiomes from 1000- and 2000- year-old human teeth. The datasets originated from our previous studies on human ancient DNA (aDNA) and on microbial DNA accompanying human remains. We previously noticed that in many samples infection-related species have been identified, among them Tannerella forsythia, one of the most prevalent oral human pathogens. Samples containing sufficient amount of T. forsythia aDNA for a complete genome assembly were selected for thorough analyses. We confirmed that the T. forsythia-containing samples have higher amounts of the periodontitis-associated species than the control samples. Despites, other pathogens-derived aDNA was found in the tested samples it was too fragmented and damaged to allow any reasonable reconstruction of these bacteria genomes. The anthropological examination of ancient skulls from which the T. forsythia-containing samples were obtained revealed the pathogenic alveolar bone loss in tooth areas characteristic for advanced periodontitis. Finally, we analyzed the genetic material of ancient T. forsythia strains. As a result, we assembled four ancient T. forsythia genomes - one 2000- and three 1000- year-old. Their comparison with contemporary T. forsythia genomes revealed a lower genetic diversity within the four ancient strains than within contemporary strains. We also investigated the genes of T. forsythia virulence factors and found that several of them (KLIKK protease and bspA genes) differ significantly between ancient and modern bacteria.

CONCLUSIONS: In summary, we showed that NGS screening of the ancient human microbiome is a valid approach for the identification of disease-associated microbes. Following this protocol, we provided a new set of information on the emergence, evolution and virulence factors of T. forsythia, the member of the oral dysbiotic microbiome.

RevDate: 2020-06-15

Jian C, Luukkonen P, Sädevirta S, et al (2020)

Impact of short-term overfeeding of saturated or unsaturated fat or sugars on the gut microbiota in relation to liver fat in obese and overweight adults.

Clinical nutrition (Edinburgh, Scotland) pii:S0261-5614(20)30224-7 [Epub ahead of print].

BACKGROUNDS & AIMS: Intestinal microbiota may be causally involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). We aimed to study the effect of short-term overfeeding on human gut microbiota in relation to baseline and overfeeding-induced liver steatosis. We also asked whether the baseline microbiota composition is associated to the overfeeding-induced increase in liver fat.

METHODS: In a randomized trial, 38 overweight and obese subjects were assigned to consume an excess of 1000 kcal/day of diets rich in either saturated fat, unsaturated fat, or simple sugars for 3 weeks. Fasting blood samples and 1H-MR spectroscopy were used for extensive clinical phenotyping as previously reported (PMID: 29844096). Fecal samples were collected for the analysis of the gut microbiota using 16S rRNA amplicon sequencing, imputed metagenomics and qPCR. Microbiota results were correlated with dietary intakes and clinical measurements before and during overfeeding.

RESULTS: The overall community structure of the microbiota remained highly stable and personalized during overfeeding based on between-sample Bray-Curtis dissimilarity, but the relative abundances of individual taxa were altered in a diet-specific manner: overfeeding saturated fat increased Proteobacteria, while unsaturated fat increased butyrate producers. Sugar overfeeding increased Lactococcus and Escherichia coli. Imputed functions of the gut microbiota were not affected by overfeeding. Several taxa affected by overfeeding significantly correlated with the changes in host metabolic markers. The baseline levels of proteobacterial family Desulfovibrionaceae, and especially genus Bilophila, were significantly associated to overfeeding-induced liver fat increase independently of the diet arm. In general, limited overlap was observed between the overfeeding-induced microbiota changes and the liver fat-associated microbiota features at baseline.

CONCLUSIONS: Our work indicates that the human gut microbiota is resilient to short-term overfeeding on community level, but specific taxa are altered on diet composition-dependent manner. Generalizable microbiota signatures directly associated with liver steatosis could not be identified. Instead, the carriage of Bilophila was identified as a potential novel risk factor for diet-induced liver steatosis in humans. Clinical trial registry number: NCT02133144 listed on NIH website:

RevDate: 2020-06-15

Ooi DS, Tan CP, Tay MJ, et al (2020)

Developmental Origins of Health and Disease: Impact of environmental dust exposure in modulating microbiome and its association with non-communicable diseases.

Journal of developmental origins of health and disease pii:S2040174420000549 [Epub ahead of print].

Non-communicable diseases (NCDs) including obesity, diabetes, and allergy are chronic, multi-factorial conditions that are affected by both genetic and environmental factors. Over the last decade, the microbiome has emerged as a possible contributor to the pathogenesis of NCDs. Microbiome profiles were altered in patients with NCDs, and shift in microbial communities was associated with improvement in these health conditions. Since the genetic component of these diseases cannot be altered, the ability to manipulate the microbiome holds great promise for design of novel therapies in the prevention and treatment of NCDs. Together, the Developmental Origins of Health and Disease concept and the microbial hypothesis propose that early life exposure to environmental stimuli will alter the development and composition of the human microbiome, resulting in health consequences. Recent studies indicated that the environment we are exposed to in early life is instrumental in shaping robust immune development, possibly through modulation of the human microbiome (skin, airway, and gut). Despite much research into human microbiome, the origin of their constituent microbiota remains unclear. Dust (also known as particulate matter) is a key determinant of poor air quality in the modern urban environment. It is ubiquitous and serves as a major source and reservoir of microbial communities that modulates the human microbiome, contributing to health and disease. There are evidence that reported significant associations between environmental dust and NCDs. In this review, we will focus on the impact of dust exposure in shaping the human microbiome and its possible contribution to the development of NCDs.

RevDate: 2020-06-13

Rotz SJ, CE Dandoy (2020)

The microbiome in pediatric oncology.

Cancer [Epub ahead of print].

The human microbiome comprises a diverse set of microorganisms, which play a mostly cooperative role in processes such as metabolism and host defense. Next-generation genomic sequencing of bacterial nucleic acids now can contribute a much broader understanding of the diverse organisms composing the microbiome. Emerging evidence has suggested several roles of the microbiome in pediatric hematology/oncology, including susceptibility to infectious diseases, immune response to neoplasia, and contributions to the tumor microenvironment as well as changes to the microbiome from chemotherapy and antibiotics with unclear consequences. In this review, the authors have examined the evidence of the role of the microbiome in pediatric hematology/oncology, discussed how the microbiome may be modulated, and suggested key questions in need of further exploration.

RevDate: 2020-06-13

Galli I, R Fasanelli (2020)

Public understanding of science and common sense: Social representations of the human microbiome among the expert and non-expert public.

Health psychology open, 7(1):2055102920913239.

The aim of this investigation is to examine the structure and the content of different social groups' representations of the human microbiome. We employed a non-probabilistic sample comprising two groups of participants. The first group (n = 244) included university students. The second group included lay people (n = 355). We chose a mixed-method approach. The data obtained were processed using IRaMuTeQ software. The results allow us to identify the anchoring and objectification processes activated by the two different groups of interviewees. The results could be useful to those in charge of implementing campaigns aimed at promoting health literacy.

RevDate: 2020-06-14

Sui HY, Weil AA, Nuwagira E, et al (2020)

Impact of DNA Extraction Method on Variation in Human and Built Environment Microbial Community and Functional Profiles Assessed by Shotgun Metagenomics Sequencing.

Frontiers in microbiology, 11:953.

Both the host microbiome and the microbiome of the built environment can have profound impacts on human health. While prior studies have suggested that the variability introduced by DNA extraction method is less than typical biologic variation, most studies have focused on 16S rRNA amplicon sequencing or on high biomass fecal samples. Shotgun metagenomic sequencing provides advantages over amplicon sequencing for surveying the microbiome, but is a challenge to perform in lower microbial biomass samples with high human DNA content such as sputum or vacuumed dust. Here we systematically evaluate the impact of four different extraction methods (phenol:choloroform, and three high-throughput kit-based approaches, the Promega Maxwell gDNA, Qiagen MagAttract PowerSoil DNA, and ZymoBIOMICS 96 MagBead). We report the variation in microbial community structure and predicted microbial function assessed by shotgun metagenomics sequencing in human stool, sputum, and vacuumed dust obtained from ongoing cohort studies or clinical trials. The same beadbeating protocol was used for all samples to focus our evaluation on the impact of kit chemistries on sequencing results. DNA yield was overall highest in the phenol:choloroform and Promega approaches. Only the phenol:choloroform approach showed evidence of contamination in negative controls. Bias was evaluated using mock community controls, and was noted across all extraction methods, although Promega exhibited the least amount of bias. The extraction method did not impact the proportion of human reads, although stool had the lowest proportion of human reads (0.1%) as compared to dust (44.1%) and sputum (80%). We calculated Bray-Curtis dissimilarity and Aitchison distances to evaluate the impact of extraction method on microbial community structure by sample type. Extraction method had the lowest impact in stool (extraction method responsible for 3.0-3.9% of the variability), the most impact in vacuumed dust (12-16% of the variability) and intermediate values for sputum (9.2-12% variability). Similar differences were noted when evaluating microbial community function. Our results will inform investigators planning microbiome studies using diverse sample types in large clinical studies. A consistent DNA extraction approach across all sample types is recommended, particularly with lower microbial biomass samples that are more heavily influenced by extraction method.

RevDate: 2020-06-16

Fukui S, Morimoto S, Ichinose K, et al (2020)

Comparison of lung microbiota between antineutrophil cytoplasmic antibody-associated vasculitis and sarcoidosis.

Scientific reports, 10(1):9466.

Microbial involvement in the pathogenesis have been suggested in both antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and sarcoidosis, both of which have lung involvement. However, exhaustive research to assess the bacteria in the lung in AAV and in sarcoidosis have not been performed. We sought to elucidate the distinct dysbiotic lung microbiota between AAV and sarcoidosis. We used 16S rRNA gene high-throughput sequencing to obtain the bacterial community composition of bronchoalveolar lavage fluid (BALF) in patients with AAV (n = 16) compared to patients with sarcoidosis (n = 21). The patients had not undergone therapy with immunosuppressive medication when their BALF was acquired. No difference was observed in α-diversity between patients with AAV and patients with sarcoidosis when using all the detected taxa. We defined the taxa of the oral cavity by using the data of oral microbiota of healthy individuals from the Human Microbiome Project (HMP). The analysis using only oral taxa made the difference in α-diversity between AAV and sarcoidosis clearer compared with those using all the detected taxa. Besides, the analysis using detected taxa except for oral taxa also made the difference in α-diversity between AAV and sarcoidosis clearer compared with those using all the detected taxa. A linear negative relationship between the α-diversity and Birmingham vasculitis activity score (BVAS) was detected in the AAV group. The observed p-value for the effect of the disease groups on the ß-diversity was small while the effect of other factors including sex and smoking status did not have small p-values. By excluding oral taxa from all the detected taxa, we found a cluster mainly consisted of sarcoidosis patients which was characterized with microbial community monopolized by Erythrobacteraceae family. Our results suggested the importance of considering the influence of oral microbiota in evaluating lung microbiota.

RevDate: 2020-06-13

Dekaboruah E, Suryavanshi MV, Chettri D, et al (2020)

Human microbiome: an academic update on human body site specific surveillance and its possible role.

Archives of microbiology [Epub ahead of print].

Human body is inhabited by vast number of microorganisms which form a complex ecological community and influence the human physiology, in the aspect of both health and diseases. These microbes show a relationship with the human immune system based on coevolution and, therefore, have a tremendous potential to contribute to the metabolic function, protection against the pathogen and in providing nutrients and energy. However, of these microbes, many carry out some functions that play a crucial role in the host physiology and may even cause diseases. The introduction of new molecular technologies such as transcriptomics, metagenomics and metabolomics has contributed to the upliftment on the findings of the microbiome linked to the humans in the recent past. These rapidly developing technologies are boosting our capacity to understand about the human body-associated microbiome and its association with the human health. The highlights of this review are inclusion of how to derive microbiome data and the interaction between human and associated microbiome to provide an insight on the role played by the microbiome in biological processes of the human body as well as the development of major human diseases.

RevDate: 2020-06-11

Topçuoğlu BD, Lesniak NA, Ruffin MT, et al (2020)

A Framework for Effective Application of Machine Learning to Microbiome-Based Classification Problems.

mBio, 11(3): pii:mBio.00434-20.

Machine learning (ML) modeling of the human microbiome has the potential to identify microbial biomarkers and aid in the diagnosis of many diseases such as inflammatory bowel disease, diabetes, and colorectal cancer. Progress has been made toward developing ML models that predict health outcomes using bacterial abundances, but inconsistent adoption of training and evaluation methods call the validity of these models into question. Furthermore, there appears to be a preference by many researchers to favor increased model complexity over interpretability. To overcome these challenges, we trained seven models that used fecal 16S rRNA sequence data to predict the presence of colonic screen relevant neoplasias (SRNs) (n = 490 patients, 261 controls and 229 cases). We developed a reusable open-source pipeline to train, validate, and interpret ML models. To show the effect of model selection, we assessed the predictive performance, interpretability, and training time of L2-regularized logistic regression, L1- and L2-regularized support vector machines (SVM) with linear and radial basis function kernels, a decision tree, random forest, and gradient boosted trees (XGBoost). The random forest model performed best at detecting SRNs with an area under the receiver operating characteristic curve (AUROC) of 0.695 (interquartile range [IQR], 0.651 to 0.739) but was slow to train (83.2 h) and not inherently interpretable. Despite its simplicity, L2-regularized logistic regression followed random forest in predictive performance with an AUROC of 0.680 (IQR, 0.625 to 0.735), trained faster (12 min), and was inherently interpretable. Our analysis highlights the importance of choosing an ML approach based on the goal of the study, as the choice will inform expectations of performance and interpretability.IMPORTANCE Diagnosing diseases using machine learning (ML) is rapidly being adopted in microbiome studies. However, the estimated performance associated with these models is likely overoptimistic. Moreover, there is a trend toward using black box models without a discussion of the difficulty of interpreting such models when trying to identify microbial biomarkers of disease. This work represents a step toward developing more-reproducible ML practices in applying ML to microbiome research. We implement a rigorous pipeline and emphasize the importance of selecting ML models that reflect the goal of the study. These concepts are not particular to the study of human health but can also be applied to environmental microbiology studies.

RevDate: 2020-06-11

Leskinen K, Pajunen MI, Vilanova MVG, et al (2020)

YerA41, a Yersinia ruckeri Bacteriophage: Determination of a Non-Sequencable DNA Bacteriophage Genome via RNA-Sequencing.

Viruses, 12(6): pii:v12060620.

YerA41 is a Myoviridae bacteriophage that was originally isolated due its ability to infect Yersinia ruckeri bacteria, the causative agent of enteric redmouth disease of salmonid fish. Several attempts to determine its genomic DNA sequence using traditional and next generation sequencing technologies failed, indicating that the phage genome is modified in such a way that it is an unsuitable template for PCR amplification and for conventional sequencing. To determine the YerA41 genome sequence, we performed RNA-sequencing from phage-infected Y. ruckeri cells at different time points post-infection. The host-genome specific reads were subtracted and de novo assembly was performed on the remaining unaligned reads. This resulted in nine phage-specific scaffolds with a total length of 143 kb that shared only low level and scattered identity to known sequences deposited in DNA databases. Annotation of the sequences revealed 201 predicted genes, most of which found no homologs in the databases. Proteome studies identified altogether 63 phage particle-associated proteins. The RNA-sequencing data were used to characterize the transcriptional control of YerA41 and to investigate its impact on the bacterial gene expression. Overall, our results indicate that RNA-sequencing can be successfully used to obtain the genomic sequence of non-sequencable phages, providing simultaneous information about the phage-host interactions during the process of infection.

RevDate: 2020-06-09

Satokari R, Pietilä L, Mattila E, et al (2020)

Faecal banking at -20 °C facilitates faecal microbiota transplantation for recurrent Clostridioides difficile infection in clinical practice.

RevDate: 2020-06-16

Voth E, S Khanna (2020)

The Integrative Human microbiome project: a mile stone in the understanding of the gut microbiome.

RevDate: 2020-06-11

Hahn A, Burrell A, Ansusinha E, et al (2020)

Airway microbial diversity is decreased in young children with cystic fibrosis compared to healthy controls but improved with CFTR modulation.

Heliyon, 6(6):e04104.

Background: Culture-independent next generation sequencing has identified diverse microbial communities within the cystic fibrosis (CF) airway. The study objective was to test for differences in the upper airway microbiome of children with CF and healthy controls and age-related differences in children with CF.

Methods: Oropharyngeal swabs and clinical data were obtained from 25 children with CF and 50 healthy controls aged ≤6 years. Bacterial DNA was amplified and sequenced for the V4 region of 16S rRNA marker-gene. Alpha diversity was measured using operational taxonomic units (OTUs), Shannon diversity, and the inverse Simpson's index. Beta diversity was measured using Morisita-Horn and Bray-Curtis and Jaccard distances. General linear models were used for comparison of alpha diversity measures between groups to account for differences in demographics and exposures. Mixed effects general linear models were used for longitudinal comparisons 1) between children with CF of different ages and 2) between children with CF receiving CF transmembrane conductance regulator (CFTR) modulators, children with CF not receiving CFTR modulators, and healthy controls to adjust for repeated measures per subject.

Results: Children with CF were more likely to have received antibiotics in the prior year than healthy controls (92% vs 24%, p < 0.001). Controlling age, race, ethnicity, length of breastfeeding, and having siblings, children with CF had a lower richness than healthy controls: OTUs 62.1 vs 83, p = 0.022; and trended toward lower diversity: Shannon 2.09 vs 2.35, p = 0.057; inverse Simpson 5.7 vs 6.92, p = 0.118. Staphylococcus, three Rothia OTUs, and two Streptococcus OTUs were more abundant in CF children versus healthy controls (all p < 0.05). Bray-Curtis and Jaccard distances, which reflect overall microbial community composition, were also significantly different (both p = 0.001). In longitudinally collected samples from children with CF, Morisita-Horn trended toward more similarity in those aged 0-2 years compared to those aged 3-6 years (p = 0.070). In children >2 years of age, there was a significant trend in increasing alpha diversity measures between children with CF not receiving CFTR modulators, children with CF receiving CFTR modulators, and healthy controls: OTUs 63.7 vs 74.7 vs 97.6, p < 0.001; Shannon 2.11 vs 2.34 vs 2.56, p < 0.001; inverse Simpson 5.78 vs 7.23 vs 7.96, p < 0.001.

Conclusions: Children with CF have lower bacterial diversity and different composition of organisms compared with healthy controls. This appears to start in early childhood, is possibly related to the use of antibiotics, and may be partially corrected with the use of CFTR modulators.

RevDate: 2020-06-19

Chng KR, Li C, Bertrand D, et al (2020)

Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment.

Nature medicine, 26(6):941-951.

Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections.

RevDate: 2020-06-12

Douglas GM, Bielawski JP, MGI Langille (2020)

Re-evaluating the relationship between missing heritability and the microbiome.

Microbiome, 8(1):87.

Human genome-wide association studies (GWASs) have recurrently estimated lower heritability estimates than familial studies. Many explanations have been suggested to explain these lower estimates, including that a substantial proportion of genetic variation and gene-by-environment interactions are unmeasured in typical GWASs. The human microbiome is potentially related to both of these explanations, but it has been more commonly considered as a source of unmeasured genetic variation. In particular, it has recently been argued that the genetic variation within the human microbiome should be included when estimating trait heritability. We outline issues with this argument, which in its strictest form depends on the holobiont model of human-microbiome interactions. Instead, we argue that the microbiome could be leveraged to help control for environmental variation across a population, although that remains to be determined. We discuss potential approaches that could be explored to determine whether integrating microbiome sequencing data into GWASs is useful. Video abstract.

RevDate: 2020-06-20

Chopyk J, Akrami K, Bavly T, et al (2020)

Temporal variations in bacterial community diversity and composition throughout intensive care unit renovations.

Microbiome, 8(1):86.

BACKGROUND: Inanimate surfaces within a hospital serve as a reservoir of microbial life that may colonize patients and ultimately result in healthcare associated infections (HAIs). Critically ill patients in intensive care units (ICUs) are particularly vulnerable to HAIs. Little is known about how the microbiome of the ICU is established or what factors influence its evolution over time. A unique opportunity to bridge the knowledge gap into how the ICU microbiome evolves emerged in our health system, where we were able to characterize microbial communities in an established hospital ICU prior to closing for renovations, during renovations, and then after re-opening.

RESULTS: We collected swab specimens from ICU bedrails, computer keyboards, and sinks longitudinally at each renovation stage, and analyzed the bacterial compositions on these surfaces by 16S rRNA gene sequencing. Specimens collected before ICU closure had the greatest alpha diversity, while specimens collected after the ICU had been closed for over 300 days had the least. We sampled the ICU during the 45 days after re-opening; however, within that time frame, the alpha diversity never reached pre-closure levels. There were clear and significant differences in microbiota compositions at each renovation stage, which was driven by environmental bacteria after closure and human-associated bacteria after re-opening and before closure.

CONCLUSIONS: Overall, we identified significant differences in microbiota diversity and community composition at each renovation stage. These data help to decipher the evolution of the microbiome in the most critical part of the hospital and demonstrate the significant impacts that microbiota from patients and staff have on the evolution of ICU surfaces. Video Abstract.

RevDate: 2020-06-10

Liu Y, Liu Y, Du Z, et al (2020)

Skin microbiota analysis-inspired development of novel anti-infectives.

Microbiome, 8(1):85.

BACKGROUND: The alarming spread of antimicrobial resistance requires the development of novel anti-infective drugs. Despite the recent research focus on the human microbiome and its likely value to understand and exploit inter-bacterial inhibitory phenomena as a source for antimicrobial strategies, the human microbiota has barely been investigated for the purpose of drug development.

RESULTS: We performed a large screen analyzing over 3000 human skin isolates to evaluate bacterial competition within the human skin microbiota as a basis for the development of anti-infective therapeutics. We discovered a Staphylococcus hominis strain with strong and broad activity against Gram-positive pathogens that was mediated by the bacteriocin micrococcin P1 (MP1). In "probiotic" approaches, this strain led to reduced Staphylococcus aureus infection and accelerated closure of S. aureus-infected wounds. Furthermore, we used a nanoparticle strategy to overcome the physico-chemical limitations often encountered with natural substances such as MP1 and demonstrate a significant reduction of S. aureus infection by MP1-loaded nanoparticles.

CONCLUSIONS: Our study gives examples of how analysis of bacterial interactions in the human microbiota can be explored for the development of novel, effective anti-infective strategies. Video Abstract.

RevDate: 2020-06-05

Moles L, D Otaegui (2020)

The Impact of Diet on Microbiota Evolution and Human Health. Is Diet an Adequate Tool for Microbiota Modulation?.

Nutrients, 12(6): pii:nu12061654.

The human microbiome is emerging as an interesting field in research into the prevention of health problems and recovery from illness in humans. The complex ecosystem formed by the microbiota is continuously interacting with its host and the environment. Diet could be assumed to be one of the most prominent factors influencing the microbiota composition. Nevertheless, and in spite of numerous strategies proposed to modulate the human microbiota through dietary means, guidelines to achieve this goal have yet to be established. This review assesses the correlation between social and dietary changes over the course of human evolution and the adaptation of the human microbiota to those changes. In addition, it discusses the main dietary strategies for modulating the microbiota and the difficulties of putting them properly into practice.

RevDate: 2020-06-04

Wang CZ, Wan JY, Wan J, et al (2020)

Human intestinal microbiota derived metabolism signature from a North American native botanical Oplopanax horridus with UPLC/Q-TOF-MS analysis.

Biomedical chromatography : BMC [Epub ahead of print].

Oplopanax horridus, distributed in North America, is an herbal medicine traditionally used by Pacific indigenous peoples for various medical conditions. After oral ingestion, constituents in O. horridus extract (OhE) could be converted to their metabolites by enteric microbiome before absorption. In this study, in order to mimic gut environment, the OhE was biotransformed by using the enteric microbiome of healthy human subjects. For accurate and reliable data collection with optimized approaches in sample preparation and analytical conditions, ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) were used to characterize parent constituents and their metabolites. In the extract, 20 parent compounds were identified including polyynes, sesquiterpenes, monoterpeondids, phenylpropanoids, and phenolic acids. After the biotransformation, a total of 78 metabolites were identified, of which 37 of them belong to polyynes metabolites. The common biotransformation pathways are hydroxylation, acetylization, methylation, and demethylation. Based on the pathway distributions, the metabolism signature of OhE has been explored. The metabolism pathways of OhE compounds are dependent on their structural classifications and hydrophilic/hydrophobic properties. In summary, with comprehensive analysis, we systematically investigated human microbiome-derived OhE metabolites. The enteric microbial metabolism signature provides novel information for future effective use of Oplopanax horridus.

RevDate: 2020-06-04

Gascon M, Harrall KK, Beavers AW, et al (2020)

Feasibility of collection and analysis of microbiome data in a longitudinal randomized trial of community gardening.

Future microbiology [Epub ahead of print].

Aim: We explored the feasibility of collecting and analyzing human microbiome data in a longitudinal randomized controlled trial of community gardening. Methods & materials: Participants were randomly assigned to gardening (N = 8) or control (N = 8). Participants provided stool, mouth, hand and forehead microbiome samples at six timepoints. Analyses combined mixed models with Qiita output. Results: Participant satisfaction was high, with 75% of participants completing evaluations. While no microbial effects were statistically significant due to small sample size, the analysis pipeline utility was tested. Conclusion: Longitudinal collection and analysis of microbiome data in a community gardening randomized controlled trial is feasible. The analysis pipeline will be useful in larger studies for assessment of the pathway between microbiota, gardening and health outcomes.

RevDate: 2020-06-03

Rasmussen MA, Thorsen J, Dominguez-Bello MG, et al (2020)

Ecological succession in the vaginal microbiota during pregnancy and birth.

The ISME journal pii:10.1038/s41396-020-0686-3 [Epub ahead of print].

The mother's vaginal microbiota represents the first microbes to which a child is exposed when delivered vaginally. However, little is known about the composition and development of the vaginal microbiota during pregnancy and birth. Here, we analyzed the vaginal microbiota of 57 women in pregnancy week 24, 36 and at birth after rupture of membranes but before delivery, and further compared the composition with that of the gut and airways of the 1-week-old child. The vaginal community structure had dramatic changes in bacterial diversity and taxonomic distribution, yet carried an individual-specific signature. The relative abundance of most bacterial taxa increased stepwise from week 24 of pregnancy until birth, with a gradual decline of Lactobacillus. Mother-to-child vertical transfer, as suggested by sharing, was modest, with the strongest transfer being for Clostridiales followed by Lactobacillales and Enterobacteriales. In conclusion, late gestation is associated with an increase in maternal vaginal microbiota diversity, and vaginal bacteria at birth only modestly predict the composition of the neonatal microbiota.

RevDate: 2020-06-03

Brenes LR, Lohse MB, Hartooni N, et al (2020)

A Set of Diverse Genes Influence the Frequency of White-Opaque Switching in Candida albicans.

G3 (Bethesda, Md.) pii:g3.120.401249 [Epub ahead of print].

The fungal species Candida albicans is both a member of the human microbiome and a fungal pathogen. C. albicans undergoes several different morphological transitions, including one called white-opaque switching. Here, cells reversibly switch between two states, "white" and "opaque," and each state is heritable through many cell generations. Each cell type has a distinct cellular and colony morphology and they differ in many other properties including mating, nutritional specialization, and interactions with the innate immune system. Previous genetic screens to gain insight into white-opaque switching have focused on certain classes of genes (for example transcriptional regulators or chromatin modifying enzymes). In this paper, we examined 172 deletion mutants covering a broad range of cell functions. We identified 28 deletion mutants with at least a five-fold effect on switching frequencies; these cover a wide variety of functions ranging from membrane sensors to kinases to proteins of unknown function. In agreement with previous reports, we found that components of the pheromone signaling cascade affect white-to-opaque switching; however, our results suggest that the major effect of Cek1 on white-opaque switching occurs through the cell wall damage response pathway. Most of the genes we identified have not been previously implicated in white-opaque switching and serve as entry points to understand new aspects of this morphological transition.

RevDate: 2020-06-03

Badawy S, Pajunen MI, Haiko J, et al (2020)

Identification and Functional Analysis of Temperate Siphoviridae Bacteriophages of Acinetobacter baumannii.

Viruses, 12(6): pii:v12060604.

Acinetobacter baumannii is an opportunistic pathogen that presents a serious clinical challenge due to its increasing resistance to all available antibiotics. Phage therapy has been introduced recently to treat antibiotic-incurable A. baumannii infections. In search for new A. baumannii specific bacteriophages, 20 clinical A. baumannii strains were used in two pools in an attempt to enrich phages from sewage. The enrichment resulted in induction of resident prophage(s) and three temperate bacteriophages, named vB_AbaS_fEg-Aba01, vB_AbaS_fLi-Aba02 and vB_AbaS_fLi-Aba03, all able to infect only one strain (#6597) of the 20 clinical strains, were isolated. Morphological characteristics obtained by transmission electron microscopy together with the genomic information revealed that the phages belong to the family Siphoviridae. The ca. 35 kb genomic sequences of the phages were >99% identical to each other. The linear ds DNA genomes of the phages contained 10 nt cohesive end termini, 52-54 predicted genes, an attP site and one tRNA gene each. A database search revealed an >99% identical prophage in the genome of A.baumannii strain AbPK1 (acc. no. CP024576.1). Over 99% identical prophages were also identified from two of the original 20 clinical strains (#5707 and #5920) and both were shown to be spontaneously inducible, thus very likely being the origins of the isolated phages. The phage vB_AbaS_fEg-Aba01 was also able to lysogenize the susceptible strain #6597 demonstrating that it was fully functional. The phages showed a very narrow host range infecting only two A.baumannii strains. In conclusion, we have isolated and characterized three novel temperate Siphoviridae phages that infect A.baumannii.

RevDate: 2020-06-09

Singh A, Nayak N, Rathi P, et al (2020)

Microbiome and host crosstalk: A new paradigm to cancer therapy.

Seminars in cancer biology pii:S1044-579X(20)30110-3 [Epub ahead of print].

The commensal microbiome of humans has co-evolved for thousands of years. The microbiome regulates human health and is also linked to several diseases, including cancer. The advances in next-generation sequencing have significantly contributed to our understanding of the microbiome and its association with cancer and cancer therapy. Recent studies have highlighted a close relationship of the microbiome to the pharmacological effect of chemotherapy and immunotherapy. The chemo-drugs usually interfere with the host immune system and reduces the microbiome diversity inside the body, which in turn leads to decreased efficacy of these drugs. The human microbiome, specifically the gut microbiome, increases the potency of chemo-drugs through metabolism, enzymatic degradation, ecological differences, and immunomodulation. Recent research exploits the involvement of microbiome to shape the efficacy and decrease the toxicity of these chemo-drugs. In this review, we have highlighted the recent development in understanding the relationship of the human microbiome with cancer and also emphasize on various roles of the microbiome in the modulation of cancer therapy. Additionally, we also summarize the ongoing research focussed on the improved efficacy of chemotherapy and immunotherapy using the host microbiome.

RevDate: 2020-06-09

Dahl WJ, Rivero Mendoza D, JM Lambert (2020)

Diet, nutrients and the microbiome.

Progress in molecular biology and translational science, 171:237-263.

Although there is associative evidence linking fecal microbiome profile to health and disease, many studies have not considered the confounding effects of dietary intake. Consuming food provides fermentable substrate which sustains the microbial ecosystem that resides with most abundance in the colon. Western, Mediterranean and vegetarian dietary patterns have a role in modulating the gut microbiota, as do trending restrictive diets such the paleolithic and ketogenic. Altering the amount or ratio of carbohydrate, protein and fat, particularly at the extremes of intake, impacts the microbiome. Diets high in fermentable carbohydrates support the relative abundance of Bifidobacterium, Prevotella, Ruminococcus, Dorea and Roseburia, among others, capable of degrading polysaccharides, oligosaccharides and sugars. Conversely, very high fat diets increase bile-resistant organisms such as Bilophila and Bacteroides. Food form, whole foods vs. ultra-processed, alters the provision of macronutrient substrate to the colon due to differing digestibility, and thereby may impact the microbiota and its metabolic activity. In addition, phytochemicals in plant-based foods have specific and possibly prebiotic effects on the microbiome. Further, food ingredients such as certain low-calorie sweeteners enhance Bifidobacterium spp. The weight of evidence to date suggests a high level of interindividual variability in the human microbiome vs. clearly defined, dietary-induced profiles. Healthful dietary patterns, emphasizing plant foods high in microbial-available carbohydrate, support favorable microbiome profiles active in saccharolytic fermentation. Future research into diet and microbiome should consider the balance of gut microbial-generated metabolites, an important link between microbiome profile and human health.

RevDate: 2020-06-03

Prescott SL (2020)

A Butterfly Flaps its Wings: Extinction of Biological Experience and the Origins of Allergy.

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology [Epub ahead of print].

OBJECTIVE: The grand global challenges of the Anthropocene are interdependent with ample evidence that reduced early-life 'experience' of biodiversity primes for immune dysregulation and a higher propensity low-grade inflammation, increasing the risk of allergy many other later-onset NCDs -also now implicated in the susceptibility to acute inflammation in COVID-19 infection. The objective of this review is to explore links between biodiversity on all scales and allergic disease as a measure of immune dysregulation.

DATA SOURCES: Were identified from PubMed and Web of Science using search terms pertaining to biodiversity, nature-relatedness, allergic disease, microbiome, NCDs, COVID-19 and associated terms.

STUDY SELECTIONS: Studies were selected based on relevance to human health and biodiversity.

RESULTS: Contact with natural environments enriches the human microbiome, promotes regulated immune responses, and protects from allergy and both acute and chronic inflammatory disorders. These important links to eco-psychological constructs of the 'extinction of experience' which indicates that loss of direct, personal contact with biodiversity-wildlife and the more visible elements of the natural world-might lead to emotional apathy and irresponsible behaviors toward the environment.

CONCLUSION: The immune system is a useful early barometer of environmental impacts, and via the microbiome, a measure of the way in which our current experiences differ from our ancestral past. While we would benefit from further research, efforts to increase direct, personal contact with biodiversity have clear benefits for multiple aspect of physical and mental health, the skin and gut microbiome, immune function, food choices, sleep, physical activity, and promotes environmental responsibility.

RevDate: 2020-06-20

Wu AH, Tseng C, Vigen C, et al (2020)

Gut microbiome associations with breast cancer risk factors and tumor characteristics: a pilot study.

Breast cancer research and treatment, 182(2):451-463.

OBJECTIVE: To investigate the association between gut microbiome with breast tumor characteristics (receptor status, stage and grade) and known breast cancer risk factors.

METHODS: In a pilot cross-sectional study of 37 incident breast cancer patients, fecal samples collected prior to chemotherapy were analyzed by 16S ribosomal RNA (rRNA) gene-based sequencing protocol. Alpha diversity and specific taxa by tumor characteristics and breast cancer risk factors were tested by Wilcoxon rank sum test, and by differential abundance analysis, using a zero-inflated negative binomial regression model with adjustment for total counts, age and race/ethnicity.

RESULTS: There were no significant alpha diversity or phyla differences by estrogen/progesterone receptor status, tumor grade, stage, parity and body mass index. However, women with human epidermal growth factor receptor 2 positive (HER2+) (n = 12) compared to HER2- (n = 25) breast cancer showed 12-23% lower alpha diversity [number of species (OTU) p = 0.033, Shannon index p = 0.034], lower abundance of Firmicutes (p = 0.005) and higher abundance of Bacteroidetes (p = 0.089). Early menarche (ages ≤ 11) (n = 11) compared with later menarche (ages ≥ 12) (n = 26) was associated with lower OTU (p = 0.036), Chao1 index (p = 0.020) and lower abundance of Firmicutes (p = 0.048). High total body fat (TBF) (> 46%) (n = 12) compared to lower (≤ 46%) TBF was also associated with lower Chao 1 index (p = 0.011). There were other significant taxa abundance differences by HER2 status, menarche age, as well as other tumor and breast cancer risk factors.

CONCLUSIONS AND RELEVANCE: Further studies are needed to identify characteristics of the human microbiome and the interrelationships between breast cancer hormone receptor status and established breast cancer risk factors.

RevDate: 2020-06-19

Vernocchi P, Del Chierico F, L Putignani (2020)

Gut Microbiota Metabolism and Interaction with Food Components.

International journal of molecular sciences, 21(10):.

The human gut contains trillions of microbes that play a central role in host biology, including the provision of key nutrients from the diet. Food is a major source of precursors for metabolite production; in fact, diet modulates the gut microbiota (GM) as the nutrients, derived from dietary intake, reach the GM, affecting both the ecosystem and microbial metabolic profile. GM metabolic ability has an impact on human nutritional status from childhood. However, there is a wide variability of dietary patterns that exist among individuals. The study of interactions with the host via GM metabolic pathways is an interesting field of research in medicine, as microbiota members produce myriads of molecules with many bioactive properties. Indeed, much evidence has demonstrated the importance of metabolites produced by the bacterial metabolism from foods at the gut level that dynamically participate in various biochemical mechanisms of a cell as a reaction to environmental stimuli. Hence, the GM modulate homeostasis at the gut level, and the alteration in their composition can concur in disease onset or progression, including immunological, inflammatory, and metabolic disorders, as well as cancer. Understanding the gut microbe-nutrient interactions will increase our knowledge of how diet affects host health and disease, thus enabling personalized therapeutics and nutrition.

RevDate: 2020-05-26

Thapa S, Runge JK, Venkatachalam A, et al (2020)

The Nasopharyngeal and Gut Microbiota in Children in a Pediatric Otolaryngology Practice.

The Pediatric infectious disease journal [Epub ahead of print].

BACKGROUND: The human microbiome evolves rapidly in early life with contributions from various factors such as diet, delivery mode, medical history, antibiotics exposure, genetics, immunomodulators and the environment. A high use of antibiotics in pediatric outpatient settings has been well documented, and improvement in antibiotic selection is required to reduce the risks of antibiotic resistance and disruption of the microbiome.

METHODS: We performed an exploratory study using 16S rRNA gene-based sequencing to characterize the gut and nasopharyngeal microbiome of children (n = 50) age 1-6 years of age in a pediatric otolaryngology practice.

RESULTS: Relative abundance of Haemophilus and Moraxella were higher in nasopharyngeal swabs, while Prevotella, Bacteroides, Porphyromonas and Faecalibacterium were highly abundant in rectal swabs. The gut microbiome composition in children <2 years old was different compared with children ≥2 years age. Gut bacterial diversity increased with an increase in age of the children. Children taking probiotics had a notable increase in abundance of potentially beneficial gut bacteria such as Bacteroides and Akkermansia. The nasopharyngeal microbiome differed between children who received antibiotics in the 3 months before sample collection compared with those that did not. Haemophilus spp. was highly abundant in children who received antibiotics 3 months before sampling.

CONCLUSIONS: The pediatric nasopharyngeal and rectal microbiomes differ in bacterial composition and diversity. The increased abundance of Haemophilus spp. in the nasopharyngeal microbiome of children who received antibiotics during the 3 months before sampling suggests a potential impact of antibiotics in colonization with the otopathogen and may be relevant to clinical practice.

RevDate: 2020-05-25

Sharma D, Paterson AD, W Xu (2020)

TaxoNN: Ensemble of Neural Networks on Stratified Microbiome Data for Disease Prediction.

Bioinformatics (Oxford, England) pii:5843784 [Epub ahead of print].

MOTIVATION: Research supports the potential use of microbiome as a predictor of some diseases. Motivated by the findings that microbiome data is complex in nature and there is an inherent correlation due to hierarchical taxonomy of microbial Operational Taxonomic Units (OTUs), we propose a novel machine learning method incorporating a stratified approach to group OTUs into phylum clusters. Convolutional Neural Networks (CNNs) were used to train within each of the clusters individually. Further, through an ensemble learning approach, features obtained from each cluster were then concatenated to improve prediction accuracy. Our two-step approach comprising of stratification prior to combining multiple CNNs, aided in capturing the relationships between OTUs sharing a phylum efficiently, as compared to using a single CNN ignoring OTU correlations.

RESULTS: We used simulated datasets containing 168 OTUs in 200 cases and 200 controls for model testing. Thirty-two OTUs, potentially associated with risk of disease were randomly selected and interactions between three OTUs were used to introduce non-linearity. We also implemented this novel method in two human microbiome studies: (i) cirrhosis with 118 cases, 114 controls; (ii) type 2 diabetes with 170 cases, 174 controls; to demonstrate the model's effectiveness. Extensive experimentation and comparison against conventional machine learning techniques yielded encouraging results. We obtained mean AUC values of 0.88, 0.92, 0.75, showing a consistent increment (5%, 3%, 7%) in simulations, cirrhosis and type 2 diabetes data respectively, against the next best performing method, Random Forest.


RevDate: 2020-05-24

Dannenberg L, Zikeli D, Benkhoff M, et al (2020)

Targeting the human microbiome and its metabolite TMAO in cardiovascular prevention and therapy.

Pharmacology & therapeutics pii:S0163-7258(20)30112-1 [Epub ahead of print].

The human gut microbiota is the most important active part of the intestinal micro-ecosystem. Lifestyle modification, drug intake and nutrition have an impact on the composition of the gut microbiota and its metabolites. This review focuses on the effects of changes in the gut microbiota as well as the important metabolite Trimethylamine-N-oxide (TMAO). Furthermore, relevant therapeutic options to target the human microbiome in patients with cardiovascular disease are presented.

RevDate: 2020-06-17

Ang QY, Alexander M, Newman JC, et al (2020)

Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells.

Cell, 181(6):1263-1275.e16.

Very low-carbohydrate, high-fat ketogenic diets (KDs) induce a pronounced shift in metabolic fuel utilization that elevates circulating ketone bodies; however, the consequences of these compounds for host-microbiome interactions remain unknown. Here, we show that KDs alter the human and mouse gut microbiota in a manner distinct from high-fat diets (HFDs). Metagenomic and metabolomic analyses of stool samples from an 8-week inpatient study revealed marked shifts in gut microbial community structure and function during the KD. Gradient diet experiments in mice confirmed the unique impact of KDs relative to HFDs with a reproducible depletion of bifidobacteria. In vitro and in vivo experiments showed that ketone bodies selectively inhibited bifidobacterial growth. Finally, mono-colonizations and human microbiome transplantations into germ-free mice revealed that the KD-associated gut microbiota reduces the levels of intestinal pro-inflammatory Th17 cells. Together, these results highlight the importance of trans-kingdom chemical dialogs for mediating the host response to dietary interventions.

RevDate: 2020-05-23

Ma ZS (2020)

Assessing and Interpreting the Metagenome Heterogeneity With Power Law.

Frontiers in microbiology, 11:648.

There are two major sequencing technologies for investigating the microbiome: the amplicon sequencing that generates the OTU (operational taxonomic unit) tables of marker genes (e.g., bacterial 16S-rRNA), and the metagenomic shotgun sequencing that generates metagenomic gene abundance (MGA) tables. The OTU table is the counterpart of species abundance tables in macrobial ecology of plants and animals, and has been the target of numerous ecological and network analyses in recent gold rush for microbiome research and in great efforts for establishing an inclusive theoretical ecology. Nevertheless, MGA analyses have been largely limited to bioinformatics pipelines and ad hoc statistical methods, and systematic approaches to MGAs guided by classic ecological theories are still few. Here, we argue that, the difference between "gene kinds" and "gene species" are nominal, and the metagenome that a microbiota carries is essentially a 'community' of metagenomic genes (MGs). Each row of a MGA table represents a metagenome of a microbiota, and the whole MGA table represents a 'meta-metagenome' (or an assemblage of metagenomes) of N microbiotas (microbiome samples). Consequently, the same ecological/network analyses used in OTU analyses should be equally applicable to MGA tables. Here we choose to analyze the heterogeneity of metagenome by introducing classic Taylor's power law (TPL) and its recent extensions in community ecology. Heterogeneity is a fundamental property of metagenome, particularly in the context of human microbiomes. Recent studies have shown that the heterogeneity of human metagenomes is far more significant than that of human genomes. Therefore, without deep understanding of the human metagenome heterogeneity, personalized medicine of the human microbiome-associated diseases is hardly feasible. The TPL extensions have been successfully applied to measure the heterogeneity of human microbiome based on amplicon-sequencing reads of marker genes (e.g., 16s-rRNA). In this article, we demonstrate the analysis of the metagenomic heterogeneity of human gut microbiome at whole metagenome scale (with type-I power law extension) and metagenomic gene scale (type-III), as well as the heterogeneity of gene clusters, respectively. We further examine the influences of obesity, IBD and diabetes on the heterogeneity, which is of important ramifications for the diagnosis and treatment of human microbiome-associated diseases.

RevDate: 2020-05-23

Sewall JM, Oliver A, Denaro K, et al (2020)

Fiber Force: A Fiber Diet Intervention in an Advanced Course-Based Undergraduate Research Experience (CURE) Course.

Journal of microbiology & biology education, 21(1):.

Course-based undergraduate research experiences (CUREs) are an effective way to introduce students to contemporary scientific research. Research experiences have been shown to promote critical thinking, improve understanding and proper use of the scientific method, and help students learn practical skills including writing and oral communication. We aimed to improve scientific training by engaging students enrolled in an upper division elective course in a human microbiome CURE. The "Fiber Force" course is aimed at studying the effect of a wholesome high-fiber diet (40 to 50 g/day for two weeks) on the students' gut microbiomes. Enrolled students participated in a noninvasive diet intervention, designed health surveys, tested hypotheses on the effect of a diet intervention on the gut microbiome, and analyzed their own samples (as anonymized aggregates). The course involved learning laboratory techniques (e.g., DNA extraction, PCR, and 16S sequencing) and the incorporation of computational techniques to analyze microbiome data with QIIME2 and within the R software environment. In addition, the learning objectives focused on effective student performance in writing, data analysis, and oral communication. Enrolled students showed high performance grades on writing, data analysis and oral communication assignments. Pre- and post-course surveys indicate that the students found the experience favorable, increased their interest in science, and heightened awareness of their diet habits. Fiber Force constitutes a validated case of a research experience on microbiology with the capacity to improve research training and promote healthy dietary habits.

RevDate: 2020-05-20

Gosens R, Hiemstra PS, Adcock IM, et al (2020)

Host-microbe cross-talk in the lung microenvironment: implications for understanding and treating chronic lung disease.

The European respiratory journal pii:13993003.02320-2019 [Epub ahead of print].

Chronic respiratory diseases are highly prevalent worldwide and will continue to rise in the foreseeable future. Despite intensive efforts over the recent decades, the development of novel and effective therapeutic approaches has been slow. There is however new and increasing evidence that communities of microorganisms in our body, the human microbiome, are crucially involved in the development and progression of chronic respiratory diseases. Understanding the detailed mechanisms underlying this cross-talk between host and microbiota is critical for development of microbiome- or host-targeted therapeutics and prevention strategies. Here we review and discuss the most recent knowledge on the continuous reciprocal interaction between the host and microbes in health and respiratory disease. Furthermore, we highlight promising developments in microbiome-based therapies and discuss the need to employ more holistic approaches of restoring both the pulmonary niche and the microbial community.

RevDate: 2020-06-19

Spruit CM, Wicklund A, Wan X, et al (2020)

Discovery of Three Toxic Proteins of Klebsiella Phage fHe-Kpn01.

Viruses, 12(5):.

The lytic phage, fHe-Kpn01 was isolated from sewage water using an extended-spectrum beta-lactamase-producing strain of Klebsiella pneumoniae as a host. The genome is 43,329 bp in size and contains direct terminal repeats of 222 bp. The genome contains 56 predicted genes, of which proteomics analysis detected 29 different proteins in purified phage particles. Comparison of fHe-Kpn01 to other phages, both morphologically and genetically, indicated that the phage belongs to the family Podoviridae and genus Drulisvirus. Because fHe-Kpn01 is strictly lytic and does not carry any known resistance or virulence genes, it is suitable for phage therapy. It has, however, a narrow host range since it infected only three of the 72 tested K. pneumoniae strains, two of which were of capsule type KL62. After annotation of the predicted genes based on the similarity to genes of known function and proteomics results on the virion-associated proteins, 22 gene products remained annotated as hypothetical proteins of unknown function (HPUF). These fHe-Kpn01 HPUFs were screened for their toxicity in Escherichia coli. Three of the HPUFs, encoded by the genes g10, g22, and g38, were confirmed to be toxic.

RevDate: 2020-05-22

Herman RA (2020)

Increasing allergy: are antibiotics the elephant in the room?.

Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology, 16:35.

Antibiotics cause dramatic changes to the human microbiome. The composition of the microbiome has been associated with changes in the immune system and these changes are beginning to be linked to immune diseases. Thus, antibiotics have been implicated as a significant contributor to the continual rise of allergies and autoimmune disease in developed countries. This recognition will hopefully result in the development of post-antibiotic therapies that restore a healthy microbiome and reduce immune system disorders.

RevDate: 2020-06-20

Chipollini J, Wright JR, Nwanosike H, et al (2020)

Characterization of urinary microbiome in patients with bladder cancer: Results from a single-institution, feasibility study.

Urologic oncology, 38(7):615-621.

OBJECTIVES: The human microbiome has been linked to the development of several malignancies, but there is scarcity of data on the microbiome of bladder cancer patients. In this study, we analyzed microbial composition and diversity among patients with and without bladder cancer.

MATERIAL AND METHODS: Samples were collected from 38 urothelial carcinoma (UC) patients and 10 noncancer controls from August 2018 to May 2019. DNA was extracted and processed for 16 S ribosomal RNA sequencing. Alpha diversity community characteristics including evenness and richness as well as beta diversity metrics were obtained. Linear discriminant analysis effect size was used to identify microbial components whose sequences were more abundant. Pairwise statistics provided quantitative assessment of significant distributions among groups.

RESULTS: Thirty seven total samples contained high quality sequence data for subsequent analyses and divided into 3 cohorts: control (n = 10), muscle-invasive (n = 15) and superficial UC (n = 12). Control samples had significantly higher species evenness when compared to invasive (P = 0.031) and superficial tumors (P = 0.002). In addition, higher species richness was observed in noncancer versus cancer samples (Faith phylogenetic diversity, P < 0.05). Significantly enriched taxa were found in both control (Bacteroides, Lachnoclostridium, Burkholderiaceae) and cancer samples (Bacteroides and Faecalbacterium).

CONCLUSION: Significantly decreased microbial community diversity was seen in the urine of patients with bladder cancer when compared to a noncancer group. Distinct taxa were noted suggesting unique microbial communities in the urine of bladder cancer patients.

RevDate: 2020-05-18

Pinto D, Calabrese FM, De Angelis M, et al (2020)

Predictive Metagenomic Profiling, Urine Metabolomics, and Human Marker Gene Expression as an Integrated Approach to Study Alopecia Areata.

Frontiers in cellular and infection microbiology, 10:146.

Involvement of the microbiome in many different scalp conditions has been investigated over the years. Studies on the role of the scalp microbiome in specific diseases, such as those involving hair growth alterations like non-cicatricial [androgenetic alopecia (AGA), alopecia areata (AA)] and cicatricial alopecia lichen planopilaris, are of major importance. In the present work, we highlighted the differences in microbial populations inhabiting the scalp of AA subjects and a healthy sample cohort by using an integrated approach relying on metagenomic targeted 16S sequencing analysis, urine metabolomics, and human marker gene expression. Significant differences in genera abundances (p < 0.05) were found in the hypodermis and especially the dermis layer. Based on 16S sequencing data, we explored the differences in predicted KEGG pathways and identified some significant differences in predicted pathways related to the AA pathologic condition such as flagellar, assembly, bacterial chemotaxis, mineral absorption, ABC transporters, cellular antigens, glycosaminoglycan degradation, lysosome, sphingolipid metabolism, cell division, protein digestion and absorption, and energy metabolism. All predicted pathways were significantly enhanced in AA samples compared to expression in healthy samples, with the exceptions of mineral absorption, and ABC transporters. We also determined the expression of TNF-α, FAS, KCNA3, NOD-2, and SOD-2 genes and explored the relationships between human gene expression levels and microbiome composition by Pearson's correlation analysis; here, significant correlations both positive (SOD vs. Staphylococcus, Candidatus Aquiluna) and negative (FAS and SOD2 vs. Anaerococcus, Neisseria, and Acinetobacter) were highlighted. Finally, we inspected volatile organic metabolite profiles in urinary samples and detected statistically significant differences (menthol, methanethiol, dihydrodehydro-beta-ionone, 2,5-dimethylfuran, 1,2,3,4, tetrahydro-1,5,7-trimethylnapthalene) when comparing AA and healthy subject groups. This multiple comparison approach highlighted potential traits associated with AA and their relationship with the microbiota inhabiting the scalp, opening up novel therapeutic interventions in such kind of hair growth disorders mainly by means of prebiotics, probiotics, and postbiotics.

RevDate: 2020-06-02

Qureshi SS, Kedo M, ST Berthrong (2020)

Gender-neutral bathroom surfaces recolonized by microbes more quickly than single-gender bathrooms.

Letters in applied microbiology [Epub ahead of print].

As humans become increasingly urban and spend more time inside the built environment, there will be increased interactions between humans and shared public surface microbiomes. Recent cultural changes in the United States have led to increased numbers of gender-neutral bathrooms. Given that bathroom surfaces are frequently sanitized, we used this increased availability of gender-neutral bathrooms to examine how single-gender or gender-neutral surfaces are recolonized with microbes. Given that male and female microbiomes vary, we hypothesized that rates of recolonization would differ between male, female and gender-neutral bathroom surfaces. We collected swabs from common hand-contacted surfaces in bathrooms and cultured microbes on selective and rich media to determine microbial abundance after cleaning. Recolonization was dominated by Gram-positive bacteria and was slowest on male, intermediate on female and fastest on gender-neutral surfaces. These results imply that gender-neutral surfaces approach normal climax microbial communities more quickly than single-gender bathrooms.

RevDate: 2020-05-14

Whitmont RD (2020)

The Human Microbiome, Conventional Medicine, and Homeopathy.

Homeopathy : the journal of the Faculty of Homeopathy [Epub ahead of print].

Human health is intimately linked to the ecology and diversity of the human microbiome. Together, the human organism and the human microbiome work as a complex super-organism throughout the human life cycle. Microbiome science provides direct evidence and substantiation of the fundamental principles of homeopathy, including holism, psychosomatics, direction of cure, the Law of Similars, individuality and susceptibility, minimum dose, and homeostasis. Whilst many conventional (allopathic) medical treatments irreversibly damage the ecology of the microbiome and trigger chronic immune dysfunction and inflammation, the future sustainability of the entire field of medicine depends on the ability to recognize these inconvenient biological truths and to embrace a safer approach based on this evidence. Fortunately, one of the oldest forms of clinically verifiable, evidence-based, and ecologically sustainable medicine, that does not harm the microbiome, already exists in the form of homeopathy.

RevDate: 2020-06-15

Ma ZS (2020)

Heterogeneity-disease relationship in the human microbiome-associated diseases.

FEMS microbiology ecology, 96(7):.

Space is a critical and also challenging frontier in human microbiome research. It has been found that lack of consideration of scales beyond individual and ignoring of microbe dispersal are two crucial roadblocks in preventing deep understanding of the spatial heterogeneity of human microbiome. Assessing and interpreting the heterogeneity and dispersal in microbiomes explicitly are particularly challenging, but implicit approaches such as Taylor's power law (TPL) can be rather effective. Based on TPL, which achieved a rare status of ecological laws, we introduce a general methodology for characterizing the spatial heterogeneity of microbiome (i.e. characterization of microbial spatial distribution) and further apply it for investigating the heterogeneity-disease relationship (HDR) via analyzing a big dataset of 26 MAD (microbiome-associated disease) studies covering nearly all high-profile MADs including obesity, diabetes and gout. It was found that in majority of the MAD cases, the microbiome was sufficiently resilient to endure the disease disturbances. Specifically, in ∼10-16% cases, disease effects were significant-the healthy and diseased cohorts exhibited statistically significant differences in the TPL heterogeneity parameters. We further compared HDR with classic diversity-disease relationship (DDR) and explained their mechanistic differences. Both HDR and DDR cross-verified remarkable resilience of the human microbiomes against MADs.

RevDate: 2020-05-14

Wang Y, Bhattacharya T, Jiang Y, et al (2020)

A novel deep learning method for predictive modeling of microbiome data.

Briefings in bioinformatics pii:5835556 [Epub ahead of print].

With the development and decreasing cost of next-generation sequencing technologies, the study of the human microbiome has become a rapid expanding research field, which provides an unprecedented opportunity in various clinical applications such as drug response predictions and disease diagnosis. It is thus essential and desirable to build a prediction model for clinical outcomes based on microbiome data that usually consist of taxon abundance and a phylogenetic tree. Importantly, all microbial species are not uniformly distributed in the phylogenetic tree but tend to be clustered at different phylogenetic depths. Therefore, the phylogenetic tree represents a unique correlation structure of microbiome, which can be an important prior to improve the prediction performance. However, prediction methods that consider the phylogenetic tree in an efficient and rigorous way are under-developed. Here, we develop a novel deep learning prediction method MDeep (microbiome-based deep learning method) to predict both continuous and binary outcomes. Conceptually, MDeep designs convolutional layers to mimic taxonomic ranks with multiple convolutional filters on each convolutional layer to capture the phylogenetic correlation among microbial species in a local receptive field and maintain the correlation structure across different convolutional layers via feature mapping. Taken together, the convolutional layers with its built-in convolutional filters capture microbial signals at different taxonomic levels while encouraging local smoothing and preserving local connectivity induced by the phylogenetic tree. We use both simulation studies and real data applications to demonstrate that MDeep outperforms competing methods in both regression and binary classifications. Availability and Implementation: MDeep software is available at

RevDate: 2020-05-19

Salehi B, Dimitrijević M, Aleksić A, et al (2020)

Human microbiome and homeostasis: insights into the key role of prebiotics, probiotics, and symbiotics.

Critical reviews in food science and nutrition [Epub ahead of print].

The interest in the study of the gut microbiome has grown exponentially. Indeed, its impact on health and disease has been increasingly reported, and the importance of keeping gut microbiome homeostasis clearly highlighted. However, and despite many advances, there are still some gaps, as well as the real discernment on the contribution of some species falls far short of what is needed. Anyway, it is already more than a solid fact of its importance in maintaining health and preventing disease, as well as in the treatment of some pathologies. In this sense, and given the existence of some ambiguous opinions, the present review aims to discuss the importance of gut microbiome in homeostasis maintenance, and even the role of probiotics, prebiotics, and symbiotics in both health promotion and disease prevention.

RevDate: 2020-06-16

Satokari R (2020)

High Intake of Sugar and the Balance between Pro- and Anti-Inflammatory Gut Bacteria.

Nutrients, 12(5):.

The so-called Western diet is rich in saturated fat and sugars and poor in plant-derived fibers, and it is associated with an increased risk of metabolic and cardiovascular diseases, as well as chronic (low grade) inflammation. The detrimental effects of poor diet are in part mediated by gut microbiota, whose composition, functionality and metabolic end products respond to dietary changes. Recent studies have shown that high intake of sugars increase the relative abundance of Proteobacteria in the gut, while simultaneously decreasing the abundance of Bacteroidetes, which can mitigate the effects of endotoxin, as well as reinforce gut barrier function. Thus, a high sugar intake may stagger the balance of microbiota to have increased pro-inflammatory properties and decreased the capacity to regulate epithelial integrity and mucosal immunity. Consequently, high dietary sugar can, through the modulation of microbiota, promote metabolic endotoxemia, systemic (low grade) inflammation and the development of metabolic dysregulation and thereby, high dietary sugar may have many-fold deleterious health effects, in addition to providing excess energy.

RevDate: 2020-06-19

Bangayan NJ, Shi B, Trinh J, et al (2020)

MG-MLST: Characterizing the Microbiome at the Strain Level in Metagenomic Data.

Microorganisms, 8(5):.

The microbiome plays an important role in human physiology. The composition of the human microbiome has been described at the phylum, class, genus, and species levels, however, it is largely unknown at the strain level. The importance of strain-level differences in microbial communities has been increasingly recognized in understanding disease associations. Current methods for identifying strain populations often require deep metagenomic sequencing and a comprehensive set of reference genomes. In this study, we developed a method, metagenomic multi-locus sequence typing (MG-MLST), to determine strain-level composition in a microbial community by combining high-throughput sequencing with multi-locus sequence typing (MLST). We used a commensal bacterium, Propionibacterium acnes, as an example to test the ability of MG-MLST in identifying the strain composition. Using simulated communities, MG-MLST accurately predicted the strain populations in all samples. We further validated the method using MLST gene amplicon libraries and metagenomic shotgun sequencing data of clinical skin samples. MG-MLST yielded consistent results of the strain composition to those obtained from nearly full-length 16S rRNA clone libraries and metagenomic shotgun sequencing analysis. When comparing strain-level differences between acne and healthy skin microbiomes, we demonstrated that strains of RT2/6 were highly associated with healthy skin, consistent with previous findings. In summary, MG-MLST provides a quantitative analysis of the strain populations in the microbiome with diversity and richness. It can be applied to microbiome studies to reveal strain-level differences between groups, which are critical in many microorganism-related diseases.

RevDate: 2020-05-19

Koh H, N Zhao (2020)

A powerful microbial group association test based on the higher criticism analysis for sparse microbial association signals.

Microbiome, 8(1):63.

BACKGROUND: In human microbiome studies, it is crucial to evaluate the association between microbial group (e.g., community or clade) composition and a host phenotype of interest. In response, a number of microbial group association tests have been proposed, which account for the unique features of the microbiome data (e.g., high-dimensionality, compositionality, phylogenetic relationship). These tests generally fall in the class of aggregation tests which amplify the overall group association by combining all the underlying microbial association signals, and, therefore, they are powerful when many microbial species are associated with a given host phenotype (i.e., low sparsity). However, in practice, the microbial association signals can be highly sparse, and this is especially the situation where we have a difficulty to discover the microbial group association.

METHODS: Here, we introduce a powerful microbial group association test for sparse microbial association signals, namely, microbiome higher criticism analysis (MiHC). MiHC is a data-driven omnibus test taken in a search space spanned by tailoring the higher criticism test to incorporate phylogenetic information and/or modulate sparsity levels and including the Simes test for excessively high sparsity levels. Therefore, MiHC robustly adapts to diverse phylogenetic relevance and sparsity levels.

RESULTS: Our simulations show that MiHC maintains a high power at different phylogenetic relevance and sparsity levels with correct type I error controls. We also apply MiHC to four real microbiome datasets to test the association between respiratory tract microbiome and smoking status, the association between the infant's gut microbiome and delivery mode, the association between the gut microbiome and type 1 diabetes status, and the association between the gut microbiome and human immunodeficiency virus status.

CONCLUSIONS: In practice, the true underlying association pattern on the extent of phylogenetic relevance and sparsity is usually unknown. Therefore, MiHC can be a useful analytic tool because of its high adaptivity to diverse phylogenetic relevance and sparsity levels. MiHC can be implemented in the R computing environment using our software package freely available at

RevDate: 2020-05-15

Thomas G, Bain JM, Budge S, et al (2020)

Identifying Candida albicans Gene Networks Involved in Pathogenicity.

Frontiers in genetics, 11:375.

Candida albicans is a normal member of the human microbiome. It is also an opportunistic pathogen, which can cause life-threatening systemic infections in severely immunocompromized individuals. Despite the availability of antifungal drugs, mortality rates of systemic infections are high and new drugs are needed to overcome therapeutic challenges including the emergence of drug resistance. Targeting known disease pathways has been suggested as a promising avenue for the development of new antifungals. However, <30% of C. albicans genes are verified with experimental evidence of a gene product, and the full complement of genes involved in important disease processes is currently unknown. Tools to predict the function of partially or uncharacterized genes and generate testable hypotheses will, therefore, help to identify potential targets for new antifungal development. Here, we employ a network-extracted ontology to leverage publicly available transcriptomics data and identify potential candidate genes involved in disease processes. A subset of these genes has been phenotypically screened using available deletion strains and we present preliminary data that one candidate, PEP8, is involved in hyphal development and immune evasion. This work demonstrates the utility of network-extracted ontologies in predicting gene function to generate testable hypotheses that can be applied to pathogenic systems. This could represent a novel first step to identifying targets for new antifungal therapies.

RevDate: 2020-05-15

Peroni DG, Nuzzi G, Trambusti I, et al (2020)

Microbiome Composition and Its Impact on the Development of Allergic Diseases.

Frontiers in immunology, 11:700.

Allergic diseases, such as food allergy (FA), atopic dermatitis (AD), and asthma, are heterogeneous inflammatory immune-mediated disorders that currently constitute a public health issue in many developed countries worldwide. The significant increase in the prevalence of allergic diseases reported over the last few years has closely paralleled substantial environmental changes both on a macro and micro scale, which have led to reduced microbial exposure in early life and perturbation of the human microbiome composition. Increasing evidence shows that early life interactions between the human microbiome and the immune cells play a pivotal role in the development of the immune system. Therefore, the process of early colonization by a "healthy" microbiome is emerging as a key determinant of life-long health. In stark contrast, the perturbation of such a process, which results in changes in the host-microbiome biodiversity and metabolic activities, has been associated with greater susceptibility to immune-mediated disorders later in life, including allergic diseases. Here, we outline recent findings on the potential contribution of the microbiome in the gastrointestinal tract, skin, and airways to the development of FA, AD, and asthma. Furthermore, we address how the modulation of the microbiome composition in these different body districts could be a potential strategy for the prevention and treatment of allergic diseases.

RevDate: 2020-05-15

Jiang T, Chen W, Cao L, et al (2020)

Abundance, Functional, and Evolutionary Analysis of Oxalyl-Coenzyme A Decarboxylase in Human Microbiota.

Frontiers in microbiology, 11:672.

Oxalic acid and its oxalate salts have been linked to kidney stones and other health problems and about 80% kidney stones are made up of calcium oxalate. Oxalyl coenzyme A decarboxylase (OXC) is a key enzyme in the catabolism of oxalate. In this study, we performed bioinformatic and biochemical analysis of OXC. First, we mined the OXC sequences from a public protein database and collected 1396 putative OXC sequences. These sequences were widely spread and mainly distributed in Actinobacteria, Alphaproteobacteria, Gammaproteobacteria, and Betaproteobacteria and classified into seven clusters. The phylogenetic relationship and evolutionary rate of the 7 clusters showed that OXC are highly conserved. Second, the abundance of the different clusters of OXC was explored in 380 human microbiome datasets, which showed that OXCs in Cluster 1 were relatively high in the gut while OXCs in Clusters 2-4 were relatively enriched in the vagina. Third, we measured the activity of one OXC from Mycobacterium mageritense (OXCmm) in Cluster 3, in which there was no experimentally characterized enzymes. Mutation analysis showed that OXCmm shared the same active sites with the OXC from Oxalobacter formigenes. Taken together, this analysis provides a better insight into the distribution and catalysis of OXC and further potential alternative application of OXC active bacteria as probiotics in the management of kidney stone disease.

RevDate: 2020-06-13

Caparrós-Martín JA, Flynn S, Reen FJ, et al (2020)

The Detection of Bile Acids in the Lungs of Paediatric Cystic Fibrosis Patients Is Associated with Altered Inflammatory Patterns.

Diagnostics (Basel, Switzerland), 10(5):.

Background: Cystic fibrosis (CF) is a hereditary disorder in which persistent unresolved inflammation and recurrent airway infections play major roles in the initiation and progression of the disease. Little is known about triggering factors modulating the transition to chronic microbial infection and inflammation particularly in young children. Cystic fibrosis respiratory disease starts early in life, with the detection of inflammatory markers and infection evident even before respiratory symptoms arise. Thus, identifying factors that dysregulate immune responsiveness at the earliest stages of the disease will provide novel targets for early therapeutic intervention. Methods: We evaluated the clinical significance of bile acid detection in the bronchoalveolar lavage fluid of clinically stable preschool-aged children diagnosed with CF. Results: We applied an unbiased classification strategy to categorize these specimens based on bile acid profiles. We provide clear associations linking the presence of bile acids in the lungs with alterations in the expression of inflammatory markers. Using multiple regression analysis, we also demonstrate that clustering based on bile acid profiles is a meaningful predictor of the progression of structural lung disease. Conclusions: Altogether, our work has identified a clinically relevant host-derived factor that may participate in shaping early events in the aetiology of CF respiratory disease.

RevDate: 2020-05-07

Price TK, Lin H, Gao X, et al (2020)

Bladder Bacterial Diversity Differs In Continent and Incontinent Women: A Cross-Sectional Study.

American journal of obstetrics and gynecology pii:S0002-9378(20)30512-3 [Epub ahead of print].

BACKGROUND: Since the discovery of the bladder microbiome (urobiome), interest has grown in learning whether urobiome characteristics have a role in clinical phenotyping and/or provide opportunities for novel therapeutic approaches for women with common forms of urinary incontinence (UI).

OBJECTIVES: To test our hypothesis that the bladder urobiome differs between continent women and women affected by UI by assessing associations between UI status and the cultured urobiome.

STUDY DESIGN: With IRB oversight, transurethral catheterized urine specimens were collected from 309 adult women, who were categorized into three groups using response to the validated Pelvic Floor Distress Inventory (PFDI): Continent Controls (N=150) and 2 Urinary Incontinence (UI cohorts) - Stress Urinary Incontinence (SUI) (N=50) and Urgency Urinary Incontinence (UUI) (N=109). Symptom severity was assessed with the Urinary Distress Inventory (UDI) subscale score of the PFDI. Microbes were assessed by the Expanded Quantitative Urine Culture protocol, which detects the most common bladder microbes (bacteria and yeast). Microbes were identified to the species level by MALDI-TOF mass spectrometry. Alpha diversity indices were calculated for culture-positive samples and compared across the three groups. The association between UDI scores versus alpha diversity indices and species abundance were estimated.

RESULTS: Participants had a mean age of 53 years (range 22-90); most were Caucasian (65%). Women with UI were slightly older (Control=47, SUI=54, UUI=61). By design, UDI symptom scores differed (Control = 8.43 (10.1), SUI = 97.95 (55.36), UUI = 93.71 (49.12), p<0.001). While most participants (216, 70%) had Expanded Quantitative Urine Culture-detected bacteria, the UI cohorts had a higher detection frequency than did the Control cohort (Control=57%, SUI 86%, UUI 81%, p<0.001). The most frequently detected species were as follows: Controls, Lactobacillus iners (12.7%), Streptococcus anginosus (12.7%), L. crispatus (10.7%), and L. gasseri (10%); SUI, S. anginosus (26%), L. iners (18%), Staphylococcus epidermidis (18%), and L. jensenii (16%); UUI, S. anginosus (30.3%), L. gasseri (22%), Aerococcus urinae (18.3%), and Gardnerella vaginalis (17.4%). However, only Actinotignum (formerly Actinobaculum) schaalii, A. urinae, A. sanguinicola, and Corynebacterium lipophile group were found at significantly higher mean abundances in at least one of the UI cohorts when compared to the Control cohort (Wilcoxon p<0.02), and no individual genus differed significantly between the two UI cohorts. Both UI cohorts had increased alpha diversity relative to continent controls with indices of species richness, but not evenness, strongly associated with UI.

CONCLUSIONS: In adult women, the composition of the culturable bladder urobiome is associated with UI, regardless of common incontinence subtype. Detection of more unique living microbes was associated with worse incontinence severity. Culturable species richness is significantly greater in the UI cohorts than continent controls.

RevDate: 2020-06-04

Liu S, Wang Y, Zhao L, et al (2020)

Microbiome succession with increasing age in three oral sites.

Aging, 12(9):7874-7907.

The incidence of oral diseases is remarkably increased with age, and it may be related to oral microbiota. In this study, we systematically investigated the microbiota of gingival crevicular fluid (GCF), tongue back (TB) and saliva (SAL) from various age groups in healthy populations. The microbial diversity results indicated that the α-diversity of bacteria had a tendency to decrease in aging mouth, whereas the β-diversity showed an opposite increasing trend in all three sites. Next, the microbial structure exploration revealed a divergence in bacterial profile in three sites in response to aging, but the intersite differential bacteria demonstrated a uniform bell-shaped variation trend with age. Meanwhile, several age-differentiated genera were shared by GCF, SAL and TB sites, and the bacterial correlation analysis demonstrated a clear shift in the pattern of bacterial correlations with age. Moreover, both the intra- and intersite "core microbiome" showed significantly decreased bacterial diversities with age. Finally, the trending differential bacteria species were used as a biomarker to distinguish the different age groups, and the prediction accuracies in GCF were 0.998, 0.809, 0.668, 0.675 and 0.956. Our results revealed the characteristics of intra- and intersite bacterial succession with age, providing novel insights into senile oral diseases.

RevDate: 2020-05-07

Tomaiuolo R, Veneruso I, Cariati F, et al (2020)

Microbiota and Human Reproduction: The Case of Female Infertility.

High-throughput, 9(2): pii:ht9020012.

During the last decade, the availability of next-generation sequencing-based approaches has revealed the presence of microbial communities in almost all the human body, including the reproductive tract. As for other body sites, this resident microbiota has been involved in the maintenance of a healthy status. As a consequence, alterations due to internal or external factors may lead to microbial dysbiosis and to the development of pathologies. Female reproductive microbiota has also been suggested to affect infertility, and it may play a key role in the success of assisted reproductive technologies, such as embryo implantation and pregnancy care. While the vaginal microbiota is well described, the uterine microbiota is underexplored. This could be due to technical issues, as the uterus is a low biomass environment. Here, we review the state of the art regarding the role of the female reproductive system microbiota in women's health and human reproduction, highlighting its contribution to infertility.

RevDate: 2020-05-06

Bartolomaeus TUP, Birkner T, Bartolomaeus H, et al (2020)

Quantifying Technical Confounders in Microbiome Studies.

Cardiovascular research pii:5831292 [Epub ahead of print].

AIMS: Recent technical developments have allowed the study of the human microbiome to accelerate at an unprecedented pace. Methodological differences may have considerable impact on the results obtained. Thus, we investigated how different storage, isolation and DNA extraction methods can influence the characterization of the intestinal microbiome, compared to the impact of true biological signals such as intraindividual variability, nutrition, health and demographics.

METHODS AND RESULTS: An observative cohort study in 27 healthy subjects was performed. Participants were instructed to collect stool samples twice spaced by a week, using six different methods (naive and Zymo DNA/RNA Shield on dry ice, OMNIgene GUT, RNALater, 95% ethanol, Zymo DNA/RNA Shield at room temperature). DNA extraction from all samples was performed comparatively using QIAamp Power Fecal and ZymoBIOMICS DNA kits. 16S rRNA sequencing of the gut microbiota as well as qPCRs were performed on the isolated DNA. Metrics included alpha diversity as well as multivariate and univariate comparisons of samples, controlling for covariate patterns computationally. Interindividual differences explained 7.4% of overall microbiome variability, whereas the choice of DNA extraction method explained a further 5.7%. At phylum level, the tested kits differed in their recovery of gram-positive bacteria, which is reflected in a significantly skewed enterotype distribution.

CONCLUSIONS: DNA extraction methods had the highest impact on observed microbiome variability, and were comparable to interindividual differences, thus may spuriously mimic the microbiome signatures of various health and nutrition factors. Conversely, collection methods had a relatively small influence on microbiome composition. The present study provides necessary insight into the technical variables which can lead to divergent results from seemingly similar study designs. We anticipate that these results will contribute to future efforts towards standardization of microbiome quantification procedures in clinical research.

TRANSLATIONAL PERSPECTIVES: By applying a framework which is typical for the investigation of the microbiome in cardiovascular disease patients, we assess the role of these confounders under realistic circumstances. Our work allows quality control and design improvement for upcoming translational microbiome studies such as the search for disease biomarkers or efficacy predictors for personalized treatment regimes.

RevDate: 2020-05-06

Zhu C, Yuan C, Wei FQ, et al (2020)

Intraindividual Variation and Personal Specificity of Salivary Microbiota.

Journal of dental research [Epub ahead of print].

Salivary microbiota is a typical habitat of the human microbiome. This study intended to use salivary microbiota as a model aiming to systematically address the influence of collection methods and temporal dynamics on the human microbiota compared to personal specificity. We carried out a supervised short-term longitudinal study to evaluate the influence of the change of collection methods and sampling time point on salivary microbiota in 10 systemically and orally healthy individuals with certain confounding factors (sex, oral and general health state, medication history, physical exercise, diet, and oral hygiene behavior) controlled before and during the sampling period. The microbial profiles were analyzed by 16S rDNA V3 to V4 hypervariable region amplicon sequencing. The taxonomic structure represented by the dominant species and the weighted UniFrac distance algorithm were used to demonstrate the individual specificity and the intraindividual variation introduced by the change of collection method and sampling time point. The findings suggested individual specificity existed in salivary microbiota from individuals with similar oral and general health status. The intraindividual variation brought by the change of collection method or sampling time point might introduce remarkable perturbation with the personal specificity. Insights into the intraindividual variation and personal specificity of salivary microbiota will enhance our understanding in salivary microbiota-related research. We recommend keeping collection conditions consistent within a study to avoid interference brought by the sampling. The strategy of repeated sampling at multiple time points as representative samples, as well as thorough interpretation of the complex relationships and causality between microbiome composition and disease without the interference of temporal dynamics, is optimal for research exploring the relationship between the salivary microbiome and disease.

RevDate: 2020-05-08

Woods DF, Kozak IM, F O'Gara (2020)

Microbiome and Functional Analysis of a Traditional Food Process: Isolation of a Novel Species (Vibrio hibernica) With Industrial Potential.

Frontiers in microbiology, 11:647.

Traditional food preservation processes are vital for the food industry. They not only preserve a high-quality protein and nutrient source but can also provide important value-added organoleptic properties. The Wiltshire process is a traditional food curing method applied to meat, and special recognition is given to the maintenance of a live rich microflora within the curing brine. We have previously analyzed a curing brine from this traditional meat process and characterized a unique microbial core signature. The characteristic microbial community is actively maintained and includes the genera, Marinilactibacillus, Carnobacterium, Leuconostoc, and Vibrio. The bacteria present are vital for Wiltshire curing compliance. However, the exact function of this microflora is largely unknown. A microbiome profiling of three curing brines was conducted and investigated for functional traits by the robust bioinformatic tool, Tax4Fun. The key objective was to uncover putative metabolic functions associated with the live brine and to identify changes over time. The functional bioinformatic analysis revealed metabolic enrichments over time, with many of the pathways identified as being involved in organoleptic development. The core bacteria present in the brine are Lactic Acid Bacteria (LAB), with the exception of the Vibrio genus. LAB are known for their positive contribution to food processing, however, little work has been conducted on the use of Vibrio species for beneficial processes. The Vibrio genome was sequenced by Illumina MiSeq technologies and annotated in RAST. A phylogenetic reconstruction was completed using both the 16S rRNA gene and housekeeping genes, gapA, ftsZ, mreB, topA, gyrB, pyrH, recA, and rpoA. The isolated Vibrio species was defined as a unique novel species, named Vibrio hibernica strain B1.19. Metabolic profiling revealed that the bacterium has a unique substrate scope in comparison to other closely related Vibrio species tested. The possible function and industrial potential of the strain was investigated using carbohydrate metabolizing profiling under food processing relevant conditions. Vibrio hibernica is capable of metabolizing a unique carbohydrate profile at low temperatures. This characteristic provides new application options for use in the industrial food sector, as well as highlighting the key role of this bacterium in the Wiltshire curing process.

RevDate: 2020-05-08

Abdelsalam NA, Ramadan AT, ElRakaiby MT, et al (2020)

Toxicomicrobiomics: The Human Microbiome vs. Pharmaceutical, Dietary, and Environmental Xenobiotics.

Frontiers in pharmacology, 11:390.

The harmful impact of xenobiotics on the environment and human health is being more widely recognized; yet, inter- and intraindividual genetic variations among humans modulate the extent of harm, mostly through modulating the outcome of xenobiotic metabolism and detoxification. As the Human Genome Project revealed that host genetic, epigenetic, and regulatory variations could not sufficiently explain the complexity of interindividual variability in xenobiotics metabolism, its sequel, the Human Microbiome Project, is investigating how this variability may be influenced by human-associated microbial communities. Xenobiotic-microbiome relationships are mutual and dynamic. Not only does the human microbiome have a direct metabolizing potential on xenobiotics, but it can also influence the expression of the host metabolizing genes and the activity of host enzymes. On the other hand, xenobiotics may alter the microbiome composition, leading to a state of dysbiosis, which is linked to multiple diseases and adverse health outcomes, including increased toxicity of some xenobiotics. Toxicomicrobiomics studies these mutual influences between the ever-changing microbiome cloud and xenobiotics of various origins, with emphasis on their fate and toxicity, as well the various classes of microbial xenobiotic-modifying enzymes. This review article discusses classic and recent findings in toxicomicrobiomics, with examples of interactions between gut, skin, urogenital, and oral microbiomes with pharmaceutical, food-derived, and environmental xenobiotics. The current state and future prospects of toxicomicrobiomic research are discussed, and the tools and strategies for performing such studies are thoroughly and critically compared.

RevDate: 2020-06-16

Lee-Sarwar KA, Lasky-Su J, Kelly RS, et al (2020)

Metabolome-Microbiome Crosstalk and Human Disease.

Metabolites, 10(5):.

In this review, we discuss the growing literature demonstrating robust and pervasive associations between the microbiome and metabolome. We focus on the gut microbiome, which harbors the taxonomically most diverse and the largest collection of microorganisms in the human body. Methods for integrative analysis of these "omics" are under active investigation and we discuss the advances and challenges in the combined use of metabolomics and microbiome data. Findings from large consortia, including the Human Microbiome Project and Metagenomics of the Human Intestinal Tract (MetaHIT) and others demonstrate the impact of microbiome-metabolome interactions on human health. Mechanisms whereby the microbes residing in the human body interact with metabolites to impact disease risk are beginning to be elucidated, and discoveries in this area will likely be harnessed to develop preventive and treatment strategies for complex diseases.

RevDate: 2020-05-05

Zhou X, Johnson JS, Spakowicz D, et al (2020)

Longitudinal Analysis of Serum Cytokine Levels and Gut Microbial Abundance Links IL-17/IL-22 with Clostridia and Insulin Sensitivity in Humans.

Diabetes pii:db19-0592 [Epub ahead of print].

Recent studies using mouse models suggest that interaction between the gut microbiome and IL-17/IL-22 producing cells plays a role in the development of metabolic diseases. We investigated this relationship in humans using data from the prediabetes study of the Integrated Human Microbiome Project (iHMP). Specifically, we addressed the hypothesis that early in the onset of metabolic diseases there is a decline in serum levels of IL-17/IL-22, with concomitant changes in the gut microbiome. Clustering iHMP study participants on the basis of longitudinal IL-17/IL-22 profiles identified discrete groups. Individuals distinguished by low levels of IL-17/IL-22 were linked to established markers of metabolic disease, including insulin sensitivity. These individuals also displayed gut microbiome dysbiosis, characterized by decreased diversity, and IL-17/IL-22-related declines in the phylum Firmicutes, class Clostridia, and order Clostridiales. This ancillary analysis of the iHMP data therefore supports a link between the gut microbiome, IL-17/IL-22 and the onset of metabolic diseases. This raises the possibility for novel, microbiome-related therapeutic targets that may effectively alleviate metabolic diseases in humans as they do in animal models.

RevDate: 2020-06-09

Piggott DA, S Tuddenham (2020)

The gut microbiome and frailty.

Translational research : the journal of laboratory and clinical medicine pii:S1931-5244(20)30062-1 [Epub ahead of print].

The human microbiome is constituted by an extensive network of organisms that lie at the host/environment interface and transduce signals that play vital roles in human health and disease across the lifespan. Frailty is a critical aging-related syndrome marked by diminished physiological reserve and heightened vulnerability to stress, predictive of major adverse clinical outcomes including death. While recent studies suggest the microbiome may impact key pathways critical to frailty pathophysiology, direct evaluation of the microbiome-frailty relationship remains limited. In this article, we review the complex interplay of biological, behavioral, and environmental factors that may influence shifts in gut microbiome composition and function in aging populations and the putative implications of such shifts for progression to frailty. We discuss HIV infection as a key prototype for elucidating the complex pathways via which the microbiome may precipitate frailty. Finally, we review considerations for future research efforts.

RevDate: 2020-04-30

Ndika J, Ilves M, Kooter IM, et al (2020)

Mechanistic Similarities between 3D Human Bronchial Epithelium and Mice Lung, Exposed to Copper Oxide Nanoparticles, Support Non-Animal Methods for Hazard Assessment.

Small (Weinheim an der Bergstrasse, Germany) [Epub ahead of print].

The diversity and increasing prevalence of products derived from engineered nanomaterials (ENM), warrants implementation of non-animal approaches to health hazard assessment for ethical and practical reasons. Although non-animal approaches are becoming increasingly popular, there are almost no studies of side-by-side comparisons with traditional in vivo assays. Here, transcriptomics is used to investigate mechanistic similarities between healthy/asthmatic models of 3D air-liquid interface (ALI) cultures of donor-derived human bronchial epithelia cells, and mouse lung tissue, following exposure to copper oxide ENM. Only 19% of mouse lung genes with human orthologues are not expressed in the human 3D ALI model. Despite differences in taxonomy and cellular complexity between the systems, a core subset of matching genes cluster mouse and human samples strictly based on ENM dose (exposure severity). Overlapping gene orthologue pairs are highly enriched for innate immune functions, suggesting an important and maybe underestimated role of epithelial cells. In conclusion, 3D ALI models based on epithelial cells, are primed to bridge the gap between traditional 2D in vitro assays and animal models of airway exposure, and transcriptomics appears to be a unifying dose metric that links in vivo and in vitro test systems.

RevDate: 2020-06-02
CmpDate: 2020-05-15

Xiao J, Fiscella KA, SR Gill (2020)

Oral microbiome: possible harbinger for children's health.

International journal of oral science, 12(1):12.

The human microbiome functions as an intricate and coordinated microbial network, residing throughout the mucosal surfaces of the skin, oral cavity, gastrointestinal tract, respiratory tract, and reproductive system. The oral microbiome encompasses a highly diverse microbiota, consisting of over 700 microorganisms, including bacteria, fungi, and viruses. As our understanding of the relationship between the oral microbiome and human health has evolved, we have identified a diverse array of oral and systemic diseases associated with this microbial community, including but not limited to caries, periodontal diseases, oral cancer, colorectal cancer, pancreatic cancer, and inflammatory bowel syndrome. The potential predictive relationship between the oral microbiota and these human diseases suggests that the oral cavity is an ideal site for disease diagnosis and development of rapid point-of-care tests. The oral cavity is easily accessible with a non-invasive collection of biological samples. We can envision a future where early life salivary diagnostic tools will be used to predict and prevent future disease via analyzing and shaping the infant's oral microbiome. In this review, we present evidence for the establishment of the oral microbiome during early childhood, the capability of using childhood oral microbiome to predict future oral and systemic diseases, and the limitations of the current evidence.

RevDate: 2020-05-25

Lahtinen P, Jalanka J, Hartikainen A, et al (2020)

Randomised clinical trial: faecal microbiota transplantation versus autologous placebo administered via colonoscopy in irritable bowel syndrome.

Alimentary pharmacology & therapeutics, 51(12):1321-1331.

BACKGROUND: Irritable bowel syndrome (IBS) has been associated with microbial dysbiosis.

AIM: To investigate the efficacy of faecal microbiota transplantation (FMT) in the treatment of IBS.

METHODS: Forty-nine IBS patients were randomised to receive autologous or allogenic FMT via colonoscopy. The primary endpoint was a sustained, minimum of 50-point, reduction in the IBS Symptom Severity Score. The secondary outcomes were levels of anxiety and depression, changes in quality of life, gut microbiota and faecal water content as assessed with validated questionnaires, intestinal microbiota composition and stool dry weight.

RESULTS: The primary endpoint was not achieved in either group. However, there was a transient reduction in the mean IBS Symptom Severity Score in the FMT group at 12 weeks after treatment as compared to baseline (P = 0.01). The groups did not differ in the number of patients achieving clinical response at 12 weeks. In the FMT-treated patients, microbial composition had changed to resemble that of the donor and the stool water content decreased significantly compared to baseline. The depression score decreased in patients with a reduction in IBS symptoms after FMT, but not in those placebo-treated patients who experienced a reduction in IBS symptoms.

CONCLUSIONS: FMT provided only a transient relief of symptoms, although it induced a sustained alteration in the microbiota of IBS patients. Therefore, FMT delivered by a single infusion via colonoscopy cannot be recommended as a treatment for IBS in clinical practice. ClinicalTrials.Org, Trial registration number: NCT03561519.

RevDate: 2020-06-19

Gotschlich EC, Colbert RA, T Gill (2019)

Methods in microbiome research: Past, present, and future.

Best practice & research. Clinical rheumatology, 33(6):101498.

The human microbiome is impressively immense and participates in many aspects of our health and wellness, particularly involving the development and maintenance of a healthy immune system. Not only do our microbes teach the immune system to fight infection, they also teach immune tolerance and help maintain homeostasis. From this knowledge, we have learned that the loss of tolerance to microbiota in both innate and adaptive processes plays an important role in immune-mediated and autoimmune disease. In this chapter, we will be discussing about methods used to study the microbiome, both old and new methods, fundamental concepts that have taken hold within the field, and how these principles relate to rheumatology, including thoughts on how microbiome research may be focused in the next decade.

RevDate: 2020-06-20

Zhou J, Sun T, Kang W, et al (2020)

Pathogenic and antimicrobial resistance genes in Streptococcus oralis strains revealed by comparative genome analysis.

Genomics pii:S0888-7543(19)30957-7 [Epub ahead of print].

Streptococcus oralis is an early colonizer bacterium in dental plaques and is considered a potential pathogen of infective endocarditis (IE) disease. In this study, we built a complete genome map of Streptococcus oralis strain SOT, Streptococcus oralis strain SOD and Streptococcus infantis strain SO and performed comparative genomic analysis among these three strains. The results showed that there are five genomic islands (GIs) in strain SOT and one CRISPR in strain SOD. Each genome harbors various pathogenic genes related to diseases and drug resistance, while the antibiotic resistance genes in strains SOT and SOD were quite similar but different from those in strain SO. In addition, we identified 17 main virulence factors and capsule-related genes in three strains. These results suggest the pathogenic potential of Streptococcus strains, which lay a foundation for the prevention and treatment of a Streptococcus oralis infection.

RevDate: 2020-06-21

Manasson J, Blank RB, JU Scher (2020)

The microbiome in rheumatology: Where are we and where should we go?.

Annals of the rheumatic diseases, 79(6):727-733.

From birth, humans coexist and coevolve with trillions of micro-organisms inhabiting most body surfaces and cavities, referred to as the human microbiome. Advances in sequencing technologies and computational methods have propelled the exploration of the microbiome's contribution to human health and disease, spearheaded by massive efforts such as the Human Microbiome Project and the Europe-based MetaHit Consortium. Yet, despite the accumulated body of literature and a growing awareness among patients, microbiome research in rheumatology has not had a key impact on clinical practice. Herein, we describe some of the landmark microbiome studies in autoimmunity and rheumatology, the challenges and opportunities of microbiome research and how to navigate them, advances in related fields that have overcome these pitfalls, and future directions of harnessing the microbiome for diagnostic and therapeutic purposes.

RevDate: 2020-04-24

Jia B, Park D, Hahn Y, et al (2020)

Metagenomic analysis of the human microbiome reveals the association between the abundance of gut bile salt hydrolases and host health.

Gut microbes [Epub ahead of print].

Bile acid metabolism by the gut microbiome exerts both beneficial and harmful effects on host health. Microbial bile salt hydrolases (BSHs), which initiate bile acid metabolism, exhibit both positive and negative effects on host physiology. In this study, 5,790 BSH homologs were collected and classified into seven clusters based on a sequence similarity network. Next, the abundance and distribution of BSH in 380 metagenomes from healthy participants were analyzed. It was observed that different clusters occupied diverse ecological niches in the human microbiome and that the clusters with signal peptides were relatively abundant in the gut. Then, the association between BSH clusters and 12 human diseases was analyzed by comparing the abundances of BSH genes in patients (n = 1,605) and healthy controls (n = 1,540). The analysis identified a significant association between BSH gene abundance and 10 human diseases, including gastrointestinal diseases, obesity, type 2 diabetes, liver diseases, cardiovascular diseases, and neurological diseases. The associations were further validated by separate cohorts with inflammatory bowel diseases and colorectal cancer. These large-scale studies of enzyme sequences combined with metagenomic data provide a reproducible assessment of the association between gut BSHs and human diseases. This information can contribute to future diagnostic and therapeutic applications of BSH-active bacteria for improving human health.

RevDate: 2020-04-30

Yang H, Zhang J, Xue Z, et al (2020)

Potential Pathogenic Bacteria in Seminal Microbiota of Patients with Different Types of Dysspermatism.

Scientific reports, 10(1):6876.

Human microbiota play an important role in the health of their human hosts. Recent studies have demonstrated that microbiota exist in seminal plasma. The current study aims to elucidate whether seminal microbiota exist in patients with different types of dysspermatism and whether bacterial biomarkers can be identified for them. A total of 159 study participants were recruited, including 22 patients with oligoasthenospermia, 58 patients with asthenospermia, 8 patients with azoospermia, 13 patients with oligospermia, and 58 matched healthy controls. Seminal microbiota composition was analyzed using 16S rRNA gene-based sequencing. The results showed that the composition of seminal microbiota of patients with dysspermatism differed from those of healthy controls. Comparison of the microbiota composition in semen samples from patients with different types of dysspermatism showed that microbiota in patients with asthenospermia and oligoasthenospermia were distinct from healthy controls in beta diversity (P < 0.05). Characteristic biomarkers, including Ureaplasma, Bacteroides, Anaerococcus, Finegoldia, Lactobacillus and Acinetobacter lwoffii, were identified based on LEfSe analysis. Inferred functional analysis based on seminal microbiome data further indicated the presence of potential pathogenic biomarkers in patients with asthenospermia and oligoasthenospermia. These results provided profiles of seminal microbiota exhibited in different types of dysspermatism, thus providing new insights into their pathogenesis.

RevDate: 2020-04-24

Garcia-Mazcorro JF, Minamoto Y, Kawas JR, et al (2020)

Akkermansia and Microbial Degradation of Mucus in Cats and Dogs: Implications to the Growing Worldwide Epidemic of Pet Obesity.

Veterinary sciences, 7(2): pii:vetsci7020044.

Akkermansia muciniphila is a mucin-degrading bacterium that has shown the potential to provide anti-inflammatory and anti-obesity effects in mouse and man. We here focus on companion animals, specifically cats and dogs, and evaluate the microbial degradation of mucus and its health impact in the context of the worldwide epidemic of pet obesity. A literature survey revealed that the two presently known Akkermansia spp., A. muciniphila and A. glycaniphila, as well as other members of the phylum of Verrucomicrobia seem to be neither very prevalent nor abundant in the digestive tract of cats and dog. While this may be due to methodological aspects, it suggests that bacteria related to Akkermansia are not the major mucus degraders in these pets and hence other mucus-utilizing taxa may deserve attention. Hence, we will discuss the potential of these endogenous mucus utilizers and dietary interventions to boost these as well as the use of Akkermansia spp. related bacteria or their components as strategies to target feline and canine obesity.

RevDate: 2020-06-16

Samples RM, MJ Balunas (2020)

Bridging the Gap: Plant-Endophyte Interactions as a Roadmap to Understanding Small-Molecule Communication in Marine Microbiomes.

Chembiochem : a European journal of chemical biology [Epub ahead of print].

Probing the composition of the microbiome and its association with health and disease states is more accessible than ever due to the rise of affordable sequencing technology. Despite advances in our ability to identify members of symbiont communities, untangling the chemical signaling that they use to communicate with host organisms remains challenging. In order to gain a greater mechanistic understanding of how the microbiome impacts health, and how chemical ecology can be leveraged to advance small-molecule drug discovery from microorganisms, the principals governing communication between host and symbiont must be elucidated. Herein, we review common modes of interkingdom small-molecule communication in terrestrial and marine environments, describe the differences between these environments, and detail the advantages and disadvantages for studies focused on the marine environment. Finally, we propose the use of plant-endophyte interactions as a stepping stone to a greater understanding of similar interactions in marine invertebrates, and ultimately in humans.


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 )