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Bibliography on: Microbiome

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ESP: PubMed Auto Bibliography 17 Sep 2020 at 01:54 Created: 


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

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

Citations The Papers (from PubMed®)


RevDate: 2020-09-16

Ganesan SM, Dabdoub SM, Nagaraja HN, et al (2020)

Adverse effects of electronic cigarettes on the disease-naive oral microbiome.

Science advances, 6(22): pii:6/22/eaaz0108.

Six percent of Americans, including 3 million high schoolers, use e-cigarettes, which contain potentially toxic substances, volatile organic compounds, and metals. We present the first human study on the effects of e-cigarette exposure in the oral cavity. By interrogating both immunoinflammatory responses and microbial functional dynamics, we discovered pathogen overrepresentation, higher virulence signatures, and a brisk proinflammatory signal in clinically healthy e-cigarette users, equivalent to patients with severe periodontitis. Using RNA sequencing and confocal and electron microscopy to validate these findings, we demonstrate that the carbon-rich glycol/glycerol vehicle is an important catalyst in transforming biofilm architecture within 24 hours of exposure. Last, a machine-learning classifier trained on the metagenomic signatures of e-cigarettes identified as e-cigarette users both those individuals who used e-cigarettes to quit smoking, and those who use both e-cigarettes and cigarettes. The present study questions the safety of e-cigarettes and the harm reduction narrative promoted by advertising campaigns.

RevDate: 2020-09-16

Campbell DE, Ly LK, Ridlon JM, et al (2020)

Infection with Bacteroides Phage BV01 Alters the Host Transcriptome and Bile Acid Metabolism in a Common Human Gut Microbe.

Cell reports, 32(11):108142.

Gut-associated phages are hypothesized to alter the abundance and activity of their bacterial hosts, contributing to human health and disease. Although temperate phages constitute a significant fraction of the gut virome, the effects of lysogenic infection are underexplored. We report that the temperate phage, Bacteroides phage BV01, broadly alters its host's transcriptome, the prominent human gut symbiont Bacteroides vulgatus. This alteration occurs through phage-induced repression of a tryptophan-rich sensory protein (TspO) and represses bile acid deconjugation. Because microbially modified bile acids are important signals for the mammalian host, this is a mechanism by which a phage may influence mammalian phenotypes. Furthermore, BV01 and its relatives in the proposed phage family Salyersviridae are ubiquitous in human gut metagenomes, infecting a broad range of Bacteroides hosts. These results demonstrate the complexity of phage-bacteria-mammal relationships and emphasize a need to better understand the role of temperate phages in the gut microbiome.

RevDate: 2020-09-16

Hu X, Xie Y, Xiao Y, et al (2020)

Longitudinal analysis of fecal microbiome and metabolome during renal fibrotic progression in a unilateral ureteral obstruction animal model.

European journal of pharmacology pii:S0014-2999(20)30647-6 [Epub ahead of print].

Renal fibrosis is a major pathological process in the progression of various chronic kidney diseases to end-stage renal disease (ESRD). Growing evidence has suggested that gut microbiota dysbiosis is closely related to ESRD. However, the interplay between altered fecal microbiome and metabolome during the renal fibrotic process remains unclear. Herein, an integrated approach of 16S ribosomal DNA sequencing combined with an ultra-high performance liquid chromatography-mass spectrometry-based metabolomics platform was applied to investigate the dynamic changes of fecal microbiota and metabolites throughout renal fibrosis progression in a mouse model of unilateral ureteral obstruction (UUO). The composition of gut microbiota changed markedly before and after UUO surgery. UUO mice showed a decrease in short-chain fatty acids-producing genera, including Bacteroides, Prevotellaceae_UCG-001, Roseburia, and Lachnospiraceae_NK4A136_group, as well as an increase in the genera Parasutterella and Alistipes, which changed dynamically over time. Additionally, 41 differential metabolites, mainly involved in 12 metabolic pathways, including inositol phosphate metabolism, primary bile acid biosynthesis, biosynthesis of unsaturated fatty acids, taurine and hypotaurine metabolism, purine metabolism, were identified in the UUO mice before and after surgery. Four fecal metabolites, myo-inositol, dodecanoic acid, N-acetylputrescine, and anthranilic acid, were positively associated with the progression of renal fibrosis. Moreover, by using multi-omics analyses, we found the alteration in UUO-related gut microbiota was correlated with a change in fecal metabolites. Therefore, our results provide insights into disturbances of the microbiome-metabolome interface in the progression of UUO-related renal fibrosis.

RevDate: 2020-09-16

Burton MJ, Clarkson JE, Goulao B, et al (2020)

Use of antimicrobial mouthwashes (gargling) and nasal sprays by healthcare workers to protect them when treating patients with suspected or confirmed COVID-19 infection.

The Cochrane database of systematic reviews, 9:CD013626.

BACKGROUND: COVID-19 infection poses a serious risk to patients and - due to its contagious nature - to those healthcare workers (HCWs) treating them. If the mouth and nose of HCWs are irrigated with antimicrobial solutions, this may help reduce the risk of active infection being passed from infected patients to HCWs through droplet transmission or direct contact. However, the use of such antimicrobial solutions may be associated with harms related to the toxicity of the solutions themselves, or alterations in the natural microbial flora of the mouth or nose. Understanding these possible side effects is particularly important when the HCWs are otherwise fit and well.

OBJECTIVES: To assess the benefits and harms of antimicrobial mouthwashes and nasal sprays used by healthcare workers (HCWs) to protect themselves when treating patients with suspected or confirmed COVID-19 infection.

SEARCH METHODS: Information Specialists from Cochrane ENT and Cochrane Oral Health searched the Central Register of Controlled Trials (CENTRAL 2020, Issue 6); Ovid MEDLINE; Ovid Embase and additional sources for published and unpublished trials. The date of the search was 1 June 2020. SELECTION CRITERIA: This is a question that urgently requires evidence, however at the present time we did not anticipate finding many completed randomised controlled trials (RCTs). We therefore planned to include the following types of studies: RCTs; quasi-RCTs; non-randomised controlled trials; prospective cohort studies; retrospective cohort studies; cross-sectional studies; controlled before-and-after studies. We set no minimum duration for the studies. We sought studies comparing any antimicrobial mouthwash and/or nasal spray (alone or in combination) at any concentration, delivered to HCWs, with or without the same intervention being given to the patients with COVID-19.

DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were: 1) incidence of symptomatic or test-positive COVID-19 infection in HCWs; 2) significant adverse event: anosmia (or disturbance in sense of smell). Our secondary outcomes were: 3) viral content of aerosol, when present (if intervention administered to patients); 4) other adverse events: changes in microbiome in oral cavity, nasal cavity, oro- or nasopharynx; 5) other adverse events: allergy, irritation/burning of nasal, oral or oropharyngeal mucosa (e.g. erosions, ulcers, bleeding), long-term staining of mucous membranes or teeth, accidental ingestion. We planned to use GRADE to assess the certainty of the evidence for each outcome.

MAIN RESULTS: We found no completed studies to include in this review. We identified three ongoing studies (including two RCTs), which aim to enrol nearly 700 participants. The interventions included in these trials are povidone iodine, nitric oxide and GLS-1200 oral spray (the constituent of this spray is unclear and may not be antimicrobial in nature). AUTHORS' CONCLUSIONS: We identified no studies for inclusion in this review. This is not surprising given the relatively recent emergence of COVID-19 infection. It is promising that the question posed in this review is being addressed by two RCTs and a non-randomised study. We are concerned that only one of the ongoing studies specifically states that it will evaluate adverse events and it is not clear if this will include changes in the sense of smell or to the oral and nasal microbiota, and any consequences thereof. Very few interventions have large and dramatic effect sizes. If a positive treatment effect is demonstrated when studies are available for inclusion in this review, it may not be large. In these circumstances in particular, where those receiving the intervention are otherwise fit and well, it may be a challenge to weigh up the benefits against the harms if the latter are of uncertain frequency and severity.

RevDate: 2020-09-16

Burton MJ, Clarkson JE, Goulao B, et al (2020)

Antimicrobial mouthwashes (gargling) and nasal sprays administered to patients with suspected or confirmed COVID-19 infection to improve patient outcomes and to protect healthcare workers treating them.

The Cochrane database of systematic reviews, 9:CD013627.

BACKGROUND: COVID-19 infection poses a serious risk to patients and - due to its contagious nature - to those healthcare workers (HCWs) treating them. If the mouth and nose of patients with infection are irrigated with antimicrobial solutions, this may help the patients by killing any coronavirus present at those sites. It may also reduce the risk of the active infection being passed to HCWs through droplet transmission or direct contact. However, the use of such antimicrobial solutions may be associated with harms related to the toxicity of the solutions themselves or alterations in the natural microbial flora of the mouth or nose.

OBJECTIVES: To assess the benefits and harms of antimicrobial mouthwashes and nasal sprays administered to patients with suspected or confirmed COVID-19 infection to both the patients and the HCWs caring for them.

SEARCH METHODS: Information Specialists from Cochrane ENT and Cochrane Oral Health searched the Central Register of Controlled Trials (CENTRAL 2020, Issue 6); Ovid MEDLINE; Ovid Embase and additional sources for published and unpublished trials. The date of the search was 1 June 2020. SELECTION CRITERIA: This is a question that urgently requires evidence, however at the present time we did not anticipate finding many completed RCTs. We therefore planned to include the following types of studies: randomised controlled trials (RCTs); quasi-RCTs; non-randomised controlled trials; prospective cohort studies; retrospective cohort studies; cross-sectional studies; controlled before-and-after studies. We set no minimum duration for the studies. We sought studies comparing antimicrobial mouthwash and/or nasal spray (alone or in combination) at any concentration, delivered with any frequency or dosage to suspected/confirmed COVID-19 patients.

DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were: 1) RECOVERY* ( outcomes in patients (mortality; hospitalisation status; use of ventilation; use of renal dialysis or haemofiltration); 2) incidence of symptomatic or test-positive COVID-19 infection in HCWs; 3) significant adverse event: anosmia (or disturbance in sense of smell). Our secondary outcomes were: 4) change in COVID-19 viral load in patients; 5) COVID-19 viral content of aerosol (when present); 6) other adverse events: changes in microbiome in oral cavity, nasal cavity, oro- or nasopharynx; 7) other adverse events: allergy, irritation/burning of nasal, oral or oropharyngeal mucosa (e.g. erosions, ulcers, bleeding), long-term staining of mucous membranes or teeth, accidental ingestion. We planned to use GRADE to assess the certainty of the evidence for each outcome.

MAIN RESULTS: We found no completed studies to include in this review. We identified 16 ongoing studies (including 14 RCTs), which aim to enrol nearly 1250 participants. The interventions included in these trials are ArtemiC (artemisinin, curcumin, frankincense and vitamin C), Citrox (a bioflavonoid), cetylpyridinium chloride, chlorhexidine, chlorine dioxide, essential oils, hydrogen peroxide, hypertonic saline, Kerecis spray (omega 3 viruxide - containing neem oil and St John's wort), neem extract, nitric oxide releasing solution, povidone iodine and saline with baby shampoo. AUTHORS' CONCLUSIONS: We identified no studies for inclusion in this review. This is not surprising given the relatively recent emergence of COVID-19 infection. It is promising that the question posed in this review is being addressed by a number of RCTs and other studies. We are concerned that few of the ongoing studies specifically state that they will evaluate adverse events such as changes in the sense of smell or to the oral and nasal microbiota, and any consequences thereof. Very few interventions have large and dramatic effect sizes. If a positive treatment effect is demonstrated when studies are available for inclusion in this review, it may not be large. In these circumstances in particular it may be a challenge to weigh up the benefits against the harms if the latter are of uncertain frequency and severity.

RevDate: 2020-09-16

Burton MJ, Clarkson JE, Goulao B, et al (2020)

Antimicrobial mouthwashes (gargling) and nasal sprays to protect healthcare workers when undertaking aerosol-generating procedures (AGPs) on patients without suspected or confirmed COVID-19 infection.

The Cochrane database of systematic reviews, 9:CD013628.

BACKGROUND: COVID-19 infection poses a serious risk to patients and - due to its contagious nature - to those healthcare workers (HCWs) treating them. The risks of transmission of infection are greater when a patient is undergoing an aerosol-generating procedure (AGP). Not all those with COVID-19 infection are symptomatic, or suspected of harbouring the infection. If a patient who is not known to have or suspected of having COVID-19 infection is to undergo an AGP, it would nonetheless be sensible to minimise the risk to those HCWs treating them. If the mouth and nose of an individual undergoing an AGP are irrigated with antimicrobial solutions, this may be a simple and safe method of reducing the risk of any covert infection being passed to HCWs through droplet transmission or direct contact. Alternatively, the use of antimicrobial solutions by the HCW may decrease the chance of them acquiring COVID-19 infection. However, the use of such antimicrobial solutions may be associated with harms related to the toxicity of the solutions themselves or alterations in the natural microbial flora of the mouth or nose.

OBJECTIVES: To assess the benefits and harms of antimicrobial mouthwashes and nasal sprays administered to HCWs and/or patients when undertaking AGPs on patients without suspected or confirmed COVID-19 infection.

SEARCH METHODS: Information Specialists from Cochrane ENT and Cochrane Oral Health searched the Central Register of Controlled Trials (CENTRAL 2020, Issue 6); Ovid MEDLINE; Ovid Embase and additional sources for published and unpublished trials. The date of the search was 1 June 2020. SELECTION CRITERIA: This is a question that urgently requires evidence, however at the present time we did not anticipate finding many completed RCTs. We therefore planned to include the following types of studies: randomised controlled trials (RCTs); quasi-RCTs; non-randomised controlled trials; prospective cohort studies; retrospective cohort studies; cross-sectional studies; controlled before-and-after studies. We set no minimum duration for the studies. We sought studies comparing any antimicrobial mouthwash and/or nasal spray (alone or in combination) at any concentration, delivered to the patient or HCW before and/or after an AGP.

DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were: 1) incidence of symptomatic or test-positive COVID-19 infection in HCWs or patients; 2) significant adverse event: anosmia (or disturbance in sense of smell). Our secondary outcomes were: 3) COVID-19 viral content of aerosol (when present); 4) change in COVID-19 viral load at site(s) of irrigation; 5) other adverse events: changes in microbiome in oral cavity, nasal cavity, oro- or nasopharynx; 6) other adverse events: allergy, irritation/burning of nasal, oral or oropharyngeal mucosa (e.g. erosions, ulcers, bleeding), long-term staining of mucous membranes or teeth, accidental ingestion. We planned to use GRADE to assess the certainty of the evidence for each outcome.

MAIN RESULTS: We found no completed studies to include in this review. AUTHORS' CONCLUSIONS: We identified no studies for inclusion in this review, nor any ongoing studies. The absence of completed studies is not surprising given the relatively recent emergence of COVID-19 infection. However, we are disappointed that this important clinical question is not being addressed by ongoing studies.

RevDate: 2020-09-16

Faits T, Walker ME, Rodriguez-Morato J, et al (2020)

Exploring changes in the human gut microbiota and microbial-derived metabolites in response to diets enriched in simple, refined, or unrefined carbohydrate-containing foods: a post hoc analysis of a randomized clinical trial.

The American journal of clinical nutrition pii:5906568 [Epub ahead of print].

BACKGROUND: Dietary carbohydrate type may influence cardiometabolic risk through alterations in the gut microbiome and microbial-derived metabolites, but evidence is limited.

OBJECTIVES: We explored the relative effects of an isocaloric exchange of dietary simple, refined, and unrefined carbohydrate on gut microbiota composition/function, and selected microbial metabolite concentrations.

METHODS: Participants [n = 11; age: 65 ± 8 y; BMI (in kg/m2): 29.8 ± 3.2] were provided with each of 3 diets for 4.5 wk with 2-wk washout, according to a randomized, crossover design. Diets [60% of energy (%E) carbohydrate, 15%E protein, and 25%E fat] differed in type of carbohydrate. Fecal microbial composition, metatranscriptomics, and microbial-derived SCFA and secondary bile acid (SBA) concentrations were assessed at the end of each phase and associated with cardiometabolic risk factors (CMRFs).

RESULTS: Roseburia abundance was higher (11% compared with 5%) and fecal SBA concentrations were lower (lithocolic acid -50% and deoxycholic acid -64%) after consumption of the unrefined carbohydrate diet relative to the simple carbohydrate diet [false discovery rate (FDR): all P < 0.05), whereas Anaerostipes abundance was higher (0.35% compared with 0.12%; FDR: P = 0.04) after the simple carbohydrate diet relative to the refined carbohydrate diet. Metatranscriptomics indicated upregulation of 2 cellular stress genes (FDR: P < 0.1) after the unrefined carbohydrate diet compared with the simple carbohydrate or refined carbohydrate diets. The microbial expression of 3 cellular/oxidative stress and immune response genes was higher (FDR: P < 0.1) after the simple carbohydrate diet relative to the refined carbohydrate diet. No significant diet effect was observed in fecal SCFA concentrations. Independent of diet, we observed 16 associations (all FDR: P < 0.1) of taxon abundance (15 phylum and 1 genera) with serum inflammatory markers and also with fecal SCFA and SBA concentrations.

CONCLUSIONS: Consuming an unrefined carbohydrate-rich diet had a modest effect on the gut microbiome and SBAs, resulting in favorable associations with selected CMRFs. Simple carbohydrate- and refined carbohydrate-rich diets have distinctive effects on the gut microbiome, suggesting differential mechanisms mediate their effects on cardiometabolic health. This trial was registered at as NCT01610661.

RevDate: 2020-09-16

Dong TS, Mayer EA, Osadchiy V, et al (2020)

A Distinct Brain-Gut-Microbiome Profile Exists for Females with Obesity and Food Addiction.

Obesity (Silver Spring, Md.), 28(8):1477-1486.

BACKGROUND: Alterations in brain-gut-microbiome interactions have been implicated as an important factor in obesity. This study aimed to explore the relationship between food addiction (FA) and the brain-gut-microbiome axis, using a multi-omics approach involving microbiome data, metabolomics, and brain imaging.

METHODS: Brain magnetic resonance imaging was obtained in 105 females. FA was defined by using the Yale Food Addiction Scale. Fecal samples were collected for sequencing and metabolomics. Statistical analysis was done by using multivariate analyses and machine learning algorithms.

RESULTS: Of the females with obesity, 33.3% exhibited FA as compared with 5.3% and 0.0% of females with overweight and normal BMI, respectively (P = 0.0001). Based on a multilevel sparse partial least square discriminant analysis, there was a difference in the gut microbiome of females with FA versus those without. Differential abundance testing showed Bacteroides, Megamonas, Eubacterium, and Akkermansia were statistically associated with FA (q < 0.05). Metabolomics showed that indolepropionic acid was inversely correlated with FA. FA was also correlated with increased connectivity within the brain's reward network, specifically between the intraparietal sulcus, brain stem, and putamen.

CONCLUSIONS: This is the first study to examine FA along the brain-gut-microbiome axis and it supports the idea of targeting the brain-gut-microbiome axis for the treatment of FA and obesity.

RevDate: 2020-09-16

Abbasi-Oshaghi E, Mirzaei F, I Khodadadi (2020)

Letter from Iran: Experiences with COVID-19.

RevDate: 2020-09-16

Livyatan I, Nejman D, Shental N, et al (2020)

Characterization of the human tumor microbiome reveals tumor-type specific intra-cellular bacteria.

Oncoimmunology, 9(1):1800957 pii:1800957.

Many characteristics of cancer such as proliferation, survival, progression, immunogenicity, sensitivity, and resistance to therapy are not just endogenously driven by the tumor cells themselves, but are greatly affected by their interaction with the components of their microenvironment. In our recent report, we comprehensively characterized the bacterial content of solid tumors, which is strongly related to tumor type and subtype, largely presenting as metabolically-active and intra-cellular. Our integration with clinical patient data indicates potential avenues of cross-talk between the tumors and their bacterial counterparts paving the way for a deeper understanding of the physiological/biological context of the tumor and how to harness bacteria in therapy settings.

RevDate: 2020-09-16

Daillère R, Derosa L, Bonvalet M, et al (2020)

Trial watch : the gut microbiota as a tool to boost the clinical efficacy of anticancer immunotherapy.

Oncoimmunology, 9(1):1774298 pii:1774298.

Accumulating evidence demonstrates the decisive role of the gut microbiota in determining the effectiveness of anticancer therapeutics such as immunogenic chemotherapy or immune checkpoint blockade in preclinical tumor models, as well as in cancer patients. In synthesis, it appears that a normal intestinal microbiota supports therapeutic anticancer responses, while a dysbiotic microbiota that lacks immunostimulatory bacteria or contains overabundant immunosuppressive species causes treatment failure. These findings have led to the design of clinical trials that evaluate the capacity of modulation of the gut microbiota to synergize with treatment and hence limit tumor progression. Along the lines of this Trial Watch, we discuss the rationale for harnessing the gut microbiome in support of cancer therapy and the progress of recent clinical trials testing this new therapeutic paradigm in cancer patients.

RevDate: 2020-09-16

Hernandez-Sanabria E, Vázquez-Castellanos JF, J Raes (2020)

In vitro ecology: a discovery engine for microbiome therapies.

Nature reviews. Gastroenterology & hepatology pii:10.1038/s41575-020-00364-7 [Epub ahead of print].

RevDate: 2020-09-16

Verma A, Sharda S, Rathi B, et al (2020)

Elucidating potential molecular signatures through host-microbe interactions for reactive arthritis and inflammatory bowel disease using combinatorial approach.

Scientific reports, 10(1):15131 pii:10.1038/s41598-020-71674-8.

Reactive Arthritis (ReA), a rare seronegative inflammatory arthritis, lacks exquisite classification under rheumatic autoimmunity. ReA is solely established using differential clinical diagnosis of the patient cohorts, where pathogenic triggers linked to enteric and urogenital microorganisms e.g. Salmonella, Shigella, Yersinia, Campylobacter, Chlamydia have been reported. Inflammatory Bowel Disease (IBD), an idiopathic enteric disorder co-evolved and attuned to present gut microbiome dysbiosis, can be correlated to the genesis of enteropathic arthropathies like ReA. Gut microbes symbolically modulate immune system homeostasis and are elementary for varied disease patterns in autoimmune disorders. The gut-microbiota axis structured on the core host-microbe interactions execute an imperative role in discerning the etiopathogenesis of ReA and IBD. This study predicts the molecular signatures for ReA with co-evolved IBD through the enveloped host-microbe interactions and microbe-microbe 'interspecies communication', using synonymous gene expression data for selective microbes. We have utilized a combinatorial approach that have concomitant in-silico work-pipeline and experimental validation to corroborate the findings. In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. Cross validation of the target/s or biomarker/s was done by targeted gene expression analysis following a non-probabilistic convenience sampling. Studies were performed to substantiate the host-microbe disease network consisting of protein-marker-symptom/disease-pathway-drug associations resulting in possible identification of vital drug targets, biomarkers, pathways and inhibitors for IBD and ReA.Our study identified Na(+)/H(+) anti-porter (NHAA) and Kynureninase (KYNU) to be robust early and essential host-microbe interacting targets for IBD co-evolved ReA. Other vital host-microbe interacting genes, proteins, pathways and drugs include Adenosine Deaminase (ADA), Superoxide Dismutase 2 (SOD2), Catalase (CAT), Angiotensin I Converting Enzyme (ACE), carbon metabolism (folate biosynthesis) and methotrexate. These can serve as potential prognostic/theranostic biomarkers and signatures that can be extrapolated to stratify ReA and related autoimmunity patient cohorts for further pilot studies.

RevDate: 2020-09-16

Lee JH, Choi JP, Yang J, et al (2020)

Metagenome analysis using serum extracellular vesicles identified distinct microbiota in asthmatics.

Scientific reports, 10(1):15125 pii:10.1038/s41598-020-72242-w.

Different patterns of bacterial communities have been reported in the airways and gastrointestinal tract of asthmatics when compared to healthy controls. However, the blood microbiome of asthmatics is yet to be investigated. Therefore, we aimed to determine whether a distinct serum microbiome is observed in asthmatics by metagenomic analysis of serum extracellular vesicles (EVs). We obtained serum from 190 adults with asthma and 260 healthy controls, from which EVs were isolated and analyzed. The bacterial composition of asthmatics was significantly different from that of healthy controls. Chao 1 index was significantly higher in the asthma group, while Shannon and Simpson indices were higher in the control group. At the phylum level, Bacteroidetes was more abundant in asthmatics, while Actinobacter, Verrucomicrobia, and Cyanobacteria were more abundant in healthy controls. At the genus level, 24 bacterial genera showed differences in relative abundance between asthmatics and controls, with linear discriminant analysis scores greater than 3. Further, in a diagnostic model based on these differences, a high predictive value with a sensitivity of 0.92 and a specificity of 0.93 was observed. In conclusion, we demonstrated distinct blood microbiome in asthma indicating the role of microbiome as a potential diagnostic marker of asthma.

RevDate: 2020-09-16

Gupta VK, Kim M, Bakshi U, et al (2020)

A predictive index for health status using species-level gut microbiome profiling.

Nature communications, 11(1):4635 pii:10.1038/s41467-020-18476-8.

Providing insight into one's health status from a gut microbiome sample is an important clinical goal in current human microbiome research. Herein, we introduce the Gut Microbiome Health Index (GMHI), a biologically-interpretable mathematical formula for predicting the likelihood of disease independent of the clinical diagnosis. GMHI is formulated upon 50 microbial species associated with healthy gut ecosystems. These species are identified through a multi-study, integrative analysis on 4347 human stool metagenomes from 34 published studies across healthy and 12 different nonhealthy conditions, i.e., disease or abnormal bodyweight. When demonstrated on our population-scale meta-dataset, GMHI is the most robust and consistent predictor of disease presence (or absence) compared to α-diversity indices. Validation on 679 samples from 9 additional studies results in a balanced accuracy of 73.7% in distinguishing healthy from non-healthy groups. Our findings suggest that gut taxonomic signatures can predict health status, and highlight how data sharing efforts can provide broadly applicable discoveries.

RevDate: 2020-09-16

Bech PK, Lysdal KL, Gram L, et al (2020)

Marine Sediments Hold an Untapped Potential for Novel Taxonomic and Bioactive Bacterial Diversity.

mSystems, 5(5): pii:5/5/e00782-20.

Novel natural products have traditionally been sourced from culturable soil microorganisms, whereas marine sources have been less explored. The purpose of this study was to profile the microbial biosynthetic potential in coastal surface seawater and sandy sediment samples and to evaluate the feasibility of capturing this potential using traditional culturing methods. Amplicon sequencing of conserved ketosynthase (KS) and adenylation (AD) domains within polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) genes showed that seawater and, in particular, sandy sediment had a high biosynthetic potential with 6,065 and 11,072 KS operational biosynthetic units (OBUs) and 3,292 and 5,691 AD OBUs, respectively, compared to that of four soil samples collected by Charlop-Powers et al. (Z. Charlop-Powers, C. C. Pregitzer, C. Lemetre, M. A. Ternei, et al., Proc Natl Acad Sci U S A 113:14811-14816, 2016, with 7,067 KS and 1,629 AD OBUs. All three niches harbored unique OBUs (P = 0.001 for KS and P = 0.002 for AD by permutational multivariate analysis of variance [PERMANOVA]). The total colonial growth captured 1.9% of KS and 13.6% of AD OBUs from seawater and 2.2% KS and 12.5% AD OBUs from sediment. In a subset of bioactive isolates, only four KS OBUs and one AD OBU were recovered from whole-genome sequencing (WGS) of seven seawater-derived strains and one AD OBU from a sediment-derived strain, adding up to 0.028% of the original OBU diversity. Using a pairwise regression model of classified amplicon sequence variants (ASVs) to the species level, and OBUs, we suggest a method to estimate possible links between taxonomy and biosynthetic potential, which indicated that low abundance organisms may hold a disproportional share of the biosynthetic potential. Thus, marine microorganisms are a rich source of novel bioactive potential, which is difficult to access with traditional culturing methods.IMPORTANCE Since bacterial resistance to antibiotics is developing worldwide, new antibiotics are needed. Most antibiotics discovered so far have been found in soil-dwelling bacteria, so we instead targeted marine environments as a novel source of bioactive potential. We used amplicon sequencing of bioactive gene clusters in the microbiome of coastal seawater and sandy sediments and found the bioactive potential to be comparable to, but distinct from, the bioactive potential of selected soil microbiomes. Moreover, most of this potential is not captured by culturing. Comparing the biosynthetic potential to the corresponding microbiome composition suggested that minor constituents of the microbiome likely hold a disproportionally large fraction of the biosynthesis potential.

RevDate: 2020-09-16

Ibarra-Juarez LA, Burton MAJ, Biedermann PHW, et al (2020)

Evidence for Succession and Putative Metabolic Roles of Fungi and Bacteria in the Farming Mutualism of the Ambrosia Beetle Xyleborus affinis.

mSystems, 5(5): pii:5/5/e00541-20.

The bacterial and fungal community involved in ambrosia beetle fungiculture remains poorly studied compared to the famous fungus-farming ants and termites. Here we studied microbial community dynamics of laboratory nests, adults, and brood during the life cycle of the sugarcane shot hole borer, Xyleborus affinis We identified a total of 40 fungal and 428 bacterial operational taxonomic units (OTUs), from which only five fungi (a Raffaelea fungus and four ascomycete yeasts) and four bacterial genera (Stenotrophomonas, Enterobacter, Burkholderia, and Ochrobactrum) can be considered the core community playing the most relevant symbiotic role. Both the fungal and bacterial populations varied significantly during the beetle's life cycle. While the ascomycete yeasts were the main colonizers of the gallery early on, the Raffaelea and other filamentous fungi appeared after day 10, at the time when larval hatching happened. Regarding bacteria, Stenotrophomonas and Enterobacter dominated overall but decreased in foundresses and brood with age. Finally, inferred analyses of the putative metabolic capabilities of the bacterial microbiome revealed that they are involved in (i) degradation of fungal and plant polymers, (ii) fixation of atmospheric nitrogen, and (iii) essential amino acid, cofactor, and vitamin provisioning. Overall, our results suggest that yeasts and bacteria are more strongly involved in supporting the beetle-fungus farming symbiosis than previously thought.IMPORTANCE Ambrosia beetles farm their own food fungi within tunnel systems in wood and are among the three insect lineages performing agriculture (the others are fungus-farming ants and termites). In ambrosia beetles, primary ambrosia fungus cultivars have been regarded essential, whereas other microbes have been more or less ignored. Our KEGG analyses suggest so far unknown roles of yeasts and bacterial symbionts, by preparing the tunnel walls for the primary ambrosia fungi. This preparation includes enzymatic degradation of wood, essential amino acid production, and nitrogen fixation. The latter is especially exciting because if it turns out to be present in vivo in ambrosia beetles, all farming animals (including humans) are dependent on atmospheric nitrogen fertilization of their crops. As previous internal transcribed spacer (ITS) metabarcoding approaches failed on covering the primary ambrosia fungi, our 18S metabarcoding approach can also serve as a template for future studies on the ambrosia beetle-fungus symbiosis.

RevDate: 2020-09-16

Woodhouse C, Singanayagam A, VC Patel (2020)

Modulating the gut-liver axis and the pivotal role of the faecal microbiome in cirrhosis.

Clinical medicine (London, England), 20(5):493-500.

Cirrhosis is associated with intestinal dysbiosis, with specific alterations in the gut microbiota linked to particular aetiologies and manifestations of the disease. We review the role of the gut microbiome and the importance of the intestinal barrier in cirrhosis, provide an overview of the terminology and techniques relevant to this emerging area, and discuss the latest developments in therapies targeting the gut-liver axis.

RevDate: 2020-09-16

Susic D, Davis G, O' Sullivan AJ, et al (2020)

Microbiome Understanding in Maternity Study (MUMS), an Australian prospective longitudinal cohort study of maternal and infant microbiota: study protocol.

BMJ open, 10(9):e040189 pii:bmjopen-2020-040189.

INTRODUCTION: Pregnancy induces significant physiological and cardiometabolic changes, and is associated with alterations in the maternal microbiota. Increasing rates of prepregnancy obesity, metabolic abnormalities and reduced physical activity, all impact negatively on the microbiota causing an imbalance between the commensal microorganisms (termed dysbiosis), which may drive complications, such as gestational diabetes or hypertensive disorders. Considerable work is needed to define the inter-relationships between the microbiome, nutrition, physical activity and pregnancy outcomes. The role of the microbiota during pregnancy remains unclear. The aim of the study is to define microbiota signatures longitudinally throughout pregnancy and the first year post birth, and to identify key clinical and environmental variables that shape the female microbiota profile during and following pregnancy.

METHODS AND ANALYSIS: The Microbiome Understanding in Maternity Study (MUMS) is an Australian prospective longitudinal cohort study involving 100 mother-infant pairs. Women are enrolled in their first trimester and followed longitudinally. Assessment occurs at <13+0, 20+0-24+6 and 32+0-36+6 weeks gestation, birth and 6 weeks, 6 months and 12 months postpartum. At each assessment, self-collected oral, vaginal and faecal samples are collected with an additional postpartum skin swab and breastmilk sample. Each infant will have oral, faecal and skin swab samples collected. Measurements include anthropometrics, body composition, blood pressure, serum hormonal and metabolic parameters and vaginal pH. Dietary intake, physical activity and psychological state will be assessed using validated self-report questionnaires, and pregnancy and infant outcomes recorded. Parametric and non-parametric hypothesis tests will be used to test the association between high-risk and low-risk pregnancies and their outcomes.

ETHICS AND DISSEMINATION: The study received the following approval: South Eastern Sydney Local Health District Research Ethics Committee (17/293 (HREC/17/POWH/605). Results will be made available to the participants of MUMS, their families and the funding bodies; in the form of a summary document. Results for the greater maternity care community and other researchers will be disseminated through conferences, local, national and international presentations and peer-reviewed publications.

TRIAL REGISTRATION NUMBER: ACTRN12618000471280 (prospectively registered).

RevDate: 2020-09-16

AlHilli MM, V Bae-Jump (2020)

Diet and gut microbiome interactions in gynecologic cancer.

Gynecologic oncology pii:S0090-8258(20)33828-2 [Epub ahead of print].

Over the last decade, there has been a dramatic surge in research exploring the human gut microbiome and its role in health and disease. It is now widely accepted that commensal microorganisms coexist within the human gastrointestinal tract and other organs, including those of the reproductive tract. These microorganisms, which are collectively known as the "microbiome", contribute to maintaining host physiology and to the development of pathology. Next generation sequencing and multi-'omics' technology has enriched our understanding of the complex and interdependent relationship that exists between the host and microbiome. Global changes in the microbiome are known to be influenced by dietary, genetic, lifestyle, and environmental factors. Accumulating data have shown that alterations in the gut microbiome contribute to the development, prognosis and treatment of many disease states including cancer primarily through interactions with the immune system. However, there are large gaps in knowledge regarding the association between the gut microbiome and gynecologic cancers, and research characterizing the reproductive tract microbiome is insufficient. Herein, we explore the mechanisms by which alterations in the gut and reproductive tract microbiome contribute to carcinogenesis focusing on obesity, hyperestrogenism, inflammation and altered tumor metabolism. The impact of the gut microbiome on response to anti-cancer therapy is highlighted with an emphasis on immune checkpoint inhibitor efficacy in gynecologic cancers. We discuss dietary interventions that are likely to modulate the metabolic and immunologic milieu as well as tumor microenvironment through the gut microbiome including intermittent fasting/ketogenic diet, high fiber diet, use of probiotics and the metabolic management of obesity. We conclude that enhanced understanding of the microbiome in gynecologic cancers coupled with thorough evaluation of metabolic and metagenomic analyses would enable us to integrate novel preventative strategies and adjunctive interventions into the care of women with gynecologic cancers.

RevDate: 2020-09-16

Villasante A, Catalán N, Rojas R, et al (2020)

Microbiota of the Digestive Gland of Red Abalone (Haliotis rufescens) Is Affected by Withering Syndrome.

Microorganisms, 8(9): pii:microorganisms8091411.

Withering syndrome (WS), an infectious disease caused by intracellular bacteria Candidatus Xenohaliotis californiensis, has provoked significant economic losses in abalone aquaculture. The pathogen infects gastroenteric epithelia, including digestive gland, disrupting the digestive system and causing a progressive wilting in abalone. Nonetheless, our knowledge about WS implications in digestive gland microbiota, and its role in diseases progress remains largely unknown. This study aims to determine whether digestive gland-associated microbiota differs between healthy red abalone (Haliotis rufescens) and red abalone affected with WS. Using high-throughput sequencing of the V4 region of the 16S rRNA gene, our results revealed differences in microbiota between groups. Bacterial genera, including Mycoplasma, Lactobacillus, Cocleimonas and Tateyamaria were significantly more abundant in healthy abalones, whilst Candidatus Xenohaliotis californiensis and Marinomonas were more abundant in WS-affected abalones. Whilst Mycoplasma was the dominant genus in the healthy group, Candidatus Xenohaliotis californiensis was dominant in the WS group. However, Candidatus Xenohaliotis californiensis was present in two healthy specimens, and thus the Mycoplasma/Candidatus Xenohaliotis californiensis ratio appears to be more determinant in specimens affected with WS. Further research to elucidate the role of digestive gland microbiota ecology in WS pathogenesis is required.

RevDate: 2020-09-16

Dabrowski W, Siwicka-Gieroba D, Gasinska-Blotniak M, et al (2020)

Pathomechanisms of Non-Traumatic Acute Brain Injury in Critically Ill Patients.

Medicina (Kaunas, Lithuania), 56(9): pii:medicina56090469.

Delirium, an acute alteration in mental status characterized by confusion, inattention and a fluctuating level of arousal, is a common problem in critically ill patients. Delirium prolongs hospital stay and is associated with higher mortality. The pathophysiology of delirium has not been fully elucidated. Neuroinflammation and neurotransmitter imbalance seem to be the most important factors for delirium development. In this review, we present the most important pathomechanisms of delirium in critically ill patients, such as neuroinflammation, neurotransmitter imbalance, hypoxia and hyperoxia, tryptophan pathway disorders, and gut microbiota imbalance. A thorough understanding of delirium pathomechanisms is essential for effective prevention and treatment of this underestimated pathology in critically ill patients.

RevDate: 2020-09-16

Kovaleva O, Podlesnaya P, Rashidova M, et al (2020)

Lung Microbiome Differentially Impacts Survival of Patients with Non-Small Cell Lung Cancer Depending on Tumor Stroma Phenotype.

Biomedicines, 8(9): pii:biomedicines8090349.

The link between a lung tumor and the lung microbiome is a largely unexplored issue. To investigate the relationship between a lung microbiome and the phenotype of an inflammatory stromal infiltrate, we studied a cohort of 89 patients with non-small cell lung cancer. The microbiome was analyzed in tumor and adjacent normal tissue by 16S rRNA amplicon sequencing. Characterization of the tumor stroma was done using immunohistochemistry. We demonstrated that the bacterial load was higher in adjacent normal tissue than in a tumor (p = 0.0325) with similar patterns of taxonomic structure and alpha diversity. Lung adenocarcinomas did not differ in their alpha diversity from squamous cell carcinomas, although the content of Gram-positive bacteria increased significantly in the adenocarcinoma group (p = 0.0419). An analysis of an inflammatory infiltrate of tumor stroma showed a correlation of CD68, iNOS and FOXP3 with a histological type of tumor. For the first time we showed that high bacterial load in the tumor combined with increased iNOS expression is a favorable prognostic factor (HR = 0.1824; p = 0.0123), while high bacterial load combined with the increased number of FOXP3+ cells is a marker of poor prognosis (HR = 4.651; p = 0.0116). Thus, we established that bacterial load of the tumor has an opposite prognostic value depending on the status of local antitumor immunity.

RevDate: 2020-09-16

Paqué PN, Herz C, Jenzer JS, et al (2020)

Microbial Analysis of Saliva to Identify Oral Diseases Using a Point-of-Care Compatible qPCR Assay.

Journal of clinical medicine, 9(9): pii:jcm9092945.

Oral health is maintained by a healthy microbiome, which can be monitored by state-of-the art diagnostics. Therefore, this study evaluated the presence and quantity of ten oral disease-associated taxa (P. gingivalis, T. forsythia, T. denticola, F. nucleatum, C. rectus, P. intermedia, A. actinomycetemcomitans, S. mutans, S. sobrinus, oral associated Lactobacilli) in saliva and their clinical status association in 214 individuals. Upon clinical examination, study subjects were grouped into healthy, caries and periodontitis and their saliva was collected. A highly specific point-of-care compatible dual color qPCR assay was developed and used to study the above-mentioned bacteria of interest in the collected saliva. Assay performance was compared to a commercially available microbial reference test. Eight out of ten taxa that were investigated during this study were strong discriminators between the periodontitis and healthy groups: C. rectus, T. forsythia, P. gingivalis, S. mutans, F. nucleatum, T. denticola, P. intermedia and oral Lactobacilli (p < 0.05). Significant differentiation between the periodontitis and caries group microbiome was only shown for S. mutans (p < 0.05). A clear distinction between oral health and disease was enabled by the analysis of quantitative qPCR data of target taxa levels in saliva.

RevDate: 2020-09-16

Perez-Garcia J, Hernández-Pérez JM, González-Pérez R, et al (2020)

The Genomics and Metagenomics of Asthma Severity (GEMAS) Study: Rationale and Design.

Journal of personalized medicine, 10(3): pii:jpm10030123.

Asthma exacerbations are a major contributor to the global disease burden, but no significant predictive biomarkers are known. The Genomics and Metagenomics of Asthma Severity (GEMAS) study aims to assess the role of genomics and the microbiome in severe asthma exacerbations. Here, we present the design of GEMAS and the characteristics of patients recruited from March 2018 to March 2020. Different biological samples and demographic and clinical variables were collected from asthma patients recruited by allergy and pulmonary medicine units in several hospitals from Spain. Cases and controls were defined by the presence/absence of severe asthma exacerbations in the past year (oral corticosteroid use, emergency room visits, and/or asthma-related hospitalizations). A total of 137 cases and 120 controls were recruited. After stratifying by recruitment location (i.e., Canary Islands and Basque Country), cases and controls did not differ for most demographic and clinical variables (p > 0.05). However, cases showed a higher proportion of characteristics inherent to asthma exacerbations (impaired lung function, severe disease, uncontrolled asthma, gastroesophageal reflux, and use of asthma medications) compared to controls (p < 0.05). Similar results were found after stratification by recruitment unit. Thereby, asthma patients enrolled in GEMAS are balanced for potential confounders and have clinical characteristics that support the phenotype definition. GEMAS will improve the knowledge of potential biomarkers of asthma exacerbations.

RevDate: 2020-09-16

Hori T, Matsuda K, K Oishi (2020)

Probiotics: A Dietary Factor to Modulate the Gut Microbiome, Host Immune System, and Gut-Brain Interaction.

Microorganisms, 8(9): pii:microorganisms8091401.

Various benefits of probiotics to the host have been shown in numerous human clinical trials. These organisms have been proposed to act by improving the balance of the gut microbiota and enhancing the production of short-chain fatty acids, as well as by interacting with host cells in the gastrointestinal tract, including immune cells, nerve cells, and endocrine cells. Although the stimulation of host cells by probiotics and subsequent signaling have been explained by in vitro experiments and animal studies, there has been some skepticism as to whether probiotics can actually interact with host cells in the human gastrointestinal tract, where miscellaneous indigenous bacteria coexist. Most recently, it has been shown that the ileal microbiota in humans after consumption of a fermented milk is occupied by probiotics for several hours, indicating that there is adequate opportunity for the ingested strain to stimulate the host cells continuously over a period of time. As the dynamics of ingested probiotics in the human gastrointestinal tract become clearer, further progress in this research area is expected to elucidate their behavior within the tract, as well as the mechanism of their physiological effects on the host.

RevDate: 2020-09-16

Zou X, Liu G, Meng F, et al (2020)

Exploring the Rumen and Cecum Microbial Community from Fetus to Adulthood in Goat.

Animals : an open access journal from MDPI, 10(9): pii:ani10091639.

The present study aimed to investigate the colonization process of epithelial bacteria attached to the rumen and intestinal tract tissue during the development of goats after birth. However, this process from fetus to adulthood was very limited. In goats, the rumen and cecum are two important fermentation organs, and it is important to study the acquisition and development of the neonatal microbiome, as well as the difference between these two organs. To characterize the microbial establishment and dynamic changes in the rumen and cecum from fetus to adulthood, we performed 16S rRNA gene sequencing for 106 samples from 47 individuals of nine pregnant mother-fetus pairs and 16 kids from birth up to 6 months. The diversity, structure and composition of the microbial communities were distinct between the rumen and cecum after birth, while they were similar in the fetal period. The study showed a rapid loss and influx of microbes at birth, followed by slight selection after drinking colostrum, and then a strong selection after weaning, suggesting that the establishment and dynamic fluctuations of the gut microbiome undergoes three distinct phases of microbiome progression in life: a conserved phase (during late pregnancy in the fetus), a transitional phase (newborn until weaning), and a stable phase (from weaning to adulthood). The results supported the view that microbes exist in the fetus, and revealed the establishment and dynamic fluctuations of the gut microbiome from fetus to adulthood in goats.

RevDate: 2020-09-16

Lee B, Lee J, Woo MY, et al (2020)

Modulation of the Gut Microbiota Alters the Tumour-Suppressive Efficacy of Tim-3 Pathway Blockade in a Bacterial Species- and Host Factor-Dependent Manner.

Microorganisms, 8(9): pii:microorganisms8091395.

T cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) is an immune checkpoint molecule and a target for anti-cancer therapy. In this study, we examined whether gut microbiota manipulation altered the anti-tumour efficacy of Tim-3 blockade. The gut microbiota of mice was manipulated through the administration of antibiotics and oral gavage of bacteria. Alterations in the gut microbiome were analysed by 16S rRNA gene sequencing. Gut dysbiosis triggered by antibiotics attenuated the anti-tumour efficacy of Tim-3 blockade in both C57BL/6 and BALB/c mice. Anti-tumour efficacy was restored following oral gavage of faecal bacteria even as antibiotic administration continued. In the case of oral gavage of Enterococcus hirae or Lactobacillus johnsonii, transferred bacterial species and host mouse strain were critical determinants of the anti-tumour efficacy of Tim-3 blockade. Bacterial gavage did not increase the alpha diversity of gut microbiota in antibiotic-treated mice but did alter the microbiome composition, which was associated with the restoration of the anti-tumour efficacy of Tim-3 blockade. Conclusively, our results indicate that gut microbiota modulation may improve the therapeutic efficacy of Tim-3 blockade during concomitant antibiotic treatment. The administered bacterial species and host factors should be considered in order to achieve therapeutically beneficial modulation of the microbiota.

RevDate: 2020-09-16

Wallace RK (2020)

The Microbiome in Health and Disease from the Perspective of Modern Medicine and Ayurveda.

Medicina (Kaunas, Lithuania), 56(9): pii:medicina56090462.

The role of the microbiome in health and disease helps to provide a scientific understanding of key concepts in Ayurveda. We now recognize that virtually every aspect of our physiology and health is influenced by the collection of microorganisms that live in various parts of our body, especially the gut microbiome. There are many external factors which influence the composition of the gut microbiome but one of the most important is diet and digestion. Ayurveda and other systems of traditional health have for thousands of years focused on diet and digestion. Recent research has helped us understand the connection between the microbiome and the many different prevention and therapeutic treatment approaches of Ayurveda.

RevDate: 2020-09-16

Ntemiri A, Ghosh TS, Gheller ME, et al (2020)

Whole Blueberry and Isolated Polyphenol-Rich Fractions Modulate Specific Gut Microbes in an In Vitro Colon Model and in a Pilot Study in Human Consumers.

Nutrients, 12(9): pii:nu12092800.

Blueberry (BB) consumption is linked to improved health. The bioconversion of the polyphenolic content of BB by fermentative bacteria in the large intestine may be a necessary step for the health benefits attributed to BB consumption. The identification of specific gut microbiota taxa that respond to BB consumption and that mediate the bioconversion of consumed polyphenolic compounds into bioactive forms is required to improve our understanding of how polyphenols impact human health. We tested the ability of polyphenol-rich fractions purified from whole BB-namely, anthocyanins/flavonol glycosides (ANTH/FLAV), proanthocyanidins (PACs), the sugar/acid fraction (S/A), and total polyphenols (TPP)-to modulate the fecal microbiota composition of healthy adults in an in vitro colon system. In a parallel pilot study, we tested the effect of consuming 38 g of freeze-dried BB powder per day for 6 weeks on the fecal microbiota of 17 women in two age groups (i.e., young and older). The BB ingredients had a distinct effect on the fecal microbiota composition in the artificial colon model. The ANTH/FLAV and PAC fractions were more effective in promoting microbiome alpha diversity compared to S/A and TPP, and these effects were attributed to differentially responsive taxa. Dietary enrichment with BB resulted in a moderate increase in the diversity of the microbiota of the older subjects but not in younger subjects, and certain health-relevant taxa were significantly associated with BB consumption. Alterations in the abundance of some gut bacteria correlated not only with BB consumption but also with increased antioxidant activity in blood. Collectively, these pilot data support the notion that BB consumption is associated with gut microbiota changes and health benefits.

RevDate: 2020-09-16

Bi K, Zhang X, Chen W, et al (2020)

MicroRNAs Regulate Intestinal Immunity and Gut Microbiota for Gastrointestinal Health: A Comprehensive Review.

Genes, 11(9): pii:genes11091075.

MicroRNAs are small non-coding RNAs regulating gene expression at the post-transcriptional level. The regulation of microRNA expression in the gut intestine is gradually recognized as one of the crucial contributors of intestinal homeostasis and overall health. Recent studies indicated that both the microRNAs endogenous in the gut intestine and exogenous from diets could play influential roles in modulating microbial colonization and intestinal immunity. In this review, we discuss the biological functions of microRNAs in regulating intestinal homeostasis by modulating intestinal immune responses and gut microbiota. We particularly focus on addressing the microRNA-dependent communication and interactions among microRNA, gut microbiota, and intestinal immune system. Besides, we also summarize the roles of diet-derived microRNAs in host-microbiome homeostasis and their benefits on intestinal health. A better understanding of the relationships among intestinal disorders, microRNAs, and other factors influencing intestinal health can facilitate the application of microRNA-based therapeutics for gastrointestinal diseases.

RevDate: 2020-09-16

Wu IW, Lee CC, Hsu HJ, et al (2020)

Compositional and Functional Adaptations of Intestinal Microbiota and Related Metabolites in CKD Patients Receiving Dietary Protein Restriction.

Nutrients, 12(9): pii:nu12092799.

The relationship between change of gut microbiota and host serum metabolomics associated with low protein diet (LPD) has been unraveled incompletely in CKD patients. Fecal 16S rRNA gene sequencing and serum metabolomics profiling were performed. We reported significant changes in the β-diversity of gut microbiota in CKD patients having LPD (CKD-LPD, n = 16). We identified 19 genera and 12 species with significant differences in their relative abundance among CKD-LPD patients compared to patients receiving normal protein diet (CKD-NPD, n = 27) or non-CKD controls (n = 34), respectively. CKD-LPD had a significant decrease in the abundance of many butyrate-producing bacteria (family Lachnospiraceae and Bacteroidaceae) associated with enrichment of functional module of butanoate metabolism, leading to concomitant reduction in serum levels of SCFA (acetic, heptanoic and nonanoic acid). A secondary bile acid, glyco λ-muricholic acid, was significantly increased in CKD-LPD patients. Serum levels of indoxyl sulfate and p-cresyl sulfate did not differ among groups. The relationship between abundances of microbes and metabolites remained significant in subset of resampling subjects of comparable characteristics. Enrichment of bacterial gene markers related to D-alanine, ketone bodies and glutathione metabolism was noted in CKD-LPD patients. Our analyses reveal signatures and functions of gut microbiota to adapt dietary protein restriction in renal patients.

RevDate: 2020-09-15

Nakamura A, Yokoyama Y, Tanaka K, et al (2020)

Asperuloside Improves Obesity and Type 2 Diabetes through Modulation of Gut Microbiota and Metabolic Signaling.

iScience, 23(9):101522 pii:S2589-0042(20)30714-8 [Epub ahead of print].

Asperuloside (ASP) is an iridoid glycoside that is extracted from Eucommia leaves. Eucommia is used in traditional Chinese medicine and has a long history of benefits on health and longevity. Here, we investigated the impact of ASP on obesity-related metabolic disorders and show that ASP reduces body weight gain, glucose intolerance, and insulin resistance effectively in mice fed with a high-fat diet (HFD). Intestinal dysbiosis is closely linked with metabolic disorders. Our data indicate that ASP achieves these benefits on metabolic homeostasis by reversing HFD-induced gut dysbiosis and by changing gut-derived secondary metabolites and metabolic signaling. Our results indicate that ASP may be used to regulate gut microbiota for the treatment of obesity and type 2 diabetes.

RevDate: 2020-09-15

Chen R, Wang L, Koch T, et al (2020)

Gender effects in the association between airway microbiome and asthma.

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology pii:S1081-1206(20)31006-1 [Epub ahead of print].

BACKGROUND: Gender differences are found in asthma susceptibility and severity. Accumulating evidence has linked airway microbiome dysbiosis with asthma and the airway microbial communities are found to be different by gender. However, whether gender modifies the link between airway microbiome and asthma has not been investigated.

OBJECTIVE: We aim to evaluate gender effects in the association between airway microbiome and asthma.

METHODS: We analyzed induced sputum samples from 47 subjects (n =23 asthmatics and n =24 normal controls) using 16S ribosomal RNA gene sequencing methods. The bacterial composition was analyzed for gender differences. Bacterial associations with asthma were assessed in each gender at the core taxa and genus level.

RESULTS: The microbiome in induced sputum differed in females versus males at the community level. There are five core bacterial taxa that appear in all samples. No gender-specific core taxa was detected. The most abundant core taxon, Streptococcus salivarius , was significantly enriched in females than in males (p=0.02). Within each gender, individuals with relatively lower abundance of S. salivarius were more likely to be asthmatic (p=0.006). Asthmatic patients of both genders contained increased Lactobacillus spp. in their sputum compared to normal controls (adjusted p=0.01). Haemophilus spp. were associated with asthma in males and not in females.

CONCLUSION: The airway microbiome differed by gender and gender effects exist in the association of airway microbial markers and asthma. Future airway microbiome studies may yield better resolution if the context of specific gender is considered. The airway microbiome is a potential mechanism driving gender differences in asthma.

RevDate: 2020-09-15

Morales Moreira ZP, Helgason BL, JJ Germida (2020)

Crop, genotype, and field environmental conditions shape bacterial and fungal seed epiphytic microbiomes.

Canadian journal of microbiology [Epub ahead of print].

Seeds are reproductive structures able to carry and transfer microorganisms that play an important role in plant fitness. Genetic and external factors are reported to be partly responsible for the plant microbiome assemblage, but their contribution in seeds is poorly understood. In this study, wheat, canola, and lentil seeds were analyzed to characterize diversity, structure, and persistence of seed-associated microbial communities. Five lines and two generations of each crop were subjected to high-throughput amplicon sequencing of the 16S rRNA and ITS regions. Bacterial and fungal communities differed most by crop type (30% and 47% of the variance), while generation explained an additional 10% and 15% of the variance. The offspring (i.e. generation harvested in 2016 at the same location) exhibited a higher number of common amplicon sequence variants (ASVs) and less variability in microbial composition. Additionally, in every sample analyzed, a "core microbiome" was detected consisting of five bacterial and twelve fungal ASVs. Our results suggest that crop, genotype, and field environmental conditions contributed to the seed-associated microbial assemblage. These findings not only expand our understanding of the factors influencing the seed microbiome but may also help us to manipulate and exploit the microbiota naturally carried by seeds.

RevDate: 2020-09-15

Kumar A, Palit P, Thomas S, et al (2020)

Osteoarthritis: Prognosis and emerging therapeutic approach for disease management.

Drug development research [Epub ahead of print].

Osteoarthritis (OA), a disorder of joints, is prevalent in older age. The contemporary cure for OA is aimed to confer symptomatic relief, consisting of temporary pain and swelling relief. In this paper, we discuss various modalities responsible for the onset of OA and associated with its severity. Inhibition of chondrocytes receptors such as DDR2, SDF-1, Asporin, and CXCR4 by specific pharmacological inhibitors attenuates OA, a critical step for finding potential disease modifying drugs. We critically analyzed recent OA studies with an emphasis on intermediate target molecules for OA intervention. We also explored some novel and safe treatments for OA by considering disease prognosis crosstalk with cellular signaling pathways.

RevDate: 2020-09-15

Díez-Vives C, Taboada S, Leiva C, et al (2020)

On the way to specificity - Microbiome reflects sponge genetic cluster primarily in highly structured populations.

Molecular ecology [Epub ahead of print].

Most animals, including sponges (Porifera), have species-specific microbiomes. Which genetic or environmental factors play major roles structuring the microbial community at the intraspecific level in sponges is, however, largely unknown. In this study, we tested whether geographic location or genetic structure of conspecific sponges influences their microbial assembly. For that, we used three sponge species with different rates of gene flow, and collected samples along their entire distribution range (two from the Mediterranean and one from the Southern Ocean) yielding a total of 393 samples. These three sponge species have been previously analysed by microsatellites or single nucleotide polymorphisms, and here we investigate their microbiomes by amplicon sequencing of the microbial 16S rRNA gene. The sponge Petrosia ficiformis, with highly isolated populations (low gene flow), showed a stronger influence of the host genetic distance on the microbial composition than the spatial distance. Host-specificity was therefore detected at the genotypic level, with individuals belonging to the same host genetic cluster harbouring more similar microbiomes than distant ones. On the contrary, the microbiome of Ircinia fasciculata and Dendrilla antarctica - both with weak population structure (high gene flow) - seemed influenced by location rather than by host genetic distance. Our results suggest that in sponge species with high population structure, the host genetic cluster influence the microbial community more than the geographic location.

RevDate: 2020-09-15

Moran MM, Wilson BM, Li J, et al (2020)

The gut microbiota may be a novel pathogenic mechanism in loosening of orthopedic implants in rats.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology [Epub ahead of print].

Particles released from implants cause inflammatory bone loss, which is a key factor in aseptic loosening, the most common reason for joint replacement failure. With the anticipated increased incidence of total joint replacement in the next decade, implant failure will continue to burden patients. The gut microbiome is increasingly recognized as an important factor in bone physiology, however, its role in implant loosening is currently unknown. We tested the hypothesis that implant loosening is associated with changes in the gut microbiota in a preclinical model. When the particle challenge caused local joint inflammation, decreased peri-implant bone volume, and decreased implant fixation, the gut microbiota was affected. When the particle challenge did not cause this triad of local effects, the gut microbiota was not affected. Our results suggest that cross-talk between these compartments is a previously unrecognized mechanism of failure following total joint replacement.

RevDate: 2020-09-15

Traussnigg S, Halilbasic E, Hofer H, et al (2020)

Open-label phase II study evaluating safety and efficacy of the non-steroidal farnesoid X receptor agonist PX-104 in non-alcoholic fatty liver disease.

Wiener klinische Wochenschrift pii:10.1007/s00508-020-01735-5 [Epub ahead of print].

BACKGROUND: The PX-104 is an oral non-steroidal agonist for the farnesoid X receptor (FXR), a key regulator of bile acid (BA), glucose and lipid homeostasis.

AIMS AND METHODS: This single center, proof of concept study evaluated the efficacy, safety and tolerability of PX-104 in non-diabetic NAFLD patients. 12 individuals were treated daily with 5 mg of PX-104 orally for 4 weeks. Serum liver enzymes, insulin sensitivity by clamp like index (CLIX) and hepatic fat by proton 1H‑MRS, MRI-PDFF and CAP were assessed. Hepatic energy metabolism and Kupffer cell function were evaluated by phosphorus 31P‑MRS and superparamagnetic iron oxide MRI (SPIO-MRI). Other readouts included serum lipids and markers of BA metabolism/signaling besides fecal microbiome and BA analysis.

RESULTS: A significant decrease in ALT (p = 0.027; 1‑tailed) and GGT (p = 0.019) was observed, without changes in serum alkaline phosphatase or serum lipids. Insulin sensitivity improved in 92% of patients (p = 0.02). However, hepatic steatosis measured by PDFF-MRI, 1H‑MRS and CAP besides extended serum lipoprotein and BA profiles did not change. NADPH/γATP ratios at 31P‑MRS significantly decreased (p = 0.022) possibly reflecting reduced hepatic inflammatory stress, but SPIO-MRI remained unchanged. Reduced preponderance of Coriobacteriaceae (p = 0.036) correlated with a relative reduction of total fecal BAs. There were no serious adverse events but short intervals of cardiac arrhythmia recorded in 2 patients led to termination of the study.

CONCLUSION: The non-steroidal FXR agonist PX-104 improved insulin sensitivity and liver enzymes after 4 weeks of treatment in non-diabetic NAFLD patients. Changes in fecal BAs and gut microbiota deserve more extensive investigations.

RevDate: 2020-09-15

Song S, Liu J, Zhang F, et al (2020)

Norepinephrine depleting toxin DSP-4 and LPS alter gut microbiota and induce neurotoxicity in α-synuclein mutant mice.

Scientific reports, 10(1):15054 pii:10.1038/s41598-020-72202-4.

This study examined the genetic mutation and toxicant exposure in producing gut microbiota alteration and neurotoxicity. Homozygous α-synuclein mutant (SNCA) mice that overexpress human A53T protein and littermate wild-type mice received a single injection of LPS (2 mg/kg) or a selective norepinephrine depleting toxin DSP-4 (50 mg/kg), then the motor activity, dopaminergic neuron loss, colon gene expression and gut microbiome were examined 13 months later. LPS and DSP-4 decreased rotarod and wirehang activity, reduced dopaminergic neurons in substantia nigra pars compacta (SNpc), and SNCA mice were more vulnerable. SNCA mice had 1,000-fold higher human SNCA mRNA expression in the gut, and twofold higher gut expression of NADPH oxidase (NOX2) and translocator protein (TSPO). LPS further increased expression of TSPO and IL-6 in SNCA mice. Both LPS and DSP-4 caused microbiome alterations, and SNCA mice were more susceptible. The altered colon microbiome approximated clinical findings in PD patients, characterized by increased abundance of Verrucomicrobiaceae, and decreased abundance of Prevotellaceae, as evidenced by qPCR with 16S rRNA primers. The Firmicutes/Bacteroidetes ratio was increased by LPS in SNCA mice. This study demonstrated a critical role of α-synuclein and toxins interactions in producing gut microbiota disruption, aberrant gut pro-inflammatory gene expression, and dopaminergic neuron loss.

RevDate: 2020-09-14

Phour M, Sehrawat A, Sindhu SS, et al (2020)

Interkingdom signaling in plant-rhizomicrobiome interactions for sustainable agriculture.

Microbiological research, 241:126589 pii:S0944-5013(20)30457-2 [Epub ahead of print].

The rhizosphere is a complex ecosystem around plant roots that comprises an integrated network of plant roots, the microbiome and soil. Wide spread communication between prokaryotes and eukaryotes occurs within this integrated network via a complex set of signal molecules secreted during both beneficial and harmful interactions. Intra- and inter-species communication among microbes occurs through various signal molecules that coordinate and control the behaviours of microorganisms in mixed communities. In addition, interkingdom signal exchange between plants and microbes occurs through the release of root exudates from the host plants. The diverse chemical substances released in root exudates affect the structural and physical heterogeneity of the soil. Moreover, chemical compounds released in root exudates trigger various signaling pathways in microbial populations that influence rhizosphere biology. Therefore, deciphering the language of interkingdom communication and understanding the mechanisms involved is innovative and promising approach for improving crop production in sustainable agriculture. This chapter describes briefly the shaping of the rhizomicrobiome in response to released root exudates. Moreover, predicting and controlling the microbiome structure and its function in the rhizosphere by understanding of rhizomicrobiome communication through different secreted compounds will allow us to better harness beneficial plant-microbe interactions. The recent progress in understanding interkingdom communication and interactions between plants and microbes is discussed in relation to plant growth, gene expression, nutrient uptake and resistance to pests and diseases along with mitigation of abiotic stresses in plants to improve plant ecosystem productivity for sustainable agriculture.

RevDate: 2020-09-14

Deeg HJ (2020)

Individuals, Boundaries and GVHD.

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation pii:S1083-8791(20)30586-3 [Epub ahead of print].

Hematopoietic cell transplantation generates new individuals, transplant chimeras, composed of two genetic partners - the patient and donor-derived cells - no longer restricted by their original genomes. Interactions of donor-derived and recipient cells occur prominently at the boundary of the recipient with a third partner, the microbiome, in particular skin and intestinal tract, leading to disruption of microbiome homeostasis. These interactions of donor and patient cells at the boundary set the stage for the development of graft versus host disease, an expression of the defense of individuality by recipient and donor. Establishment of tolerance and return of homeostasis at the boundary will allow for the survival of the new integrated, physiological individual.

RevDate: 2020-09-14

Centanni M, Bell TJ, Sims IM, et al (2020)

Preferential use of plant glycans for growth by Bacteroides ovatus.

Anaerobe pii:S1075-9964(20)30132-3 [Epub ahead of print].

B. ovatus is a member of the human gut microbiota with a broad capability to degrade complex glycans. Here we show that B. ovatus degrades plant polysaccharides in a preferential order, and that glycan structural complexity plays a role in determining the prioritisation of polysaccharide usage.

RevDate: 2020-09-14

Correia MSP, Jain A, Alotaibi W, et al (2020)

Comparative dietary sulfated metabolome analysis reveals unknown metabolic interactions of the gut microbiome and the human host.

Free radical biology & medicine pii:S0891-5849(20)31243-0 [Epub ahead of print].

The gut microbiome converts dietary compounds that are absorbed in the gastrointestinal tract and further metabolized by the human host. Sulfated metabolites are a major compound class derived from this co-metabolism and have been linked to disease development. In the present multidisciplinary study, we have investigated human urine samples from a dietary intervention study with 22 individuals collected before and after consumption of a polyphenol rich breakfast. These samples were analyzed utilizing our method combining enzymatic metabolite hydrolysis using an arylsulfatase and mass spectrometric metabolomics. Key to this study is the validation of 235 structurally diverse sulfated metabolites. We have identified 48 significantly upregulated metabolites upon dietary intervention including 11 previously unknown sulfated metabolites for this diet. We observed a large variation in subjects based on their potential to sulfate metabolites, which may be the foundation for classification of subjects as high and low sulfate metabolizers in future large cohort studies. The reported sulfatase-based method is a robust tool for the discovery of unknown microbiota-derived metabolites in human samples.

RevDate: 2020-09-14

Louise-Eva VANDENBORGHT, Enaud R, Urien C, et al (2020)

Type 2-high asthma is associated with a specific indoor mycobiome and microbiome.

The Journal of allergy and clinical immunology pii:S0091-6749(20)31248-3 [Epub ahead of print].

BACKGROUND: The links between microbial environmental exposures and asthma are well documented, but no study has combined deep-sequencing results from pulmonary and indoor microbiomes of asthmatic patients with spirometry, clinical and endotype parameters.

OBJECTIVE: The goal of this study was to investigate the links between indoor microbial exposures and pulmonary microbial communities and to document the role of microbial exposures on inflammatory and clinical outcomes of patients with severe asthma (SA).

METHODS: Fifty-five SA patients from the national COBRA cohort were enrolled for analyzing their indoor microbial flora through the use of electrostatic dust collectors (EDCs). Among these patients, 22 were able to produce sputa during stable or pulmonary exacerbation periods and had complete pairs of EDC and sputum samples, both collected and analysed. We used amplicon targeted metagenomics to compare microbial communities from EDC and sputum samples of patients according to type 2 (T2)-asthma endotypes.

RESULTS: Compared to patients with T2-low SA, patients with T2-high SA exhibited an increase in bacterial alpha-diversity and a decrease in fungal alpha-diversity of their indoor microbial floras, the latter being significantly correlated with FeNO levels. The beta-diversity of the EDC mycobiome significantly clustered according to T2 endotypes. Moreover, the proportion of fungal taxa in common between sputum and EDC samples was significantly higher when patients exhibited acute exacerbation.

CONCLUSION: These results illustrated, for the first time, a potential association between the indoor mycobiome and clinical features of SA patients, which should renew interest in deciphering the interactions between indoor environment, fungi, and host in asthma.

RevDate: 2020-09-14

Liu R, Wei P, Keller C, et al (2020)

Integrated Label-Free and 10-plex DiLeu Isobaric Tag Quantitative Methods for Profiling Changes in the Mouse Hypothalamic Neuropeptidome and Proteome: Assessment of the Impact of the Gut Microbiome.

Analytical chemistry [Epub ahead of print].

Gut microbiota can regulate host physiological and pathological status through gut-brain communications or pathways. However, the impact of the gut microbiome on neuropeptides and proteins involved in regulating brain functions and behaviors is still not clearly understood. To address the problem, integrated label-free and 10-plex DiLeu isobaric tag-based quantitative methods were implemented to compare the profiling of neuropeptides and proteins in the hypothalamus of germ-free (GF) vs. conventionally-raised (ConvR) mice. A total of 2,943 endogenous peptides from 63 neuropeptide precursors and 3,971 proteins in the mouse hypothalamus were identified. Among these 368 significantly changed peptides (fold changes over 1.5, and p-value < 0.05), 73.6% of the peptides showed higher levels in GF-mice than in ConvR-mice, and 26.4% of the peptides had higher levels in ConvR-mice than in GF-mice. These peptides were mainly from Secretogranin-2, Phosphatidylethanolamine-binding protein-1, ProSAAS, and Proenkephalin-A. Quantitative proteomic analysis employing DiLeu isobaric tags revealed that 282 proteins were significantly up- or down-regulated (fold changes over 1.2, and p-value < 0.05) among the 3,277 quantified proteins. These neuropeptides and proteins were mainly involved in regulating behaviors, transmitter release, signaling pathways, and synapses. Interestingly, pathways including long-term potentiation, long-term depression, and circadian entrainment were involved. In the present study, a combined label-free and 10-plex DiLeu-based quantitative method enable a comprehensive profiling of gut microbiome induced dynamic changes of neuropeptides and proteins in the hypothalamus, suggesting that the gut microbiome might mediate a range of behavioral changes, brain development, learning, and memory through these neuropeptides and proteins.

RevDate: 2020-09-14

Wang P, Ning Y, Huang J, et al (2020)

Intestinal Tract Microbe Communities Associated with Horseshoe Crabs from Beibu Gulf, China.

Current microbiology pii:10.1007/s00284-020-02140-x [Epub ahead of print].

Until now, there has been little research on the intestinal microbial community of horseshoe crabs. To fill this gap, we investigated the microbiome composition of the Chinese horseshoe crab, Tachypleus tridentatus, and the mangrove horseshoe crab, Carcinoscorpius rotundicauda. We sequenced the 16S rRNA gene of intestinal bacterial species and compared the microbial community structure and diversity. Next, we show that the total effective bacterial sequence was 36,865 reads, and the average annotated operational taxonomic unit (OTU) number was 240. Through hierarchical clustering analysis and principal coordinate analysis samples from two horseshoe crab species, we found that the intestinal flora of the same horseshoe crab species was relatively concentrated, while the microbiome of a different horseshoe crab species were significantly separated. Cluster analysis showed that two samples, one from Chinese horseshoe crabs and one from mangrove horseshoe crabs, had similar microbial community structure, while other samples were relatively discrete. The gut microbiota of the mangrove horseshoe crab were dominated by the phyla Tenericutes (42.71%), Firmicutes (24.27%), and Proteobacteria (20.39%), while the top three phyla in the Chinese horseshoe crab intestinal tract were Tenericutes (57.19%), Proteobacteria (22.14%), and Bacteroidetes (7.38%). To intuitively understand the similarity and overlap of the OTU composition of each group, we performed Venn diagram analysis. The two species shared 284 OTUs, accounting for 81.8% of the total. This indicates that although there is high similarity between mangrove and Chinese horseshoe crab in gastrointestinal microbial community structure, there are also some differences, which deserve further discussion.

RevDate: 2020-09-14

Chu CY, Qiu X, McCall MN, et al (2020)

Airway gene expression correlates of RSV disease severity and microbiome composition in infants.

The Journal of infectious diseases pii:5905187 [Epub ahead of print].

RATIONALE: Respiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants. The causes and correlates of severe illness in the majority of infants are poorly defined.

OBJECTIVES: We identified molecular correlates of illness severity from the airways of infants infected with RSV.

METHODS: We recruited a cohort of RSV-infected infants and simultaneously assayed the molecular status of their airways and the presence of airway microbiota. Rigorous statistical approaches identified gene expression patterns associated with disease severity and microbiota composition, separately and in combination.

MEASUREMENTS AND MAIN RESULTS: We measured comprehensive airway gene expression patterns in 106 infants with primary RSV infection. We identified an airway gene expression signature of severe illness dominated by excessive chemokine expression. We also found an association between H. influenzae, disease severity and airway lymphocyte accumulation. Exploring the time of onset of clinical symptoms revealed acute activation of interferon (IFN) signaling following RSV infection in infants with mild or moderate illness, which was absent in subjects with severe illness.

CONCLUSION: Our data reveal that airway gene expression patterns distinguish mild/moderate from severe illness severity. Furthermore, our data identify biomarkers that may be therapeutic targets or useful for measuring efficacy of intervention responses.

RevDate: 2020-09-14

Shiroda M, SD Manning (2020)

Lactobacillus strains vary in their ability to interact with human endometrial stromal cells.

PloS one, 15(9):e0238993 pii:PONE-D-19-35076.

The placental membranes that surround the fetus during pregnancy were suggested to contain a low abundance microbiota. Specifically, abundance of Lactobacillus, a probiotic and dominant member of the microbiome of the lower reproductive tract, has been shown to correlate with healthy, term pregnancies. We therefore sought to assess the interactions between four different Lactobacillus strains with immortalized decidualized endometrial cells (dT-HESCs), which were used as a model to represent the outermost layer of the placental membranes. Notably, we demonstrated that all four Lactobacillus strains could associate with dT-HESCs in vitro. L. crispatus was significantly more successful (p < 0.00005), with 10.6% of bacteria attaching to the host cells compared to an average of 0.8% for the remaining three strains. The four strains also varied in their ability to form biofilms. Dependent on media type, L. reuteri 6475 formed the strongest biofilms in vitro. To examine the impact on immune responses, levels of total and phosphorylated protein p38, a member of the Mitogen Activated Protein Kinase (MAPK) pathway, were examined following Lactobacillus association with dT-HESCs. Total levels of p38 were reduced to an average of 44% that of the cells without Lactobacillus (p < 0.05). While a trend towards a reduction in phosphorylated p38 was observed, this difference was not significant (p > 0.05). In addition, association with Lactobacillus did not result in increased host cell death. Collectively, these data suggest that varying types of Lactobacillus can attach to the outermost cells of the placental membranes and that these interactions do not contribute to inflammatory responses or host cell death. To our knowledge this is the first in vitro study to support the ability of Lactobacillus to interact with placental cells, which is important when considering its use as a potential probiotic within the reproductive tract.

RevDate: 2020-09-14

Li L, J Ye (2020)

Characterization of gut microbiota in patients with primary hepatocellular carcinoma received immune checkpoint inhibitors: A Chinese population-based study.

Medicine, 99(37):e21788.

Hepatocellular carcinoma (HCC) is one of the most common neoplasms encountered, and its incidence is increasing worldwide. In this study, we explored the characteristics of gut microbiota in patients with primary hepatocellular carcinoma in advanced stage who received immune checkpoint inhibitors (ICIs) based on a large population with hepatitis B virus infection. An initial cohort of 65 patients with metastatic melanoma were included in this study. All patients were treated with ICIs at Fujian provincial geriatric hospital between August 2016 and June 2018. The 16S rDNA V4 region was amplified by Polymerase chain reaction and sequenced on the MiSeq platform. We found that the diversities of the gut microbiota in HCC who received ICIs were obviously increased. Negative feedback, which is controlled by interplay between microbial metabolic activities and host pathways, is thought to promote high bacterial diversity. We focused on the Faecalibacterium genus in response group, and Bacteroidales order in non-response group, and stratified patients into high versus low categories based on the median relative abundance of these taxa in the gut microbiome. Patients with high Faecalibacterium abundance had a significantly prolonged PFS versus those with a low abundance. Conversely, patients with a high abundance of Bacteroidales had a shortened progressive free survival compared to those with a low abundance. In summary, the present study examined the oral and gut microbiome of HCC patients undergoing immune checkpoint inhibitors immunotherapy. Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus non-responders.

RevDate: 2020-09-14

Redd TK, GD Seitzman (2020)

Ocular rosacea.

Current opinion in ophthalmology [Epub ahead of print].

PURPOSE OF REVIEW: To revisit ocular rosacea as an underappreciated condition which can cause permanent blindness if inadequately treated, and to review data supporting improved diagnostic and treatment strategies.

RECENT FINDINGS: Ocular rosacea has an underrecognized prevalence in children and individuals with darker skin tone. Rosacea has several associations with other significant systemic diseases. Variations in local and systemic microbiome, including demodex infestation, may play a role in pathogenesis, severity, and in explaining the different phenotypes of rosacea. The National Rosacea Society Expert Committee established an updated classification system of rosacea in 2017. New treatment algorithms based on these clinical subtypes are suggested.

SUMMARY: With continued advancements in the understanding of the epidemiology and pathogenesis of rosacea, randomized controlled trials specific for ocular rosacea remain lacking. There is overall consensus that rosacea and ocular rosacea require chronic maintenance treatment strategies involving combination topical and systemic therapies.

RevDate: 2020-09-14

Voderholzer U, Haas V, Correll CU, et al (2020)

Medical management of eating disorders: an update.

Current opinion in psychiatry [Epub ahead of print].

PURPOSE OF REVIEW: Eating disorders are associated with numerous medical complications. The aim of this study was to review recent progress in improving the medical management of patients with eating disorders.

RECENT FINDINGS: With close medical monitoring and electrolyte supplementation, accelerated refeeding protocols improve weight restoration without increasing the risk of refeeding syndrome. Olanzapine improves weight restoration better than placebo, without leading to adverse metabolic effects seen in individuals not in starvation. Alterations of the gut microbiome in anorexia nervosa have been demonstrated, but their clinical relevance remains unclear.

SUMMARY: Medical complications of eating disorders may facilitate the first contact with health professionals and treatment initiation. Medical complications of anorexia nervosa generally occur due to starvation, malnutrition and their associated physiological effects, whereas medical complications of bulimia nervosa are generally due to purging behaviors. Most medical complications in patients with binge eating disorder are secondary to obesity. Most medical complications of eating disorders can be effectively treated with nutritional management, weight normalization and the termination of purging behaviors. In summary, eating disorders are associated with many medical complications that have to be carefully assessed and managed as early as possible to improve long-term outcomes.

RevDate: 2020-09-14

Krüger-Genge A, Jung F, Hufert F, et al (2020)

Effects of gut microbial metabolite trimethylamine N-oxide (TMAO) on platelets and endothelial cells.

Clinical hemorheology and microcirculation pii:CH209206 [Epub ahead of print].

Thrombotic events result from different pathologies and are the underlying causes of severe diseases like stroke or myocardial infarction. Recent basic research now revealed a link between food uptake, food conversion and gut metabolism. Gut microbial production of trimethylamine N-oxide (TMAO) from dietary nutrients like choline, lecithin and L-carnitine was associated with the development of cardiovascular diseases. Within this review we give a systematic overview about the influence of TMAO on blood components like platelets and endothelial cells which both are involved as key players in thrombotic processes. In summary, a mechanistic correlation between the gut microbiome, TMAO and cardiovascular diseases becomes obvious and emphasizes to the significance of the intestinal microbiome.

RevDate: 2020-09-14

Diaz PI, A Dongari-Bagtzoglou (2020)

Critically Appraising the Significance of the Oral Mycobiome.

Journal of dental research [Epub ahead of print].

Recent efforts to understand the oral microbiome have focused on its fungal component. Since fungi occupy a low proportion of the oral microbiome biomass, mycobiome studies rely on sequencing of internal transcribed spacer (ITS) amplicons. ITS-based studies usually detect hundreds of fungi in oral samples. Here, we review the oral mycobiome, critically appraising the significance of such large fungal diversity. When harsh lysis methods are used to extract DNA, 2 oral mycobiome community types (mycotypes) are evident, each dominated by only 1 genus, either Candida or Malassezia. The rest of the diversity in ITS surveys represents low-abundance fungi possibly acquired from the environment and ingested food. So far, Candida is the only genus demonstrated to reach a significant biomass in the oral cavity and clearly shown to be associated with a distinct oral ecology. Candida thrives in the presence of lower oral pH and is enriched in caries, with mechanistic studies in animal models suggesting it participates in the disease process by synergistically interacting with acidogenic bacteria. Candida serves as the main etiological agent of oral mucosal candidiasis, in which a Candida-bacteriome partnership plays a key role. The function of other potential oral colonizers, such as lipid-dependent Malassezia, is still unclear, with further studies needed to establish whether Malassezia are metabolically active oral commensals. Low-abundance oral mycobiome members acquired from the environment may be viable in the oral cavity, and although they may not play a significant role in microbiome communities, they could serve as opportunistic pathogens in immunocompromised hosts. We suggest that further work is needed to ascertain the significance of oral mycobiome members beyond Candida. ITS-based surveys should be complemented with other methods to determine the in situ biomass and metabolic state of fungi thought to play a role in the oral environment.

RevDate: 2020-09-14

Valente Duarte de Sousa IC (2020)

An overview of sarecycline for the treatment of moderate-to-severe acne vulgaris.

Expert opinion on pharmacotherapy [Epub ahead of print].

INTRODUCTION: Sarecycline is a novel, tetracycline-class antibiotic specifically designed to treat inflammatory acne. It offers a narrow spectrum of activity (mainly against Cutinebacterium acnes), and it shows less in vitro activity than other tetracyclines against enteric Gram-negative bacteria, offering advantages over older tetracyclines by decreasing the disruption of the gastrointestinal microbiome and the likelihood of developing bacterial resistance.

AREAS COVERED: The drug's pharmacology, safety profile, and clinical efficacy are discussed. Results of phase I, II and III clinical trials have shown that 1.5 mg/kg/day sarecycline is safe, well tolerated and more effective than placebo in treating inflammatory acne in patients 9 years old and older. Furthermore, sarecycline's narrow spectrum of activity leads to a lower incidence of undesirable off-target antibacterial effects and consequently less adverse events such as diarrhea, fungal overgrowth and vaginal candidiasis.

EXPERT OPINION: Sarecycline could become the first-line antibiotic therapy used in acne in the near future as it is an effective option for treating inflammatory acne lesions. Due to its narrow spectrum of activity, it could have a more adequate safety profile than older tetracyclines; however, head-to-head trials comparing the efficacy and safety profile of sarecycline with other tetracyclines are still needed to prove sarecycline's superiority.

RevDate: 2020-09-14

D'Adamo GL, Widdop JT, EM Giles (2020)

The future is now? Clinical and translational aspects of "Omics" technologies.

Immunology and cell biology [Epub ahead of print].

Big data has become a central part of medical research, as well as modern life generally. "Omics" technologies include genomics, proteomics, microbiomics, and increasingly other omics. These have been driven by rapid advances in laboratory techniques and equipment. Crucially, improved information handling capabilities have allowed concepts such as artificial intelligence and machine learning to enter the research world. The Covid-19 pandemic has shown how quickly information can be generated and analysed using such approaches, but also showed its limitations. This review will look at how "omics" has begun to be translated into clinical practice. While there appears almost limitless potential in using big data for "precision" or "personalised" medicine, the reality is that this remains largely aspirational. Oncology is the only field of medicine that is widely adopting such technologies, and even in this field uptake is irregular. There are practical and ethical reasons for this lack of translation of increasingly affordable techniques into the clinic. Undoubtedly there will be increasing use of large datasets from traditional (e.g. tumour samples, patient genomics) and non-traditional (e.g. smartphone) sources. It is perhaps the greatest challenge of the healthcare sector over the coming decade to integrate these resources in an effective, practical and ethical way.

RevDate: 2020-09-14

Assa-Glazer T, Gorelick J, Sela N, et al (2020)

Cannabis Extracts Affected Metabolic Syndrome Parameters in Mice Fed High-Fat/Cholesterol Diet.

Cannabis and cannabinoid research, 5(3):202-214 pii:10.1089/can.2020.0013.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, which often includes obesity, diabetes, and dyslipidemia. Several studies in mice and humans have implicated the involvement of the gut microbiome in NAFLD. While cannabis may potentially be beneficial for treating metabolic disorders such as NAFLD, the effects of cannabis on liver diseases and gut microbiota profile are yet to be addressed. In this study, we evaluated the therapeutic effects of cannabis strains with different cannabinoid profiles on NAFLD progression. Materials and Methods: NAFLD was induced by feeding mice a high-fat/cholesterol diet (HFCD) for 6 weeks. During this period, cannabis extracts were administrated orally at a concentration of 5 mg/kg every 3 days. Profile of lipids, liver enzymes, glucose tolerance, and gene expression related to carbohydrate lipid metabolism and liver inflammation were analyzed. The effect of cannabis strains on microbiota composition in the gut was evaluated. Results: A cannabidiol (CBD)-rich extract produced an increase in inflammatory related gene expression and a less diverse microbiota profile, associated with increased fasting glucose levels in HFCD-fed mice. In contrast, mice receiving a tetrahydrocannabinol (THC)-rich extract exhibited moderate weight gain, improved glucose response curves, and a decrease in liver enzymes. Conclusions: The results of this study indicate that the administration of cannabis containing elevated levels of THC may help ameliorate symptoms of NAFLD, whereas administration of CBD-rich cannabis extracts may cause a proinflammatory effect in the liver, linked with an unfavorable change in the microbiota profile. Our preliminary data suggest that these effects are mediated by mechanisms other than increased expression of the endocannabinoid receptors cannabinoid receptor 1 (CB1) and CB2.

RevDate: 2020-09-14

Roberti MP, Picard M, Yonekura S, et al (2020)

Turning tolerogenic into immunogenic ileal cell death through ileal microbiota: the key to unlock the mystery of colon cancer immunoscore?.

Oncoimmunology, 9(1):1778834 pii:1778834.

Why PD-1 blockade is ineffective in the vast majority of colorectal cancers (CCs) lacking microsatellite instability but harboring high densities of tumor infiltrating T cells and follicular T helper (TFH) and B cells remained so far an open conundrum. In a recent report published in Nature Medicine, we bring evidence in mice and patients that ileal microbiota turns tolerogenic apoptosis of ileal intestinal epithelial cells (IEC) into immunogenic cell demise capable of eliciting IL-1β-dependent TFH responses that benefit from anti-PD1 antibodies.

RevDate: 2020-09-14

Zysset-Burri DC, Keller I, Berger LE, et al (2020)

Associations of the intestinal microbiome with the complement system in neovascular age-related macular degeneration.

NPJ genomic medicine, 5:34 pii:141.

Age-related macular degeneration (AMD) is a leading cause of severe vision loss in the aged population. The etiology of AMD is multifactorial including nutritional factors, genetic variants mainly in the complement pathway, environmental risk factors and alterations in the intestinal microbiome. However, it remains unexplored whether there is an interdependency of these factors leading to the development of AMD. To investigate this issue, a shotgun metagenomics analysis of 57 neovascular AMD and 58 healthy controls as well as of 16 complement C3-deficient mice and 16 wildtypes was performed. Whereas the class Negativicutes was more abundant in patients, the genus Oscillibacter and species Bacteroides had a significantly higher prevalence in persons without AMD. Similar taxonomic features were identified that distinguished wildtype mice from C3-deficient mice. Moreover, several purine signaling pathways were associated with both, neovascular AMD and C3 deficiency. While SNPs within the complement factor B gene were more abundant in controls, SNPs within the high temperature requirement A serine peptidase 1 and complement factor H (CFH) genes were associated with neovascular AMD. Using a classification model, Negativicutes was identified as a potential biomarker for AMD and furthermore, it positively correlated with CFH. This study suggests an association between the intestinal microbiome and the complement system in neovascular AMD.

RevDate: 2020-09-14

Li S, Mao Y, Zhou F, et al (2020)

Gut microbiome and osteoporosis: a review.

Bone & joint research, 9(8):524-530 pii:BJR-9-524.

Osteoporosis (OP) is a chronic metabolic bone disease characterized by the decrease of bone tissue per unit volume under the combined action of genetic and environmental factors, which leads to the decrease of bone strength, makes the bone brittle, and raises the possibility of bone fracture. However, the exact mechanism that determines the progression of OP remains to be underlined. There are hundreds of trillions of symbiotic bacteria living in the human gut, which have a mutually beneficial symbiotic relationship with the human body that helps to maintain human health. With the development of modern high-throughput sequencing (HTS) platforms, there has been growing evidence that the gut microbiome may play an important role in the programming of bone metabolism. In the present review, we discuss the potential mechanisms of the gut microbiome in the development of OP, such as alterations of bone metabolism, bone mineral absorption, and immune regulation. The potential of gut microbiome-targeted strategies in the prevention and treatment of OP was also evaluated. Cite this article: Bone Joint Res 2020;9(8):524-530.

RevDate: 2020-09-14

Sanada TJ, Hosomi K, Shoji H, et al (2020)

Gut microbiota modification suppresses the development of pulmonary arterial hypertension in an SU5416/hypoxia rat model.

Pulmonary circulation, 10(3):2045894020929147 pii:10.1177_2045894020929147.

The pathogenesis of pulmonary arterial hypertension is closely associated with dysregulated inflammation. Recently, abnormal alterations in gut microbiome composition and function were reported in a pulmonary arterial hypertension experimental animal model. However, it remains unclear whether these alterations are a result or the cause of pulmonary arterial hypertension. The purpose of this study was to investigate whether alterations in the gut microbiome affected the hemodynamics in SU5416/hypoxia rats. We used the SU5416/hypoxia rat model in our study. SU5416/hypoxia rats were treated with a single SU5416 injection (30 mg/kg) and a three-week hypoxia exposure (10% O2). Three SU5416/hypoxia rats were treated with a combination of four antibiotics (SU5416/hypoxia + ABx group) for four weeks. Another group was exposed to hypoxia (10% O2) without the SU5416 treatment, and control rats received no treatment. Fecal samples were collected from each animal, and the gut microbiota composition was analyzed by 16S rRNA sequencing. The antibiotic treatment significantly suppressed the vascular remodeling, right ventricular hypertrophy, and increase in the right ventricular systolic pressure in SU5416/hypoxia rats. 16S rRNA sequencing analysis revealed gut microbiota modification in SU5416/hypoxia + ABx group. The Firmicutes-to-Bacteroidetes ratio in SU5416/hypoxia rats was significantly higher than that in control and hypoxia rats. Compared with the control microbiota, 14 bacterial genera, including Bacteroides and Akkermansia, increased, whereas seven bacteria, including Rothia and Prevotellaceae, decreased in abundance in SU5416/hypoxia rats. Antibiotic-induced modification of the gut microbiota suppresses the development of pulmonary arterial hypertension. Dysbiosis may play a causal role in the development and progression of pulmonary arterial hypertension.

RevDate: 2020-09-14

Wirth R, Maróti G, Mihók R, et al (2020)

A case study of salivary microbiome in smokers and non-smokers in Hungary: analysis by shotgun metagenome sequencing.

Journal of oral microbiology, 12(1):1773067 pii:1773067.

Objective: To investigate the role of cigarette smoking in disease-development through altering the composition of the oral microbial community. Periodontitis and oral cancer are highly prevalent in Hungary; therefore, the salivary microbiome of smoker and non-smoker Hungarian adults was characterized.

Methods: Shotgun metagenome sequencing of salivary DNA samples from 22 individuals (11 non-smokers and 11 current smokers) was performed using the Ion Torrent PGMTM platform. Quality-filtered reads were analysed by both alignment-based sequence similarity searches and genome-centric binning.

Results: Prevotella, Veillonella and Streptococcus were the predominant genera in the saliva of both groups. Although the overall composition and diversity of the microbiota were similar, Prevotella was significantly more abundant in salivary samples of current smokers compared to non-smokers. Members of the genus Prevotella were implicated in the development of inflammatory diseases and oral cancer. The abundance of the genus Megasphaera also increased in current smokers, whereas the genera Neisseria, Oribacterium, Capnocytophaga and Porphyromonas were significantly reduced. The data generated by read-based taxonomic classification and genome-centric binning mutually validated the two distinct metagenomic approaches.

Conclusion: Smoking-associated dysbiosis of the salivary microbiome in current cigarette smokers, especially increased abundance of Prevotella and Megasphaera genera, may facilitate disease development.

RevDate: 2020-09-14

Butler TD, JE Gibbs (2020)

Circadian Host-Microbiome Interactions in Immunity.

Frontiers in immunology, 11:1783.

The gut microbiome plays a critical role in regulating host immunity and can no longer be regarded as a bystander in human health and disease. In recent years, circadian (24 h) oscillations have been identified in the composition of the microbiota, its biophysical localization within the intestinal tract and its metabolic outputs. The gut microbiome and its key metabolic outputs, such as short chain fatty acids and tryptophan metabolites contribute to maintenance of intestinal immunity by promoting barrier function, regulating the host mucosal immune system and maintaining the function of gut-associated immune cell populations. Loss of rhythmic host-microbiome interactions disrupts host immunity and increases risk of inflammation and metabolic complications. Here we review factors that drive circadian variation in the microbiome, including meal timing, dietary composition and host circadian clocks. We also consider how host-microbiome interactions impact the core molecular clock and its rhythmic outputs in addition to the potential impact of this relationship on circadian control of immunity.

RevDate: 2020-09-14

Greger M (2020)

A Whole Food Plant-Based Diet Is Effective for Weight Loss: The Evidence.

American journal of lifestyle medicine, 14(5):500-510 pii:10.1177_1559827620912400.

What does the best available balance of scientific evidence show is the optimum way to lose weight? Calorie density, water content, protein source, and other components significantly influence the effectiveness of different dietary regimes for weight loss. By "walling off your calories," preferentially deriving your macronutrients from structurally intact plant foods, some calories remain trapped within indigestible cell walls, which then blunts the glycemic impact, activates the ileal brake, and delivers prebiotics to the gut microbiome. This may help explain why the current evidence indicates that a whole food, plant-based diet achieves greater weight loss compared with other dietary interventions that do not restrict calories or mandate exercise. So, the most effective diet for weight loss appears to be the only diet shown to reverse heart disease in the majority of patients. Plant-based diets have also been found to help treat, arrest, and reverse other leading chronic diseases such as type 2 diabetes and hypertension, whereas low-carbohydrate diets have been found to impair artery function and worsen heart disease, the leading killer of men and women in the United States. A diet centered on whole plant foods appears to be a safe, simple, sustainable solution to the obesity epidemic.

RevDate: 2020-09-14

Angurana SK, A Bansal (2020)

Probiotics and COVID-19: Think about the link.

The British journal of nutrition pii:S000711452000361X [Epub ahead of print].

The pandemic of Coronavirus disease 2019 (COVID-19) is rapidly progressing, causing significant morbidity and mortality. Various antiviral drugs, anti-inflammatory drugs, and immunomodulators have been tried without substantial clinical benefits. The severe and critical cases of COVID-19 disease are characterised by gut microbiome dysbiosis, immune dysregulation, hyper-inflammation, and hypercytokinemia (cytokine storm). Therefore, the strategies which target these pathophysiological processes may be beneficial. Probiotics are one such strategy that exerts beneficial effects by manipulation of the gut microbiota, suppression of opportunistic pathogens in the gut, decrease translocation of opportunistic organisms, activate mucosal immunity, and modulation of the innate and adaptive immune response. Probiotics are the potential candidates to be tested in moderate and severe cases of COVID-19 due to several beneficial effects, including easy availability, easy to administer, and safe, and economical to use.

RevDate: 2020-09-14

Zhang C, Zhang T, Lu W, et al (2020)

Altered Airway Microbiota Composition in Patients With Pulmonary Hypertension.

Hypertension (Dallas, Tex. : 1979) [Epub ahead of print].

Alteration in microbiota composition of respiratory tract has been reported in the progression of many chronic lung diseases, yet, the correlation and causal link between respiratory tract microbiota and the disease development of pulmonary hypertension (PH) remain largely unknown. This study aims to define and compare the respiratory microbiota composition in pharyngeal swab samples between patients with PH and reference subjects. A total of 118 patients with PH and 79 reference subjects were recruited, and the pharyngeal swab samples were collected to sequence the 16S ribosomal RNA (16S rRNA) V3-V4 region of respiratory microbiome. The relative abundances in patients with PH were profoundly different from reference subjects. The Ace and Sobs indexes indicated that the microbiota richness of pharynx value is significantly higher; while the community diversity value is markedly lower in patients with PH, comparing to those of the reference subjects. The microbiota on pharynx showed a different profile between the 2 groups by principal component analysis. The linear discriminant analysis effect size also revealed a significantly higher proportion of Streptococcus, Lautropia, and Ralstonia in patients with PH than reference subjects. The linear discriminant analysis effect size output, which represents the microbial gene functions, suggest genes related to bacterial invasion of epithelial cells, bacterial toxins were enhanced, while genes related to energy metabolism, protein digestion and absorption, and cell division pathways were attenuated in patients with PH versus reference subjects. In summary, our study reports the first systematic definition and divergent profile of the upper respiratory tract microbiota between patients with PH and reference subjects.

RevDate: 2020-09-13

Qin T, Fu J, HJ Verkade (2020)

The role of the gut microbiome in graft fibrosis after pediatric liver transplantation.

Human genetics pii:10.1007/s00439-020-02221-8 [Epub ahead of print].

Liver transplantation (LT) is a life-saving option for children with end-stage liver disease. However, about 50% of patients develop graft fibrosis in 1 year after LT, with normal liver function. Graft fibrosis may progress to cirrhosis, resulting in graft dysfunction and ultimately the need for re-transplantation. Previous studies have identified various risk factors for the post-LT fibrogenesis, however, to date, neither of the factors seems to fully explain the cause of graft fibrosis. Recently, evidence has accumulated on the important role of the gut microbiome in outcomes after solid organ transplantation. As an altered microbiome is present in pediatric patients with end-stage liver diseases, we hypothesize that the persisting alterations in microbial composition or function contribute to the development of graft fibrosis, for example by bacteria translocation due to increased intestinal permeability, imbalanced bile acids metabolism, and/or decreased production of short-chain fatty acids (SCFAs). Subsequently, an immune response can be activated in the graft, together with the stimulation of fibrogenesis. Here we review current knowledge about the potential mechanisms by which alterations in microbial composition or function may lead to graft fibrosis in pediatric LT and we provide prospective views on the efficacy of gut microbiome manipulation as a therapeutic target to alleviate the graft fibrosis and to improve long-term survival after LT.

RevDate: 2020-09-13

Knowles TA, Hosfield BD, Pecoraro AR, et al (2020)

It's all in the milk: chondroitin sulfate as potential preventative therapy for necrotizing enterocolitis.

Pediatric research pii:10.1038/s41390-020-01125-7 [Epub ahead of print].

Necrotizing enterocolitis (NEC) is a devastating condition affecting up to 5% of neonatal intensive care unit (NICU) admissions. Risk factors include preterm delivery, low birth weight, and antibiotic use. The pathogenesis is characterized by a combination of intestinal ischemia, necrosis of the bowel, reperfusion injury, and sepsis typically resulting in surgical resection of afflicted bowel. Targeted medical therapy remains elusive. Chondroitin sulfate (CS) holds the potential to prevent the onset of NEC through its anti-inflammatory properties and protective effect on the gut microbiome. The purpose of this review is to outline the many properties of CS to highlight its potential use in high-risk infants and attenuate the severity of NEC. The purpose of this review is to (1) discuss the interaction of CS with the infant microbiome, (2) review the anti-inflammatory properties of CS, and (3) postulate on the potential role of CS in preventing NEC. IMPACT: NEC is a costly medical burden in the United States.Breast milk is the best preventative measure for NEC, but not all infants in the NICU have access to breast milk.Novel therapies and diagnostic tools are needed for NEC.CS may be a potential therapy for NEC due to its potent anti-inflammatory properties.CS could be added to the formula in an attempt to mitigate breast milk disparities.Fig. 1HUMAN BREAST MILK HAS MANY PROTECTIVE PROPERTIES.: Multiple protective compounds are found in breast milk.93,94Fig. 2POTENTIAL MECHANISMS OF CS IN THE NEONATAL POPULATION.: Chondroitin sulfate works to decrease pro-inflammatory mediators while working to modulate the intestinal microbiome.

RevDate: 2020-09-13

Ewbank AC, Esperón F, Sacristán C, et al (2020)

Seabirds as anthropization indicators in two different tropical biotopes: A One Health approach to the issue of antimicrobial resistance genes pollution in oceanic islands.

The Science of the total environment, 754:142141 pii:S0048-9697(20)35670-9 [Epub ahead of print].

Antimicrobial resistance is a quintessential One Health issue, among the most serious 21st century global threats to human health. Seabirds may act as sentinels of natural and anthropogenic changes in the marine ecosystem health, including pollution by antimicrobial resistance genes (ARGs). We used real time PCR to identify and quantify 22 plasmid-mediated ARGs in the gastrointestinal microbiome of six wild seabird species, comparing an anthropized (Fernando de Noronha Archipelago - FNA) and a pristine biotope (Rocas Atoll - ROA), Brazil. Of 257 birds, 218 (84.8%) were positive to at least one ARG. ARG classes encoding resistance to tetracyclines (75.1%), quinolones (10.5%) and phenicols (10.5%) were the most prevalent, with tetracyclines significantly greater than the remaining classes (p < 0.05). Genes tet(S) (29.2%), tet(A) (28.8%), and tet(B) (24.9%) were the most commonly found and had a significantly greater prevalence when compared to the remaining ARGs (p < 0.05). The anthropized biotope presented statistically significant higher prevalence of sulfonamide- and quinolone-encoding ARGs in comparison with the pristine (respectively, p = 0.01 and p = 0.03), and higher sulII gene prevalence (p = 0.04), consistent with anthropogenic pressure. Migratory species (only present in ROA) showed statistically significant higher mcr-1 (polymyxins) and blaTEM (betalactam) prevalences (respectively, p = 0.009 and p = 0.02), and mcr-1 percentage load (p = 0.0079) in comparison with non-migratory. To our knowledge, this is the largest ARGs survey based on direct detection and quantification in seabirds worldwide, and the first to evaluate non-synanthropic species in oceanic islands. This is the first detection of mcr-1 in wild free-ranging seabirds in Brazil and in free-ranging migratory non-synanthropic seabirds worldwide. Our findings show the importance of biological and ecological factors, highlighting the role of seabirds as anthropization sentinels and ARGs-pollution environmental indicators (even in a pristine biotope), and their involvement in the One Health epidemiological chain of ARGs.

RevDate: 2020-09-13

Amatullah H, KL Jeffrey (2020)

Epigenome-metabolome-microbiome axis in health and IBD.

Current opinion in microbiology, 56:97-108 pii:S1369-5274(20)30101-6 [Epub ahead of print].

Environmental triggers in the context of genetic susceptibility drive phenotypes of complex immune disorders such as Inflammatory bowel disease (IBD). One such trigger of IBD is perturbations in enteric commensal bacteria, fungi or viruses that shape both immune and neuronal state. The epigenome acts as an interface between microbiota and context-specific gene expression and is thus emerging as a third key contributor to IBD. Here we review evidence that the host epigenome plays a significant role in orchestrating the bidirectional crosstalk between mammals and their commensal microorganisms. We discuss disruption of chromatin regulatory regions and epigenetic enzyme mutants as a causative factor in IBD patients and mouse models of intestinal inflammation and consider the possible translation of this knowledge. Furthermore, we present emerging insights into the intricate connection between the microbiome and epigenetic enzyme activity via host or bacterial metabolites and how these interactions fine-tune the microorganism-host relationship.

RevDate: 2020-09-13

Elmassry MM, Chung E, Cao JJ, et al (2020)

Osteoprotective effect of green tea polyphenols and annatto-extracted tocotrienol in obese mice is associated with enhanced microbiome vitamin K2 biosynthetic pathways.

The Journal of nutritional biochemistry pii:S0955-2863(20)30524-6 [Epub ahead of print].

The role of the gut microbiome in bone health has received significant attention in the past decade. We investigated the effects of green tea polyphenols (GTP) and annatto-extracted tocotrienols (AT) on bone properties and gut microbiome in obese mice. Male mice were assigned to a two (no AT vs. 400 mg/kg diet AT)×two (no GTP vs. 0.5% w/v GTP) factorial design, namely control, G, T, and G+T group respectively, for 14 weeks. The 4th lumbar vertebra (LV-4) and femur were harvested for bone microstructural analysis using μ-CT. Microbiome analysis using 16S rRNA gene sequencing of cecal feces was performed. AT increased bone volume at distal femur. GTP increased serum procollagen type 1 N-terminal propeptide concentration, bone volume at the distal femur and the LV-4, and trabecular number at distal femur; whereas GTP decreased trabecular separation at distal femur. Interactions between GTP and AT were observed in serum C-terminal telopeptide of type I collagen level (control>G=T=G+T) as well as the cortical bone area (control

RevDate: 2020-09-13

Seong H, Lee SK, Cheon JH, et al (2020)

Fecal Microbiota Transplantation for multidrug-resistant organism: Efficacy and Response prediction.

The Journal of infection pii:S0163-4453(20)30597-1 [Epub ahead of print].

OBJECTIVES: The increasing prevalence of multidrug-resistant microorganisms (MDRO) is increasing the frequency of poor clinical outcomes, prolonging hospitalizations, and raising healthcare costs. This study evaluated the eradication efficacy of fecal microbiota transplantation (FMT) and identified microbial and functional biomarkers of MDRO decolonization.

METHODS: Fecal solution obtained from healthy unrelated donors was infused in the participants' guts which had been colonized with carbapenemase-producing enterobacteriacea (CPE), vancomycin-resistant enterococci (VRE), or both CPE and VRE. Fecal samples from recipients were collected and microbiome changes before and after FMT were assessed.

RESULTS: Twenty-four (68.6%) out of 35 patients were decolonized within one year of receiving FMT. Multivariate analysis showed that FMT (FMT: hazard ratio (HR) = 5.343, 95% confidence interval (CI) = 1.877-15.212, p = 0.002) and MDRO types (CPE: HR = 11.146, 95% CI = 2.420-51.340, p = 0.002; CPE/VRE: HR = 2.948, 95% CI = 1.200-7.246, p = 0.018; VRE served as the reference) were significant independent factors associated with time to decolonization. Microbiota analysis showed higher richness and biodiversity before FMT resulted in VRE decolonization. The species Clostridium ramosum and the genuses Anaerostipes and Eisenbergiella could serve as taxonomic biomarkers and K02017 could serve as a functional biomarker for VRE clearance.

CONCLUSION: FMT is an effective way to decolonize MDRO and its effectiveness may be predicted by microbiome analysis.

RevDate: 2020-09-13

Zhu F (2020)

Dietary fiber polysaccharides of amaranth, buckwheat and quinoa grains: A review of chemical structure, biological functions and food uses.

Carbohydrate polymers, 248:116819.

Seeds of amaranth (Amaranthus spp.), buckwheat (Fagopyrum esculentum and F. tataricum) and quinoa (Chenopodium quinoa) become popular foods due to their attractive health effects. Cell wall polysaccharides are the major components of dietary fiber and significantly contribute to diverse health effects of the grains. This review summarizes chemical and physical structure, biological functions and food uses of the cell wall polysaccharides and fractions as fiber components from the 3 pseudocereals. The properties and uses of the polysaccharides and fractions are compared with those of fiber polysaccharides from common sources such as fruits and vegetables. Overall, the fiber polysaccharide composition of the pseudocereals is more similar to that of fruits and vegetables than to that of cereals. The fiber polysaccharides showed a range of biological functions such as antioxidation, anticancer and immunomodulation. The fiber polysaccharides of amaranth, buckwheat and quinoa have potential to be used in formulations of functional foods.

RevDate: 2020-09-12

Hickey MK, Miller NC, Haapala J, et al (2020)

Infants exposed to antibiotics after birth have altered recognition memory responses at one month of age.

Pediatric research pii:10.1038/s41390-020-01117-7 [Epub ahead of print].

BACKGROUND: Neonatal exposure to antibiotics, in the absence of infection, results in abnormal learning and memory in animals and is linked to changes in gut microbes. The relevance of early-life antibiotic exposure to brain function in humans is not known.

METHODS: Recognition memory was assessed at 1 month of age in 15 term-born infants exposed to antibiotics (with negative cultures) and 57 unexposed infants using event-related potentials (ERPs). Linear regression analysis, adjusting for covariates, was employed to compare groups with respect to ERP features representing early stimulus processing (P2 amplitude) and discrimination between mother and stranger voices.

RESULTS: Infants exposed to antibiotics exhibited smaller P2 amplitudes for both voice conditions (p = 0.001), with greatest reductions observed for mother's voice in frontal and central scalp regions (p < 0.04). Infants exposed to antibiotics showed larger P2 amplitudes to stranger's as compared to mother's voice, a reversal of the typical response exhibited by unexposed infants. Abnormal ERP responses did not consistently correlate with increased inflammatory cytokines within the antibiotic-exposed group.

CONCLUSIONS: Otherwise healthy infants exposed to antibiotics soon after birth demonstrated altered auditory processing and recognition memory responses, supporting the possibility of a microbiota-gut-brain axis in humans during early life.

IMPACT: Infants exposed to antibiotics after birth demonstrate altered auditory processing and recognition memory responses at 1 month of age.Preclinical models support a role for gut microbiomes in modulating brain function and behavior, particularly in developing brains. This study is one of the first to explore the relevance of these findings for human infants.The findings of this study have implications for the management and follow-up of at-risk infants with exposure to gut-microbiome disrupting factors and lay foundation for future studies to further characterize the short- and long-term effects of gut microbiome perturbation on brain development. Fig. 1SCHEMATIC OF THE 64-CHANNEL HYDROCEL GEODESIC SENSOR NET (NETSTATION, EGI) AND CLUSTERS OF ELECTRODES (CIRCLED) USED FOR DATA ANALYSIS OF P2 WAVEFORMS.: Leads 7, 9, and 12 make up the right frontal group; leads 16, 20, and 22 comprise the right central lead grouping; leads 3, 54, and 60 the left frontal, and 49, 50, and 51 the left central lead grouping.Fig. 2GRANDMEAN EVENT-RELATED POTENTIALS IN RESPONSE TO MOTHER'S VOICE (BLACK LINE) AND STRANGER'S VOICE (GRAY LINE).: Each row contains a representative lead from each scalp electrode region cluster. Arrowheads denote P2. Equivalent of 10-10 scalp net system lead is indicated in the box to the right of each grandmean x-axis.Fig. 3HEAT MAPS OF P2 AMPLITUDE RESPONSES (ELECTRICAL POTENTIALS DEPICTED AS A COLOR GRADIENT) TO MOTHER AND STRANGER VOICE IN INFANTS EXPOSED TO ANTIBIOTICS OR NOT.: Cranium orientation indicated by letters (A: anterior, P: posterior, L: left, R: right). Black dots represent individual scalp electrode locations.Fig. 4DIFFERENCE IN P2 AMPLITUDE (FAMILIAR-NOVEL) BY SCALP REGION.: Dark gray, control group; light gray, antibiotic-treated group. *p < 0.05.

RevDate: 2020-09-12

Mirpuri J (2020)

Evidence for maternal diet-mediated effects on the offspring microbiome and immunity: implications for public health initiatives.

Pediatric research pii:10.1038/s41390-020-01121-x [Epub ahead of print].

Diets rich in saturated fats have become a staple globally. Fifty percent of women of childbearing age in the United States are obese or overweight, with diet being a significant contributor. There is increasing evidence of the impact of maternal high-fat diet on the offspring microbiome. Alterations of the neonatal microbiome have been shown to be associated with multiple morbidities, including the development of necrotizing enterocolitis, atopy, asthma, metabolic dysfunction, and hypertension among others. This review provides an overview of the recent studies and mechanisms being examined on how maternal diet can alter the immune response and microbiome in offspring and the implications for directed public health initiatives for women of childbearing age. IMPACT: Maternal diet is important in shaping the offspring microbiome and neonatal immune system.Reviews the current literature in the field and suggests potential mechanisms and areas of research to be targeted.Highlights the current scope of our knowledge of ideal nutrition during pregnancy and consideration for enhanced public health initiatives to promote well-being of the future generation.Fig. 1POTENTIAL MECHANISMS FOR MATERNAL DIET-MEDIATED EFFECTS ON THE FETUS AFFECTING POSTNATAL COLONIZATION AND IMMUNITY.: a Maternal diet may modify the maternal microbiome resulting in altered exposure to live bacteria in utero and at birth via the vaginal canal or skin. b Maternal diet may alter the microbial processing of macro- and micronutrients and microbial colonization resulting in differential exposure in utero to microbial products, immunoglobulins, and cytokines. c Maternal diet can modulate the amount of beneficial and harmful dietary metabolites and dietary TLR ligands which the fetus becomes exposed to in utero. d Potential ways to maximize benefit for offspring microbiota and immune development include enhanced dietary guidelines for gravid women, probiotic supplementation, and nutraceutical supplementation either pre- or post-natally.Fig. 2MACRONUTRIENT CONSUMPTION IN WOMEN OF CHILD BEARING AGE AND RECOMMENDED RANGES IN USA.: Data compiled from the USDA and DHHS dietary intake interviews conducted yearly "What we eat in America" (WWEIA) with average protein, carbohydrate, and fat intake in women aged between 19 and 50 years (green bars) between 2015 and 2016. Red floating bars are recommendation ranges of macronutrient consumption from the ACOG, USDA, and Office of Disease Prevention and Health Promotion.

RevDate: 2020-09-12

Casterline BW, AS Paller (2020)

Early development of the skin microbiome: therapeutic opportunities.

Pediatric research pii:10.1038/s41390-020-01146-2 [Epub ahead of print].

As human skin hosts a diverse microbiota in health and disease, there is an emerging consensus that dysregulated interactions between host and microbiome may contribute to chronic inflammatory disease of the skin. Neonatal skin is a unique habitat, structurally similar to the adult but with a different profile of metabolic substrates, environmental stressors, and immune activity. The surface is colonized within moments of birth with a bias toward maternal strains. Initial colonists are outcompeted as environmental exposures increase and host skin matures. Nonetheless, early life microbial acquisitions may have long-lasting effects on health through modulation of host immunity and competitive interactions between bacteria. Microbial ecology and its influence on health have been of interest to dermatologists for >50 years, and an explosion of recent interest in the microbiome has prompted ongoing investigations of several microbial therapeutics for dermatological disease. In this review, we consider how recent insight into the host and microbial factors driving development of the skin microbiome in early life offers new opportunities for therapeutic intervention. IMPACT: Advancement in understanding molecular mechanisms of bacterial competition opens new avenues of investigation into dermatological disease.Primary development of the skin microbiome is determined by immunological features of the cutaneous habitat.Understanding coordinated microbial and immunological development in the pediatric patient requires a multidisciplinary synthesis of primary literature.

RevDate: 2020-09-12

Zhang H, Wang Q, Zhao J, et al (2020)

Quantitative microbiome profiling links microbial community variation to the intestine regeneration rate of the sea cucumber Apostichopus japonicus.

Genomics pii:S0888-7543(20)30875-2 [Epub ahead of print].

The intestinal microbiota may play important roles in regenerating intestine of the sea cucumber Apostichopus japonicus, the underlying mechanism remains unclear. In the present study, a germ-free sea cucumber model was developed, and the intestinal microbial differentiation of faster and slower regenerating A. japonicus individuals during intestine regeneration was analyzed. The results revealed that depletion of the intestinal microbiota resulted in elevated abundance of the potential key players Flavobacteriaceae and Rhodobacteraceae during intestine regeneration and thus promoted the intestine regeneration rate of A. japonicus. Metagenomic analysis revealed that the increased abundance of Flavobacteriaceae elevated the enrichment of genes associated with carbohydrate utilization, whereas the abundant Rhodobacteraceae-enriched genes were associated with polyhydroxybutyrate production. We identified microbiota abundance as a key driver of microbial community alterations, especially beneficial microbiota members, in the developing intestine of A. japonicus. This study provides new insights into the mechanism of host-microbiota interactions related to organ regeneration.

RevDate: 2020-09-12

Song BC, J Bai (2020)

Microbiome-gut-brain axis in cancer treatment-related psychoneurological toxicities and symptoms: a systematic review.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer pii:10.1007/s00520-020-05739-9 [Epub ahead of print].

PURPOSE: The microbiome-gut-brain (MGB) axis provides a dynamic model to understand associations between the gut microbiota and psychoneurological comorbidities. The role of the MGB axis in cancer treatment-related psychoneurological symptoms (PNS) remains unknown. The purpose of this study was to conduct a systematic review of the existing literature to identify the influence of the gut microbiota on cancer and cancer treatment-related PNS and toxicities mediated by the MGB axis.

METHODS: We searched the databases of PubMed, Embase, and Web of Science from their earliest records to October 2019. All studies identified in the database searches were screened by title and abstract, followed by a review of the full texts. The Johns Hopkins Nursing Evidence-Based Practice Model was adopted to assess the evidence levels and qualities; the Joanna Briggs Institute critical appraisal tools were used to assess the methodological quality and the possibility of bias for each included study. All the study findings were combined, synthesized, and presented through narrative format.

RESULTS: Six studies were included in this systematic review. These studies primarily focused on cancer survivorship while receiving chemotherapy, and they were conducted between 2016 and 2019. The gut microbiome was assessed via fecal samples, which were analyzed using 16S rRNA sequencing approaches. With small-scale studies, the gut microbiota was associated with cancer treatment-related PNS, including fatigue, anxiety, depression, sleep disturbance, cognitive impairment, and chemotherapy-induced peripheral neuropathy. A higher relative abundance of Bacteroides was associated with a higher level of fear of cancer recurrence but a higher relative abundance of Lachnospiraceae.g and Ruminococcus was associated with a lower level in fear of cancer recurrence. Changes in fatigue interference were associated with the frequency of genera Faecalibacterium and Prevotella, and changes in anxiety were associated with the frequency of genera Coprococcus and Bacteroides.

CONCLUSIONS: The gut microbiota showed significant associations with cancer treatment-related PNS. Recent work regarding the MGB axis in cancer psychoneurological toxicities focused primarily on individual toxicity and symptoms in cancer survivors with chemotherapy exposure. Associations between the gut microbiota and PNS should be further studied in cancer populations across different ages, cancer types, and treatment modalities.

RevDate: 2020-09-12

Ennis NJ, Dharumaduri D, Bryce JG, et al (2020)

Metagenome Across a Geochemical Gradient of Indian Stone Ruins Found at Historic Sites in Tamil Nadu, India.

Microbial ecology pii:10.1007/s00248-020-01598-3 [Epub ahead of print].

Although stone surfaces seem unlikely to be habitable, they support microbial life. Life on these surfaces are subjected to many varying harsh conditions and require the inhabitants to exhibit resistance to environmental factors including UV irradiation, toxic metal exposure, and fluctuating temperatures and humidity. Here we report the effect of hosting stone geochemistry on the microbiome of stone ruins found in Tamil Nadu, India. The microbial communities found on the two lithologies, granite and granodiorite, hosted distinct populations of bacteria. Geochemical composition analysis of sampled stones revealed quartz mineral content as a major driver of microbial community structure, particularly promoting community richness and proportions of Cyanobacteria and Deinococcus-Thermus. Other geochemical parameters including ilmenite, albite, anorthite, and orthoclase components or elemental concentrations (Ti, Fe, Mn, Na, and K) also influenced community structure to a lesser degree than quartz. Core members of the stone microbiome community found on both lithologies were also identified and included Cyanobacteria (Chroococcidiopsaceae and Dapisostemonum CCIBt 3536), Rubrobacter, and Deinococcus. A cluster of taxa including Sphingomonas, Geodermatophilus, and Truepera were mostly found in the granodiorite samples. Community diversity correlated with quartz mineral content in these samples may indicate that the microbial communities that attach to quartz surfaces may be transient and regularly changing. This work has expanded our understanding of built-stone microbial community structure based on lithology and geochemistry.

RevDate: 2020-09-12

Seo JH, Bortolin K, NL Jones (2020)

Review: Helicobacter pylori infection in children.

Helicobacter, 25 Suppl 1:e12742.

Helicobacter pylori infection in children and adolescents differs in comparison to adults with respect to epidemiology, host responses, and disease manifestations. Furthermore, treatment options are limited in this population and antibiotic resistance rates continue to increase. Therefore, ongoing research is vital to understand disease pathogenesis and provide optimal management of children with infection. This review summarizes relevant publications from April 2019 to March 2020. Similar to adults, recent studies show a decreasing prevalence of infection in the pediatric population. Studies of pathogenesis investigated serum immune responses and the potential inverse association of infection and allergy. Several studies investigated the effect of H pylori and related inflammation on the gut microbiome. The recommendation of endoscopy-based testing to identify the cause of symptoms and not just H pylori, reserving noninvasive UBT or stool antigen tests for post-eradication follow-up, was supported by the current literature.

RevDate: 2020-09-12

Pellicano R, Ianiro G, Fagoonee S, et al (2020)

Review: Extragastric diseases and Helicobacter pylori.

Helicobacter, 25 Suppl 1:e12741.

The involvement of Helicobacter pylori infection in many extra-gastroduodenal manifestations remains a fascinating field of investigation. However, for several of these supposed associations, the potential pathogenic mechanism remains unclear. The present review highlights the main associations of H pylori with extra-gastroduodenal manifestations reported during the last year. We searched for the most relevant studies on this topic, published between April 2019 and March 2020, identified using the term "Helicobacter" in the MEDLINE/Pubmed database. Consistent data emerged from studies investigating metabolic syndrome and ischaemic cardiovascular diseases. Other reported fields of investigation were hepatology, especially focused on non-alcoholic steatohepatitis, neurology, including Parkinson's disease and Alzheimer's disease, as well as dermatology. Inflammatory bowel disease (IBD), that comprises Crohn's disease and ulcerative colitis, may originate from a dysregulation of the host's immune response to commensal bacteria in individuals with genetic predisposition. The reduction of biodiversity and other specific imbalances in the faecal microbiome composition of IBD patients compared to that of healthy controls support this hypothesis. In this context, an inverse correlation between H pylori infection and IBD prevalence has been confirmed. Similar results were found in patients with kidney diseases and allergic manifestations. There are indications of the possible involvement of H pylori infection in metabolic syndrome and ischaemic cardiovascular diseases. However, due to a series of factors linked to study designs and the multifactorial pathogenesis of some diseases, further studies are needed.

RevDate: 2020-09-12

Rudnicka L, A Waśkiel-Burnat (2020)

Systemic aspects of alopecia areata Comment to the article by Lai and Sinclair.

We read with great interest the article by Lai and Sinclair (1), which presented the significant role of azathioprine, methotrexate and cyclosporine as systemic steroid-sparing agents with beneficial effect on hair regrowth in patients with chronic alopecia areata. It is in line with the current tendency of treatment strategies in alopecia areata moving from locally active drugs towards systemic management options.

RevDate: 2020-09-12

Birg A, Lin HC, N Kanagy (2020)

Portal Venous Flow Is Increased by Jejunal but Not Colonic Hydrogen Sulfide in a Nitric Oxide-Dependent Fashion in Rats.

Digestive diseases and sciences pii:10.1007/s10620-020-06597-5 [Epub ahead of print].

Hydrogen sulfide (H2S) is a recently discerned endogenous signaling molecule that modulates the vascular system. Endogenous hydrogen sulfide has been shown to dilate both the mesenteric and portal vasculature. Gut microbiome, via sulfur reducing bacteria, is another source of H2S production within the gut lumen; this source of H2S is primarily produced and detoxified in the colon under physiologic conditions. Nitric oxide (NO), a major endogenous vasodilator in the portal circulation, participates in H2S-induced vasodilation in some vascular beds. We hypothesize that jejunal but not colonic H2S increases portal vein flow in a NO-dependent fashion. To evaluate the effects of luminal H2S, venous blood flow, portal venous pressure, and systemic venous pressure were measured in rats after administration of either vehicle or an H2S donor (NaHS) into the jejunum or the colon. We found that portal venous pressure and systemic pressure did not change and were similar between the three study groups. However, portal venous blood flow significantly increased following jejunal administration of NaHS but not in response to colonic NaHS or vehicle administration. To test the contribution of NO production to this response, another group of animals was treated with either an NO synthase inhibitor (N-Ω-nitro-L-arginine, L-NNA) or saline prior to jejunal NaHS infusion. After L-NNA pretreatment, NaHS caused a significant fall rather than increase in portal venous flow compared to saline pretreatment. These data demonstrate that H2S within the small intestine significantly increases portal venous blood flow in a NO-dependent fashion.

RevDate: 2020-09-12

Boonchooduang N, Louthrenoo O, Chattipakorn N, et al (2020)

Possible links between gut-microbiota and attention-deficit/hyperactivity disorders in children and adolescents.

European journal of nutrition pii:10.1007/s00394-020-02383-1 [Epub ahead of print].

An association between gut-microbiota and several neuropsychiatric conditions including autism, depression, anxiety, schizophrenia, and attention-deficit/hyperactivity disorder (ADHD) has been observed. Despite being the most prevalent neurodevelopmental disorders in children and adolescents worldwide, the etiology and curative approaches to treatment of ADHD remain unclear. There is a probability that gut-microbiota may contribute to ADHD via bidirectional communication between the gut and brain, a system known as the "gut-brain axis". Although a mechanistic link in the gut-brain axis in ADHD has been proposed, there is still a lack of information about the correlation of the microbiome profile with the mechanisms involved. The objective of this review was to summarize the diversity of the gut-microbiota and taxonomic profiles in children and adolescents with ADHD. In this review, we have provided an overview of the association between ADHD and gut-microbiota. The evidence pertinent to potentially distinctive gut-microbiota in children and adolescents with ADHD is also discussed and compared to that of their non-ADHD peers. Finally, the implications and future directions for investigation into the gut microbiome in ADHD patients are proposed.

RevDate: 2020-09-12

Garber K (2020)

First microbiome-based drug clears phase III, in clinical trial turnaround.

RevDate: 2020-09-12

Vaga S, Lee S, Ji B, et al (2020)

Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals.

Scientific reports, 10(1):14977 pii:10.1038/s41598-020-71939-2.

Gut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most studies have employed sequencing technologies to investigate faecal microbiota only. This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities' compositions of terminal ileum and large intestine in 5 healthy individuals. Functional annotations and genome-scale metabolic modelling of selected species were then employed to identify local functional enrichments. While faecal metagenomics provided a good approximation of the average gut mucosal microbiome composition, mucosal biopsies allowed detecting the subtle variations of local microbial communities. Given their significant enrichment in the mucosal microbiota, we highlight the roles of Bacteroides species and describe the antimicrobial resistance biogeography along the intestine. We also detail which species, at which locations, are involved with the tryptophan/indole pathway, whose malfunctioning has been linked to pathologies including inflammatory bowel disease. Our study thus provides invaluable resources for investigating mechanisms connecting gut microbiota and host pathophysiology.

RevDate: 2020-09-12

Yang H, Guo R, Li S, et al (2020)

Systematic analysis of gut microbiota in pregnant women and its correlations with individual heterogeneity.

NPJ biofilms and microbiomes, 6(1):32 pii:10.1038/s41522-020-00142-y.

The woman's gut microbiota during pregnancy may support nutrient acquisition, is associated with diseases, and has been linked to infant health. However, there is limited information on gut microbial characteristics and dependence in pregnant women. In this study, we provide a comprehensive overview of the gut microbial characteristics of 1479 pregnant women using 16S rRNA gene sequencing of fecal samples. We identify a core microbiota of pregnant women, which displays a similar overall structure to that of age-matched nonpregnant women. Our data show that the gestational age-associated variation in the gut microbiota, from the ninth week of gestation to antepartum, is relatively limited. Building upon rich metadata, we reveal a set of exogenous and intrinsic host factors that are highly correlated with the variation in gut microbial community composition and function. These microbiota covariates are concentrated in basic host properties (e.g., age and residency status) and blood clinical parameters, suggesting that individual heterogeneity is the major force shaping the gut microbiome during pregnancy. Moreover, we identify microbial and functional markers that are associated with age, pre-pregnancy body mass index, residency status, and pre-pregnancy and gestational diseases. The gut microbiota during pregnancy is also different between women with high or low gestational weight gain. Our study demonstrates the structure, gestational age-associated variation, and associations with host factors of the gut microbiota during pregnancy and strengthens the understanding of microbe-host interactions. The results from this study offer new materials and prospects for gut microbiome research in clinical and diagnostic fields.

RevDate: 2020-09-12

Paone P, PD Cani (2020)

Mucus barrier, mucins and gut microbiota: the expected slimy partners?.

Gut pii:gutjnl-2020-322260 [Epub ahead of print].

The gastrointestinal tract is often considered as a key organ involved in the digestion of food and providing nutrients to the body for proper maintenance. However, this system is composed of organs that are extremely complex. Among the different parts, the intestine is viewed as an incredible surface of contact with the environment and is colonised by hundreds of trillions of gut microbes. The role of the gut barrier has been studied for decades, but the exact mechanisms involved in the protection of the gut barrier are various and complementary. Among them, the integrity of the mucus barrier is one of the first lines of protection of the gastrointestinal tract. In the past, this 'slimy' partner was mostly considered a simple lubricant for facilitating the progression of the food bolus and the stools in the gut. Since then, different researchers have made important progress, and currently, the regulation of this mucus barrier is gaining increasing attention from the scientific community. Among the factors influencing the mucus barrier, the microbiome plays a major role in driving mucus changes. Additionally, our dietary habits (ie, high-fat diet, low-fibre/high-fibre diet, food additives, pre- probiotics) influence the mucus at different levels. Given that the mucus layer has been linked with the appearance of diseases, proper knowledge is highly warranted. Here, we debate different aspects of the mucus layer by focusing on its chemical composition, regulation of synthesis and degradation by the microbiota as well as some characteristics of the mucus layer in both physiological and pathological situations.

RevDate: 2020-09-12

Karpinets TV, Solley TN, Mikkelson MD, et al (2020)

Effect of antibiotics on gut and vaginal microbiomes associated with cervical cancer development in mice.

Cancer prevention research (Philadelphia, Pa.) pii:1940-6207.CAPR-20-0103 [Epub ahead of print].

Antibiotics affect microbial diversity in the gut, leading to dysbiosis and impaired immunity. However, the impact of antibiotics on microbial communities at other sites, such as vagina is less understood. It is also not clear if changes induced by antibiotics in both microbiomes affect the development of cervical cancer. In this study we utilized the murine model to evaluate these questions. We show that oral application of broad-spectrum antibiotics in mice changed not only diversity, but composition and sharing of gut and vaginal microbiomes in mice and influenced cervical cancer development in an orthotopic tumor model. Antibiotics decreased richness and diversity indexes in the gut but increased them in the vagina. Some beneficial taxa, such as Bacteroides, Ruminococcaceae and Lachnospiraceae increased their abundance in the vagina while other pathogenic species, such as Proteobacteria, were decreased. As a result of the changes, mice with greater richness and diversity of the vaginal microbiome after antibiotics exposure were less likely developed tumors. No association between richness and diversity of the gut microbiome and tumor development was identified.

RevDate: 2020-09-12

Leonard MM, Karathia H, Pujolassos M, et al (2020)

Multi-omics analysis reveals the influence of genetic and environmental risk factors on developing gut microbiota in infants at risk of celiac disease.

Microbiome, 8(1):130 pii:10.1186/s40168-020-00906-w.

BACKGROUND: Celiac disease (CD) is an autoimmune digestive disorder that occurs in genetically susceptible individuals in response to ingesting gluten, a protein found in wheat, rye, and barley. Research shows that genetic predisposition and exposure to gluten are necessary but not sufficient to trigger the development of CD. This suggests that exposure to other environmental stimuli early in life, e.g., cesarean section delivery and exposure to antibiotics or formula feeding, may also play a key role in CD pathogenesis through yet unknown mechanisms. Here, we use multi-omics analysis to investigate how genetic and early environmental risk factors alter the development of the gut microbiota in infants at risk of CD.

RESULTS: Toward this end, we selected 31 infants from a large-scale prospective birth cohort study of infants with a first-degree relative with CD. We then performed rigorous multivariate association, cross-sectional, and longitudinal analyses using metagenomic and metabolomic data collected at birth, 3 months and 6 months of age to explore the impact of genetic predisposition and environmental risk factors on the gut microbiota composition, function, and metabolome prior to the introduction of trigger (gluten). These analyses revealed several microbial species, functional pathways, and metabolites that are associated with each genetic and environmental risk factor or that are differentially abundant between environmentally exposed and non-exposed infants or between time points. Among our significant findings, we found that cesarean section delivery is associated with a decreased abundance of Bacteroides vulgatus and Bacteroides dorei and of folate biosynthesis pathway and with an increased abundance of hydroxyphenylacetic acid, alterations that are implicated in immune system dysfunction and inflammatory conditions. Additionally, longitudinal analysis revealed that, in infants not exposed to any environmental risk factor, the abundances of Bacteroides uniformis and of metabolite 3-3-hydroxyphenylproprionic acid increase over time, while those for lipoic acid and methane metabolism pathways decrease, patterns that are linked to beneficial immunomodulatory and anti-inflammatory effects.

CONCLUSIONS: Overall, our study provides unprecedented insights into major taxonomic and functional shifts in the developing gut microbiota of infants at risk of CD linking genetic and environmental risk factors to detrimental immunomodulatory and inflammatory effects. Video Abstract.

RevDate: 2020-09-12

Golovko G, Kamil K, Albayrak L, et al (2020)

Identification of multidimensional Boolean patterns in microbial communities.

Microbiome, 8(1):131 pii:10.1186/s40168-020-00853-6.

BACKGROUND: Identification of complex multidimensional interaction patterns within microbial communities is the key to understand, modulate, and design beneficial microbiomes. Every community has members that fulfill an essential function affecting multiple other community members through secondary metabolism. Since microbial community members are often simultaneously involved in multiple relations, not all interaction patterns for such microorganisms are expected to exhibit a visually uninterrupted pattern. As a result, such relations cannot be detected using traditional correlation, mutual information, principal coordinate analysis, or covariation-based network inference approaches.

RESULTS: We present a novel pattern-specific method to quantify the strength and estimate the statistical significance of two-dimensional co-presence, co-exclusion, and one-way relation patterns between abundance profiles of two organisms as well as extend this approach to allow search and visualize three-, four-, and higher dimensional patterns. The proposed approach has been tested using 2380 microbiome samples from the Human Microbiome Project resulting in body site-specific networks of statistically significant 2D patterns as well as revealed the presence of 3D patterns in the Human Microbiome Project data.

CONCLUSIONS: The presented study suggested that search for Boolean patterns in the microbial abundance data needs to be pattern specific. The reported presence of multidimensional patterns (which cannot be reduced to a combination of two-dimensional patterns) suggests that multidimensional (multi-organism) relations may play important roles in the organization of microbial communities, and their detection (and appropriate visualization) may lead to a deeper understanding of the organization and dynamics of microbial communities. Video Abstract.

RevDate: 2020-09-12

Chen CY, Chen CK, Chen YY, et al (2020)

Maternal gut microbes shape the early-life assembly of gut microbiota in passerine chicks via nests.

Microbiome, 8(1):129 pii:10.1186/s40168-020-00896-9.

BACKGROUND: Knowledge is growing on how gut microbiota are established, but the effects of maternal symbiotic microbes throughout early microbial successions in birds remain elusive. In this study, we examined the contributions and transmission modes of maternal microbes into the neonatal microbiota of a passerine, the zebra finch (Taeniopygia guttata), based on fostering experiments.

RESULTS: Using 16S rRNA amplicon sequencing, we found that zebra finch chicks raised by their biological or foster parents (the society finch Lonchura striata domestica) had gut microbial communities converging with those of the parents that reared them. Moreover, source-tracking models revealed high contribution of zebra finches' oral cavity/crop microbiota to their chicks' early gut microbiota, which were largely replaced by the parental gut microbiota at later stages. The results suggest that oral feeding only affects the early stage of hatchling gut microbial development.

CONCLUSIONS: Our study indicates that passerine chicks mainly acquire symbionts through indirect maternal transmission-passive environmental uptake from nests that were smeared with the intestinal and cloacal microbes of parents that raised them. Gut microbial diversity was low in hand-reared chicks, emphasizing the importance of parental care in shaping the gut microbiota. In addition, several probiotics were found in chicks fostered by society finches, which are excellent foster parents for other finches in bird farms and hosts of brood parasitism by zebra finches in aviaries; this finding implies that avian species that can transfer probiotics to chicks may become selectively preferred hosts of brood parasitism in nature. Video Abstract.

RevDate: 2020-09-12

Proffitt C, Bidkhori G, Moyes D, et al (2020)

Disease, Drugs and Dysbiosis: Understanding Microbial Signatures in Metabolic Disease and Medical Interventions.

Microorganisms, 8(9): pii:microorganisms8091381.

Since the discovery of the potential role for the gut microbiota in health and disease, many studies have gone on to report its impact in various pathologies. These studies have fuelled interest in the microbiome as a potential new target for treating disease Here, we reviewed the key metabolic diseases, obesity, type 2 diabetes and atherosclerosis and the role of the microbiome in their pathogenesis. In particular, we will discuss disease associated microbial dysbiosis; the shift in the microbiome caused by medical interventions and the altered metabolite levels between diseases and interventions. The microbial dysbiosis seen was compared between diseases including Crohn's disease and ulcerative colitis, non-alcoholic fatty liver disease, liver cirrhosis and neurodegenerative diseases, Alzheimer's and Parkinson's. This review highlights the commonalities and differences in dysbiosis of the gut between diseases, along with metabolite levels in metabolic disease vs. the levels reported after an intervention. We identify the need for further analysis using systems biology approaches and discuss the potential need for treatments to consider their impact on the microbiome.

RevDate: 2020-09-12

Nasr R, Shamseddine A, Mukherji D, et al (2020)

The Crosstalk between Microbiome and Immune Response in Gastric Cancer.

International journal of molecular sciences, 21(18): pii:ijms21186586.

Gastric cancer is the end result of a complex interplay between host genetics, environmental factors, and microbial factors. The link between gut microbiome and gastric cancer has been attributed to persistent activation of the host's immune system by gut microbiota. The end result of this dysregulated interaction between host epithelium and microbes is a state of chronic inflammation. Gut bacteria can promote anti-tumor immune responses through several mechanisms. These include triggering T-cell responses to bacterial antigens that can cross-react with tumor antigens or cause tumor-specific antigen recognition; engagement of pattern recognition receptors that mediate pro-immune or anti-inflammatory effects or via small metabolites that mediate systemic effects on the host. Here we review the role of the gut microbiome including H. pylori and non-H. pylori gastric bacteria, the immune response, and immunotherapy using checkpoint inhibitors. We also review the evidence for cross talk between the gut microbiome and immune response in gastric cancer.

RevDate: 2020-09-12

Zinn MK, Schages L, D Bockmühl (2020)

The Toothbrush Microbiome: Impact of User Age, Period of Use and Bristle Material on the Microbial Communities of Toothbrushes.

Microorganisms, 8(9): pii:microorganisms8091379.

Toothbrushes play a central role in oral hygiene and must be considered one of the most common articles of daily use. We analysed the bacterial colonization of used toothbrushes by next generation sequencing (NGS) and by cultivation on different media. Furthermore, we determined the occurrence of antibiotic resistance genes (ARGs) and the impact of different bristle materials on microbial growth and survival. NGS data revealed that Enterobacteriaceae, Micrococcaceae, Actinomycetaceae, and Streptococcaceae comprise major parts of the toothbrush microbiome. The composition of the microbiome differed depending on the period of use or user age. While higher fractions of Actinomycetales, Lactobacillales, and Enterobacterales were found after shorter periods, Micrococcales dominated on both toothbrushes used for more than four weeks and on toothbrushes of older users, while in-vitro tests revealed increasing counts of Micrococcus on all bristle materials as well. Compared to other environments, we found a rather low frequency of ARGs. We determined bacterial counts between 1.42 × 106 and 1.19 × 107 cfu/toothbrush on used toothbrushes and no significant effect of different bristles materials on bacterial survival or growth. Our study illustrates that toothbrushes harbor various microorganisms and that both period of use and user age might affect the microbial composition.

RevDate: 2020-09-11

Ellermann M, V Sperandio (2020)

Bacterial signaling as an antimicrobial target.

Current opinion in microbiology, 57:78-86 pii:S1369-5274(20)30097-7 [Epub ahead of print].

Antibiotics profoundly reduced worldwide mortality. However, the emergence of resistance to the growth inhibiting effects of these drugs occurred. New approaches to treat infectious disease that reduce the likelihood for resistance are needed. In bacterial pathogens, complex signaling networks regulate virulence. Anti-virulence therapies aim to disrupt these networks to attenuate virulence without affecting growth. Quorum-sensing, a cell-to-cell communication system, represents an attractive anti-virulence target because it often activates virulence. The challenge is to identify druggable targets that inhibit virulence, while also minimizing the likelihood of mutations promoting resistance. Moreover, given the ubiquity of quorum-sensing systems in commensals, any potential effects of anti-virulence therapies on microbiome function should also be considered. Here we highlight the efficacy and drawbacks of anti-virulence approaches.

RevDate: 2020-09-11

Zeng C, Yang P, Cao T, et al (2020)

Gut microbiota: An intermediary between metabolic syndrome and cognitive deficits in schizophrenia.

Progress in neuro-psychopharmacology & biological psychiatry pii:S0278-5846(20)30413-9 [Epub ahead of print].

Gut microbiome interacts with the central nervous system tract through the gut-brain axis. Such communication involves neuronal, endocrine, and immunological mechanisms, which allows for the microbiota to affect and respond to various behaviors and psychiatric conditions. In addition, the use of atypical antipsychotic drugs (AAPDs) may interact with and even change the abundance of microbiome to potentially cause adverse effects or aggravate the disorders inherent in the disease. The regulate effects of gut microbiome has been described in several psychiatric disorders including anxiety and depression, but only a few reports have discussed the role of microbiota in AAPDs-induced Metabolic syndrome (MetS) and cognitive disorders. The following review systematically summarizes current knowledge about the gut microbiota in behavior and psychiatric illness, with the emphasis of an important role of the microbiome in the metabolism of schizophrenia and the potential for AAPDs to change the gut microbiota to promote adverse events. Prebiotics and probiotics are microbiota-management tools with documented efficacy for metabolic disturbances and cognitive deficits. Novel therapies for targeting microbiota for alleviating AAPDs-induced adverse effects are also under fast development.

RevDate: 2020-09-11

Mars RAT, Yang Y, Ward T, et al (2020)

Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome.

Cell pii:S0092-8674(20)30998-3 [Epub ahead of print].

The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease has been difficult due to apparent disconnects between animal and human studies and lack of an integrated multi-omics view of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome, and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases. VIDEO ABSTRACT.

RevDate: 2020-09-11

Yamauchi T, Oi A, Kosakamoto H, et al (2020)

Gut Bacterial Species Distinctively Impact Host Purine Metabolites during Aging in Drosophila.

iScience pii:S2589-0042(20)30669-6 [Epub ahead of print].

Gut microbiota impacts the host metabolome and affects its health span. How bacterial species in the gut influence age-dependent metabolic alteration has not been elucidated. Here we show in Drosophila melanogaster that allantoin, an end product of purine metabolism, is increased during aging in a microbiota-dependent manner. Allantoin levels are low in young flies but are commonly elevated upon lifespan-shortening dietary manipulations such as high-purine, high-sugar, or high-yeast feeding. Removing Acetobacter persici in the Drosophila microbiome attenuated age-dependent allantoin increase. Mono-association with A. persici, but not with Lactobacillus plantarum, increased allantoin in aged flies. A. persici increased allantoin via activation of innate immune signaling IMD pathway in the renal tubules. On the other hand, analysis of bacteria-conditioned diets revealed that L. plantarum can decrease allantoin by reducing purines in the diet. These data together demonstrate species-specific regulations of host purine levels by the gut microbiome.

RevDate: 2020-09-11

Xu P (2020)

Dynamics of microbial competition, commensalism and cooperation and its implications for coculture and microbiome engineering.

Biotechnology and bioengineering [Epub ahead of print].

Microbial consortium is a complex adaptive system with higher order dynamic characteristics that are not present by individual members. To accurately predict the social interactions, we formulate a set of unstructured kinetic models to quantitatively capture the dynamic interactions of multiple microbial species. By introducing an interaction coefficient, we analytically derived the steady state solutions for the interacting species and the substrate-depleting profile in the chemostat. We analyzed the stability of the possible co-existing states defined by competition, parasitism, amensalism, commensalism and cooperation. Our model predicts that only parasitism, commensalism and cooperation could lead to stable co-existing states. We also determined the optimal social interaction criteria of microbial coculture when sequential metabolic reactions are compartmentalized into two distinct species. Coupled with Luedeking-Piret and Michaelis-Menten equations, accumulation of metabolic intermediates in one species and formation of end-product in another species could be derived and assessed. We discovered that parasitism consortia disfavor the bioconversion of intermediate to final product; and commensalism consortia could efficiently convert metabolic intermediates to final product and maintain metabolic homeostasis with a broad range of operational conditions (i.e., dilution rates); whereas cooperative consortia leads to highly nonlinear pattern of precursor accumulation and end-product formation. The underlying dynamics and emergent properties of microbial consortia may provide critical knowledge for us to understand ecological co-existing states, engineer efficient bioconversion process, deliver effective gut therapeutics as well as elucidate probiotic-pathogen or tumor-host interactions in general. This article is protected by copyright. All rights reserved.


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 )