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Bibliography on: Microbiome

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ESP: PubMed Auto Bibliography 24 Aug 2019 at 01:44 Created: 


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

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

Citations The Papers (from PubMed®)

RevDate: 2019-08-23

Henrick BM, Chew S, Casaburi G, et al (2019)

Colonization by B. infantis EVC001 modulates enteric inflammation in exclusively breastfed infants.

Pediatric research pii:10.1038/s41390-019-0533-2 [Epub ahead of print].

BACKGROUND: Infant gut dysbiosis, often associated with low abundance of bifidobacteria, is linked to impaired immune development and inflammation-a risk factor for increased incidence of several childhood diseases. We investigated the impact of B. infantis EVC001 colonization on enteric inflammation in a subset of exclusively breastfed term infants from a larger clinical study.

METHODS: Stool samples (n = 120) were collected from infants randomly selected to receive either 1.8 × 1010 CFU B. infantis EVC001 daily for 21 days (EVC001) or breast milk alone (controls), starting at day 7 postnatal. The fecal microbiome was analyzed using 16S ribosomal RNA, proinflammatory cytokines using multiplexed immunoassay, and fecal calprotectin using ELISA at three time points: days 6 (baseline), 40, and 60 postnatal.

RESULTS: Fecal calprotectin concentration negatively correlated with Bifidobacterium abundance (P = 0.0001; ρ = -0.72), and proinflammatory cytokines correlated with Clostridiaceae and Enterobacteriaceae, yet negatively correlated with Bifidobacteriaceae abundance. Proinflammatory cytokines were significantly lower in EVC001-fed infants on days 40 and 60 postnatally compared to baseline and compared to control infants.

CONCLUSION: Our findings indicate that gut dysbiosis (absence of B. infantis) is associated with increased intestinal inflammation. Early addition of EVC001 to diet represents a novel strategy to prevent enteric inflammation during a critical developmental phase.

RevDate: 2019-08-23

Renelies-Hamilton J, Noguera-Julian M, Parera M, et al (2019)

Exploring interactions between Blastocystis sp., Strongyloides spp. and the gut microbiomes of wild chimpanzees in Senegal.

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases pii:S1567-1348(19)30237-0 [Epub ahead of print].

BACKGROUND: Gut parasites exert an important influence on the gut microbiome, with many studies focusing on the human gut microbiome. It has, however, undergone severe richness depletion. Hygienic lifestyle, antimicrobial treatments and altered gut homeostasis (e.g., chronic inflammation) reduce gut microbiome richness and also parasite prevalence; which may confound results. Studying species closely related to humans could help overcome this problem by providing insights into the ancestral relationship between humans, their gut microbiome and their gut parasites. Chimpanzees are a particularly promising model as they have similar gut microbiomes to humans and many parasites infect both species.

AIMS: We study the interaction between gut microbiome and enteric parasites in chimpanzees. Investigating what novel insights a closely related species can reveal when compared to studies on humans.

METHODS: Using eighty-seven faecal samples from wild western chimpanzees (Pan troglodytes verus) in Senegal, we combine 16S rRNA gene amplicon sequencing for gut microbiome characterization PCR detection of parasite taxa (Blastocystis sp., Strongyloides spp., Giardia duodenalis, Cryptosporidium spp., Plasmodium spp., Filariae and Trypanosomatidae). We test for differences in gut microbiota ecosystem traits and taxonomical composition between Blastocystis and Strongyloides bearing and non-bearing samples.

RESULTS: For Blastocystis, twelve differentially abundant taxa (e.g., Methanobrevibacter), including Prevotella and Ruminococcus-Methanobrevibacter enterotype markers, replicate findings in humans. However, several richness indices are lower in Blastocystis carriers, contradicting human studies. This indicates Blastocystis, unlike Strongyloides, is associated to a "poor health" gut microbiome, as does the fact that Faecalibacterium, a bacterium with gut protective traits, is absent in Blastocystis-positive samples. Strongyloides was associated to Alloprevotella and five other taxonomic groups. Each parasite had its unique impact on the gut microbiota indicating parasite-specific niches. Our results suggest that studying the gut microbiomes of wild chimpanzees could help disentangle biological from artefactual associations between gut microbiomes and parasites.

RevDate: 2019-08-23

Serrano CA, Pierre R, Van Der Pol WJ, et al (2019)

Eradication of Helicobacter pylori in Children Restores the Structure of the Gastric Bacterial Community to That of Non-infected Children.

Gastroenterology pii:S0016-5085(19)41231-6 [Epub ahead of print].

RevDate: 2019-08-23

Plichta DR, Graham DB, Subramanian S, et al (2019)

Therapeutic Opportunities in Inflammatory Bowel Disease: Mechanistic Dissection of Host-Microbiome Relationships.

Cell, 178(5):1041-1056.

The current understanding of inflammatory bowel disease (IBD) pathogenesis implicates a complex interaction between host genetics, host immunity, microbiome, and environmental exposures. Mechanisms gleaned from genetics and molecular pathogenesis offer clues to the critical triggers of mucosal inflammation and guide the development of therapeutic interventions. A complex network of interactions between host genetic factors, microbes, and microbial metabolites governs intestinal homeostasis, making classification and mechanistic dissection of involved pathways challenging. In this Review, we discuss these challenges, areas of active translation, and opportunities for development of next-generation therapies.

RevDate: 2019-08-23

Mittelman K, D Burstein (2019)

Tiny Hidden Genes within Our Microbiome.

Cell, 178(5):1034-1035.

Exploration of tiny protein-coding sequences within the human microbiome reveals thousands of conserved gene families that have been overlooked by traditional analyses. These small proteins may play key roles in the crosstalk among bacteria within the microbiome and in interactions with their human hosts.

RevDate: 2019-08-23

Chen F, Esmaili S, Rogers G, et al (2019)

Lean NAFLD: A Distinct Entity Shaped by Differential Metabolic Adaptation.

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

Nonalcoholic fatty liver disease (NAFLD) affects a quarter of the adult population. A significant subset of patients are lean, but their underlying pathophysiology is not well understood. We investigated the role of bile acids (BAs) and the gut microbiome in the pathogenesis of lean NAFLD. BA and fibroblast growth factor 19 (FGF19) levels (a surrogate for intestinal farnesoid X receptor [FXR] activity), patatin-like phospholipase domain-containing 3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) variants, and gut microbiota profiles in lean and non-lean NAFLD were investigated in a cohort of Caucasian patients with biopsy-proven NAFLD (n = 538), lean healthy controls (n = 30), and experimental murine models. Patients with lean NAFLD had a more favorable metabolic and histological profile compared to those with non-lean NAFLD (P < 0.05 for all). BA levels were significantly higher in NAFLD with advanced compared to earlier stages of liver fibrosis. Patients with lean NAFLD had higher serum secondary BA and FGF19 levels and reduced 7-alpha-hydroxy-4-cholesten-3-one (C4) levels (P < 0.05 for all). These differences were more profound in early compared to advanced stages of fibrosis (P < 0.05 for both). Lean patients demonstrated an altered gut microbiota profile. Similar findings were demonstrated in lean and non-lean murine models of NAFLD. Treating mice with an apical sodium-dependent bile acid transporter inhibitor (ASBTi) (SC-435) resulted in marked increases in fgf15, a shift in the BA and microbiota profiles, and improved steatohepatitis in the lean model. CONCLUSION: Differences in metabolic adaptation between lean and non-lean NAFLD patients, at least in part, explain the pathophysiology and provide novel options for therapy. This article is protected by copyright. All rights reserved.

RevDate: 2019-08-23

Chen Y, Agnello M, Dinis M, et al (2019)

Lollipop containing Glycyrrhiza uralensis extract reduces Streptococcus mutans colonization and maintains oral microbial diversity in Chinese preschool children.

PloS one, 14(8):e0221756 pii:PONE-D-19-16585.

The anticariogenic activity of the extract of Glycyrrhiza uralensis (licorice) has been well documented. We recently developed an herbal lollipop containing licorice extracts with Glycyrrhizol A, the compound displaying strong antimicrobial activity against Streptococcus mutans. Preliminary testing showed that the herbal lollipop reduced salivary S. mutans counts in vivo. In this study, we aimed to further test the efficacy of this herbal lollipop for reducing salivary S. mutans levels, and investigate its impact on salivary microbiome. Using a well-established in vitro oral microbiome model, we showed that licorice extract displays targeted killing against S. mutans without affecting the biodiversity of the community. In vivo study corroborated in vitro findings, showing for high caries-risk children aged 3-6 with salivary S. mutans levels >5x105 cells/ml, daily use of 2 licorice-containing lollipops for 3 weeks significantly reduced salivary S. mutans levels compared to the control group. Salivary microbiome analysis showed either no change or even increase in phylogenetic diversity of the oral community following herbal lollipop usage. Although further study with longer term observation is needed, these results suggest that use of licorice extract-containing lollipops can be as a simple and effective way to reduce the risk of dental caries in children.

RevDate: 2019-08-23

Tipton CD, Sanford NE, Everett JA, et al (2019)

Chronic wound microbiome colonization on mouse model following cryogenic preservation.

PloS one, 14(8):e0221565 pii:PONE-D-18-32776.

Chronic wound infections are increasingly recognized to be dynamic and polymicrobial in nature, necessitating the development of wound models which reflect the complexities of infection in a non-healing wound. Wound slough isolated from human chronic wounds and transferred to mice was recently shown to create polymicrobial infection in mice, and there is potential this tool may be improved by cryogenic preservation. The purpose of this study was to investigate the application of cryogenic preservation to transferring polymicrobial communities, specifically by quantifying the effects of cryopreservation and wound microbiome transplantation. Slough from an established murine polymicrobial surgical excision model and five patients were subjected to three preservation strategies: refrigeration until infection, freezing in liquid nitrogen, or freezing in liquid nitrogen with glycerol solution prior to infection in individual mice. Four days following inoculation onto mice, wound microbiota were quantified using either culture isolation or by 16s rRNA gene community profiling and quantitative PCR. Cryogenic preservation did not significantly reduce bacterial viability. Reestablished microbial communities were significantly associated with patient of origin as well as host context (i.e., originally preserved from a patient versus mouse infection). Whereas preservation treatment did not significantly shape community composition, the transfers of microbiomes from human to mouse were characterized by reduced diversity and compositional changes. These findings indicated that changes should be expected to occur to community structure after colonization, and that compositional change is likely due to the rapid change in infection context as opposed to preservation strategy. Furthermore, species that were present in higher relative abundance in wound inoculate were more likely to colonize subsequent wounds, and wound inoculate with higher bacterial load established wound communities that were more compositionally similar. Results inform expectations for the complementation of chronic wound in vivo modeling with cryogenic preservation archives.

RevDate: 2019-08-23

Weitzman CL, Kaestli M, Gibb K, et al (2019)

Disease Exposure and Antifungal Bacteria on Skin of Invasive Cane Toads, Australia.

Emerging infectious diseases, 25(9):1770-1771.

Cane toads, an invasive species in Australia, are resistant to fungal pathogens affecting frogs worldwide (Batrachochytrium dendrobatidis). From toad skin swabs, we detected higher proportions of bacteria with antifungal properties in Queensland, where toad and pathogen distributions overlap, than in other sites. This finding suggests that site-specific pathogen pressures help shape skin microbial communities.

RevDate: 2019-08-23

Galloway DA, Gowing E, Setayeshgar S, et al (2019)

Inhibitory milieu at the multiple sclerosis lesion site and the challenges for remyelination.

Glia [Epub ahead of print].

Regeneration of myelin, following injury, can occur within the central nervous system to reinstate proper axonal conductance and provide trophic support. Failure to do so renders the axons vulnerable, leading to eventual degeneration, and neuronal loss. Thus, it is essential to understand the mechanisms by which remyelination or failure to remyelinate occur, particularly in the context of demyelinating and neurodegenerative disorders. In multiple sclerosis, oligodendrocyte progenitor cells (OPCs) migrate to lesion sites to repair myelin. However, during disease progression, the ability of OPCs to participate in remyelination diminishes coincident with worsening of the symptoms. Remyelination is affected by a broad range of cues from intrinsic programming of OPCs and extrinsic local factors to the immune system and other systemic elements including diet and exercise. Here we review the literature on these diverse inhibitory factors and the challenges they pose to remyelination. Results spanning several disciplines from fundamental preclinical studies to knowledge gained in the clinic will be discussed.

RevDate: 2019-08-23

Huang Y, Chen A, Guo F, et al (2019)

Severe Intestinal Dysbiosis in Rat Models of Short Bowel Syndrome with Ileocecal Resection.

Digestive diseases and sciences pii:10.1007/s10620-019-05802-4 [Epub ahead of print].

BACKGROUND: Short bowel syndrome (SBS) resulting from extensive intestinal resection is thought to significantly affect gut microbiota. Data are limited on the signatures of the intestinal microbiome in SBS with different anatomical types.

AIMS: The aim of our investigation was to characterize the composition and function of gut microbiota in SBS with or without ileocecal resection (ICR).

METHODS: Six-week-old male Sprague-Dawley rats underwent 75% small bowel resection (SBR) with the ileocecal junction intact (SBR group, jejunoileal anastomosis, n = 10) or removed (ICR group, jejunocolic anastomosis, n = 10), or sham surgery (sham group, n = 10). Colonic contents of the rats were collected 28 days after operation, and 16S rRNA gene sequencing was performed on the MiSeq Illumina platform to analyze bacterial composition.

RESULTS: Overall structures of the gut microbiome differed significantly among the three groups. The bacterial α-diversity of the ICR group was remarkably lower than that of the sham group. ICR rats were enriched with Lactobacillus and opportunistic pathogens from Proteobacteria but depleted of commensal genera belonging to the Lachnospiraceae, Ruminococcaceae and Erysipelotrichaceae families. Genera from the Bacteroidales S24-7 group, Porphyromonadaceae, Prevotellaceae, Rikenellaceae and Christensenellaceae were prevalent in SBR rats. Functional pathways of branched-chain and aromatic amino acid biosynthesis, lipopolysaccharide biosynthesis and infectious diseases were abundant in the ICR group, while SBR rats featured pathways of C5 branched dibasic acid metabolism, biotin metabolism and one carbon pool folate.

CONCLUSIONS: ICR causes dramatically more severe intestinal dysbiosis than SBR only in SBS rat models, resulting in altered functional profiles of the gut microbiome.

RevDate: 2019-08-23

Singh M, Ganguli S, MM Ghosh (2019)

Comparative metagenomic dataset of hospital effluent microbiome from rural and urban hospitals in West Bengal.

Data in brief, 25:104264 pii:104264.

The unsafe disposal of hospital effluents contributes to gross contamination of water bodies with antibiotic residues, antibiotic resistance genes and antibiotic resistance bacteria. This study reports the microbial community profile of hospital wastes collected from various regions of West Bengal, India, using 16S rRNA gene amplicon sequencing. The data set Liquid Sludge (LS) contains 15,372,973 reads with an average length of 301 bps with average 52 ± 5% GC content. The data set Solid Sludge (SS) contains 16,071,594 reads with an average length of 301 bps with average 53 ± 4% GC content. Data of this study are available at NCBI BioProject (PRJNA360379). In sample LS, an abundance of 19.3% for the members of Bacteroidetes was observed. In sample SS, an abundance of 19.7% for the members of Euryarchaeota was observed.

RevDate: 2019-08-23

Mu X, Zhao C, Yang J, et al (2019)

Group B Streptococcus colonization induces Prevotella and Megasphaera abundance-featured vaginal microbiome compositional change in non-pregnant women.

PeerJ, 7:e7474 pii:7474.

Background: Previous studies have indicated that variations in the vaginal microbiome result in symptomatic conditions. Group B Streptococcus (GBS) is a significant neonatal pathogen and maternal vaginal colonization has been recognized as an important risk factor for neonatal disease. Therefore, it is important to discover the relationship between the composition of the vaginal microbiome and GBS colonization. This study explores the potential relationship between the composition of the vaginal microbiome and GBS colonization in non-pregnant Chinese women.

Methods: A total of 22 GBS-positive, non-pregnant women and 44 matched GBS-negative women were recruited for the current study. The composition of the vaginal microbiome was profiled by sequencing the 16S rRNA genes. The microbiome diversity and variation were then evaluated.

Results: The vaginal microbiome of the 66 subjects enrolled in the current study were compared and the results showed that GBS-positive women exhibited significant vaginal microbial differences compared with the GBS-negative women based on the analysis of similarities (r = 0.306, p < 0.01). The relative abundance of the bacterial genus Lactobacillus (p < 0.01) was significantly lower in the GBS-positive group, while the abundances of the bacterial genera Prevotella (p < 0.01), Megasphaera (p < 0.01), and Streptococcus (p < 0.01) were significantly higher in the GBS-positive group.

Discussion: The current study addressed significant variations across the communities of the vaginal microbiome in GBS-positive and GBS-negative women in a Chinese cohort, which paves the way for a larger cohort-based clinical validation study and the development of therapeutic probiotics in the future.

RevDate: 2019-08-23

Guo J, Lv Q, Ariff A, et al (2019)

Western oropharyngeal and gut microbial profiles are associated with allergic conditions in Chinese immigrant children.

The World Allergy Organization journal, 12(8):100051 pii:100051.

Background: The allergy epidemic resulting from western environment/lifestyles is potentially due to modifications of the human microbiome. Therefore, it is of interest to study immigrants living in a western environment as well as their counterparts in the country of origin to understand differences in their microbiomes and health status.

Methods: We investigated 58 Australian Chinese (AC) children from Perth, Western Australia as well as 63 Chinese-born Chinese (CC) children from a city in China. Oropharyngeal (OP) and fecal samples were collected. To assess the microbiomes, 16s ribosomal RNA (rRNA) sequencing for variable regions V3 and V4 was used. Skin prick tests (SPT) were performed to measure the children's atopic status. Information on food allergy and wheezing were acquired from a questionnaire.

Results: AC children had more allergic conditions than CC children. The alpha diversity (mean species diversity) of both OP and gut microbiome was lower in AC children compared to CC children for richness estimate (Chao1), while diversity evenness (Shannon index) was higher. The beta diversity (community similarity) displayed a distinct separation of the OP and gut microbiota between AC and CC children. An apparent difference in microbial abundance was observed for many bacteria. In AC children, we sought to establish consistent trends in bacterial relative abundance that are either higher or lower in AC versus CC children and higher or lower in children with allergy versus those without allergy. The majority of OP taxa showed a consistent trend while the majority of fecal taxa showed a contrasting trend.

Conclusion: Distinct differences in microbiome compositions were found in both oropharyngeal and fecal samples of AC and CC children. The association of the OP microbiome with allergic condition is different from that of the gut microbiome in AC children. The microbiome profiles are changed by the western environment/lifestyle and are associated with allergies in Chinese immigrant children in Australia.

RevDate: 2019-08-23

Lima J, Auffret MD, Stewart RD, et al (2019)

Identification of Rumen Microbial Genes Involved in Pathways Linked to Appetite, Growth, and Feed Conversion Efficiency in Cattle.

Frontiers in genetics, 10:701.

The rumen microbiome is essential for the biological processes involved in the conversion of feed into nutrients that can be utilized by the host animal. In the present research, the influence of the rumen microbiome on feed conversion efficiency, growth rate, and appetite of beef cattle was investigated using metagenomic data. Our aim was to explore the associations between microbial genes and functional pathways, to shed light on the influence of bacterial enzyme expression on host phenotypes. Two groups of cattle were selected on the basis of their high and low feed conversion ratio. Microbial DNA was extracted from rumen samples, and the relative abundances of microbial genes were determined via shotgun metagenomic sequencing. Using partial least squares analyses, we identified sets of 20, 14, 17, and 18 microbial genes whose relative abundances explained 63, 65, 66, and 73% of the variation of feed conversion efficiency, average daily weight gain, residual feed intake, and daily feed intake, respectively. The microbial genes associated with each of these traits were mostly different, but highly correlated traits such as feed conversion ratio and growth rate showed some overlapping genes. Consistent with this result, distinct clusters of a coabundance network were enriched with microbial genes identified to be related with feed conversion ratio and growth rate or daily feed intake and residual feed intake. Microbial genes encoding for proteins related to cell wall biosynthesis, hemicellulose, and cellulose degradation and host-microbiome crosstalk (e.g., aguA, ptb, K01188, and murD) were associated with feed conversion ratio and/or average daily gain. Genes related to vitamin B12 biosynthesis, environmental information processing, and bacterial mobility (e.g., cobD, tolC, and fliN) were associated with residual feed intake and/or daily feed intake. This research highlights the association of the microbiome with feed conversion processes, influencing growth rate and appetite, and it emphasizes the opportunity to use relative abundances of microbial genes in the prediction of these performance traits, with potential implementation in animal breeding programs and dietary interventions.

RevDate: 2019-08-23

Gorecki AM, Preskey L, Bakeberg MC, et al (2019)

Altered Gut Microbiome in Parkinson's Disease and the Influence of Lipopolysaccharide in a Human α-Synuclein Over-Expressing Mouse Model.

Frontiers in neuroscience, 13:839.

The interaction between the gut microbiota and alpha-synuclein (αSyn) aggregation in Parkinson's disease (PD) is receiving increasing attention. The objective of this study was to investigate gut microbiota, and effects of an inflammatory lipopolysaccharide (LPS) trigger in a human αSyn over-expressing mouse model of PD (Thy1-αSyn). Stool samples from patients with confirmed PD and Thy1-αSyn mice were analyzed using 16S ribosomal RNA sequencing. Compared to healthy controls, the relative abundance of mucin-degrading Verrucomicrobiae and LPS-producing Gammaproteobacteria were greater in PD patients. In mice, the abundance of Gammaproteobacteria was negligible in both Thy1-αSyn and wild-type (WT) animals, while Verrucomicrobiae were reduced in Thy1-αSyn mice. The effect of LPS on intestinal barrier function was investigated in vitro using intestinal epithelial (IEC-6) cells, and in vivo via administration of LPS in drinking water to Thy1-αSyn mice. Acute exposure to LPS in vitro resulted in a reduction and altered distribution of the tight junction markers ZO-1 and e-Cadherin around the cell membrane in IEC-6 cells, as shown by immunohistochemistry. LPS administration in Thy1-αSyn mice resulted in the emergence of early motor manifestations at 10 weeks, compared to untreated mice who were still asymptomatic at this age. This study reaffirms that an altered microbiome exists in patients with PD, and supports the notion of a proinflammatory gut microbiome environment as a trigger for PD pathogenesis.

RevDate: 2019-08-23

Kado T, Nawaz A, Takikawa A, et al (2019)

Linkage of CD8+ T cell exhaustion with high-fat diet-induced tumourigenesis.

Scientific reports, 9(1):12284 pii:10.1038/s41598-019-48678-0.

Obesity increases the risk of cancer. Increased levels of hormones (such as oestrogen, insulin, insulin-like growth factor, and leptin), free fatty acid-induced production of reactive oxygen species, an altered intestinal microbiome and chronic inflammation are known to be associated with an increased cancer risk in obese subjects. However, the mechanism underlying the connection between obesity and cancer development remains elusive. Here, we show that a high-fat diet (HFD) promotes tumour initiation/progression and induces a phenotypic switch from PD-1- CD8+ non-exhausted T cells to PD-1+ CD8+ exhausted T cells in a murine breast cancer model. While PD-1- CD8+ non-exhausted T cells predominated in the mammary glands of normal diet (ND)-fed mice, PD-1+ CD8+ exhausted T cells accumulated in the developing tumours of HFD-fed mice. Gene expression profiles indicated that PD-1+ CD8+ T cells expressed higher levels of the tumour-trophic gene Opn and lower levels of the cytotoxic genes Ifng and Gzmb than did PD-1- CD8+ T cells. Our study provides a possible mechanistic linkage between obesity and cancer.

RevDate: 2019-08-23

Bevivino A, Bacci G, Drevinek P, et al (2019)

Deciphering the Ecology of Cystic Fibrosis Bacterial Communities: Towards Systems-Level Integration.

Trends in molecular medicine pii:S1471-4914(19)30185-6 [Epub ahead of print].

Despite over a decade of cystic fibrosis (CF) microbiome research, much remains to be learned about the overall composition, metabolic activities, and pathogenicity of the microbes in CF airways, limiting our understanding of the respiratory microbiome's relation to disease. Systems-level integration and modeling of host-microbiome interactions may allow us to better define the relationships between microbiological characteristics, disease status, and treatment response. In this way, modeling could pave the way for microbiome-based development of predictive models, individualized treatment plans, and novel therapeutic approaches, potentially serving as a paradigm for approaching other chronic infections. In this review, we describe the challenges facing this effort and propose research priorities for a systems biology approach to CF lung disease.

RevDate: 2019-08-23

Varun CN, Venkataswamy MM, Ravikumar R, et al (2019)

Th17 and MAIT cell mediated inflammation in antipsychotic free schizophrenia patients.

Schizophrenia research pii:S0920-9964(19)30354-8 [Epub ahead of print].

The immune hypothesis of schizophrenia has gained significant popularity in recent years in schizophrenia research. Evidence suggests that the peripheral immune system communicates with central nervous system and the effect propagates through microglial and lymphocyte crosstalk, especially during neuro-inflammation. Although, there is previous literature indicating changes in lymphocyte population in schizophrenia, detailed studies with respect to T and B cells are scarce. Mucosal associated invariant T (MAIT) cells are functionally associated with the gut microbiome. The gut microbiome has been implicated in the pathogenesis of schizophrenia. However, there is no information on the frequency of MAIT cells in schizophrenia. Hence, we investigated changes in proportions of T cells, B cells and MAIT cells in peripheral blood mononuclear cells derived from antipsychotic-free patients with schizophrenia in comparison to healthy controls. In line with earlier reports, we noted perturbations in Th17 cells. This study for the first time reports changes in frequencies of MAIT cells in a homogenous population of antipsychotic-free patients with schizophrenia. These changes, though not common across all patients nevertheless point to the fact that inflammation is prevalent in a significant subset of schizophrenia cases.

RevDate: 2019-08-23

Zhang Y, Huang R, Cheng M, et al (2019)

Gut microbiota from NLRP3-deficient mice ameliorates depressive-like behaviors by regulating astrocyte dysfunction via circHIPK2.

Microbiome, 7(1):116 pii:10.1186/s40168-019-0733-3.

BACKGROUND: Inflammasomes have been found to interact with the gut microbiota, and this effect is associated with depression, but the mechanisms underlying this interaction have not been elucidated in detail.

RESULTS: The locomotor activity of NLRP3 KO mice was significantly greater than that of their WT littermates, while cohousing and transplantation of the NLRP3 KO gut microbiota avoid the effects of NLRP3 KO on the general locomotor activity at baseline. Meanwhile, transplantation of the NLRP3 KO microbiota alleviated the CUS-induced depressive-like behaviors. The compositions of the gut microbiota in NLRP3 KO mice and WT mice were significantly different in terms of the relative abundance of Firmicutes, Proteobacteria, and Bacteroidetes. Fecal microbiota transplantation (FMT) from NLRP3 KO mice significantly ameliorated the depressive-like behavior induced by chronic unpredictable stress (CUS) in recipient mice. Given the correlation between circular RNA HIPK2 (circHIPK2) and depression and the observation that the level of circHIPK2 expression was significantly increased in CUS-treated mice compared with that in the control group, further experiments were performed. FMT significantly ameliorated astrocyte dysfunction in recipient mice treated with CUS via inhibition of circHIPK2 expression.

CONCLUSIONS: Our study illustrates the involvement of the gut microbiota-circHIPK2-astrocyte axis in depression, providing translational evidence that transplantation of the gut microbiota from NLRP3 KO mice may serve as a novel therapeutic strategy for depression.

RevDate: 2019-08-23

Li C, Chng KR, Kwah JS, et al (2019)

An expectation-maximization algorithm enables accurate ecological modeling using longitudinal microbiome sequencing data.

Microbiome, 7(1):118 pii:10.1186/s40168-019-0729-z.

BACKGROUND: The dynamics of microbial communities is driven by a range of interactions from symbiosis to predator-prey relationships, the majority of which are poorly understood. With the increasing availability of high-throughput microbiome taxonomic profiling data, it is now conceivable to directly learn the ecological models that explicitly define microbial interactions and explain community dynamics. The applicability of these approaches is severely limited by the lack of accurate absolute cell density measurements (biomass).

METHODS: We present a new computational approach that resolves this key limitation in the inference of generalized Lotka-Volterra models (gLVMs) by coupling biomass estimation and model inference with an expectation-maximization algorithm (BEEM).

RESULTS: BEEM outperforms the state-of-the-art methods for inferring gLVMs, while simultaneously eliminating the need for additional experimental biomass data as input. BEEM's application to previously inaccessible public datasets (due to the lack of biomass data) allowed us to construct ecological models of microbial communities in the human gut on a per-individual basis, revealing personalized dynamics and keystone species.

CONCLUSIONS: BEEM addresses a key bottleneck in "systems analysis" of microbiomes by enabling accurate inference of ecological models from high throughput sequencing data without the need for experimental biomass measurements.

RevDate: 2019-08-23

Hammer TJ, NA Moran (2019)

Links between metamorphosis and symbiosis in holometabolous insects.

Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 374(1783):20190068.

Many animals depend on microbial symbionts to provide nutrition, defence or other services. Holometabolous insects, as well as other animals that undergo metamorphosis, face unique constraints on symbiont maintenance. Microbes present in larvae encounter a radical transformation of their habitat and may also need to withstand chemical and immunological challenges. Metamorphosis also provides an opportunity, in that symbiotic associations can be decoupled over development. For example, some holometabolous insects maintain the same symbiont as larvae and adults, but house it in different tissues; in other species, larvae and adults may harbour entirely different types or numbers of microbes, in accordance with shifts in host diet or habitat. Such flexibility may provide an advantage over hemimetabolous insects, in which selection on adult-stage microbial associations may be constrained by its negative effects on immature stages, and vice versa. Additionally, metamorphosis itself can be directly influenced by symbionts. Across disparate insect taxa, microbes protect hosts from pathogen infection, supply nutrients essential for rebuilding the adult body and provide cues regulating pupation. However, microbial associations remain completely unstudied for many families and even orders of Holometabola, and future research will undoubtedly reveal more links between metamorphosis and microbiota, two widespread features of animal life. This article is part of the theme issue 'The evolution of complete metamorphosis'.

RevDate: 2019-08-21

Karponis D (2017)

Rheumatoid arthritis: the journey in pursuit of a cure.

Rheumatology advances in practice, 1(1):rkx008 pii:rkx008.

RevDate: 2019-08-22

López Caro JC, Santibáñez M, García Rivero JL, et al (2019)

Sputum Microbiome Dynamics in Chronic Obstructive Pulmonary Disease Patients during an Exacerbation Event and Post-Stabilization.

Respiration; international review of thoracic diseases pii:000501988 [Epub ahead of print].

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects up to 65 million people worldwide, and COPD exacerbation causes tissue damage and subsequent loss of lung function. It is a multifactorial event in which respiratory infections are involved, but little is known about its dynamics.

OBJECTIVES: The objective of our study was to determine the microbiome composition during an exacerbation event and post-stabilization.

METHODS: We conducted an observational analytical study of a cohort of 55 COPD patients in which 2 sputum samples (the first taken during an exacerbation event and the second during clinical post-stabilization) were submitted to 16s RNA ribosomal analysis by Illumina Miseq Next Generation Sequencing (NGS). The presence of respiratory viruses was also determined.

RESULTS: Our study found a stable microbiome composition in the post-stabilization sputum samples of COPD patients, and 4 additional microbiomes in samples taken during the exacerbation, 3 of which showed a marked dysbiosis by Haemophilus, Pseudomonas, and Serratia. The fourth exacerbation microbiome had a very similar composition to post-stabilization samples, but some pathogens such as Moraxella and respiratory viruses were also found.

CONCLUSIONS: Our study reveals the main protagonists involved in lung microbiome dynamics during an exacerbation event and post-stabilization in COPD patients by NGS analysis.

RevDate: 2019-08-22

Chen YH, Bai J, Wu D, et al (2019)

Association between fecal microbiota and generalized anxiety disorder: Severity and early treatment response.

Journal of affective disorders, 259:56-66 pii:S0165-0327(19)31154-1 [Epub ahead of print].

BACKGROUND: Associations between abnormal gut microbiome compositions and anxiety-like behaviors are well established. However, it is unknown whether the gut microbiome composition is associated with the severity of generalized anxiety disorder (GAD) and relief from clinical symptoms in patients.

METHODS: Stool samples from 36 patients with active GAD (A-GAD group) and 24 matched healthy control subjects (HC group) were analyzed by 16S rRNA gene sequencing. Anxiety was assessed with the Hamilton Anxiety Rating Scale and the Self-rating Anxiety Scale, and global assessments of functioning were performed at baseline and 1 month after drug treatment.

RESULTS: Gut microbiome compositions were altered in A-GAD patients, with fewer operational taxonomic units and lower fecal bacterial α-diversity. Specifically, Firmicutes and Tenericutes abundances were lower in A-GAD patients, and several genera were differentially represented in the A-GAD and HC groups. The abundances of Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-014, and Prevotella_9 correlated negatively with the anxiety severity and positively with anxiety reduction, whereas the abundances of Bacteroides and Escherichia-Shigella were positively associated with anxiety severity. Sex, smoking, and alcohol intake influenced the gut microbiome composition.

LIMITATIONS: The sample sizes were small and the stool samples were collected only at baseline; therefore, a causal association between changes in intestinal flora and disease remission was not established. Moreover, the effects of different drugs on gut microbiome composition were not investigated.

CONCLUSIONS: Altered gut microbiome composition may contribute to GAD pathogenesis and remission.

RevDate: 2019-08-22

Vierhout BP, Ott A, Kruithof I, et al (2019)

Inguinal microbiome in patients undergoing an endovascular aneurysm repair: Application of next-generation sequencing of the 16S-23S rRNA regions.

Medical hypotheses, 132:109358 pii:S0306-9877(19)30228-2 [Epub ahead of print].

BACKGROUND: Surgical site infection (SSI) remains a hazardous complication after vascular surgery. In this pilot study we investigated the inguinal microbiome in skin biopsies using histology and 16S-23S rDNA Next Generation Sequencing (NGS). Our hypothesis was that causative microorganisms of SSI are present in the inguinal microbiome.

METHODS: Data on surgical site infections and skin samples from the Percutaneous in Endovascular Repair versus Open (PiERO) trail were evaluated. Two patients with SSI were matched for age and comorbidity to eight matching patients of the PiERO trial. All patients were treated for an abdominal aortic aneurysm with endovascular repair. Nasal and perineal cultures were taken preoperatively to detect Staphylococcus aureus carriage. After disinfection with chlorhexidine, groin biopsies were taken to identify bacteria in deeper skin layers. All samples were subjected to histological analysis and culture-free 16S-23S rDNA NGS.

RESULTS: Staphylococcus aureus species were cultured in 5 out of 20 preoperative nasal and perineal swaps. Histology detected only a few bacteria. NGS of the 16S-23S rRNA regions identified DNA of bacterial species in all biopsies (20/20). Most identified genera and species proved to be known skin flora bacteria. No relation was found between SSIs and the preoperative microbiome.

CONCLUSION: In this pilot study, an innovative analysis of the preoperative microbiome using 16S-23S rDNA NGS did not show a relation with the occurrence of a surgical site infection. No pathogenic bacterial species were present in the inguinal skin after disinfection with chlorhexidine.

RevDate: 2019-08-22

Tuomisto S, Huhtala H, Martiskainen M, et al (2019)

Age-dependent association of gut bacteria with coronary atherosclerosis: Tampere Sudden Death Study.

PloS one, 14(8):e0221345 pii:PONE-D-19-02635.

BACKGROUND: The gut microbiome is thought to remain stable into old age. Gut bacteria and their translocation may play a role in the development of coronary heart disease (CHD) by modulating cholesterol levels and immune responses, as well as by producing toxic metabolites and bacterial endotoxins. The association of changes in the gut microbiome with the severity of coronary atherosclerosis and the ability of gut bacteria themselves to translocate into coronary plaques has not been studied.

MATERIALS AND METHODS: As a part of the Tampere Sudden Death Study, we measured age-dependent changes in the relative ratios of major intestinal bacterial communities (Bacteroides species [spp.], the Clostridium leptum group, the Clostridium coccoides group, Bifidobacterium spp., Enterobactericeae, Lactobacillus spp.) and Streptococcus spp. in both feces and coronary plaques of the same male autopsy cases (n = 67, age range 44-95) using real-time quantitative PCR (qPCR). The area of coronary atherosclerotic lesions were measured by computer-assisted morphometry. Fecal bacterial DNA measurements from healthy volunteers served as a control for gut bacterial analyses of autopsy cases. The relative amount of bacterial DNA in a sample was determined with the comparative Cq method.

RESULTS: The relative ratios of fecal Lactobacillus spp., Bifidobacterium spp., the Clostridium coccoides group, and Bacteroides spp. did not differ between controls and autopsy cases and showed no age-dependence. In contrast, the ratios of the Clostridium leptum group, Enterobactericeae, and Streptococcus spp. increased with age. Elevated relative ratios of fecal Enterobactericeae associated with a larger coronary plaque fibrotic area (p = 0.001), and the Clostridium leptum group with a larger calcification area (p = 0.015). Intestinal bacterial DNA could be amplified in 67.6% of the coronary plaques, the most common being Streptococcus spp. (41.0%), followed by Enterobactericeae (12.1%), Clostridium leptum (2.4%), and Lactobacillus spp. (2.4%). The percentages of Streptococcus spp. DNA decreased, and those of Enterobactericeae increased in coronary plaques along with age.

CONCLUSIONS: DNA of the Clostridium leptum group and pathogenic Enterobactericeae increase in the gut microbiome with age and can be detected in the same individual's coronary plaques along with pathogenic Streptococcus spp., associating with more severe coronary atherosclerosis.

RevDate: 2019-08-22

Pendegraft AH, Guo B, N Yi (2019)

Bayesian hierarchical negative binomial models for multivariable analyses with applications to human microbiome count data.

PloS one, 14(8):e0220961 pii:PONE-D-18-33781.

The analyses of large volumes of metagenomic data extracted from aggregate populations of microscopic organisms residing on and in the human body are advancing contemporary understandings of the integrated participation of microbes in human health and disease. Next generation sequencing technology facilitates said analyses in terms of diversity, community composition, and differential abundance by filtering and binning microbial 16S rRNA genes extracted from human tissues into operational taxonomic units. However, current statistical tools restrict study designs to investigations of limited numbers of host characteristics mediated by limited numbers of samples potentially yielding a loss of relevant information. This paper presents a Bayesian hierarchical negative binomial model as an efficient technique capable of compensating for multivariable sets including tens or hundreds of host characteristics as covariates further expanding analyses of human microbiome count data. Simulation studies reveal that the Bayesian hierarchical negative binomial model provides a desirable strategy by often outperforming three competing negative binomial model in terms of type I error while simultaneously maintaining consistent power. An application of the Bayesian hierarchical negative binomial model using subsets of the open data published by the American Gut Project demonstrates an ability to identify operational taxonomic units significantly differentiable among persons diagnosed by a medical professional with either inflammatory bowel disease or irritable bowel syndrome that are consistent with contemporary gastrointestinal literature.

RevDate: 2019-08-22

Balaban M, Moshiri N, Mai U, et al (2019)

TreeCluster: Clustering biological sequences using phylogenetic trees.

PloS one, 14(8):e0221068 pii:PONE-D-19-14871.

Clustering homologous sequences based on their similarity is a problem that appears in many bioinformatics applications. The fact that sequences cluster is ultimately the result of their phylogenetic relationships. Despite this observation and the natural ways in which a tree can define clusters, most applications of sequence clustering do not use a phylogenetic tree and instead operate on pairwise sequence distances. Due to advances in large-scale phylogenetic inference, we argue that tree-based clustering is under-utilized. We define a family of optimization problems that, given an arbitrary tree, return the minimum number of clusters such that all clusters adhere to constraints on their heterogeneity. We study three specific constraints, limiting (1) the diameter of each cluster, (2) the sum of its branch lengths, or (3) chains of pairwise distances. These three problems can be solved in time that increases linearly with the size of the tree, and for two of the three criteria, the algorithms have been known in the theoretical computer scientist literature. We implement these algorithms in a tool called TreeCluster, which we test on three applications: OTU clustering for microbiome data, HIV transmission clustering, and divide-and-conquer multiple sequence alignment. We show that, by using tree-based distances, TreeCluster generates more internally consistent clusters than alternatives and improves the effectiveness of downstream applications. TreeCluster is available at

RevDate: 2019-08-22

Galloway-Peña JR, Shi Y, Peterson CB, et al (2019)

Gut Microbiome Signatures are Predictive of Infectious Risk Following Induction Therapy for Acute Myeloid Leukemia.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America pii:5553100 [Epub ahead of print].

BACKGROUND: The majority of studies providing insights on the influence of the microbiome on the health of hematologic malignancy patients have concentrated on the transplant setting. Herein, we sought to assess the predictive capacity of the gastrointestinal microbiome and its relationship to clinical outcomes, with a specific focus on infection, in patients with acute myeloid leukemia (AML).

METHODS: 16s rRNA based analysis was performed on oral swabs and stool samples obtained biweekly from baseline until neutrophil recovery following induction chemotherapy (IC) in 97 AML patients. Microbiome characteristics were correlated with clinical outcomes both during and after IC completion.

RESULTS: At the start of IC, higher stool Shannon diversity (HR, 0.36; 95% CI, 0.18-0.74) and higher relative abundance of Porphyromonadaceae (HR, 0.36; 95% CI, 0.18-0.73) were associated with increased probability of remaining infection-free during neutropenia. A baseline stool Shannon diversity cut-off of <2 had optimal operating characteristics for predicting infectious complications during neutropenia. Although 56 patients received therapy >72 hours with a carbapenem, none of the patients had an infection with an extended spectrum beta-lactamase (ESBL) producing organism. Patients receiving carbapenems for >72hrs prior to neutrophil recovery had significantly lower α-diversity at neutrophil recovery (P=0.001) and were approximately 4 times more likely to have infection in the 90 days following neutrophil recovery (HR, 4.55; 95% CI, 1.73-11.93).

CONCLUSIONS: Our results suggest that gut microbiome evaluation could assist with infectious risk stratification and that improved targeting of antibiotic administration during IC could decrease subsequent infectious complications of AML patients.

RevDate: 2019-08-22

Minard G, Tikhonov G, Ovaskainen O, et al (2019)

The microbiome of the Melitaea cinxia butterfly shows marked variation but is only little explained by the traits of the butterfly or its host plant.

Environmental microbiology [Epub ahead of print].

Understanding of the ecological factors that shape intraspecific variation of insect microbiota in natural populations is relatively poor. In lepidopteran caterpillars, microbiota is assumed to be mainly composed of transient bacterial symbionts acquired from the host plant. We sampled Glanville fritillary (Melitaea cinxia) caterpillars from natural populations to describe their gut microbiome, and to identify potential ecological factors that determine its structure. Our results demonstrate high variability of microbiota composition even among caterpillars that shared the same host plant individual and most likely the same genetic background. We observed that the caterpillars harbored microbial classes that varied among individuals and alternated between two distinct communities (one composed of mainly Enterobacteriaceae and another with more variable microbiota community). Even though the general structure of the microbiota was not attributed to the measured ecological factors, we found that phylogenetically similar microbiota showed corresponding responses to the sex and the parasitoid infection of the caterpillar and to those of the host plant's microbial and chemical composition. Our results indicate high among-individual variability in the microbiota of the M. cinxia caterpillar and contradict previous findings that the host plant is the major driver of the microbiota communities of insect herbivores. This article is protected by copyright. All rights reserved.

RevDate: 2019-08-22

Kaunitz JD, Y Akiba (2019)

Control of Intestinal Epithelial Proliferation and Differentiation: The Microbiome, Enteroendocrine L Cells, Telocytes, Enteric Nerves, and GLP, Too.

RevDate: 2019-08-22

Anderson G, G Mazzoccoli (2019)

Left Ventricular Hypertrophy: Roles of Mitochondria CYP1B1 and Melatonergic Pathways in Co-Ordinating Wider Pathophysiology.

International journal of molecular sciences, 20(16): pii:ijms20164068.

Left ventricular hypertrophy (LVH) can be adaptive, as arising from exercise, or pathological, most commonly when driven by hypertension. The pathophysiology of LVH is consistently associated with an increase in cytochrome P450 (CYP)1B1 and mitogen-activated protein kinases (MAPKs) and a decrease in sirtuins and mitochondria functioning. Treatment is usually targeted to hypertension management, although it is widely accepted that treatment outcomes could be improved with cardiomyocyte hypertrophy targeted interventions. The current article reviews the wide, but disparate, bodies of data pertaining to LVH pathoetiology and pathophysiology, proposing a significant role for variations in the N-acetylserotonin (NAS)/melatonin ratio within mitochondria in driving the biological underpinnings of LVH. Heightened levels of mitochondria CYP1B1 drive the 'backward' conversion of melatonin to NAS, resulting in a loss of the co-operative interactions of melatonin and sirtuin-3 within mitochondria. NAS activates the brain-derived neurotrophic factor receptor, TrkB, leading to raised trophic signalling via cyclic adenosine 3',5'-monophosphate (cAMP)-response element binding protein (CREB) and the MAPKs, which are significantly increased in LVH. The gut microbiome may be intimately linked to how stress and depression associate with LVH and hypertension, with gut microbiome derived butyrate, and other histone deacetylase inhibitors, significant modulators of the melatonergic pathways and LVH more generally. This provides a model of LVH that has significant treatment and research implications.

RevDate: 2019-08-22

Di Marzo V, C Silvestri (2019)

Lifestyle and Metabolic Syndrome: Contribution of the Endocannabinoidome.

Nutrients, 11(8): pii:nu11081956.

Lifestyle is a well-known environmental factor that plays a major role in facilitating the development of metabolic syndrome or eventually exacerbating its consequences. Various lifestyle factors, especially changes in dietary habits, extreme temperatures, unusual light-dark cycles, substance abuse, and other stressful factors, are also established modifiers of the endocannabinoid system and its extended version, the endocannabinoidome. The endocannabinoidome is a complex lipid signaling system composed of a plethora (>100) of fatty acid-derived mediators and their receptors and anabolic and catabolic enzymes (>50 proteins) which are deeply involved in the control of energy metabolism and its pathological deviations. A strong link between the endocannabinoidome and another major player in metabolism and dysmetabolism, the gut microbiome, is also emerging. Here, we review several examples of how lifestyle modifications (westernized diets, lack or presence of certain nutritional factors, physical exercise, and the use of cannabis) can modulate the propensity to develop metabolic syndrome by modifying the crosstalk between the endocannabinoidome and the gut microbiome and, hence, how lifestyle interventions can provide new therapies against cardiometabolic risk by ensuring correct functioning of both these systems.

RevDate: 2019-08-22

Kim SK, Guevarra RB, Kim YT, et al (2019)

Role of Probiotics in Human Gut Microbiome-associated Diseases.

Journal of microbiology and biotechnology pii:10.4014/jmb.1906.06064 [Epub ahead of print].

Probiotics are live microorganisms, including bacteria and yeast, which have been demonstrated to have beneficial effects on human health. Since probiotic bacteria have been constantly being studied, applications of probiotics have been considered as promising adjuvant treatment for various intestinal diseases. Clinical trials and in vivo experiments have extended our current understanding of the important roles that probiotics play in human gut microbiome-associated diseases. Many clinical trials have documented that probiotics could shape the intestinal microbiota leading to potential control of multiple bowel diseases to promote overall wellness. In this review, we focused on the relationship between probiotics and the human gut microbiota and its roles in gut microbiome-associated diseases. Here, we also discussed future directions and research areas that need further elucidation in order to better understand the roles of probiotics in the treatment of intestinal diseases.

RevDate: 2019-08-21

Loebinger MR, Polverino E, Blasi F, et al (2019)

Efficacy and safety of tobramycin inhalation powder in bronchiectasis patients with P. aeruginosa infection: Design of a dose-finding study (iBEST-1).

Pulmonary pharmacology & therapeutics pii:S1094-5539(19)30192-0 [Epub ahead of print].

In patients with bronchiectasis (BE), infection with Pseudomonas aeruginosa (Pa) results in disease progression, frequent pulmonary exacerbations and lung function decline. However, at present, no inhaled antibiotics have been approved for the treatment of these patients. Tobramycin inhalation powder (TIP), approved for treatment of Pa infection in cystic fibrosis, could be a promising candidate. We aimed to assess effective and well-tolerated doses and regimens of TIP in BE patients with Pa infection. In this phase II, double-blind, placebo-controlled, randomised study, three different daily doses of TIP are administered either as continuous or cyclical regimens. The study protocol comprises 7-28 days of screening, 112 days of double-blind treatment and 56 days of follow-up. The plan was to enrol 180 patients (aged ≥18 years) with BE, documented Pa infection and a history of exacerbations. The primary outcome is change in sputum Pa density from baseline. Key secondary outcomes include number of pulmonary exacerbations, use of antipseudomonal antibiotics, serum and sputum tobramycin concentrations, quality of life and safety. Exploratory endpoints include lung clearance index, sputum inflammatory markers and microbiome analysis. As of October 2018, 107/180 patients were enrolled at 34 sites (six countries) following which recruitment was closed for administrative reasons unrelated to safety findings. Despite a reduced sample size from initially planned enrolment, the unique design may inform the benefit-risk profile of TIP in BE patients with chronic Pa infection. Moreover, several novel and exploratory endpoints (lung clearance index, inflammatory biomarkers, lung microbiome), will contribute to the advancement of research in this area.

RevDate: 2019-08-21

Litvak Y, AJ Bäumler (2019)

Microbiota-Nourishing Immunity: A Guide to Understanding Our Microbial Self.

Immunity, 51(2):214-224.

In ecological terms, the microbiome is defined as the microbiota and its environment, a definition that encompasses the human host. The size, species composition, and biogeography of microbial communities is shaped by host interactions, and, in turn, the microbiota influences many aspects of human health. Here we discuss the concept of microbiota-nourishing immunity, a host-microbe chimera composed of the microbiota and host factors that shape the microbial ecosystem, which functions in conferring colonization resistance against pathogens. We propose that dysbiosis is a biomarker of a weakening in microbiota-nourishing immunity and that homeostasis can be defined as a state of immune competence. Microbiota-nourishing immunity thus provides a conceptual framework to further examine the mechanisms that preserve a healthy microbiome and the drivers and consequences of dysbiosis.

RevDate: 2019-08-21

Gómez-Gallego C, García-Mantrana I, Martínez-Costa C, et al (2019)

The Microbiota and Malnutrition: Impact of Nutritional Status During Early Life.

Annual review of nutrition, 39:267-290.

According to the developmental origins of health and disease hypothesis, our health is determined by events experienced in utero and during early infancy. Indeed, both our prenatal and postnatal nutrition conditions have an impact on the initial architecture and activity of our microbiota. Recent evidence has underlined the importance of the composition of the early gut microbiota in relation to malnutrition, whether it be undernutrition or overnutrition, that is, in terms of both stunted and overweight development. It remains unclear how early microbial contact is linked to the risk of disease, as well as whether alterations in the microbiome underlie the pathogenesis of malnutrition or are merely the end result of it, which indicates that thequestion of causality must urgently be answered. This review provides information on the complex interaction between the microbiota and nutrition during the first 1,000 days of life, taking into account the impact of both undernutrition and overnutrition on the microbiota and on infants' health outcomes in the short- and long-term.

RevDate: 2019-08-21

Padhi E, Maharaj N, Lin SY, et al (2019)

Metabolome and microbiome signatures in the roots of citrus affected by Huanglongbing.

Phytopathology [Epub ahead of print].

Huanglongbing (HLB) is a severe, incurable citrus disease caused by the bacterium Candidatus Liberibacter asiaticus (CLas). Although citrus leaves serve as the site of initial infection, CLas is known to migrate to and colonize the root system, but little is known about the impact of CLas infection on root metabolism and resident microbial communities. Scions of 'Lisbon' lemon and 'Washington Navel' orange grafted onto 'Carrizo' rootstock were grafted with either CLas-infected citrus budwood or uninfected budwood. Roots were obtained from trees 46 weeks post-grafting and analyzed via 1H NMR spectroscopy to identify water-soluble root metabolites, and high-throughput sequencing of 16S rRNA and ITS gene amplicons to determine the relative abundance of bacterial and fungal taxa in the root rhizosphere and endosphere. In both citrus varieties, 27 metabolites were identified of which several were significantly different between CLas(+) and control plants. CLas infection also appeared to alter the microbial community structure near and inside the roots of citrus plants. Non-metric multidimensional scaling (NMDS) and principal coordinate analysis (PCoA) revealed distinct metabolite and microbial profiles, demonstrating that CLas impacts the root metabolome and microbiome in a manner that is variety-specific.

RevDate: 2019-08-21

Mager R, A Neisius (2019)

[Current concepts on the pathogenesis of urinary stones].

Der Urologe. Ausg. A pii:10.1007/s00120-019-1017-z [Epub ahead of print].

The process of kidney stone formation is complex and still not completely understood. Supersaturation and crystallization are the main drivers for the etiopathogenesis of uric acid, xanthine and cystine stones but this physicochemical concept fails to adequately explain the formation of calcium-based nephrolithiasis, which represents the majority of kidney stones. Contemporary concepts of the pathogenesis of calcium-based nephrolithiasis focus on a nidus-associated stone formation of calcium-based nephrolithiasis on Randall's plaques or on plugs of Bellini's duct. Randall's plaques originate from the interaction of interstitial calcium supersaturation in the renal papilla, vascular and interstitial inflammatory processes and mineral deposits of calcifying nanoparticles on the basal membrane of the thin ascending branch of the loop of Henle; however, plugs of Bellini's duct are assumed to be caused by mineral deposits on the wall of the collecting ducts. Aggregation and overgrowth are influenced by the interaction of matrix proteins with calcium supersaturated urine, by an imbalance between promoters and inhibitors of stone formation in the calyceal urine. Current research has elucidated many factors contributing to stone formation by revealing novel insights into the physiology of nephron and papilla, by analyzing vascular, inflammatory and calcifying processes in the renal medulla, by examining the proteome, the microbiome, promoters and inhibitors of stone formation in the urine and by conducting the first genome-wide association studies; however, more future research is mandatory to fill the gap of knowledge and hopefully, to obtain novel prophylactic, therapeutic and metaphylactic tools beyond the current state of knowledge.

RevDate: 2019-08-21

Moon D, Kim J, SP Yoon (2019)

Yeast extract inhibits the proliferation of renal cell carcinoma cells via regulation of iron metabolism.

Molecular medicine reports [Epub ahead of print].

The microbiome has recently attracted research interest in a variety of subjects, including cancer. In the present study, it was determined that reinforced clostridium media (RCM) for microbiome culture, exerts antitumor effects on renal cell carcinoma cells when compared to the microbiome 'X'. The antitumor effects of RCM were investigated for all ingredients of RCM, and the results revealed that yeast extract could be a candidate for the ingredient driving this phenomenon. Further experiments including MTT assay, cell counting, cell death analysis, cell cycle analysis and western blotting were conducted with yeast extract on renal cell carcinoma cells (Caki‑1 and Caki‑2) and normal human proximal tubular cells (HK‑2). As a result, yeast extract exhibited dose‑dependent antitumor effects on Caki‑1 and Caki‑2, but only slight effects on HK‑2. In addition, yeast extract only exhibited slight effects on necrosis, autophagy, or apoptosis of Caki‑1 and Caki‑2. Yeast extract produced cell cycle arrest with an increased G0/G1 fraction and a decreased S fraction, and this was considered to be related to the decreased cyclin D1. Although yeast extract treatment increased anti‑oxidant activities, the antitumor effects of yeast extract were also related to iron metabolism, based on the decreased transferrin receptor and increased ferritin. In addition, decreased GPX4 may be related to iron‑dependent cell death, particularly in Caki‑2. These results revealed that yeast extract may inhibit proliferation of renal cell carcinoma cells by regulating iron metabolism. Since an increased iron requirement is a classic phenomenon of cancer cells, yeast extract may be a candidate for adjuvant treatment of renal cell carcinoma.

RevDate: 2019-08-21

Bodkhe R, Balakrishnan B, V Taneja (2019)

The role of microbiome in rheumatoid arthritis treatment.

Therapeutic advances in musculoskeletal disease, 11:1759720X19844632 pii:10.1177_1759720X19844632.

Rheumatoid arthritis (RA) is an autoimmune disorder with multifactorial etiology; both genetic and environmental factors are known to be involved in pathogenesis. Treatment with disease-modifying antirheumatic drugs (DMARDs) plays an essential role in controlling disease progression and symptoms. DMARDs have immunomodulatory properties and suppress immune response by interfering in various pro-inflammatory pathways. Recent evidence has shown that the gut microbiota directly and indirectly modulates the host immune system. RA has been associated with dysbiosis of the gut microbiota. Patients with RA treated with DMARDs show partial restoration of eubiotic gut microbiome. Hence, it is essential to understand the impact of DMARDs on the microbial composition and its consequent influences on the host immune system to identify novel therapies for RA. In this review, we discuss the importance of antirheumatic-drug-induced host microbiota modulations and possible probiotics that can generate eubiosis.

RevDate: 2019-08-21

Reardon S (2019)

Do C-section babies need mum's microbes? Trials tackle controversial idea.

Nature, 572(7770):423-424.

RevDate: 2019-08-21

Taroni JN (2019)

Making Workshops Work: Insights from EDAMAME.

mSystems, 4(4): pii:4/4/e00467-19.

Microbiology, like many areas of life science research, is increasingly data-intensive. As such, bioinformatics and data science skills have become essential to leverage microbiome sequencing data for discovery. Short intensive courses have sprung up as formal computational training opportunities at individual institutions fail to meet demands. In this issue, Shade et al. (A. Shade, T. K. Dunivin, J. Choi, T. K. Teal, et al., mSystems 4:e00297-19, 2019, share their experience and approach in executing the annual, weeklong Explorations in Data Analysis for Metagenomic Advances in Microbial Ecology (EDAMAME) workshop from 2014 to 2018. EDAMAME introduced learners to general scientific computing concepts and domain-specific data analysis approaches. Workshop learners self-reported appreciable gains in understanding and ability. This report on the EDAMAME workshop strategy and lessons learned will help others in the life sciences to plan, execute, and assess short hands-on computing-intensive courses that support research in a particular domain.

RevDate: 2019-08-21

Shade A, Dunivin TK, Choi J, et al (2019)

Strategies for Building Computing Skills To Support Microbiome Analysis: a Five-Year Perspective from the EDAMAME Workshop.

mSystems, 4(4): pii:4/4/e00297-19.

Here, we report our educational approach and learner evaluations of the first 5 years of the Explorations in Data Analysis for Metagenomic Advances in Microbial Ecology (EDAMAME) workshop, held annually at Michigan State University's Kellogg Biological Station from 2014 to 2018. We hope this information will be useful for others who want to organize computing-intensive workshops and will encourage quantitative skill development among microbiologists.IMPORTANCE High-throughput sequencing and related statistical and bioinformatic analyses have become routine in microbiology in the past decade, but there are few formal training opportunities to develop these skills. A weeklong workshop can offer sufficient time for novices to become introduced to best computing practices and common workflows in sequence analysis. We report our experiences in executing such a workshop targeted to professional learners (graduate students, postdoctoral scientists, faculty, and research staff).

RevDate: 2019-08-21

Sun Z, Huang S, Zhu P, et al (2019)

A Microbiome-Based Index for Assessing Skin Health and Treatment Effects for Atopic Dermatitis in Children.

mSystems, 4(4): pii:4/4/e00293-19.

A quantitative and objective indicator for skin health via the microbiome is of great interest for personalized skin care, but differences among skin sites and across human populations can make this goal challenging. A three-city (two Chinese and one American) comparison of skin microbiota from atopic dermatitis (AD) and healthy pediatric cohorts revealed that, although city has the greatest effect size (the skin microbiome can predict the originated city with near 100% accuracy), a microbial index of skin health (MiSH) based on 25 bacterial genera can diagnose AD with 83 to ∼95% accuracy within each city and 86.4% accuracy across cities (area under the concentration-time curve [AUC], 0.90). Moreover, nonlesional skin sites across the bodies of AD-active children (which include shank, arm, popliteal fossa, elbow, antecubital fossa, knee, neck, and axilla) harbor a distinct but lesional state-like microbiome that features relative enrichment of Staphylococcus aureus over healthy individuals, confirming the extension of microbiome dysbiosis across body surface in AD patients. Intriguingly, pretreatment MiSH classifies children with identical AD clinical symptoms into two host types with distinct microbial diversity and treatment effects of corticosteroid therapy. These findings suggest that MiSH has the potential to diagnose AD, assess risk-prone state of skin, and predict treatment response in children across human populations.IMPORTANCE MiSH, which is based on the skin microbiome, can quantitatively assess pediatric skin health across cohorts from distinct countries over large geographic distances. Moreover, the index can identify a risk-prone skin state and compare treatment effect in children, suggesting applications in diagnosis and patient stratification.

RevDate: 2019-08-21

Keating JA, Shaughnessy C, Baubie K, et al (2019)

Characterising the gut microbiome in veterans with Gulf War Illness: a protocol for a longitudinal, prospective cohort study.

BMJ open, 9(8):e031114 pii:bmjopen-2019-031114.

INTRODUCTION: Approximately 25%-35% of the 1991 Gulf War Veteran population report symptoms consistent with Gulf War Illness (GWI), a chronic, multi-symptom illness characterised by fatigue, pain, irritable bowel syndrome and problems with cognitive function. GWI is a disabling problem for Gulf War Veterans, and there remains a critical need to identify innovative, novel therapies.Gut microbiota perturbation plays a key role in the symptomatology of other chronic multi-symptom illnesses, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Given similarities between ME/CFS and GWI and the presence of gastrointestinal disorders in GWI patients, Veterans with GWI may also have gut abnormalities like those seen with ME/CFS. In this longitudinal cohort study, we are comparing the diversity (structure) and the metagenomes (function) of the gut microbiome between Gulf War Veterans with and without GWI. If we find differences in Veterans with GWI, the microbiome could be a target for therapeutic intervention to alleviate GWI symptoms.

METHODS AND ANALYSIS: Participants answer questions about diet, exercise and lifestyle factors. Participants also complete a questionnaire (based on the Kansas case definition of GWI) regarding their medical history and symptoms; we use this questionnaire to group participants into GWI versus healthy control cohorts. We plan to enrol 52 deployed Gulf War Veterans: 26 with GWI and 26 healthy controls. Participants provide stool and saliva samples weekly for an 8-week period for microbiome analyses. Participants also provide blood samples at the beginning and end of this period, which we will use to compare measures of inflammation markers between the groups.

ETHICS AND DISSEMINATION: The protocol was approved by the University of Wisconsin-Madison Health Sciences Institutional Review Board and the William S. Middleton Memorial Veterans Hospital Research and Development Committee. Results of this study will be submitted for publication in a peer-reviewed journal.

RevDate: 2019-08-20

Cherif-Silini H, Thissera B, Bouket AC, et al (2019)

Durum Wheat Stress Tolerance Induced by Endophyte Pantoea agglomerans with Genes Contributing to Plant Functions and Secondary Metabolite Arsenal.

International journal of molecular sciences, 20(16): pii:ijms20163989.

In the arid region Bou-Saâda at the South of Algeria, durum wheat Triticum durum L. cv Waha production is severely threatened by abiotic stresses, mainly drought and salinity. Plant growth-promoting rhizobacteria (PGPR) hold promising prospects towards sustainable and environmentally-friendly agriculture. Using habitat-adapted symbiosis strategy, the PGPR Pantoea agglomerans strain Pa was recovered from wheat roots sampled in Bou-Saâda, conferred alleviation of salt stress in durum wheat plants and allowed considerable growth in this unhostile environment. Strain Pa showed growth up to 35 °C temperature, 5-10 pH range, and up to 30% polyethylene glycol (PEG), as well as 1 M salt concentration tolerance. Pa strain displayed pertinent plant growth promotion (PGP) features (direct and indirect) such as hormone auxin biosynthesis, production of 1-aminocyclopropane-1-carboxylate (ACC) deaminase, and ammonia and phosphate solubilization. PGPR features were stable over wide salt concentrations (0-400 mM). Pa strain was also able to survive in seeds, in the non-sterile and sterile wheat rhizosphere, and was shown to have an endophytic life style. Phylogenomic analysis of strain Pa indicated that Pantoea genus suffers taxonomic imprecision which blurs species delimitation and may have impacted their practical use as biofertilizers. When applied to plants, strain Pa promoted considerable growth of wheat seedlings, high chlorophyll content, lower accumulation of proline, and favored K+ accumulation in the inoculated plants when compared to Na+ in control non-inoculated plants. Metabolomic profiling of strain Pa under one strain many compounds (OSMAC) conditions revealed a wide diversity of secondary metabolites (SM) with interesting salt stress alleviation and PGP activities. All these findings strongly promote the implementation of Pantoea agglomerans strain Pa as an efficient biofertilizer in wheat plants culture in arid and salinity-impacted regions.

RevDate: 2019-08-20

Meyer S, Thiel V, Joergensen RG, et al (2019)

Relationships between feeding and microbial faeces indices in dairy cows at different milk yield levels.

PloS one, 14(8):e0221266 pii:PONE-D-18-29958.

A study was carried out to gain quantitative information on the diet-dependent faecal microbial biomass of dairy cows, especially on the biomass fractions of fungi, Gram-positive (G+) and Gram-negative (G-) bacteria. Groups of high-yield, low-yield and non-lactating cows were investigated at four different farms. A mean faecal microbial biomass C (MBC) concentration of 33.5 mg g-1 DM was obtained by the chloroform fumigation extraction method. This is similar to a mean microbial C concentration of 31.8 mg g-1 DM, which is the sum of bacterial C and fungal C, estimated by cell-wall derived muramic acid (MurN) and fungal glucosamine (GlcN), respectively. However, the response of these two approaches to the feeding regime was contradictory, due to feeding effects on the conversion values. The higher neutral detergent fibre (NDF) and acid detergent fibre (ADF) concentrations in the non-lactating group led to higher (P < 0.05) concentrations of cellulose and lignin in their faeces in comparison with the lactating cows. This change in faecal chemical composition in the non-lactating group was accompanied by usually higher ratios of G+/G- phospholipid fatty acids (PLFA), ergosterol/MBC and fungal C/bacterial C. Although bacteria dominate the faecal microbial biomass, fungi contribute a considerable mean percentage of roughly 20% to the faecal microbiome, according to PLFA and amino sugar data, which requires more attention in the future. Near-infra red spectroscopic estimates of organic N and C fractions of cow faeces were able to model microbial biomarkers successfully, which might be useful in the future to predict its N2O emission potential and fertilizer value.

RevDate: 2019-08-20

Velazquez S, Griffiths W, Dietz L, et al (2019)

From one species to another: A review on the interaction of chemistry and microbiology in relation to cleaning in the built environment.

Indoor air [Epub ahead of print].

Since the advent of soap, personal hygiene practices have revolved around removal, sterilization, and disinfection - both of visible soil and microscopic organisms - for a myriad of cultural, aesthetic, or health-related reasons. Cleaning methods and products vary widely in their recommended use, effectiveness, risk to users or building occupants, environmental sustainability, and ecological impact. Advancements in science and technology have facilitated in-depth analyses of the indoor microbiome and studies in this field suggest that the traditional "scorched-earth cleaning" mentality - that surfaces must be completely sterilized and prevent microbial establishment - may contribute to long-term human health consequences. Moreover, the materials, products, activities, and microbial communities indoors all contribute to, or remove, chemical species to the indoor environment. This review examines the effects of cleaning with respect to the interaction of chemistry, indoor microbiology, and human health. PRACTICAL IMPLICATIONS: Simple interventions, such as hand washing, can dramatically improve health and reduce infectious disease. Chemical intervention, while effective, may encourage the development of microbial resistance over time if not implemented properly. Microbial communities adapt, reassemble, and persist, and recent theory in microbial ecology suggests that curating microbial communities may be more sustainable than perpetually attempting to remove them. This article is protected by copyright. All rights reserved.

RevDate: 2019-08-20

Denu L, Lubin JB, Douglas B, et al (2019)

Diet-induced microbial autofluorescence confounds flow cytometry of ex vivo isolated fecal microbes.

European journal of immunology [Epub ahead of print].

Microbial flow cytometry is a powerful emerging technology with a broad range of applications including the study of complex microbial communities. Immunologists are increasingly using this technology to study antibody responses against pathogenic and commensal microbes. We employed microbial flow cytometry to quantify the proportion of fecal microbes bound by six different immunoglobulin isotypes: IgA, IgM, IgG1, IgG2b, IgG2c, and IgG3. In healthy mammals, secretory IgA (sIgA) binds to a subset of commensal microbes in the gut whereas IgG is not typically found in the intestinal tract of healthy mammals. Unexpectedly, fecal microbes isolated from SPF C57BL/6 mice housed in the Hill facility and imported from the vendors The Jackson Laboratory (JAX) and Taconic Biosciences (TAC) showed a strong signal in the Brilliant Violet 711 (BV711) channel. Unstained fecal samples from these mice demonstrated that the BV711 signal was due to bacterial autofluorescence. We found that murine diets containing alfalfa induce ex vivo microbial autofluorescence in the far red spectrum, likely due to chlorophyll. Analysis of unstained intestinal microbes is an important step in microbial flow cytometry to identify diet-induced autofluorescence. We recommend fluorophores with emission spectra below 650 nm (e.g. BV421, PE). This article is protected by copyright. All rights reserved.

RevDate: 2019-08-20

Malard LA, Anwar MZ, Jacobsen CS, et al (2019)

Biogeographical patterns in soil bacterial communities across the Arctic region.

FEMS microbiology ecology pii:5552140 [Epub ahead of print].

The considerable microbial diversity of soils, their variety and key role in biogeochemical cycling has led to growing interest in their global distribution and the impact that environmental change might have at the regional level. In the broadest study of Arctic soil bacterial communities to date, we used high-throughput DNA sequencing to investigate the bacterial diversity from 200 independent Arctic soil samples from 43 sites. We quantified the impact of spatial and environmental factors on bacterial community structure using variation partitioning analysis, illustrating a non-random distribution across the region. pH was confirmed as the key environmental driver structuring Arctic soil bacterial communities, while total organic carbon, moisture and conductivity were shown to have little effect. Specialist taxa were more abundant in acidic and alkaline soils while generalist taxa were more abundant in acidoneutral soils. Of 48,147 bacterial taxa, a core microbiome composed of only 13 taxa that were ubiquitously distributed and present within 95% of samples was identified, illustrating the high potential for endemism in the region. Overall, our results demonstrate the importance of spatial and edaphic factors on the structure of Arctic soil bacterial communities.

RevDate: 2019-08-20

Casimiro-Soriguer CS, Loucera C, Perez Florido J, et al (2019)

Antibiotic resistance and metabolic profiles as functional biomarkers that accurately predict the geographic origin of city metagenomics samples.

Biology direct, 14(1):15 pii:10.1186/s13062-019-0246-9.

BACKGROUND: The availability of hundreds of city microbiome profiles allows the development of increasingly accurate predictors of the origin of a sample based on its microbiota composition. Typical microbiome studies involve the analysis of bacterial abundance profiles.

RESULTS: Here we use a transformation of the conventional bacterial strain or gene abundance profiles to functional profiles that account for bacterial metabolism and other cell functionalities. These profiles are used as features for city classification in a machine learning algorithm that allows the extraction of the most relevant features for the classification.

CONCLUSIONS: We demonstrate here that the use of functional profiles not only predict accurately the most likely origin of a sample but also to provide an interesting functional point of view of the biogeography of the microbiota. Interestingly, we show how cities can be classified based on the observed profile of antibiotic resistances.

REVIEWERS: Open peer review: Reviewed by Jin Zhuang Dou, Jing Zhou, Torsten Semmler and Eran Elhaik.

RevDate: 2019-08-20

Yue S, He T, Li B, et al (2019)

Effectiveness of Yi-Zhi-An-Shen granules on cognition and sleep quality in older adults with amnestic mild cognitive impairment: protocol for a randomized, double-blind, placebo-controlled trial.

Trials, 20(1):518 pii:10.1186/s13063-019-3607-x.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is a syndrome characterized by significant forgetfulness that does not meet the criteria of dementia. Individuals with aMCI are at greater risk of progressing to dementia. Current studies suggest that good sleep quality is linked with preserved cognition in the elderly, and sleep complaints are common among the elderly with amnesia. Therefore, improving their sleep may be helpful for maintaining and improving their cognitive capacity. According to the theory of traditional Chinese medicine, Yi-Zhi-An-Shen is an herbal compound which may ameliorate forgetfulness and sleep disorders. As growing evidence indicates that the gut microbiome is associated with major mental symptoms, a hypothesis was proposed that Yi-Zhi-An-Shen granules (YZASG) might work by alternating microbial abundance and diversity. In this study, the investigators intend to assess the efficacy of YZASG on global cognition in the elderly suffering from aMCI and evaluate its safety as well as its potential mechanisms via sleep quality, fecal microbial 16S ribosomal DNA and metagenomics analyses, and serum markers.

METHODS/DESIGN: This study is a randomized, double-blind, placebo-controlled clinical trial. A total of 80 patients (aged 60-85 years) will be recruited and allocated randomly to a treatment group and a placebo group in a 1:1 ratio and will then be administered YZASG or isodose placebo three times a day. The intervention course is 16 weeks, with an 18 months follow-up. The primary outcome is the Alzheimer's Disease Assessment Scale-Cognitive Subscale. Secondary outcome measures are the Mini-Mental State Examination, Montreal Cognitive Assessment, Pittsburgh Sleep Quality Index, serum concentrations of immunological factors and inflammatory cytokines, and fecal microbiota. Fecal microbiota will only be collected at the baseline and endpoint of the intervention.

DISCUSSION: The results of this trial will be conducive to assessing the safety and effectiveness on cognition of YZASG in intervening aMCI among the elderly and determining if it takes effect via the improvement of sleep quality, regulation of gut microbiota, and concentration of certain serum markers.

TRIAL REGISTRATION:, NCT03601000 . Registered on 26 July 2018.

RevDate: 2019-08-20

Siebert JC, Neff CP, Schneider JM, et al (2019)

VOLARE: visual analysis of disease-associated microbiome-immune system interplay.

BMC bioinformatics, 20(1):432 pii:10.1186/s12859-019-3021-0.

BACKGROUND: Relationships between specific microbes and proper immune system development, composition, and function have been reported in a number of studies. However, researchers have discovered only a fraction of the likely relationships. "Omic" methodologies such as 16S ribosomal RNA (rRNA) sequencing and time-of-flight mass cytometry (CyTOF) immunophenotyping generate data that support generation of hypotheses, with the potential to identify additional relationships at a level of granularity ripe for further experimentation. Pairwise linear regressions between microbial and host immune features provide one approach for quantifying relationships between "omes", and the differences in these relationships across study cohorts or arms. This approach yields a top table of candidate results. However, the top table alone lacks the detail that domain experts such as microbiologists and immunologists need to vet candidate results for follow-up experiments.

RESULTS: To support this vetting, we developed VOLARE (Visualization Of LineAr Regression Elements), a web application that integrates a searchable top table, small in-line graphs illustrating the fitted models, a network summarizing the top table, and on-demand detailed regression plots showing full sample-level detail. We applied VOLARE to three case studies-microbiome:cytokine data from fecal samples in human immunodeficiency virus (HIV), microbiome:cytokine data in inflammatory bowel disease and spondyloarthritis, and microbiome:immune cell data from gut biopsies in HIV. We present both patient-specific phenomena and relationships that differ by disease state. We also analyzed interaction data from system logs to characterize usage scenarios. This log analysis revealed that users frequently generated detailed regression plots, suggesting that this detail aids the vetting of results.

CONCLUSIONS: Systematically integrating microbe:immune cell readouts through pairwise linear regressions and presenting the top table in an interactive environment supports the vetting of results for scientific relevance. VOLARE allows domain experts to control the analysis of their results, screening dozens of candidate relationships with ease. This interactive environment transcends the limitations of a static top table.

RevDate: 2019-08-20

Finlin BS, Zhu B, Boyechko T, et al (2019)

Effect of Rifaximin Treatment on Endotoxemia and Insulin Sensitivity in Humans.

Journal of the Endocrine Society, 3(9):1641-1651 pii:jes_201900148.

Context: The gut microbiome is a source of inflammatory factors such as lipopolysaccharide (LPS; endotoxin) that influence metabolic homeostasis. Rifaximin is a well-tolerated antibiotic that may reduce LPS.

Objective: We sought to develop a method to accurately assess postprandial endotoxemia and to determine whether rifaximin treatment improves metabolic homeostasis in obese humans with metabolic syndrome.

Design and Setting: Plasma LPS, adipose inflammation, glucose and lipid metabolism, and insulin sensitivity were evaluated in a clinical research setting.

Participants: Twelve obese human research participants with prediabetes or three features of metabolic syndrome participated.

Intervention: The research participants were randomized to placebo control or rifaximin soluble solid dispersion (80 mg/d) treatment groups and treated for 12 weeks.

Outcome Measures: We evaluated changes in insulin sensitivity with a euglycemic clamp; changes in lipid and glucose metabolism with oral lipid and glucose tolerance tests; changes in plasma LPS during the lipid tolerance test; and changes in adipose tissue and systemic inflammation by measuring inflammatory cytokines.

Results: Rifaximin treatment slightly worsened insulin sensitivity (P = 0.03), did not improve glucose or lipid homeostasis, and did not significantly improve adipose tissue inflammation. Our efforts to accurately assess plasma LPS using limulus amebocyte lysate assays revealed that the majority of LPS is masked from detection by limulus amebocyte lysate assays, but can be unmasked using a pretreatment step with protease. Unmasked LPS increases during the lipid tolerance test, but rifaximin treatment did not reduce this.

Conclusions: Rifaximin treatment did not lower plasma LPS or improve metabolic homeostasis in obese humans.

RevDate: 2019-08-20

Vuik F, Dicksved J, Lam SY, et al (2019)

Composition of the mucosa-associated microbiota along the entire gastrointestinal tract of human individuals.

United European gastroenterology journal, 7(7):897-907.

Background: Homeostasis of the gastrointestinal tract depends on a healthy bacterial microbiota, with alterations in microbiota composition suggested to contribute to diseases. To unravel bacterial contribution to disease pathology, a thorough understanding of the microbiota of the complete gastrointestinal tract is essential. To date, most microbial analyses have either focused on faecal samples, or on the microbial constitution of one gastrointestinal location instead of different locations within one individual.

Objective: We aimed to analyse the mucosal microbiome along the entire gastrointestinal tract within the same individuals.

Methods: Mucosal biopsies were taken from nine different sites in 14 individuals undergoing antegrade and subsequent retrograde double-balloon enteroscopy. The bacterial composition was characterised using 16 S rRNA sequencing with Illumina Miseq.

Results: At double-balloon enteroscopy, one individual had a caecal adenocarcinoma and one individual had Peutz-Jeghers polyps. The composition of the microbiota distinctively changed along the gastrointestinal tract with larger bacterial load, diversity and abundance of Firmicutes and Bacteroidetes in the lower gastrointestinal tract than the upper gastrointestinal tract, which was predominated by Proteobacteria and Firmicutes.

Conclusions: We show that gastrointestinal location is a larger determinant of mucosal microbial diversity than inter-person differences. These data provide a baseline for further studies investigating gastrointestinal microbiota-related disease.

RevDate: 2019-08-20

George NS, Cheung L, Luthria DL, et al (2019)

Pomegranate peel extract alters the microbiome in mice and dysbiosis caused by Citrobacter rodentium infection.

Food science & nutrition, 7(8):2565-2576 pii:FSN31106.

Treatment of mice with a pomegranate peel extract (PPX) decreased the pathogenicity of Citrobacter rodentium (Cr) infections. Here, we investigate the effects of PPX on the microbiome of uninfected or Cr-infected C3H/HeNCr mice by 16S rRNA gene sequencing. Mice were treated with water or PPX for 14 days, feces were collected, and then, the mice were infected with Cr and feces collected again at day 6 postinfection. DNA was isolated from the fecal samples and subjected to 16S rRNA gene sequencing to determine the microbial composition. Differences in the composition of the microbiome were observed for untreated and PPX-treated mice with PPX mice having decreased diversity. PPX treatment decreased the Firmicutes/Bacteroidetes ratio by increasing Bacteroidetes and decreasing Firmicutes levels. The decrease in Firmicutes was driven by a large reduction in Lactobacillus. PPX treatment increased the abundance of Proteobacteria and Verrucomicrobiae and decreased Actinobacteria. The relative abundance of Cr reached 22% in water-treated but only 5% in PPX-treated infected mice. These results suggest that consumption of pomegranate polyphenols altered the microbiome, making it more resistant to displacement by infection with Cr, indicating that pomegranate polyphenols may mitigate the pathogenic effects of food-borne bacterial pathogens.

RevDate: 2019-08-20

Vital M, Rud T, Rath S, et al (2019)

Diversity of Bacteria Exhibiting Bile Acid-inducible 7α-dehydroxylation Genes in the Human Gut.

Computational and structural biotechnology journal, 17:1016-1019 pii:S2001-0370(19)30223-5.

The secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA), formed by gut microbiota from primary bile acids via a multi-step 7α-dehydroxylation reaction, have wide-ranging effects on host metabolism and play an important role in health and disease. A few 7α-dehydroxylating strains have been isolated, where bile acid-inducible (bai) genes were organized in a gene cluster and encoded major enzymes involved. However, only little is known on diversity and abundance of intestinal bacteria catalysing DCA/LCA formation in the human gut in situ. In this study, we took the opportunity to screen metagenome-assembled genomes (MAGs) from sequence data of stool samples provided by two recent studies along with newly available gut-derived isolates for the presence of the bai gene cluster. We revealed in total 765 and 620 MAGs encoding the potential to form DCA/LCA that grouped into 21 and 26 metagenomic species, respectively. The majority of MAGs (92.4 and 90.3%) were associated with a Ruminococcaceae clade that still lacks an isolate, whereas less MAGs belonged to Lachnospiraceae along with eight new isolates (n total = 11) that contained the bai genes. Only a few MAGs were linked to Peptostreptococcaceae. Signatures for horizontal transfer of bai genes were observed. This study gives a comprehensive overview of the diversity of bai-exhibiting bacteria in the human gut highlighting the application of metagenomics to unravel potential functions hidden from current isolates. Eventually, isolates of the identified main MAG clade are required in order to prove their capability of 7α-dehydroxylating primary bile acids.

RevDate: 2019-08-20

Sun L, Jia H, Li J, et al (2019)

Cecal Gut Microbiota and Metabolites Might Contribute to the Severity of Acute Myocardial Ischemia by Impacting the Intestinal Permeability, Oxidative Stress, and Energy Metabolism.

Frontiers in microbiology, 10:1745.

Emerging evidence highlights the role of gut microbiota in regulating the pathogenesis of coronary heart disease. Here, we performed 16S rRNA gene sequencing and UPLC-Q-TOF/MS-based metabolomics to investigate the gut microbiome and metabolomes of cecal contents in the isoproterenol (ISO)-induced acute myocardial ischemia (AMI) rats. As expected, considerable gut microbiota alterations were observed in the AMI rats compared with the control rats, paralleling with intestinal inflammation and apoptosis. At phylum level, the abundance of Firmicutes was significantly decreased, whereas the abundance of Bacteroidetes and Spirochaetae was strikingly enriched in the AMI group. At genus level, the significant alteration of genera Treponema 2, Rikenellaceae RC9 gut group, Prevotellaceae UCG-003, and Bacteroides may contribute to the pathogenesis of AMI. These altered microbiota might influence the intestinal permeability and subsequently impair intestinal barrier and stimulate gut inflammation. Consistently, significantly metabolic differences of cecal contents between the AMI and control groups were revealed, and threonic acid, L-urobilin and L-urobilinogen were considered the most associated cecal metabolites with AMI. These strikingly altered metabolites were mainly related to energy metabolism and oxidative stress which could lead to apoptosis and further affect gut barrier. Ultimately, we revealed the potential link of these altered gut microbiota/metabolomes and intestinal inflammatory factors and apoptotic proteins and further confirmed their intimate connections with intestinal inflammation and gut barrier. Our findings depict uncovered potential relationship among the gut microbiome, cecal metabolomes and AMI.

RevDate: 2019-08-20

Lee Y, Sugihara K, Gillilland MG, et al (2019)

Hyaluronic acid-bilirubin nanomedicine for targeted modulation of dysregulated intestinal barrier, microbiome and immune responses in colitis.

Nature materials pii:10.1038/s41563-019-0462-9 [Epub ahead of print].

While conventional approaches for inflammatory bowel diseases mainly focus on suppressing hyperactive immune responses, it remains unclear how to address disrupted intestinal barriers, dysbiosis of the gut commensal microbiota and dysregulated mucosal immune responses in inflammatory bowel diseases. Moreover, immunosuppressive agents can cause off-target systemic side effects and complications. Here, we report the development of hyaluronic acid-bilirubin nanomedicine (HABN) that accumulates in inflamed colonic epithelium and restores the epithelium barriers in a murine model of acute colitis. Surprisingly, HABN also modulates the gut microbiota, increasing the overall richness and diversity and markedly augmenting the abundance of Akkermansia muciniphila and Clostridium XIVα, which are microorganisms with crucial roles in gut homeostasis. Importantly, HABN associated with pro-inflammatory macrophages, regulated innate immune responses and exerted potent therapeutic efficacy against colitis. Our work sheds light on the impact of nanotherapeutics on gut homeostasis, microbiome and innate immune responses for the treatment of inflammatory diseases.

RevDate: 2019-08-20

Horvath A, Rainer F, Bashir M, et al (2019)

Biomarkers for oralization during long-term proton pump inhibitor therapy predict survival in cirrhosis.

Scientific reports, 9(1):12000 pii:10.1038/s41598-019-48352-5.

Proton pump inhibitors (PPI) are an invaluable therapy option for acid related diseases; however, PPI therapy is also linked to a series of side effects in cirrhosis, such as microbiome alterations, spontaneous bacterial peritonitis and hepatic encephalopathy. Decision tools to balance benefits and risks of PPI therapy are largely missing. In this study, we tested gut-derived biomarkers to identify PPI-associated dysbiosis, its association with gut barrier function and liver-related mortality. In this observational study, faecal microbiome composition data obtained from 16S rDNA sequencing of 90 cirrhotic patients with and without long-term PPI use and additional potential biomarkers identified from the literature were evaluated for their predictive value regarding PPI-associated dysbiosis and liver-related three-year mortality. In addition, faecal calprotectin, faecal zonulin and serum lipopolysaccharides were assessed as markers for intestinal inflammation, gut permeability and bacterial translocation. Streptococcus salivarius, Veillonella parvula and the genus Streptococcus were significantly increased in patients with long-term PPI therapy and performed well as biomarkers for PPI-associated dysbiosis (accuracy: 74%, 72% and 74%, respectively). The abundance of Streptococcus salivarius was linked to intestinal inflammation and gut barrier dysfunction, whereas the abundance of Veillonella parvula showed associations with liver disease severity; both were independent predictors for liver-related three-year mortality. Gut-derived biomarkers of PPI-associated dysbiosis are linked to worse outcome and a potential option to evaluate the risks of adverse events during long-term PPI therapy.

RevDate: 2019-08-20

Yang Y, Yin Y, Chen X, et al (2019)

Evaluating different extraction solvents for GC-MS based metabolomic analysis of the fecal metabolome of adult and baby giant pandas.

Scientific reports, 9(1):12017 pii:10.1038/s41598-019-48453-1.

The gut microbiome plays a fundamental role in host health and the fecal metabolome can be analysed to assess microbial activity and can be used as an intermediate phenotype monitoring the host-microbiome relationship. However, there is no established extraction protocol to study the fecal metabolome of giant pandas. The aim of this research is to optimize extraction of the fecal metabolome from adult and baby pandas for high throughput metabolomics analysis using gas chromatography-mass spectrometry (GC-MS). Fecal samples were collected from eight adult pandas and a pair of twin baby pandas. Six different extraction solvents were investigated and evaluated for their reproducibility, metabolite coverage, and extraction efficiency, particularly in relation to the biochemical compound classes such as amino acids, tricarboxylic acid (TCA) cycle intermediates, fatty acids, secondary metabolites, and vitamin and cofactors. Our GC-MS results demonstrated that the extraction solvents with isopropanol: acetonitrile: water (3:2:2 ratio) and 80% methanol were the most appropriate for studying the fecal metabolome of adult and baby giant pandas respectively. These extraction solvents can be used in future study protocols for the analysis of the fecal metabolome in giant pandas.

RevDate: 2019-08-20

Zhang J, Haines C, Watson AJM, et al (2019)

Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989-2012: a matched case-control study.

Gut pii:gutjnl-2019-318593 [Epub ahead of print].

BACKGROUND: Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and risk patterns is lacking.

OBJECTIVE: To assess the association between oral antibiotic use and CRC risk.

DESIGN: A matched case-control study (incident CRC cases and up to five matched controls) was performed using the Clinical Practice Research Datalink from 1989 to 2012.

RESULTS: 28 980 CRC cases and 137 077 controls were identified. Oral antibiotic use was associated with CRC risk, but effects differed by anatomical location. Antibiotic use increased the risk of colon cancer in a dose-dependent fashion (ptrend <0.001). The risk was observed after minimal use, and was greatest in the proximal colon and with antibiotics with anti-anaerobic activity. In contrast, an inverse association was detected between antibiotic use and rectal cancers (ptrend=0.003), particularly with length of antibiotic exposure >60 days (adjusted OR (aOR), 0.85, 95% CI 0.79 to 0.93) as compared with no antibiotic exposure. Penicillins, particularly ampicillin/amoxicillin increased the risk of colon cancer (aOR=1.09 (1.05 to 1.13)), whereas tetracyclines reduced the risk of rectal cancer (aOR=0.90 (0.84 to 0.97)). Significant interactions were detected between antibiotic use and tumour location (colon vs rectum, pinteraction<0.001; proximal colon versus distal colon, pinteraction=0.019). The antibiotic-cancer association was found for antibiotic exposure occurring >10 years before diagnosis (aOR=1.17 (1.06 to 1.31)).

CONCLUSION: Oral antibiotic use is associated with an increased risk of colon cancer but a reduced risk of rectal cancer. This effect heterogeneity may suggest differences in gut microbiota and carcinogenesis mechanisms along the lower intestinal tract.

RevDate: 2019-08-20

Misselwitz B, Butter M, Verbeke K, et al (2019)

Update on lactose malabsorption and intolerance: pathogenesis, diagnosis and clinical management.

Gut pii:gutjnl-2019-318404 [Epub ahead of print].

Lactose is the main source of calories in milk, an essential nutriedigestion, patients with visceral hypersensitivity nt in infancy and a key part of the diet in populations that maintain the ability to digest this disaccharide in adulthood. Lactase deficiency (LD) is the failure to express the enzyme that hydrolyses lactose into galactose and glucose in the small intestine. The genetic mechanism of lactase persistence in adult Caucasians is mediated by a single C→T nucleotide polymorphism at the LCTbo -13'910 locus on chromosome-2. Lactose malabsorption (LM) refers to any cause of failure to digest and/or absorb lactose in the small intestine. This includes primary genetic and also secondary LD due to infection or other conditions that affect the mucosal integrity of the small bowel. Lactose intolerance (LI) is defined as the onset of abdominal symptoms such as abdominal pain, bloating and diarrhoea after lactose ingestion by an individual with LM. The likelihood of LI depends on the lactose dose, lactase expression and the intestinal microbiome. Independent of lactose digestion, patients with visceral hypersensitivity associated with anxiety or the Irritable Bowel Syndrome (IBS) are at increased risk of the condition. Diagnostic investigations available to diagnose LM and LI include genetic, endoscopic and physiological tests. The association between self-reported LI, objective findings and clinical outcome of dietary intervention is variable. Treatment of LI can include low-lactose diet, lactase supplementation and, potentially, colonic adaptation by prebiotics. The clinical outcome of these treatments is modest, because lactose is just one of a number of poorly absorbed carbohydrates which can cause symptoms by similar mechanisms.

RevDate: 2019-08-20

Li H, Li H, Wang J, et al (2019)

The altered gut virome community in rhesus monkeys is correlated with the gut bacterial microbiome and associated metabolites.

Virology journal, 16(1):105 pii:10.1186/s12985-019-1211-z.

BACKGROUND: The gut microbiome is closely associated with the health of the host; although the interaction between the bacterial microbiome and the whole virome has rarely been studied, it is likely of medical importance. Examination of the interactions between the gut bacterial microbiome and virome of rhesus monkey would significantly contribute to revealing the gut microbiome composition.

METHODS: Here, we conducted a metagenomic analysis of the gut microbiome of rhesus monkeys in a longitudinal cohort treated with an antibiotic cocktail, and we documented the interactions between the bacterial microbiome and virome. The depletion of viral populations was confirmed at the species level by real-time PCR. We also detected changes in the gut metabolome by GC-MS and LC-MS.

RESULTS: A majority of bacteria were depleted after treatment with antibiotics, and the Shannon diversity index decreased from 2.95 to 0.22. Furthermore, the abundance-based coverage estimator (ACE) decreased from 104.47 to 33.84, and the abundance of eukaryotic viruses also changed substantially. In the annotation, 6 families of DNA viruses and 1 bacteriophage family were present in the normal monkeys but absent after gut bacterial microbiome depletion. Intriguingly, we discovered that changes in the gut bacterial microbiome composition may promote changes in the gut virome composition, and tryptophan, arginine, and quinone may play roles in the interaction between the bacterial microbiome and virome.

CONCLUSION: Our results indicated that the clearly altered composition of the virome was correlated with depletion in the bacterial community and that metabolites produced by bacteria possibly play important roles in the interaction.

RevDate: 2019-08-20

Zwinsová B, Brychtová V, Hrivňáková M, et al (2019)

Role of the Microbiome in the Formation and Development of Colorectal Cancer.

Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti, 32(4):261-269.

BACKGROUND: The clinical, histopathological, and molecular characteristics of colorectal cancer vary considerably. Factors associated with the heterogeneity of this disease and with understanding the effects of heterogeneity on disease progression and response to therapy are critical for the better stratification of patients and the development of new therapeutic methods. Although studies have focused mainly on tumor molecular profiling, current molecular predictive and prognostic factors are relevant to specific groups of colorectal cancer patients and are mostly used to predict the applicability of targeted biological agents rather than to predict their benefits. Molecular profiling fails to capture aspects important for tumor growth and aggressiveness, including the tumor microenvironment. The gut microbiome, consisting of specific communities of all commensal, symbiotic, and pathogenic microorganisms, has been shown to have a significant impact on the development of many diseases, including Crohns disease, type II diabetes, and obesity. Recent studies have indicated that long-term dysbiosis of the intestinal microflora can influence the development and progression of colorectal cancer, as well as tumor aggressiveness and response to treatment.

CONCLUSION: This review article summarizes current knowledge of the gut microbiome in colorectal cancer, including the various mechanisms by which the gut microbiome affects the intestinal wall, thereby contributing to the development and progression of colorectal cancer. This work was supported by Ministry of Health of the Czech Republic (project AZV 16-31966A), project of Ministry of Education, Youth and Sports of the Czech Republic - NPU I - LO1413 a Ministry of Health of the Czech Republic - RVO (MMCI, 00209805). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 15. 4. 2019 Accepted: 17. 6. 2019.

RevDate: 2019-08-20

Shelake RM, Pramanik D, JY Kim (2019)

Exploration of Plant-Microbe Interactions for Sustainable Agriculture in CRISPR Era.

Microorganisms, 7(8): pii:microorganisms7080269.

Plants and microbes are co-evolved and interact with each other in nature. Plant-associated microbes, often referred to as plant microbiota, are an integral part of plant life. Depending on the health effects on hosts, plant-microbe (PM) interactions are either beneficial or harmful. The role of microbiota in plant growth promotion (PGP) and protection against various stresses is well known. Recently, our knowledge of community composition of plant microbiome and significant driving factors have significantly improved. So, the use of plant microbiome is a reliable approach for a next green revolution and to meet the global food demand in sustainable and eco-friendly agriculture. An application of the multifaceted PM interactions needs the use of novel tools to know critical genetic and molecular aspects. Recently discovered clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-mediated genome editing (GE) tools are of great interest to explore PM interactions. A systematic understanding of the PM interactions will enable the application of GE tools to enhance the capacity of microbes or plants for agronomic trait improvement. This review focuses on applying GE techniques in plants or associated microbiota for discovering the fundamentals of the PM interactions, disease resistance, PGP activity, and future implications in agriculture.

RevDate: 2019-08-20

Childs CE, Calder PC, EA Miles (2019)

Diet and Immune Function.

Nutrients, 11(8): pii:nu11081933.

A well-functioning immune system is critical for survival. The immune system must be constantly alert, monitoring for signs of invasion or danger. Cells of the immune system must be able to distinguish self from non-self and furthermore discriminate between non-self molecules which are harmful (e.g., those from pathogens) and innocuous non-self molecules (e.g., from food). This Special Issue of Nutrients explores the relationship between diet and nutrients and immune function. In this preface, we outline the key functions of the immune system, and how it interacts with nutrients across the life course, highlighting the work included within this Special Issue. This includes the role of macronutrients, micronutrients, and the gut microbiome in mediating immunological effects. Nutritional modulation of the immune system has applications within the clinical setting, but can also have a role in healthy populations, acting to reduce or delay the onset of immune-mediated chronic diseases. Ongoing research in this field will ultimately lead to a better understanding of the role of diet and nutrients in immune function and will facilitate the use of bespoke nutrition to improve human health.

RevDate: 2019-08-19

Vargas-Pellicer P, Watrobska C, Knowles S, et al (2019)

How should we store avian faecal samples for microbiota analyses? Comparing efficacy and cost-effectiveness.

Journal of microbiological methods pii:S0167-7012(19)30508-1 [Epub ahead of print].

Analyses of bacterial DNA in faecal samples are becoming ever more common, yet we still do not know much about bird microbiomes. These challenges partly lie in the unique chemical nature of their faeces, and in the choice of sample storage method, which affects DNA preservation and the resulting microbiome composition. However, there is little information available on how best to preserve avian faeces for microbial analyses. This study evaluates five widely used methods for preserving nucleic acids and inferring microbiota profiles, for their relative efficacy, cost, and practicality. We tested the five methods (in-situ bead-beating with a TerraLyzer instrument, silica-bead desiccation, ethanol, refrigeration and RNAlater buffer) on 50 fresh faecal samples collected from captive House sparrows (Passer domesticus). In line with other studies, we find that different storage methods lead to distinct bacterial profiles. Storage method had a large effect on community composition and the relative abundance of dominant phyla such as Firmicutes and Proteobacteria, with the most significant changes observed for refrigerated samples. Furthermore, differences in the abundance of aerobic or facultatively aerobic taxa, particularly in refrigerated samples and those stored in ethanol, puts limits on comparisons of bacterial communities across different storage methods. Finally, the methods that did not include in-situ bead-beating did not recover comparable levels of microbiota to the samples that were immediately processed and preserved using a TerraLyzer device. However, this method is also less practical and more expensive under field work circumstances. Our study is the most comprehensive analysis to date on how storage conditions affect subsequent molecular assays applied to avian faeces and provides guidance on cost and practicality of methods under field conditions.

RevDate: 2019-08-19

Mougeot JC, Stevens CB, Morton DS, et al (2019)

Oral Microbiome and Cancer Therapy-Induced Oral Mucositis.

Journal of the National Cancer Institute. Monographs, 2019(53):.

Characterization of the role of oral microbiome in cancer therapy-induced oral mucositis (CTOM) is critical in preventing the clinically deleterious effects on patients' health that are associated with CTOM. Funding initiatives related to the National Institutes of Health human microbiome project have resulted in groundbreaking advancements in biology and medicine during the last decade. These advancements have shown that a human being is in fact a superorganism made of human cells and associated symbiotic or commensal microbiota. In this review, we describe the state of science as it relates to fundamental knowledge on oral microbiome and its role in CTOM. We also discuss how state-of-the-art technologies and systems biology tools may be used to help tackle the difficult challenges ahead to develop effective treatments or preventive therapies for oral mucositis. We make a clear distinction between disease processes pertaining to the oral microbiome, which includes opportunistic pathogens that may be defined as pathobionts, and those infectious disease processes initiated by exogenous pathogens. We also explored the extent to which knowledge from the gastrointestinal tract in disease and intestinal mucositis could help us better understand CTOM pathobiology. Finally, we propose a model in which the oral microbiome participates in the current five-step CTOM pathobiology model. With the advent of more sophisticated metagenomics technologies and methods of analysis, much hope lies ahead to implement an effective holistic approach to treat cancer patients affected by CTOM.

RevDate: 2019-08-19

Lopatto E, Choi J, Colina A, et al (2019)

Characterizing the soil microbiome and quantifying antibiotic resistance gene dynamics in agricultural soil following swine CAFO manure application.

PloS one, 14(8):e0220770 pii:PONE-D-19-15028.

As agriculture industrializes, concentrated animal feeding operations (CAFOs) are becoming more common. Feces from CAFOs is often used as fertilizer on fields. However, little is known about the effects manure has on the soil microbiome, which is an important aspect of soil health and fertility. In addition, due to the subtherapeutic levels of antibiotics necessary to keep the animals healthy, CAFO manure has elevated levels of antibiotic resistant bacteria. Using 16s rRNA high-throughput sequencing and qPCR, this study sought to determine the impact of swine CAFO manure application on both the soil microbiome and abundance of select antibiotic resistance genes (ARGs) and mobile element genes (erm(B), erm(C), sul1, str(B), intI1, IncW repA) in agricultural soil over the fall and spring seasons. We found the manure community to be distinct from the soil community, with a majority of bacteria belonging to Bacteroidetes and Firmicutes. The soil samples had more diverse communities dominated by Acidobacteria, Actinobacteria, Proteobacteria, Verrucomicrobia, and unclassified bacteria. We observed significant differences in the soil microbiome between all time points, except between the spring samples. However, by tracking manure associated taxa, we found the addition of the manure microbiome to be a minor driver of the shift. Of the measured genes, manure application only significantly increased the abundance of erm(B) and erm(C) which remained elevated in the spring. These results suggest bacteria in the manure do not survive well in soil and that ARG dynamics in soil following manure application vary by resistance gene.

RevDate: 2019-08-19

Matsuda I, Chapman CA, M Clauss (2019)

Colobine forestomach anatomy and diet.

Journal of morphology [Epub ahead of print].

Colobine monkeys have complex, multichambered, foregut-fermenting stomachs with either three ("tripartite") or four ("quadripartite," adding the praesaccus) chambers where a commensal microbiome digests plant cell walls and possibly detoxifies defensive plant chemicals. Although different potential functions for the praesaccus have been suggested, little evidence exists to support any of the proposed functions. To address the issue of the function of the praesaccus, we collated literature data on diet and compared tripartite and quadripartite species. Our results suggest that the praesaccus is an adaptation to a dietary niche with a particularly high reliance on leaves as fallback foods in colobine clades with quadripartite stomachs, and a higher reliance on fruits/seeds as foods at times of high fruit availability in clades with tripartite stomachs. This supports the notion that a large gut capacity is an important characteristic by which folivores survive on a high fiber diet, and that this large gut capacity may not be necessary for some species if there are seasonal peaks in fruit availability.

RevDate: 2019-08-19

Ahmadi S, Wang S, Nagpal R, et al (2019)

An In Vitro Batch-culture Model to Estimate the Effects of Interventional Regimens on Human Fecal Microbiota.

Journal of visualized experiments : JoVE.

The emerging role of the gut microbiome in several human diseases demands a breakthrough of new tools, techniques and technologies. Such improvements are needed to decipher the utilization of microbiome modulators for human health benefits. However, the large-scale screening and optimization of modulators to validate microbiome modulation and predict related health benefits may be practically difficult due to the need for large number of animals and/or human subjects. To this end, in vitro or ex vivo models can facilitate preliminary screening of microbiome modulators. Herein, it is optimized and demonstrated an ex vivo fecal microbiota culture system that can be used for examining the effects of various interventions of gut microbiome modulators including probiotics, prebiotics and other food ingredients, aside from nutraceuticals and drugs, on the diversity and composition of the human gut microbiota. Inulin, one of the most widely studied prebiotic compounds and microbiome modulators, is used as an example here to examine its effect on the healthy fecal microbiota composition and its metabolic activities, such as fecal pH and the fecal levels of organic acids including lactate and short-chain fatty acids (SCFAs). The protocol may be useful for studies aimed at estimating the effects of different interventions of modulators on fecal microbiota profiles and at predicting their health impacts.

RevDate: 2019-08-19

Malik F, Wickremesinghe P, J Saverimuttu (2019)

Case report and literature review of auto-brewery syndrome: probably an underdiagnosed medical condition.

BMJ open gastroenterology, 6(1):e000325 pii:bmjgast-2019-000325.

Auto-brewery syndrome (ABS), also known as gut fermentation syndrome, is a rarely diagnosed medical condition in which the ingestion of carbohydrates results in endogenous alcohol production. The patient in this case report had fungal yeast forms in the upper small bowel and cecum, which likely fermented carbohydrates to alcohol. Treatment with antifungal agents allowed subsequent ingestion of carbohydrates without symptoms. He had been exposed to a prolonged course of antibiotics before this occurred. We postulate that the antibiotic altered his gut microbiome, allowing fungal growth. This diagnosis should be considered in any patient with positive manifestations of alcohol toxicity who denies alcohol ingestion. The aim of this case report was confirmation and treatment of ABS using a standardised carbohydrate challenge test followed by upper and lower endoscopy to obtain intestinal secretions to detect fungal growth. These fungi were speciated and antifungal sensitivity performed. This allowed the use of appropriate therapy. The patient was kept on a carbohydrate-free diet during the initial 6-week period of therapy. A single-strain probiotic for competitive inhibition of fungal growth was given to the patient. This probiotic was later replaced by a multistrain bacterial probiotic hoping that the multiple bacteria would inhibit fungi better than a single-strain. The beneficial role of probiotics in this condition has not been studied. The patient was rechallenged for endogenous alcohol production prior to reintroducing carbohydrates in his diet.

RevDate: 2019-08-19

Casaburi G, Duar RM, Vance DP, et al (2019)

Early-life gut microbiome modulation reduces the abundance of antibiotic-resistant bacteria.

Antimicrobial resistance and infection control, 8:131 pii:583.

Background: Antibiotic-resistant (AR) bacteria are a global threat. AR bacteria can be acquired in early life and have long-term sequelae. Limiting the spread of antibiotic resistance without triggering the development of additional resistance mechanisms is of immense clinical value. Here, we show how the infant gut microbiome can be modified, resulting in a significant reduction of AR genes (ARGs) and the potentially pathogenic bacteria that harbor them.

Methods: The gut microbiome was characterized using shotgun metagenomics of fecal samples from two groups of healthy, term breastfed infants. One group was fed B. infantis EVC001 in addition to receiving lactation support (n = 29, EVC001-fed), while the other received lactation support alone (n = 31, controls). Coliforms were isolated from fecal samples and genome sequenced, as well as tested for minimal inhibitory concentrations against clinically relevant antibiotics.

Results: Infants fed B. infantis EVC001 exhibited a change to the gut microbiome, resulting in a 90% lower level of ARGs compared to controls. ARGs that differed significantly between groups were predicted to confer resistance to beta lactams, fluoroquinolones, or multiple drug classes, the majority of which belonged to Escherichia, Clostridium, and Staphylococcus. Minimal inhibitory concentration assays confirmed the resistance phenotypes among isolates with these genes. Notably, we found extended-spectrum beta lactamases among healthy, vaginally delivered breastfed infants who had never been exposed to antibiotics.

Conclusions: Colonization of the gut of breastfed infants by a single strain of B. longum subsp. infantis had a profound impact on the fecal metagenome, including a reduction in ARGs. This highlights the importance of developing novel approaches to limit the spread of these genes among clinically relevant bacteria. Future studies are needed to determine whether colonization with B. infantis EVC001 decreases the incidence of AR infections in breastfed infants.

Trial registration: This clinical trial was registered at, NCT02457338.

RevDate: 2019-08-19

Liu H, Macdonald CA, Cook J, et al (2019)

An Ecological Loop: Host Microbiomes across Multitrophic Interactions.

Trends in ecology & evolution pii:S0169-5347(19)30223-X [Epub ahead of print].

Our knowledge of host-associated microorganisms and their role in host functions is rapidly evolving. Stress-affected plants assemble beneficial microbes in their rhizosphere to maximize survival and growth. Similarly, insects have gut microbiomes that extend their functional repertoire in fighting stress. A strong microbial linkage between soil, plants, and pollinators is emerging and this can influence pollination services and overall ecosystem health. Yet, the nature of microbial interactions between different ecosystem components remains poorly understood. Here we highlight the acquisition pathways of beneficial microbes and their functions in protecting hosts against stress. By adopting a new 'eco-holobiont' approach, which explicitly incorporates biotic feedbacks, we can significantly expand our ecological understanding and better develop sustainable environmental management.

RevDate: 2019-08-18

Marzall-Pereira M, Savi DC, Bruscato EC, et al (2019)

Neopestalotiopsis species presenting wide dye destaining activity: report of a mycelium-associated laccase.

Microbiological research, 228:126299 pii:S0944-5013(19)30317-9 [Epub ahead of print].

Wastewaters from textile dyeing industries represent an ecological concern, notably due to the known toxicity of azo dyes to the local microbiome and human health. Although physicochemical approaches are the rule for the treatment of industrial effluents, biological strategies such as enzyme-mediated dye destaining is a promising alternative. Notwithstanding a broad range of microorganisms, including fungi, algae, yeast, and bacteria, display dye-destaining properties, most of the literature has focused in ligninolytic fungi, leaving other classes of organisms somehow ignored. In this study, six endophytic strains isolated from Maytenus ilicifolia were studied for their destaining activity. The phylogenetic and morphological analysis allowed the identification of strain LGMF1504 as Neopestalotiopsis sp. LGMF1504 that decolorized several commercial dyes as the result of a mycelium-associated laccase. The enzyme expression was modulated by carbon and nitrogen content in the culture medium, it was weakly affected by the presence of aromatic compounds and metal ions while some common laccase mediators improved the destaining activity onto dye substrates. The best culture condition observed for laccase activity was a basic culture medium containing 5 g L-1 starch and 15 g L-1 ammonium tartrate. The laccase activity showed low substrate specificity and almost unaltered performance in a wide range of pH values and NaCl concentrations, suggesting the potential of Neopestalotiopsis sp. LGMF1504 for biodegradation approaches.

RevDate: 2019-08-18

Castro I, Alba C, Aparicio M, et al (2019)

Metataxonomic and immunological analysis of milk from ewes with or without a history of mastitis.

Journal of dairy science pii:S0022-0302(19)30700-3 [Epub ahead of print].

Mastitis is a highly prevalent condition that has a great impact on milk production and animal welfare, and often requires substantial management efforts. For this reason, it is generally considered an important threat to the dairy industry. Many microbial, host, and environmental factors can protect against, predispose to, or influence the development of mastitis. The objective of this work was to characterize the milk microbiota of Manchega ewes, and to compare samples from animals with and without a history of mastitis. We analyzed milk samples from 36 ewes belonging to 2 different farms (18 ewes from each farm) using culture-dependent and culture-independent techniques. We also analyzed several immune compounds to investigate associations of mastitis with 3 main variables: farm; history of mastitis or no mastitis; and parity number. Both culture-dependent and culture-independent techniques showed that ewe milk harbored a site-specific complex microbiota and microbiome. Staphylococcus epidermidis was the main species driving the difference between farm A (where it was the dominant species) and B (where it was not). In contrast, samples from farm B were characterized by the presence of a wide spectrum of other coagulase-negative staphylococci. Some of these species have already been associated with subclinical intramammary infections in ruminants. Of the 10 immune compounds assayed in this study, 3 were related to a history of mastitis [IL-8, IFN-γ, and IFN-gamma-induced protein 10 (IP-10)]. Increases in IL-8 concentrations in milk seemed to be a feature of subclinical mastitis in sheep, and in this study, this immune factor was detected only in samples from ewes with some episodes of mastitis and from the group with the highest somatic cell count. We also observed a positive correlation between the samples with the highest somatic cell count and IFN-γ and IP-10 levels. Our results suggest that these 3 compounds could be used as biomarkers for the negative selection of mastitis-prone animals, particularly when somatic cell count is very high.

RevDate: 2019-08-18

Keshri J, Krouptiski Y, Abu-Fani L, et al (2019)

Dynamics of bacterial communities in alfalfa and mung bean sprouts during refrigerated conditions.

Food microbiology, 84:103261.

Sprouts are considered a healthy ready-to-eat food and has gained popularity in recent years. The objective of the present study was to determine the dynamics of sprouts' microbiome during cold storage to the end of their shelf-life at home. The microbiological quality of fresh alfalfa (Medicago sativa) and mung bean (Vigna radiata) sprouts from two commercial brands was tested and the number of APC ranges from 5.0 to 8.7 log CFU/g in alfalfa and 6.7 to 9.3 log CFU/g in mung bean sprouts. In the case of alfalfa, but not mung beans, there were differences in the mean numbers of APC between the two brands. The number of coliform bacteria ranges from 4.3 to 7.7 log CFU/g in alfalfa and 4.1 to 8.1 log CFU/g in mung bean sprouts. Four independent batches of sprouts were used for DNA preparation and were sampled immediately after purchase and once a week during subsequent storage in refrigerator until the end of their shelf-life. Microbial population of the sprouts was determined using next generation sequencing of 16S rRNA amplicons. Alfalfa sprouts were dominated by Pseudomonas throughout the storage time with relative abundance of >60% at 3 weeks. Fresh mung bean sprouts were dominated by both Pseudomonas and Pantoea, but Pantoea became the dominant taxa after 2 weeks of storage, with >46% of relative abundance. The bacterial communities associated with sprouts were largely dependent on the sprout type, and less dependent on the brand. The species richness and diversity declined during storage and the development of spoilage. Among the 160 genera identified on sprouts, 23 were reported to contain known spoilage-associated species and 30 genera comprise potential human pathogenic species. This study provides new insight into the microbiome dynamics of alfalfa and mung bean sprouts during cold storage.

RevDate: 2019-08-18

Vahdatzadeh M, Deveau A, R Splivallo (2019)

Are bacteria responsible for aroma deterioration upon storage of the black truffle Tuber aestivum: A microbiome and volatilome study.

Food microbiology, 84:103251.

Truffle fungi, luxurious food items with captivating aromas, are highly valued in the culinary world. However, truffles are perishable and their aroma undergoes deep changes upon storage. Additionally, truffle aroma might be partially derived from microbes. Hence, we investigated here the influence of storage on two factors, namely the volatile profile and bacterial community composition in the black truffle Tuber aestivum. The possible linkage among those factors was further explored. Our results demonstrate important changes in the volatile profiles of truffles over nine days of storage at room temperature. In the same time frame, dominant bacterial classes characteristic of fresh truffles (α-Proteobacteria, β-Proteobacteria, and Sphingobacteria classes) were gradually replaced by food spoilage bacteria (γ-Proteobacteria and Bacilli classes). Freshness and spoilage volatile markers (i.e. dimethyl sulfide (DMS), butan-2-one, 2- and, 2- and 3-methylbutan-1-ol, and 2-phenylethan-1-ol) were identified. Lastly, network analysis showed correlations between those markers and specific bacterial classes typical of fresh and spoiled truffles. Overall, our results demonstrate the profound effect of storage on the aroma and bacterial community composition of truffles and highlight how the gradual replacement of the commensal microbiome by spoilage microbes mirrors shifts in aroma profile and the possible loss of fresh truffle flavor.

RevDate: 2019-08-17

Komesu YM, Dinwiddie DL, Richter HE, et al (2019)

Drelationship Between Vaginal and Urinary Microbiomes.

American journal of obstetrics and gynecology pii:S0002-9378(19)31010-5 [Epub ahead of print].

BACKGROUND: Although the vaginal and urinary microbiomes have been increasingly well-characterized in health and disease, few have described the relationship between these neighboring environments. Elucidating this relationship has implications for understanding how manipulation of the vaginal microbiome may affect the urinary microbiome and treatment of common urinary conditions.

OBJECTIVE: To describe the relationship between urinary and vaginal microbiomes using 16S rRNA gene sequencing. We hypothesized that the composition of the urinary and vaginal microbiomes would be significantly associated, with similarities in predominant taxa.

STUDY DESIGN: This multicenter study collected vaginal swabs and catheterized urine samples from 186 women with mixed urinary incontinence (MUI) enrolled in a parent study and 84 similarly aged controls. Investigators decided a priori that if vaginal and/or urinary microbiomes differed between continent and incontinent women, the groups would be analyzed separately; if similar, samples from continent and incontinent women would be pooled and analyzed together. A central laboratory sequenced variable regions 1-3 (v1-3) and characterized bacteria to the genus level. Operational taxonomic unit (OTU) abundance was described for paired vaginal and urine samples. Pearson's correlation characterized the relationship between individual OTUs of paired samples. Canonical Correlation Analysis (CCA) evaluated the association between clinical variables (including MUI and control status) and vaginal and urinary OTUs, using the CCA function in the Vegan package (R version 3.5). Linear discriminant analysis effect size (LEfSe) was used to find taxa that discriminated between vaginal and urinary samples.

RESULTS: Urinary and vaginal samples were collected from 212 women [mean age 53 (±11 years)] and results from 197-paired samples were available for analysis. As OTUs in MUI and control samples were related in CCA and since taxa did not discriminate between MUI or controls in either vagina or urine, MUI and control samples were pooled for further analysis. CCA of vaginal and urinary samples indicated that that 60 of the 100 most abundant OTUs in the samples largely overlapped. Lactobacillus was the most abundant genus in both urine and vagina (contributing on average 53% to an individual's urine sample and 64% to an individual's vaginal sample) (Pearson correlation r=0.53). Though less abundant than Lactobacillus, other bacteria with high Pearson correlation coefficients also commonly found in vagina and urine included: Gardnerella (r=0.70), Prevotella (r=0.64), and Ureaplasma (r=0.50). LEfSe analysis identified Tepidomonas and Flavobacterium as bacteria that distinguished the urinary environment for both MUI and controls as these bacteria were absent in the vagina (Tepidimonas effect size 2.38, p<0.001, Flavobacterium effect size 2.15, p<0.001). Though Lactobacillus was the most abundant bacteria in both urine and vagina, it was more abundant in the vagina (LEfSe effect size 2.72, p<0.001).

CONCLUSIONS: Significant associations between vaginal and urinary microbiomes were demonstrated with Lactobacillus being predominant in both urine and vagina. Abundance of other bacteria also correlated highly between the vagina and urine. This inter-relatedness has implications for studying manipulation of the urogenital microbiome in treating conditions such as urgency urinary incontinence and urinary tract infections.

RevDate: 2019-08-17

Ma N, Zhang J, Reiter RJ, et al (2019)

Melatonin mediates mucosal immune cells, microbial metabolism, and rhythm crosstalk: A therapeutic target to reduce intestinal inflammation.

Medicinal research reviews [Epub ahead of print].

Nowadays, melatonin, previously considered only as a pharmaceutical product for rhythm regulation and sleep aiding, has shown its potential as a co-adjuvant treatment in intestinal diseases, however, its mechanism is still not very clear. A firm connection between melatonin at a physiologically relevant concentration and the gut microbiota and inflammation has recently established. Herein, we summarize their crosstalk and focus on four novelties. First, how melatonin is synthesized and degraded in the gut and exerts potentially diverse phenotypic effects through its diverse metabolites. Second, how melatonin mediates the activation and proliferation of intestinal mucosal immune cells with paracrine and autocrine properties. By modulating T/B cells, mast cells, macrophages and dendritic cells, melatonin immunomodulatory involved in regulating T-cell differentiation, intervening T/B cell interaction and attenuating the production of pro-inflammatory factors, achieving its antioxidant action via specific receptors. Third, how melatonin exerts antimicrobial action and modulates microbial components, such as lipopolysaccharide, amyloid-β peptides via nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) or signal transducers and activators of transcription (STAT1) pathway to modulate intestinal immune function in immune-pineal axis. The last, how melatonin mediates the effect of intestinal bacterial activity signals on the body rhythm system through the NF-κB pathway and influences the mucosal epithelium oscillation via clock gene expression. These processes are achieved at mitochondrial and nuclear levels to control the host immune cell development. Considering unclear mechanisms and undiscovered actions of melatonin in gut-microbiome-immune axis, it's time to reveal them and provide new insight for the outlook of melatonin as a potential therapeutic target in the treatment and management of intestinal diseases.

RevDate: 2019-08-17

Carabeo-Pérez A, Guerra-Rivera G, Ramos-Leal M, et al (2019)

Metagenomic approaches: effective tools for monitoring the structure and functionality of microbiomes in anaerobic digestion systems.

Applied microbiology and biotechnology pii:10.1007/s00253-019-10052-5 [Epub ahead of print].

Microbial metagenome analysis has proven its usefulness to investigate the microbiomes present in technical engineered ecosystems such as anaerobic digestion systems. The analysis of the total microbial genomic DNA allows the detailed determination of both the microbial community structure and its functionality. In addition, it enables to study the response of the microbiome to alterations in technical process parameters. Strategies of functional microbial networks to face abiotic stressors, e.g., resistance, resilience, and reorganization, can be evaluated with respect to overall process optimization. The objective of this paper is to review the main metagenomic tools used for effective studies on anaerobic digestion systems in monitoring the dynamic of the microbiomes, as well as the factors that have been identified so far as limiting the metagenomic studies in this ecosystems.

RevDate: 2019-08-17

Smith A, Pierre JF, Makowski L, et al (2019)

Distinct microbial communities that differ by race, stage, or breast-tumor subtype in breast tissues of non-Hispanic Black and non-Hispanic White women.

Scientific reports, 9(1):11940 pii:10.1038/s41598-019-48348-1.

Growing evidence highlights an association between an imbalance in the composition and abundance of bacteria in the breast tissue (referred as microbial dysbiosis) and breast cancer in women. However, studies on the breast tissue microbiome have not been conducted in non-Hispanic Black (NHB) women. We investigated normal and breast cancer tissue microbiota from NHB and non-Hispanic White (NHW) women to identify distinct microbial signatures by race, stage, or tumor subtype. Using 16S rRNA gene sequencing, we observed that phylum Proteobacteria was most abundant in normal (n = 8), normal adjacent to tumor (normal pairs, n = 11), and breast tumors from NHB and NHW women (n = 64), with fewer Firmicutes, Bacteroidetes, and Actinobacteria. Breast tissues from NHB women had a higher abundance of genus Ralstonia compared to NHW tumors, which could explain a portion of the breast cancer racial disparities. Analysis of tumor subtype revealed enrichment of family Streptococcaceae in TNBC. A higher abundance of genus Bosea (phylum Proteobacteria) increased with stage. This is the first study to identify racial differences in the breast tissue microbiota between NHB and NHW women. Further studies on the breast cancer microbiome are necessary to help us understand risk, underlying mechanisms, and identify potential microbial targets.

RevDate: 2019-08-17

Anonymous (2019)

Tumor Microbiome Composition Influences Pancreatic Cancer Survival.

Cancer discovery pii:2159-8290.CD-RW2019-128 [Epub ahead of print].

Distinct tumor microbiomes are associated with long- and short-term survival in patients with PDAC.

RevDate: 2019-08-17

Lee K, Walker AR, Chakraborty B, et al (2019)

Exploring novel probiotic mechanisms of Streptococcus A12 with functional genomics.

Applied and environmental microbiology pii:AEM.01335-19 [Epub ahead of print].

Health-associated biofilms in the oral cavity are composed of a diverse group of microbial species that can foster an environment that is less favorable for the outgrowth of dental caries pathogens, like Streptococcus mutans. A novel oral bacterium, designated Streptococcus A12, was previously isolated from supragingival dental plaque of a caries-free individual, and was shown to interfere potently with the growth and virulence properties of S. mutans Here, we apply functional genomics to begin to identify molecular mechanisms used by A12 to antagonize, and to resist the antagonistic factors of, S. mutans. Using bioinformatics, genes that could encode factors that enhance the ability of A12 to compete with S. mutans were identified. Selected genes, designated as potential competitive factors (pcf), were deleted. Certain mutant derivatives showed a reduced capacity to compete with S. mutans compared to the parental strain. The A12 pcfO mutant lost the ability to inhibit comX-inducing peptide (XIP) signaling by S. mutans, while mutants in the pcfFEG locus were impaired in sensing of, and were more sensitive to, the lantibiotic nisin. Loss of PcfV, annotated as a colicin V biosynthetic protein, resulted in diminished antagonism of S. mutans. Collectively, the data provide new insights into the complexities and variety of factors that affect biofilm ecology and virulence. Continued exploration of the genomic and physiologic factors that distinguish commensals from truly beneficial members of the oral microbiota will lead to a better understanding of the microbiome and new approaches to promote oral health.Importance Advances in defining the composition of health-associated biofilms have highlighted the important role for beneficial species in maintaining health. Comparatively little, however, has been done to address the genomic and physiological basis underlying the probiotic mechanisms of beneficial commensals. In this study, we explored the ability of a novel oral bacterial isolate, Streptococcus A12, to compete with the dental pathogen Streptococcus mutans using various gene products with diverse functions. A12 displayed enhanced competitiveness by: i) disrupting intercellular communication pathways of S. mutans, ii) sensing and resisting antimicrobial peptides, and iii) producing factors involved in the production of a putative antimicrobial compound. Research on the probiotic mechanisms employed by Streptococcus A12 is providing essential insights into how beneficial bacteria may help maintain oral health, which will aid in the development of biomarkers and therapeutics that can improve the practice of clinical dentistry.

RevDate: 2019-08-17

Zhu T, Liu X, Kong FQ, et al (2019)

Age and Mothers: Potent Influences of Children's Skin Microbiota.

The Journal of investigative dermatology pii:S0022-202X(19)31757-9 [Epub ahead of print].

The evolution of a child's skin microbiome is associated with the development of the immune system and skin environment. As only few studies have analyzed the microbiota in young children, we investigated changes in the skin microbiota of children (158 subjects; ≤10 years old) and compared the microbiota structures between children and their mothers using 16S rRNA gene amplicon sequencing. Sample location and age were the primary factors determining a child's skin bacterial composition, which differed significantly among the face, ventral forearm, and calf. Relative abundances of Streptococcus and Granulicatella were negatively correlated with age, and the alpha diversity at all body sites examined increased during the first 10 years of life, especially on the face. The facial bacterial composition of 10-year-old children was strongly associated with delivery mode at birth. Among mother-child pairs (50 pairs), the relative abundances of most bacterial genera in children were more similar to those of their own mothers than those of unrelated women. The data indicated that age and site were significantly associated with microbial composition and that maternal factors determine the child's microbiome. Further research is needed to characterize the effects of maturation of the infant microbiome on health in adulthood.

RevDate: 2019-08-17

Ryan FJ (2019)

Application of machine learning techniques for creating urban microbial fingerprints.

Biology direct, 14(1):13 pii:10.1186/s13062-019-0245-x.

BACKGROUND: Research has found that human associated microbial communities play a role in homeostasis and the disruption of these communities may be important in an array of medical conditions. However outside of the human body many of these communities remain poorly studied. The Metagenomics and Metadesign of the Subways and Urban Biomes (MetaSUB) International Consortium is characterizing the microbiomes of urban environments with the aim to improve design of mass transit systems. As part of the CAMDA 2018 MetaSUB Forensics Challenge 311 city microbiome samples were provided to create urban microbial fingerprints, as well as a further 3 mystery datasets for validation.

RESULTS: MetaSUB samples were clustered using t-SNE in an unsupervised fashion to almost discrete groups, which upon inspection represented city of origin. Based on this clustering, geographically close metropolitan areas appear to display similar microbial profiles such as those of Auckland and Hamilton. Mystery unlabeled samples were provided part of the challenge. A random forest classifier built on the initial dataset of 311 samples was capable of correctly classifying 83.3% of the mystery samples to their city of origin. Random Forest analyses also identified features with the highest discriminatory power, ranking bacterial species such as Campylobacter jejuni and Staphylococcus argenteus as highly predictive of city of origin. The surface from which the sample was collected displayed little detectable impact on the microbial profiles in the data generated here. The proportion of reads classified per sample varied greatly and so de-novo assembly was applied to recover genomic fragments representing organisms not captured in reference databases.

CONCLUSIONS: Current methods can differentiate urban microbiome profiles from each other with relative ease. De-novo assembly indicated that the MetaSUB metagenomic data contains adequate depth to recover metagenomic assembled genomes and that current databases are not sufficient to fully characterize urban microbiomes. Profiles found here indicate there may be a relationship between geographical distance between areas and the urban microbiome composition although this will need further research. The impact of these different profiles on public health is currently unknown but the MetaSUB consortium is uniquely suited to evaluate these and provide a roadmap for the inclusion of urban microbiome information for city planning and public health policy.

REVIEWERS: This article was reviewed by Dimitar Vassilev, Eran Elhaik and Chengsheng Zhu.

RevDate: 2019-08-16

Junkins EN, Speck M, DO Carter (2019)

The microbiology, pH, and oxidation reduction potential of larval masses in decomposing carcasses on Oahu, Hawaii.

Journal of forensic and legal medicine, 67:37-48 pii:S1752-928X(19)30086-1 [Epub ahead of print].

Previous studies have begun to characterize the microbial community dynamics of the skin, soil, gut, and oral cavities of decomposing remains. One area that has yet to be explored in great detail is the microbiome of the fly larval mass, the community of immature flies that plays a significant role in decomposition. The current study aimed to characterize the microbiology and chemistry of larval masses established on pig (Sus scrofa domesticus) carcasses and to determine if these characteristics have potential as temporal evidence. Carcasses (n = 3) were decomposed on the soil surface of a tropical habitat on Oahu, Hawaii, USA and sampled over three days at 74 h, 80 h, 98 h, 104 h, 122 h, and 128 h (∼85-142 Accumulated Degree Days) postmortem. Larval masses were analyzed via high-throughput 16S rRNA sequencing and in situ chemical measurements (pH, temperature, oxidation-reduction potential). A trend was observed that resulted in three distinct microbial communities (pre-98 h, 98 h, and post-98 h). The oxidation-reduction potential (Eh) of larval masses apparently regulated microbial community structure with the most negative Eh being associated with the least rich and diverse microbial communities. Overall, a significant interaction between time and taxa was observed, particularly with bacterial phyla Firmicutes and Proteobacteria. The current results provide new insight into the microbial community and chemical parameters of larval masses and indicate a temporal shift that could be further studied as a PMI estimator.

RevDate: 2019-08-16

Cox LM, Abou-El-Hassan H, Maghzi AH, et al (2019)

The sex-specific interaction of the microbiome in neurodegenerative diseases.

Brain research pii:S0006-8993(19)30439-1 [Epub ahead of print].

Several neurologic diseases exhibit different prevalence and severity in males and females, highlighting the importance of understanding the influence of biologic sex and gender. Beyond host-intrinsic differences in neurologic development and homeostasis, evidence is now emerging that the microbiota is an important environmental factor that may account for differences between men and women in neurologic disease. The gut microbiota is composed of trillions of bacteria, archaea, viruses, and fungi, that can confer benefits to the host or promote disease. There is bidirectional communication between the intestinal microbiota and the brain that is mediated via immunologic, endocrine, and neural signaling pathways. While there is substantial interindividual variation within the microbiota, differences between males and females can be detected. In animal models, sex-specific microbiota differences can affect susceptibility to chronic diseases. In this review, we discuss the ways in which neurologic diseases may be regulated by the microbiota in a sex-specific manner.

RevDate: 2019-08-16

Moreno-Arrones OM, Serrano-Villar S, Perez-Brocal V, et al (2019)

Analysis of the gut microbiota in alopecia areata: identification of bacterial biomarkers.

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

BACKGROUND: Alopecia areata is a T-cell-mediated autoimmune disease with an unknown etiopathogenesis. Gut microbiota has been revealed as a key modulator of systemic immunity.

OBJECTIVE: To determine if patients affected by alopecia universalis present differences in gut bacteria composition compared to healthy controls and investigate possible bacterial biomarkers of the disease.

METHODS: We conducted a cross-sectional study that involved 15 patients affected by alopecia universalis and 15 controls. Gut microbiome of the study subjects was analyzed by sequencing the 16SrRNA of stool samples. We searched for bacterial biomarkers of alopecia universalis using the linear discriminant analysis effect size (LEFse) tool.

RESULTS: In total, 30 study subjects (46.6% female; mean [SD] age, 40.1 [9.8] years) were enrolled. Neither alpha (Shannon diversity index 5.31 ± 0.43 vs. 5.03 ± 0.43, p 0.1) or beta diversity (ADONIS p value: 0.35) of gut microbiota showed statistically significant differences between cases and controls. In patients affected with alopecia, we found an enriched presence (LDA SCORE >2) of Holdemania filiformis, Erysipelotrichacea, Lachnospiraceae, Parabacteroides johnsonii, Clostridiales vadin BB60 group, Bacteroides eggerthii and Parabacteroides distasonis. A predictive model based on the number of bacterial counts of Parabacteroides distasonis and Clostridiales vadin BB60 group correctly predicted disease status in 80% of patients (AUC 0.804 (0.633 - 0.976), p 0.004).

CONCLUSION: Alopecia universalis does not seem to affect broadly gut microbiota structure. Bacterial biomarkers found associated with the disease (Holdemania filiformis, Erysipelotrichacea, Lachnospiraceae, Parabacteroides johnsonii, Eggerthellaceae, Clostridiales vadin BB60 group, Bacteroides eggerthii and Parabacteroides distasonis) should be further studied as they could be involved in its pathophysiology or be used as diagnostic tools. This article is protected by copyright. All rights reserved.

RevDate: 2019-08-16

Krieger Y, Horev A, Wainstock T, et al (2019)

Meconium stained amniotic fluid as a protective factor against childhood dermatitis and skin rash related hospitalization in the offspring - a population based cohort analysis.

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

BACKGROUND: Gut microbiome influences cutaneous diseases including atopic dermatitis. Possible impact of intrauterine exposure to meconium on the occurrence of dermatitis and skin rash was proposed.

OBJECTIVE: We investigated the possible influence of intrauterine exposure to meconium stained amniotic fluid (MSAF) on the occurrence of dermatitis and skin rash related hospitalizations throughout childhood.

METHODS: Singleton deliveries occurring between 1991-2014 at a single medical center were divided into two study groups based on presence or lack of MSAF during delivery. Population based cohort analysis, Kaplan-Meier survival analysis, and Cox proportional hazards model were used to study the association between MSAF and cutaneous morbidity related hospitalizations.

RESULTS: A lower rate of the total dermatitis or skin eruption related hospitalization was documented in the MSAF exposed group; 0.78 per 1,000-person years (0.9%, n=312), as compared to 0.98 per 1,000-person years in the unexposed group (1.0%, n=1992) with a hazard ratio of 0.86 (95%CI 0.76-0.96, p=0.011). The survival curve showed lower cumulative hospitalization rate in the MSAF exposed group as compared to the unexposed group (log rank p=0.01). The Cox analysis, controlled for confounders, demonstrated MSAF exposure to be an independent protective factor for dermatitis and skin rash related hospitalizations during childhood (adjusted HR 0.878 (95%CI 0.779-0.990, p=0.034).

CONCLUSION: Fetal exposure to MSAF appears to be an independent protective factor for dermatitis and skin rash related hospitalizations in the offspring throughout childhood and adolescence. This article is protected by copyright. All rights reserved.

RevDate: 2019-08-16

Kohne M, Li W, Zhu C, et al (2019)

Deuterium Kinetic Isotope Effects Resolve Low-Temperature Substrate Radical Reaction Pathways and Steps in B12-Dependent Ethanolamine Ammonia-Lyase.

Biochemistry [Epub ahead of print].

The first-order reaction kinetics of the cryotrapped 1,1,2,2-2H4-aminoethanol substrate radical intermediate state in the adenosylcobalamin (B12)-dependent ethanolamine ammonia-lyase (EAL) from Salmonella enterica serovar Typhimurium are measured over the range of 203-225 K by using time-resolved, full-spectrum electron paramagnetic resonance spectroscopy. The studies target the fundamental understanding of the mechanism of EAL, the signature enzyme in ethanolamine utilization metabolism associated with microbiome homeostasis and disease conditions in the human gut. Incorporation of 2H into the hydrogen transfer that follows the substrate radical rearrangement step in the substrate radical decay reaction sequence leads to an observed 1H/2H isotope effect of approximately 2 that preserves, with high fidelity, the idiosyncratic piecewise pattern of rate constant versus inverse temperature dependence that was previously reported for the 1H-labeled substrate, including a monoexponential regime (T ≥ 220 K) and two distinct biexponential regimes (T = 203-219 K). In the global kinetic model, reaction at ≥220 K proceeds from the substrate radical macrostate, S• , and at 203-219 K along parallel pathways from the two sequential microstates, S1 • and S2 • , that are distinguished by different protein configurations. Decay from S• , or S1 • and S2 • , is rate-determined by radical rearrangement (1H) or by contributions from both radical rearrangement and hydrogen transfer (2H). Non-native direct decay to products from S1 • is a consequence of the free energy barrier to the native S1 • → S2 • protein configurational transition. At physiological temperatures, this is averted by the fast protein configurational dynamics that guide the S1 • → S2 • transition.

RevDate: 2019-08-16

Zhao R, Huang R, Long H, et al (2019)

The dynamics of the oral microbiome and oral health among patients receiving clear aligner orthodontic treatment.

Oral diseases [Epub ahead of print].

OBJECTIVES: This 6-month prospective clinical study assessed the impacts of Invisalign appliances on the oral bacterial community and oral health of patients.

METHODS: Salivary samples were obtained from twenty-five adult patients receiving Invisalign aligner treatment before the treatment (Group B) and at a 6-month follow-up (Group P). The bacterial composition of each sample was determined using Illumina MiSeq sequencing of the bacterial 16S rRNA. Intra- and intergroup biodiversity was analyzed. Clinical periodontal parameters and daily oral hygiene habits were recorded.

RESULTS: Reduction of plaque, increased daily brushing frequency and decreased dessert intake were observed in Group P compared to in Group B. 1,853,952 valid reads were obtained from the 50 salivary samples, with 37,904 sequences per sample. No significant differences were detected in the intra- and intergroup biodiversity comparisons between the two groups. By clustering, 8885 OTUs were identified and categorized into six major phyla: Firmicutes, Proteobacteria, Bacteroidetes, Fusobacteria, Actinobacteria and Candidate_division_TM7_norank. At the genus level, compared with Group B, Group P demonstrated significantly increased Bacillus abundance and decreased Prevotella abundance.

CONCLUSIONS: Our results suggested that the general biodiversity and salivary microbial community structure did not change significantly and that patients had increased beneficial oral hygiene habits and awareness during the first six months of Invisalign treatment. Hence, on the basis of this study, it appears that Invisalign aligner treatment did not induce deterioration of oral health nor significant biodiversity changes in oral bacterial communities, assuming that detailed oral hygiene instructions for both teeth and aligners were provided. This article is protected by copyright. All rights reserved.

RevDate: 2019-08-16

Mogilevski T, Burgell R, Aziz Q, et al (2019)

Review article: the role of the autonomic nervous system in the pathogenesis and therapy of IBD.

Alimentary pharmacology & therapeutics [Epub ahead of print].

BACKGROUND: There is a growing body of evidence implicating a role for the brain-gut axis in the pathogenesis of inflammation in patients with IBD.

AIMS: To perform a narrative review of published literature regarding the association of the autonomic nervous system and intestinal inflammation and to describe the rationale for and emerging use of autonomic manipulation as a therapeutic agent METHODS: Current relevant literature was summarised and critically examined.

RESULTS: There is substantial pre-clinical and clinical evidence for a multifaceted anti-inflammatory effect of the vagus at both systemic and local intestinal levels. It acts via acetylcholine-mediated activation of α-7-acetylcholine receptors involving multiple cell types in innate and adaptive immunity and the enteric nervous system with subsequent protective influences on the intestinal barrier, inflammatory mechanisms and the microbiome. In patients with IBD, there is evidence for a sympatho-vagal imbalance, functional enteric neuronal depletion and hyporeactivity of the hypothalamic-pituitary-adrenal axis. Direct or transcutaneous vagal neuromodulation up-regulates the cholinergic anti-inflammatory pathway in pre-clinical and clinical models with down-regulation of systemic and local intestinal inflammation. This is supported by two small studies in Crohn's disease although remains to be investigated in ulcerative colitis.

CONCLUSIONS: Modulating the cholinergic anti-inflammatory pathway influences inflammation both systemically and at a local intestinal level. It represents a potentially underutilised anti-inflammatory therapeutic strategy. Given the likely pathogenic role of the autonomic nervous system in patients with IBD, vagal neuromodulation, an apparently safe and successful means of increasing vagal tone, warrants further clinical exploration.

RevDate: 2019-08-16

Eisenhauer L, Vahjen W, Dadi T, et al (2019)

Effects of brewer's spent grain and carrot pomace on digestibility, fecal microbiota, and fecal and urinary metabolites in dogs fed low or high protein diets.

Journal of animal science pii:5550707 [Epub ahead of print].

Brewer's spent grain (BSG) and carrot pomace (CAP) were used as fiber sources in low or high protein diets in dogs. Ten adult Beagles were involved in five feeding periods of 19 days in a cross-over design. Experimental diets contained 7.5 % of total dietary fiber from BSG or CAP and 20 % or 40 % of crude protein in dry matter. A diet with 3.5 % total dietary fiber from both fiber sources and 20 % crude protein was used as reference. Fecal dry matter was 27 % higher for diets with BSG compared to CAP (P < 0.001). Apparent fecal digestibility of crude protein was 7-11 % higher in diets with 40 % protein concentration (P < 0.001), while apparent digestibility of crude fat was 2-3 % higher for diets with CAP (P < 0.001). CAP increased the apparent fecal digestibility of total dietary fiber, phosphorus and magnesium (p<0.001), while 40 % protein diets had a positive impact on total dietary fiber and sodium and a negative effect on magnesium apparent fecal digestibility (p<0.001). Inclusion of CAP increased fecal short chain fatty acids (P = 0.010), mainly acetate (P = 0.001). I-butyrate (P = 0.001), i-valerate (P = 0.002), biogenic amines (P < 0.001) and ammonium (P < 0.001) increased with higher dietary protein levels. Diet induced changes in the fecal microbiome were moderate. Relative abundance of Bifidobacteriales was higher for the low protein diets (P = 0.001). To conclude, BSG and CAP can be used as fiber sources in canine diets and are well tolerated even at higher inclusion rates, the effect on microbial protein fermentation seems to be limited compared to the dietary protein level.

RevDate: 2019-08-16

Buccheri MA, Salvo E, Coci M, et al (2019)

Investigating microbial indicators of anthropogenic marine pollution by 16S and 18S High Throughput Sequencing (HTS) library analysis.

FEMS microbiology letters pii:5550730 [Epub ahead of print].

High Throughput Sequencing technologies are providing unprecedented inventories of microbial communities in aquatic samples, offering an invaluable tool to estimate the impact of anthropogenic pressure on marine communities. In this case study, the Mediterranean touristic site of Aci Castello (Italy) was investigated by High Throughput Sequencing of 16S and 18S rRNA genes. The sampling area falls within a Marine Protected Area and, notwithstanding, features an untreated urban wastewater discharge. Seawater samples were collected close to the wastewater output (COL) and at a second station about 400 m further off (PAN), before and after a summer increase in population. Prokaryotic communities clustered according to stations, rather than to seasons. While PAN showed a typical, not impacted, marine microbial composition, COL was consistently enriched in Epsilonproteobacteria and Firmicutes. Protist communities showed a peculiar clustering, as COL at springtime stood-alone and was dominated by Ciliophora, while the other samples were enriched in Dinophyta. Analysis of alternative, detectable by High Throughput Sequencing, microbial indicators, including both faecal- and sewage associated, allowed uncovering the different sources of pollution in coastal and anthropogenically-impacted marine ecosystems, underpinning the relevance of High Throughput Sequencing -based screening as rapid and precise method for water quality management.

RevDate: 2019-08-16

Jones NP (2019)

Immunosuppression in the Management of Presumed Non-infective Uveitis; Are We Sure What We are Treating? Notes on the Antimicrobial Properties of the Systemic Immunosuppressants.

Ocular immunology and inflammation [Epub ahead of print].

Purpose: To describe the antimicrobial effects of immunosuppressants used for presumed autoimmune uveitis, and to discuss the potential importance of these effects in the context of increasing knowledge of the human microbiomes and their influence on inflammation. Methods: Literature review Review of evidence: All immunosuppressants have intrinsic antimicrobial effects; these vary considerably between drugs, and include antibacterial, antiviral and antifungal action. Immunosuppression is known to affect the composition of the gut microbiome, and alterations in microbiome composition are known to affect inflammations including uveitis. Conclusions: Oral immunosuppressants are assumed to act on presumed autoimmune uveitis by downregulation of, or other interference with, an aberrant immune response. However, their antimicrobial properties are usually forgotten, and in the context of increasing knowledge of the involvement of microbes in the initiation of, and also potentially the perpetuation of, tissue inflammation, these effects may prove to be a fundamental part of their action.

RevDate: 2019-08-16

Ramayo-Caldas Y, Zingaretti L, Popova M, et al (2019)

Identification of rumen microbial biomarkers linked to methane emission in Holstein dairy cows.

Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie [Epub ahead of print].

Mitigation of greenhouse gas emissions is relevant for reducing the environmental impact of ruminant production. In this study, the rumen microbiome from Holstein cows was characterized through a combination of 16S rRNA gene and shotgun metagenomic sequencing. Methane production (CH4) and dry matter intake (DMI) were individually measured over 4-6 weeks to calculate the CH4 yield (CH4 y = CH4 /DMI) per cow. We implemented a combination of clustering, multivariate and mixed model analyses to identify a set of operational taxonomic unit (OTU) jointly associated with CH4 y and the structure of ruminal microbial communities. Three ruminotype clusters (R1, R2 and R3) were identified, and R2 was associated with higher CH4 y. The taxonomic composition on R2 had lower abundance of Succinivibrionaceae and Methanosphaera, and higher abundance of Ruminococcaceae, Christensenellaceae and Lachnospiraceae. Metagenomic data confirmed the lower abundance of Succinivibrionaceae and Methanosphaera in R2 and identified genera (Fibrobacter and unclassified Bacteroidales) not highlighted by metataxonomic analysis. In addition, the functional metagenomic analysis revealed that samples classified in cluster R2 were overrepresented by genes coding for KEGG modules associated with methanogenesis, including a significant relative abundance of the methyl-coenzyme M reductase enzyme. Based on the cluster assignment, we applied a sparse partial least-squares discriminant analysis at the taxonomic and functional levels. In addition, we implemented a sPLS regression model using the phenotypic variation of CH4 y. By combining these two approaches, we identified 86 discriminant bacterial OTUs, notably including families linked to CH4 emission such as Succinivibrionaceae, Ruminococcaceae, Christensenellaceae, Lachnospiraceae and Rikenellaceae. These selected OTUs explained 24% of the CH4 y phenotypic variance, whereas the host genome contribution was ~14%. In summary, we identified rumen microbial biomarkers associated with the methane production of dairy cows; these biomarkers could be used for targeted methane-reduction selection programmes in the dairy cattle industry provided they are heritable.


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
21454 NE 143rd Street
Woodinville, WA 98077

E-mail: RJR8222 @

Papers in Classical Genetics

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

Digital Books

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


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


Biographical information about many key scientists.

Selected Bibliographies

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

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