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Bibliography on: Microbiome

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Robert J. Robbins is a biologist, an educator, a science administrator, a publisher, an information technologist, and an IT leader and manager who specializes in advancing biomedical knowledge and supporting education through the application of information technology. More About:  RJR | OUR TEAM | OUR SERVICES | THIS WEBSITE

RJR: Recommended Bibliography 19 Nov 2018 at 01:36 Created: 

Microbiome

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: 2018-11-18

Paganini D, Uyoga MA, Kortman GAM, et al (2018)

Iron-containing micronutrient powders modify the effect of oral antibiotics on the infant gut microbiome and increase post-antibiotic diarrhoea risk: a controlled study in Kenya.

Gut pii:gutjnl-2018-317399 [Epub ahead of print].

OBJECTIVE: Many African infants receiving iron fortificants also receive antibiotics. Antibiotic efficacy against enteropathogens may be modified by high colonic iron concentrations. In this study, we evaluated the effect of antibiotics on the infant gut microbiome and diarrhoea when given with or without iron-containing micronutrient powders (MNPs).

DESIGN: In a controlled intervention trial, four groups of community-dwelling infants (n=28; aged 8-10 months) received either: (A) antibiotics for 5 days and iron-MNPs for 40 days (Fe+Ab+); (B) antibiotics and no-iron-MNPs (Fe-Ab+); (C) no antibiotics and iron-MNPs (Fe+Ab-); or (D) no antibiotics and no-iron-MNPs (Fe-Ab-). We collected a faecal sample before the first antibiotic dose (D0) and after 5, 10, 20 and 40 days (D5-D40) to assess the gut microbiome composition by 16S profiling, enteropathogens by quantitative PCR, faecal calprotectin and pH and assessed morbidity over the 40-day study period.

RESULTS: In Fe+Ab+, there was a decrease in Bifidobacterium abundances (p<0.05), but no decrease in Fe-Ab+. In Fe-Ab+, there was a decrease in abundances of pathogenic Escherichia coli (p<0.05), but no decrease in Fe+Ab+. In Fe-Ab+, there was a decrease in pH (p<0.05), but no decrease in Fe+Ab+. Longitudinal prevalence of diarrhoea was higher in Fe+Ab+ (19.6%) compared with Fe-Ab+ (12.4%) (p=0.04) and compared with Fe+Ab- (5.2%) (p=0.00).

CONCLUSION: Our findings need confirmation in a larger study but suggest that, in African infants, iron fortification modifies the response to broad-spectrum antibiotics: iron may reduce their efficacy against potential enteropathogens, particularly pathogenic E. coli, and may increase risk for diarrhoea.

TRIAL REGISTRATION NUMBER: NCT02118402; Pre-results.

RevDate: 2018-11-18

Hendrikx T, Duan Y, Wang Y, et al (2018)

Bacteria engineered to produce IL-22 in intestine induce expression of REG3G to reduce ethanol-induced liver disease in mice.

Gut pii:gutjnl-2018-317232 [Epub ahead of print].

OBJECTIVE: Antimicrobial C-type lectin regenerating islet-derived 3 gamma (REG3G) is suppressed in the small intestine during chronic ethanol feeding. Our aim was to determine the mechanism that underlies REG3G suppression during experimental alcoholic liver disease.

DESIGN: Interleukin 22 (IL-22) regulates expression of REG3G. Therefore, we investigated the role of IL-22 in mice subjected to chronic-binge ethanol feeding (NIAAA model).

RESULTS: In a mouse model of alcoholic liver disease, we found that type 3 innate lymphoid cells produce lower levels of IL-22. Reduced IL-22 production was the result of ethanol-induced dysbiosis and lower intestinal levels of indole-3-acetic acid (IAA), a microbiota-derived ligand of the aryl hydrocarbon receptor (AHR), which regulates expression of IL-22. Importantly, faecal levels of IAA were also found to be lower in patients with alcoholic hepatitis compared with healthy controls. Supplementation to restore intestinal levels of IAA protected mice from ethanol-induced steatohepatitis by inducing intestinal expression of IL-22 and REG3G, which prevented translocation of bacteria to liver. We engineered Lactobacillus reuteri to produce IL-22 (L. reuteri/IL-22) and fed them to mice along with the ethanol diet; these mice had reduced liver damage, inflammation and bacterial translocation to the liver compared with mice fed an isogenic control strain and upregulated expression of REG3G in intestine. However, L. reuteri/IL-22 did not reduce ethanol-induced liver disease in Reg3g-/- mice.

CONCLUSION: Ethanol-associated dysbiosis reduces levels of IAA and activation of the AHR to decrease expression of IL-22 in the intestine, leading to reduced expression of REG3G; this results in bacterial translocation to the liver and steatohepatitis. Bacteria engineered to produce IL-22 induce expression of REG3G to reduce ethanol-induced steatohepatitis.

RevDate: 2018-11-18

Wan Z, Wang C, Zhou J, et al (2018)

Effects of polystyrene microplastics on the composition of the microbiome and metabolism in larval zebrafish.

Chemosphere, 217:646-658 pii:S0045-6535(18)32177-5 [Epub ahead of print].

Microplastics are major pollutants in marine environment and may have health effects on aquatic organisms. In this study, we used two sizes (5 and 50 μm diameter) of fluorescent and virgin polystyrene microplastics to analyze the adverse effects on larval zebrafish. In our study, we evaluated the effects on larval zebrafish after exposure to 100 and 1000 μg/L of two sizes of polystyrene microplastics for 7 days. Our results show that polystyrene microplastics could cause alterations in the microbiome at the phylum and genus levels in larval zebrafish, including changes in abundance and diversity of the microbiome. In addition, metabolomic analysis suggested that exposure to polystyrene microplastics induced alterations of metabolic profiles in larval zebrafish, and differential metabolites were involved in energy metabolism, glycolipid metabolism, inflammatory response, neurotoxic response, nucleic acid metabolism, oxidative stress. Polystyrene microplastics also significantly decreased the activities of catalase and the content of glutathione. In addition, the results of gene transcription analysis showed that exposure to polystyrene microplastics induced changes in glycolysis-related genes and lipid metabolism-related genes, confirming that polystyrene microplastics disturbed glycolipid and energy metabolism. Taken together, the results obtained in the present study indicated that the potential effects of environmental microplastics on aquatic organisms should not be ignored.

RevDate: 2018-11-18

Metcalf JL (2018)

Estimating the postmortem interval using microbes: Knowledge gaps and a path to technology adoption.

Forensic science international. Genetics, 38:211-218 pii:S1872-4973(18)30403-4 [Epub ahead of print].

Microbes have potential to be used as physical evidence for forensic science because they are ubiquitous and have predictable ecologies. With the advent of next generation sequencing technology and the subsequent boost to microbiome science (study of the genes and molecules of microbial communities), it has become possible to develop new microbial-based tools for forensic science. One promising approach is the use of microbial succession during the ecological process of decomposition to estimate the time since death, or postmortem interval (PMI). This microbial clock of death is developed by building a regression model using microbiome data collected from postmortem samples (e.g. swab of skin) with known PMIs. In a death investigation, a similar sample type (e.g. swab of skin) would be collected, the microbes profiled using DNA sequencing, and the microbes would be matched to a point on the clock (i.e. the regression model). Recent research by several independent scientific teams has provided a proof of concept for this new microbiome forensic tool. However, developing and transitioning new forensic science technologies into the justice system requires overcoming scientific, investigative, and legal hurdles. In this article, I address the apparent knowledge gaps in the science of microbiome technology to estimate PMI, and discuss a path for bringing this technology into the justice system.

RevDate: 2018-11-18

Schlomann BH, Wiles TJ, Wall ES, et al (2018)

Bacterial Cohesion Predicts Spatial Distribution in the Larval Zebrafish Intestine.

Biophysical journal pii:S0006-3495(18)31165-2 [Epub ahead of print].

Are there general biophysical relationships governing the spatial organization of the gut microbiome? Despite growing realization that spatial structure is important for population stability, interbacterial competition, and host functions, it is unclear in any animal gut whether such structure is subject to predictive, unifying rules or if it results from contextual, species-specific behaviors. To explore this, we used light sheet fluorescence microscopy to conduct a high-resolution comparative study of bacterial distribution patterns throughout the entire intestinal volume of live, larval zebrafish. Fluorescently tagged strains of seven bacterial symbionts, representing six different species native to zebrafish, were each separately monoassociated with animals that had been raised initially germ-free. The strains showed large differences in both cohesion-the degree to which they auto-aggregate-and spatial distribution. We uncovered a striking correlation between each strain's mean position and its cohesion, whether quantified as the fraction of cells existing as planktonic individuals, the average aggregate size, or the total number of aggregates. Moreover, these correlations held within species as well; aggregates of different sizes localized as predicted from the pan-species observations. Together, our findings indicate that bacteria within the zebrafish intestine are subject to generic processes that organize populations by their cohesive properties. The likely drivers of this relationship-peristaltic fluid flow, tubular anatomy, and bacterial growth and aggregation kinetics-are common throughout animals. We therefore suggest that the framework introduced here of biophysical links between bacterial cohesion and spatial organization should be useful for directing explorations in other host-microbe systems, formulating detailed models that can quantitatively map onto experimental data, and developing new tools that manipulate cohesion to engineer microbiome function.

RevDate: 2018-11-18

Vasquez AK, Ganda EK, Capel MB, et al (2018)

The microbiome of Escherichia coli and culture-negative nonsevere clinical mastitis: Characterization and associations with linear score and milk production.

Journal of dairy science pii:S0022-0302(18)31064-6 [Epub ahead of print].

Culture-negative and Escherichia coli cases are uncommonly treated in pathogen-based protocols for nonsevere mastitis. High-throughput 16S rRNA sequencing might reveal the presence of other pathogens and can provide information on microbial diversity. The objective was to explore the milk microbiome at the time of the mastitis event (enrollment) and its association with survival in the herd, milk production, and postevent linear score (LS) for cows with clinical mastitis characterized as negative or E. coli by culture. Fifty E. coli-positive and 35 culture-negative samples from cases were enrolled. No cases were treated with antimicrobials. All E. coli-positive quarters were characterized as transient; microbiological culture of samples taken 15 d postmastitis were negative for this organism. However, a difference in α-diversity (Shannon index) was present between enrollment and follow-up samples (3.8 vs. 5.1). When α-diversity was explored for enrollment E. coli samples, no relationship was observed between the Shannon indices of these samples and postmastitis LS. Alpha-diversity of the enrollment samples was lower for E. coli-positive cows that subsequently had greater losses in milk production. This difference was explained by a greater relative abundance of the family Enterobacteriaceae (67.8 vs. 38.4%) for cows that dropped in production. Analysis of composition of the microbiome identified one phylum, Proteobacteria, that differed between E. coli-positive cows that dropped in production and those that did not. Evaluation of β-diversity found no statistical relationship between postmastitis LS and the microbiome. When evaluating α- and β-diversities and composition of the microbiomes for culture-negative quarters, no associations were found for milk production changes and postmastitis LS. Three cows did not remain in the herd, limiting the ability to analyze survival. The findings suggest that a contributing factor to negative outcomes in E. coli-positive cows is relative abundance of this pathogen, and that no single or collective group of bacterial families is associated with milk production changes or postmastitis LS in culture-negative quarters. Although additional studies should be performed, the absence of associations between outcomes explored and microbial profiles in this study suggests that we are not missing opportunities by not treating nonsevere E. coli or culture-negative mastitis cases.

RevDate: 2018-11-17

Ma J, Zhu D, Chen QL, et al (2018)

Exposure to tetracycline perturbs the microbiome of soil oligochaete Enchytraeus crypticus.

The Science of the total environment, 654:643-650 pii:S0048-9697(18)34510-8 [Epub ahead of print].

Microbial symbiosis is essential for the normal development and growth of hosts. Past attention has mostly been paid to its effects on plants and vertebrates. The effects of environmental pressures such as antibiotics on the microbiome of soil fauna remain largely elusive. We used bacterial 16S rRNA gene high-throughput sequencing to examine the response of microbiome of soil invertebrate Enchytraeus crypticus to oral tetracycline exposure. After two-week exposure, tetracycline-free oat was used as food to monitor the restoration of E. crypticus microbiome. The results showed that Proteobacteria, Actinobacteria and Planctomycetes were the three dominant phyla in all samples, Rhizobiaceae and Kaistia were the most abundant family and genus in all samples, respectively. After 14 days tetracycline exposure, Planctomycetes declined dramatically from 33.05% to 3.28% (P = 0.016), but Actinobacteria elevated substantially from 2.47% to 23.65% (P = 0.004). The alpha-diversity of microbial community increased significantly after tetracycline exposure compared to the control (P = 0.014). Terminating tetracycline exposure led to the recovery of E. crypticus microbiome back to the background level within 14 days. Our results suggest that while tetracycline can disturb the microbiome in E. crypticus significantly, the effects of the antibiotic on E. crypticus microbiome may not be permanent but reversibly diminish after stopping exposure for a period of time. The results may contribute to extending our understanding of the effect of antibiotics on microbiome of soil invertebrates. CAPSULE: The microbiome of E. crypticus exposed to tetracycline is perturbed and reversibly restored after terminating the exposure.

RevDate: 2018-11-17

Greenbaum S, Greenbaum G, Moran-Gilad J, et al (2018)

Ecological dynamics of the vaginal microbiome in relation to health and disease.

American journal of obstetrics and gynecology pii:S0002-9378(18)32114-8 [Epub ahead of print].

The bacterial composition of the vaginal microbiome is thought to be related to health and disease states of women. This microbiome is particularly dynamic, with compositional changes related to pregnancy, menstruation, and disease states such as bacterial vaginosis. In order to understand these dynamics and their impact on health and disease, ecological theories have been introduced to study the complex interactions between the many taxa in the vaginal bacterial ecosystem. The goal of this review is to introduce the ecological principles that are used in the study of the vaginal microbiome and its dynamics, and to review the application of ecology to vaginal microbial communities with respect to health and disease. While applications of vaginal microbiome analysis and modulation have not yet been introduced into the routine clinical setting, a deeper understanding of its dynamics has the potential to facilitate development of future practices, for example in the context of postmenopausal vaginal symptoms, stratifying risk for obstetric complications, and control of sexually transmitted infections.

RevDate: 2018-11-17

Parris DJ, Morgan MM, FJ Stewart (2018)

Feeding rapidly alters microbiome composition and gene transcription in the clownfish gut.

Applied and environmental microbiology pii:AEM.02479-18 [Epub ahead of print].

BackgroundDiet is a major determinant of intestinal microbiome composition. While studies have evaluated microbiome responses to diet variation, less is understood of how the act of feeding influences the microbiome, independent of diet type. Here, we use the clownfish Premnas biaculeatus, a species reared commonly in ornamental marine aquaculture, to test how the diversity, predicted gene content, and gene transcription of the microbiome vary over a two-day diurnal period with a single daily feeding event. This study used fish fed four times daily, once daily, or every three days prior to the diurnal period, allowing us also to test how feeding frequency affected microbiome diversity. The amount of time between feedings had no affect on baseline diversity of the microbiome. In contrast, the act of feeding itself caused a significant short term change in the microbiome, with microbiome diversity, predicted gene content, and gene transcription varying significantly between time points immediately before and 1.5 hours post feeding. Variation was driven by abundance shifts involving exact sequence variants (ESVs), with one ESV identified as Photobacterium sp. increasing from <0.5% of sequences immediately pre-feeding to 34% at 1.5 hours post-feeding. Other ESVs from a range of microbial groups also increased dramatically after feeding, with the majority also detected in the food. One ESV identified as Clostridium perfringens represented up to 55% of sequences but did not vary significantly over the diurnal period and was not detected in the food. Post-feeding samples were enriched in transcripts and predicted genes for social interactions, cell motility, and coping with foreign DNA, whereas time points farther from feeding were enriched in genes of diverse catabolic and biosynthetic functions. These results confirm feeding as a significant destabilizing force in clownfish intestinal microbiomes, likely due to both input of cells attached to food and stimulation of resident microbes. Microbes such as Photobacterium may episodically transition from environmental reservoirs to growth in the gut, likely in association with food particles. This transition may be facilitated by functions for navigating a new environment and interacting with neighboring microbes and host cells. Other taxa, such as Clostridium, are comparatively stable intestinal members and less likely to be affected by passing food. Conclusions about microbiome ecology may therefore differ based on when samples were collected relative to the last feeding.ImportanceDespite extensive study of intestinal microbiome diversity and the role of diet type in structuring gut microbial communities, we know very little about short-term changes in the intestinal microbiome as a result of feeding alone. Sampling microbiomes over a feeding cycle will allow us to differentiate opportunistic, feeding-responsive microbes from resident, potentially commensal members of the gut community. Also, since feeding has the potential to alter microbiome structure, sampling at different points relative to the last feeding event will likely yield different conclusions about microbiome composition and function. This variation should be addressed in comparative microbiome studies. Our study contributes to knowledge of short-term changes in the gut microbiome associated with feeding events.

RevDate: 2018-11-17

Lucking EF, O'Connor KM, Strain CR, et al (2018)

Chronic intermittent hypoxia disrupts cardiorespiratory homeostasis and gut microbiota composition in adult male guinea-pigs.

EBioMedicine pii:S2352-3964(18)30503-6 [Epub ahead of print].

BACKGROUND: Carotid body (peripheral oxygen sensor) sensitisation is pivotal in the development of chronic intermittent hypoxia (CIH)-induced hypertension. We sought to determine if exposure to CIH, modelling human sleep apnoea, adversely affects cardiorespiratory control in guinea-pigs, a species with hypoxia-insensitive carotid bodies. We reasoned that CIH-induced disruption of gut microbiota would evoke cardiorespiratory morbidity.

METHODS: Adult male guinea-pigs were exposed to CIH (6.5% O2 at nadir, 6 cycles.hour-1) for 8 h.day-1 for 12 consecutive days.

FINDINGS: CIH-exposed animals established reduced faecal microbiota species richness, with increased relative abundance of Bacteroidetes and reduced relative abundance of Firmicutes bacteria. Urinary corticosterone and noradrenaline levels were unchanged in CIH-exposed animals, but brainstem noradrenaline concentrations were lower compared with sham. Baseline ventilation was equivalent in CIH-exposed and sham animals; however, respiratory timing variability, sigh frequency and ventilation during hypoxic breathing were all lower in CIH-exposed animals. Baseline arterial blood pressure was unaffected by exposure to CIH, but β-adrenoceptor-dependent tachycardia and blunted bradycardia during phenylephrine-induced pressor responses was evident compared with sham controls.

INTERPRETATION: Increased carotid body chemo-afferent signalling appears obligatory for the development of CIH-induced hypertension and elevated chemoreflex control of breathing commonly reported in mammals, with hypoxia-sensitive carotid bodies. However, we reveal that exposure to modest CIH alters gut microbiota richness and composition, brainstem neurochemistry, and autonomic control of heart rate, independent of carotid body sensitisation, suggesting modulation of breathing and autonomic homeostasis via the microbiota-gut-brainstem axis. The findings have relevance to human sleep-disordered breathing.

FUNDING: The Department of Physiology, and APC Microbiome Ireland, UCC.

RevDate: 2018-11-17

Gao Z, Karlsson I, Geisen S, et al (2018)

Protists: Puppet Masters of the Rhizosphere Microbiome.

Trends in plant science pii:S1360-1385(18)30244-9 [Epub ahead of print].

The rhizosphere microbiome is a central determinant of plant performance. Microbiome assembly has traditionally been investigated from a bottom-up perspective, assessing how resources such as root exudates drive microbiome assembly. However, the importance of predation as a driver of microbiome structure has to date largely remained overlooked. Here we review the importance of protists, a paraphyletic group of unicellular eukaryotes, as a key regulator of microbiome assembly. Protists can promote plant-beneficial functions within the microbiome, accelerate nutrient cycling, and remove pathogens. We conclude that protists form an essential component of the rhizosphere microbiome and that accounting for predator-prey interactions would greatly improve our ability to predict and manage microbiome function at the service of plant growth and health.

RevDate: 2018-11-17

Brey CW, Akbari-Alavijeh S, Ling J, et al (2018)

Salts and energy balance: A special role for dietary salts in metabolic syndrome.

Clinical nutrition (Edinburgh, Scotland) pii:S0261-5614(18)32492-0 [Epub ahead of print].

BACKGROUND: Dietary salts sodium (Na+), potassium (K+), magnesium (Mg2+), and calcium (Ca2+) are important in metabolic diseases. Yet, we do not have sufficient understanding on the salts global molecular network in these diseases. In this systematic review we have pooled information to identify the general effect of salts on obesity, insulin resistance and hypertension.

AIMS: To assess the roles of salts in metabolic disorders by focusing on their individual effect and the network effect among these salts.

METHODS: We searched articles in PubMed, EMBASE and Google Scholar. We selected original laboratory research, systematic reviews, clinical trials, observational studies and epidemiological data that focused on dietary salts and followed the preferred reporting items for systematic review in designing the present systematic review.

RESULTS: From the initial search of 2898 studies we selected a total of 199 articles that met our inclusion criteria and data extraction. Alterations in metabolic pathways associated with the sensitivity of sodium, potassium, magnesium and calcium may lead to obesity, hypertension, and insulin resistance. We found that the results of most laboratory research, animal studies and clinical trials are coherent but some research outcome are either inconsistent or inconclusive.

CONCLUSION: Important of salts in metabolic disorder is evident. In order to assess the effects of dietary salts in metablic diseases, environmental factors, dietary habits, physical activity, and the microbiome, should be considered in any study. Although interest in this area of research continues to grow, the challenge is to integrate the action of these salts in metabolic syndrom.

RevDate: 2018-11-17

Breitwieser FP, Baker DN, SL Salzberg (2018)

KrakenUniq: confident and fast metagenomics classification using unique k-mer counts.

Genome biology, 19(1):198 pii:10.1186/s13059-018-1568-0.

False-positive identifications are a significant problem in metagenomics classification. We present KrakenUniq, a novel metagenomics classifier that combines the fast k-mer-based classification of Kraken with an efficient algorithm for assessing the coverage of unique k-mers found in each species in a dataset. On various test datasets, KrakenUniq gives better recall and precision than other methods and effectively classifies and distinguishes pathogens with low abundance from false positives in infectious disease samples. By using the probabilistic cardinality estimator HyperLogLog, KrakenUniq runs as fast as Kraken and requires little additional memory. KrakenUniq is freely available at https://github.com/fbreitwieser/krakenuniq .

RevDate: 2018-11-17

Wakita Y, Shimomura Y, Kitada Y, et al (2018)

Taxonomic classification for microbiome analysis, which correlates well with the metabolite milieu of the gut.

BMC microbiology, 18(1):188 pii:10.1186/s12866-018-1311-8.

BACKGROUND: 16S rRNA gene amplicon sequencing analysis (16S amplicon sequencing) has provided considerable information regarding the ecology of the intestinal microbiome. Recently, metabolomics has been used for investigating the crosstalk between the intestinal microbiome and the host via metabolites. In the present study, we determined the accuracy with which 16S rRNA gene data at different classification levels correspond to the metabolome data for an in-depth understanding of the intestinal environment.

RESULTS: Over 200 metabolites were identified using capillary electrophoresis and time-of-flight mass spectrometry (CE-TOFMS)-based metabolomics in the feces of antibiotic-treated and untreated mice. 16S amplicon sequencing, followed by principal component analysis (PCA) of the intestinal microbiome at each taxonomic rank, revealed differences between the antibiotic-treated and untreated groups in the first principal component in the family-, genus, and species-level analyses. These differences were similar to those observed in the PCA of the metabolome. Furthermore, a strong correlation between principal component (PC) scores of the metabolome and microbiome was observed in family-, genus-, and species-level analyses.

CONCLUSIONS: Lower taxonomic ranks such as family, genus, or species are preferable for 16S amplicon sequencing to investigate the correlation between the microbiome and metabolome. The correlation of PC scores between the microbiome and metabolome at lower taxonomic levels yield a simple method of integrating different "-omics" data, which provides insights regarding crosstalk between the intestinal microbiome and the host.

RevDate: 2018-11-17

Harhala M, Nelson DC, Miernikiewicz P, et al (2018)

Safety Studies of Pneumococcal Endolysins Cpl-1 and Pal.

Viruses, 10(11): pii:v10110638.

Bacteriophage-derived endolysins have gained increasing attention as potent antimicrobial agents and numerous publications document the in vivo efficacy of these enzymes in various rodent models. However, little has been documented about their safety and toxicity profiles. Here, we present preclinical safety and toxicity data for two pneumococcal endolysins, Pal and Cpl-1. Microarray, and gene profiling was performed on human macrophages and pharyngeal cells exposed to 0.5 µM of each endolysin for six hours and no change in gene expression was noted. Likewise, in mice injected with 15 mg/kg of each endolysin, no physical or behavioral changes were noted, pro-inflammatory cytokine levels remained constant, and there were no significant changes in the fecal microbiome. Neither endolysin caused complement activation via the classic pathway, the alternative pathway, or the mannose-binding lectin pathway. In cellular response assays, IgG levels in mice exposed to Pal or Cpl-1 gradually increased for the first 30 days post exposure, but IgE levels never rose above baseline, suggesting that hypersensitivity or allergic reaction is unlikely. Collectively, the safety and toxicity profiles of Pal and Cpl-1 support further preclinical studies.

RevDate: 2018-11-16

Zakrzewski M, Simms LA, Brown A, et al (2018)

IL23R-protective coding variant promotes beneficial bacteria and diversity in the ileal microbiome in healthy individuals without inflammatory bowel disease.

Journal of Crohn's & colitis pii:5184638 [Epub ahead of print].

Background and aims: This study aimed to characterise the mucosa-associated microbiota in ileal Crohn's disease (CD) patients and in healthy controls in terms of host genotype and inflammation status.

Methods: The mucosa-associated microbiota of intestinal pinch biopsies from 15 ileal CD patients with mild and moderate disease and from 58 healthy controls were analysed by 16S ribosomal sequencing to determine microbial profile differences between (1) IL23R, NOD2 and ATG16L1 genotypes in healthy subjects, (2) ileal CD patients and control subjects, and (3) inflamed and non-inflamed mucosal tissue in CD patients.

Results: The protective variant of the IL23R gene (rs11209026) significantly impacted the microbial composition in the ileum of healthy subjects and was associated with an increased abundance of phylotypes within the Christensenellaceae family as well as increases in diversity and richness. Comparative analysis of healthy and non-inflamed CD microbiome samples indicated notable decrease in the abundance of Faecalibacterium prausnitzii as well as Shannon diversity and richness. Inflamed and non-inflamed ileal samples of CD subjects had high intra-individual stability and inter-individual variability but no significant alterations in diversity, richness and taxa were identified. Calprotectin correlated positively with Proteobacteria abundance and negatively with diversity in the samples from healthy subjects.

Conclusions: The observation of low diversity and low abundance of beneficial bacteria in healthy control subjects carrying the IL23R (rs11209026) wild-type GG genotype indicates that the gut microbiome is influenced by host genetics and is altered prior to disease diagnosis. Fecal calprotectin may be a potential non-invasive screening tool for dysbiosis in subjects without disorders of intestinal inflammation.

RevDate: 2018-11-16

Ramos-Sevillano E, Wade WG, Mann A, et al (2018)

The Effect of Influenza Virus on the Human Oropharyngeal Microbiome.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America pii:5184302 [Epub ahead of print].

Background: Secondary bacterial infections are an important cause of morbidity and mortality associated with influenza infections. As bacterial disease can be caused by a disturbance of the host microbiome, we examined the impact of influenza on the upper respiratory tract microbiome in a human challenge study.

Methods: The dynamics and ecology of the throat microbiome were examined following an experimental influenza challenge of 52 previously-healthy adult volunteers with influenza A/Wisconsin/67/2005 (H3N2) by intranasal inoculation; 35 healthy control subjects were not subjected to the viral challenge. Serial oropharyngeal samples were taken over a 30-day period, and the V1-V3 region of the bacterial 16S ribosomal RNA sequences were amplified and sequenced to determine the composition of the microbiome. The carriage of pathogens was also detected.

Results: Of the 52 challenged individuals, 43 developed proven influenza infections, 33 of whom became symptomatic. None of the controls developed influenza, although 22% reported symptoms. The diversity of bacterial communities remained remarkably stable following the acquisition of influenza, with no significant differences over time between individuals with influenza and those in the control group. Influenza infection was not associated with perturbation of the microbiome at the level of phylum or genus. There was no change in colonization rates with Streptococcus pneumoniae or Neisseria meningitidis.

Conclusions: The throat microbiota is resilient to influenza infection, indicating the robustness of the upper-airway microbiome.

RevDate: 2018-11-16

Ozkan J, Willcox M, Wemheuer B, et al (2018)

Biogeography of the human ocular microbiota.

The ocular surface pii:S1542-0124(18)30229-5 [Epub ahead of print].

PURPOSE: The human eye is composed of numerous microhabitats. The aim of this study was to understand the communality and differences in the microbiomes of various regions of the eye.

METHODS: Four ocular sites from different subject groups were assessed including the eyelid margin tissue from patients with lid abnormalities (n = 20), fornix and limbus conjunctival tissue from patients with pterygia (n = 23), ocular (conjunctival) surface swabs (n = 45) and facial skin swabs (n = 16). Microbial communities were analysed by extracting total DNA from samples and sequencing the 16S ribosomal(r)RNA gene using the Illumina MiSeq platform. Sequences were quality filtered, clustered into unique sequences (zOTUs) using the UNOISE pipeline in USEARCH and taxonomically classified using SILVA.

RESULTS: A difference in bacterial richness and diversity was found between sites (P < 0.001) and for age (P < 0.035) but not for sex (P > 0.05). There was a difference in bacterial community structure and composition between sites (P < 0.001). Bacterial distribution could be broadly classified into three groups - zOTUs resident on the skin and lid margin but with low abundances at other sites (Corynebacterium, Staphylococcus), zOTUs found mainly on the ocular surface (Acinetobacter, Aeribacillus) and zOTUs mostly present in the conjunctiva and lid margin (Pseudomonas).

CONCLUSION: The microhabitats of the human eye (ocular surface, conjunctiva, lid margin and skin) have a distinct bacterial biogeography with some bacteria shared between multiple regions while other bacteria occupy a more confined niche.

RevDate: 2018-11-16

Avgerinos KI, Spyrou N, Mantzoros CS, et al (2018)

Obesity and Cancer Risk: Emerging biological mechanisms and perspectives.

Metabolism: clinical and experimental pii:S0026-0495(18)30232-4 [Epub ahead of print].

Continuously rising trends in obesity-related malignancies render this disease spectrum a public health priority. Worldwide, the burden of cancer attributable to obesity, expressed as population attributable fraction, is 11.9% in men and 13.1% in women. There is convincing evidence that excess body weight is associated with an increased risk for cancer of at least 13 anatomic sites, including endometrial, esophageal, renal and pancreatic adenocarcinomas; hepatocellular carcinoma; gastric cardia cancer; meningioma; multiple myeloma; colorectal, postmenopausal breast, ovarian, gallbladder and thyroid cancers. We first synopsize current epidemiologic evidence; the obesity paradox in cancer risk and mortality; the role of weight gain and weight loss in the modulation of cancer risk; reliable somatometric indicators for obesity and cancer research; and gender differences in obesity related cancers. We critically summarize emerging biological mechanisms linking obesity to cancer encompassing insulin resistance and abnormalities of the IGF-I system and signaling; sex hormones biosynthesis and pathway; subclinical chronic low-grade inflammation and oxidative stress; alterations in adipokine pathophysiology; factors deriving from ectopic fat deposition; microenvironment and cellular perturbations including vascular perturbations, epithelial-mesenchymal transition, endoplasmic reticulum stress and migrating adipose progenitor cells; disruption of circadian rhythms; dietary nutrients; factors with potential significance such as the altered intestinal microbiome; and mechanic factors in obesity and cancer. Future perspectives regarding prevention, diagnosis and therapeutics are discussed. The aim of this review is to investigate how the interplay of these main potential mechanisms and risk factors, exerts their effects on target tissues provoking them to acquire a cancerous phenotype.

RevDate: 2018-11-16

Albaugh VL, Banan B, Antoun J, et al (2018)

Role of Bile Acids and GLP-1 in Mediating the Metabolic Improvements of Bariatric Surgery.

Gastroenterology pii:S0016-5085(18)35259-4 [Epub ahead of print].

BACKGROUND AND AIMS: Bile diversion to the ileum (GB-IL) has strikingly similar metabolic and satiating effects to Roux-en-Y gastric bypass (RYGB) in rodent obesity models. The metabolic benefits of these procedures are thought to be mediated by increased bile acids, though parallel changes in body weight and other confounding variables limits this interpretation.

METHODS: Global G protein-coupled bile acid receptor-1 null (Tgr5-/-) and intestinal-specific farnesoid X receptor null (FxrΔ/E) mice on high-fat diet as well as wild-type C57BL/6 and glucagon-like polypeptide 1 receptor deficient (Glp-1r-/-) mice on chow diet were characterized following bile diversion to the ileum (GB-IL).

RESULTS: GB-IL induced weight loss and improved oral glucose tolerance in HFD-fed Tgr5-/-, but not FxrΔ/E mice, suggesting a role for intestinal Fxr. GB-IL in wild-type, chow-fed mice prompted weight-independent improvements in glycemia and glucose tolerance secondary to augmented insulin responsiveness. Improvements were concomitant with increased levels of lymphatic GLP-1 in the fasted state and increased levels of intestinal Akkermansia muciniphila. Improvements in fasting glycemia after GB-IL were mitigated with Ex-9, a GLP-1 receptor antagonist, or cholestyramine, a bile acid sequestrant. The glucoregulatory effects of GB-IL were lost in whole body Glp-1r-/- mice.

CONCLUSIONS: Bile diversion to the ileum improves glucose homeostasis via an intestinal Fxr-Glp-1 axis. Altered intestinal bile acid availability, independent of weight loss, and intestinal Akkermansia muciniphila appear to mediate the metabolic changes observed after bariatric surgery and might be manipulated for treatment of obesity and diabetes.

RevDate: 2018-11-16

O'Malley D (2018)

Endocrine regulation of gut function - a role for glucagon-like peptide-1 in the pathophysiology of irritable bowel syndrome.

Experimental physiology [Epub ahead of print].

NEW FINDINGS: Pathophysiological changes linked to Irritable Bowel Syndrome (IBS) include stress and immune activation, changes in gastrointestinal microbial and bile acids profiles and sensitisation of extrinsic and intrinsic gut neurons. This review explores the potential role for L-cells in these pathophysiological changes. L-cells, which secrete glucagon-like peptide-1 (GLP-1) in response to nutrients, microbial factors, bile acids and short-chain fatty acids, may sense IBS-related changes in the luminal environment. Glucagon-like peptide 1 can act as a hormone, a paracrine factor or a neuromodulatory factor and through its actions on central or peripheral neurons, may play a role in gastrointestinal dysfunction.

ABSTRACT: The prevalent and debilitating functional bowel disorder Irritable Bowel Syndrome (IBS), is characterized by symptoms which include abdominal pain, bloating, diarrhoea and/or constipation. The heterogeneity of IBS underscores a complex multifactorial pathophysiology, which is not completely understood, but involves dysfunction of the bidirectional signalling axis between the brain and the gut. This axis incorporates efferent and afferent branches of the autonomic nervous system, circulating endocrine hormones and immune factors, local paracrine and neurocrine factors and microbial metabolites. L-cells, which are electrically excitable biosensors embedded in the gastrointestinal epithelium, secrete glucagon-like peptide-1 (GLP-1) in response to nutrients in the small intestine. However, they appear to function differently more distally in the gastrointestinal tract, where they are activated by luminal factors including short-chain fatty acids, bile acids and microbial metabolic products, all of which are altered in IBS patients. GLP-1 can also interact with the hypothalamic-pituitary-adrenal stress axis and immune system, both of which are activated in IBS. Given that a GLP-1 mimetic has been found to alleviate acute pain symptoms in IBS patients, GLP-1 may be important in the manifestation of IBS symptoms. This review assessed the current knowledge on the role of GLP-1 in IBS pathophysiology and its potential role as a signal transducer in the microbiome-gut-brain signalling axis. This article is protected by copyright. All rights reserved.

RevDate: 2018-11-16

Adolph TE, Effenberger M, H Tilg (2018)

How our understanding of the microbiome has changed the way we look at liver diseases.

Biomarkers in medicine [Epub ahead of print].

RevDate: 2018-11-16

Hattori N, Niwa T, Ishida T, et al (2018)

Antibiotics Suppress Colon Tumorigenesis Through Inhibition of Aberrant DNA Methylation in an AOM/DSS Colitis Model.

Cancer science [Epub ahead of print].

Chronic inflammation is involved in the development of colon cancer by inducing mutations and aberrant DNA methylation in colon epithelial cells. Furthermore, there is growing evidence showing that the colonic microbiota modulates the inflammation response in the host and influences colon tumorigenesis. However, the influence of the colonic microbiota on aberrant DNA methylation remains unknown. Here, we show the effect of colonic microbes on DNA methylation and tumorigenicity using a mouse model of human ulcerative colitis. Mice treated with azoxymethane (AOM) and dextran sulfate sodium (DSS) showed an increase in degree of colitis, as estimated by body weight, occult blood, and stool consistency/diarrhea at 2 weeks after treatment, but treatment with antibiotics markedly reduced the severity of the colitis. Although mucosal hyperplasia and increased inflammation-related genes were observed in the colonic epithelial cells of the AOM/DSS-treated mice, treatment with antibiotics abrogated these changes. In addition, treatment with antibiotics significantly decreased the number of mucosal nodules from 5.9 ± 5.3 to 0.2 ± 0.6 (P < 0.01) and area of occupancy from 50.1 ± 57.4 to 0.5 ± 1.4 mm2 (P < 0.01). Aberrant DNA methylation of three marker CpG islands (Cbln4, Fosb and Msx1) was induced by AOM/DSS treatment in colonic mucosae, but this increase was suppressed by 50% to 92% (P < 0.05) with antibiotic treatment. Microbiome analysis showed that this change was associated with a decrease of the Clostridium leptum subgroup. These data demonstrate that antibiotics suppressed tumorigenesis through inhibition of aberrant DNA methylation induced by chronic inflammation. This article is protected by copyright. All rights reserved.

RevDate: 2018-11-16

Chen J, Thomsen M, L Vitetta (2018)

Interaction of gut microbiota with dysregulation of bile acids in the pathogenesis of nonalcoholic fatty liver disease and potential therapeutic implications of probiotics.

Journal of cellular biochemistry [Epub ahead of print].

The intestinal microbiota is now recognised to play key roles in health due to its involvement in many aspects of human physiology. Disturbance in gut microbiota (dysbiosis) is thus associated with many diseases including nonalcoholic fatty liver disease (NAFLD) which includes nonalcoholic fatty liver and nonalcoholic steatohepatitis. The mechanisms for the effect of dysbiosis in NAFLD pathogenesis are not completely elucidated. Many explanations have been proposed to trigger dysbiosis, leading to NAFLD including inflammation, ethanol produced by the gut bacteria and lipotoxicity. Recently the roles of bile acids and nuclear receptors are highly regarded. It is well known that gut microbes produce enzymes that convert primary bile acids into secondary bile acids in the intestines. Several studies have demonstrated that disturbance of the intestinal microbiota leads to decreased synthesis of secondary bile acids, which in turn decreases activation of nuclear receptors such as farnesoid X receptor (FXR), pregnane X receptor, Takeda G-protein-coupled bile acid protein 5 and vitamin D receptor. These receptors are important in energy regulation and their dysregulation can cause NAFLD. Therefore, stimulation of nuclear receptors especially FXR has been extensively explored for the amelioration of NAFLD. However, paradoxical effects of nuclear receptor activation are a major problem for the clinical application of nuclear receptor stimuli. We further posit that microbiome restoration could be an alternative approach for the treatment of NAFLD. Several gut bacteria are now known to be involved in bile acid metabolism. It will be necessary to identify which one/ones is/are feasible. Careful selection of commensal bacteria for probiotics may lead to an effective therapy for NAFLD.

RevDate: 2018-11-16

Hillmann B, Al-Ghalith GA, Shields-Cutler RR, et al (2018)

Evaluating the Information Content of Shallow Shotgun Metagenomics.

mSystems, 3(6): pii:mSystems00069-18.

Although microbial communities are associated with human, environmental, plant, and animal health, there exists no cost-effective method for precisely characterizing species and genes in such communities. While deep whole-metagenome shotgun (WMS) sequencing provides high taxonomic and functional resolution, it is often prohibitively expensive for large-scale studies. The prevailing alternative, 16S rRNA gene amplicon (16S) sequencing, often does not resolve taxonomy past the genus level and provides only moderately accurate predictions of the functional profile; thus, there is currently no widely accepted approach to affordable, high-resolution, taxonomic, and functional microbiome analysis. To address this technology gap, we evaluated the information content of shallow shotgun sequencing with as low as 0.5 million sequences per sample as an alternative to 16S sequencing for large human microbiome studies. We describe a library preparation protocol enabling shallow shotgun sequencing at approximately the same per-sample cost as 16S sequencing. We analyzed multiple real and simulated biological data sets, including two novel human stool samples with ultradeep sequencing of 2.5 billion sequences per sample, and found that shallow shotgun sequencing recovers more-accurate species-level taxonomic and functional profiles of the human microbiome than 16S sequencing. We discuss the inherent limitations of shallow shotgun sequencing and note that 16S sequencing remains a valuable and important method for taxonomic profiling of novel environments. Although deep WMS sequencing remains the gold standard for high-resolution microbiome analysis, we recommend that researchers consider shallow shotgun sequencing as a useful alternative to 16S sequencing for large-scale human microbiome research studies where WMS sequencing may be cost-prohibitive. IMPORTANCE A common refrain in recent microbiome-related academic meetings is that the field needs to move away from broad taxonomic surveys using 16S sequencing and toward more powerful longitudinal studies using shotgun sequencing. However, performing deep shotgun sequencing in large longitudinal studies remains prohibitively expensive for all but the most well-funded research labs and consortia, which leads many researchers to choose 16S sequencing for large studies, followed by deep shotgun sequencing on a subset of targeted samples. Here, we show that shallow- or moderate-depth shotgun sequencing may be used by researchers to obtain species-level taxonomic and functional data at approximately the same cost as amplicon sequencing. While shallow shotgun sequencing is not intended to replace deep shotgun sequencing for strain-level characterization, we recommend that microbiome scientists consider using shallow shotgun sequencing instead of 16S sequencing for large-scale human microbiome studies.

RevDate: 2018-11-16

Suwal S, Wu Q, Liu W, et al (2018)

The Probiotic Effectiveness in Preventing Experimental Colitis Is Correlated With Host Gut Microbiota.

Frontiers in microbiology, 9:2675.

Current evidence to support extensive use of probiotics in inflammatory bowel disease is limited and factors that contribute to the inconsistent effectiveness of clinical probiotic therapy are not completely known. Here, we used Bifidobacterium longum JDM 301 as a model probiotic to study potential factors that may influence the effect of probiotics in experimental colitis. We found that the effect of B. longum JDM 301 in tempering experimental colitis varied across individual mice even with the same genetic background. The probiotic efficacy was highly correlated with the host gut microbial community features. Consumption of a diet rich in fat could exacerbate mucosal injury-induced colitis but could not change the host responsiveness to B. longum JDM 301 treatment, suggesting of potential mechanistic differences between regulating colitis pathogenesis, and modulating probiotic efficacies by the gut microbiota. Together, our results suggest that personalized microbiome features may modify the probiotic therapeutic effect and support the idea of personalized probiotic medicine in inflammatory bowel disease.

RevDate: 2018-11-16

Peng M, Tabashsum Z, Patel P, et al (2018)

Linoleic Acids Overproducing Lactobacillus casei Limits Growth, Survival, and Virulence of Salmonella Typhimurium and Enterohaemorrhagic Escherichia coli.

Frontiers in microbiology, 9:2663.

Probiotics, particularly lactic acid bacteria, are biologic agents which limit the growth, virulence, and survival/colonization of various enteric bacterial pathogens and serve as potential alternatives to antibiotics. Mechanisms that contribute to this antimicrobial effect include producing bioactive metabolites/acids, increasing nutrient and receptor-mediated competition, and modulating gut microbiome ecology. However, these functions of common probiotic strains are limited due to the finite quantity of metabolites they produce and their total number in the gut ecosystem. Conjugated linoleic acids (CLAs), critical metabolites of Lactobacillus, have multiple beneficial effects on human health including anti-carcinogenesis, anti-inflammation, anti-oxidation, and anti-pathogenicity. In this study, we aim to overexpress the myosin cross-reactive antigen gene (mcra) in Lactobacillus casei (LC) to enhance the production of CLA and investigate its effectiveness against enteric bacterial pathogens, specifically Salmonella enterica serovar Typhimurium (ST) and enterohaemorrhagic Escherichia coli (EHEC). By inserting mcra in L. casei, we generated LC-CLA and found the total linoleic acid production by an individual bacterial cell was raised by 21-fold. The adherence ability of LC-CLA on human epithelial cells increased significantly and LC-CLA competitively excluded both ST and EHEC in a mixed-culture condition. Furthermore, LC-CLA significantly altered the physicochemical properties, biofilm formation abilities, interactions with host cells of both ST and EHEC, and triggered anti-inflammatory activities of host cells. These findings offer insights on applying a genetically engineered probiotic to control gut intestinal infections caused by ST and EHEC and prevent foodborne enteric illness in human.

RevDate: 2018-11-16

O'Brien PA, Smith HA, Fallon S, et al (2018)

Elevated CO2 Has Little Influence on the Bacterial Communities Associated With the pH-Tolerant Coral, Massive Porites spp.

Frontiers in microbiology, 9:2621.

Ocean acidification (OA) as a result of increased anthropogenic CO2 input into the atmosphere carries consequences for all ocean life. Low pH can cause a shift in coral-associated microbial communities of pCO2-sensitive corals, however, it remains unknown whether the microbial community is also influenced in corals known to be more tolerant to high pCO2/low pH. This study profiles the bacterial communities associated with the tissues of the pCO2-tolerant coral, massive Porites spp., from two natural CO2 seep sites in Papua New Guinea. Amplicon sequencing of the hypervariable V3-V4 regions of the 16S rRNA gene revealed that microbial communities remained stable across CO2 seep sites (pH = 7.44-7.85) and adjacent control sites (ambient pH = 8.0-8.1). Microbial communities were more significantly influenced by reef location than pH, with the relative abundance of dominant microbial taxa differing between reefs. These results directly contrast with previous findings that increased CO2 has a strong effect on structuring microbial communities. The stable structure of microbial communities associated with the tissues of massive Porites spp. under high pCO2/low pH conditions confirms a high degree of tolerance by the whole Porites holobiont to OA, and suggest that pH tolerant corals such as Porites may dominate reef assemblages in an increasingly acidic ocean.

RevDate: 2018-11-16

Chander AM, Yadav H, Jain S, et al (2018)

Cross-Talk Between Gluten, Intestinal Microbiota and Intestinal Mucosa in Celiac Disease: Recent Advances and Basis of Autoimmunity.

Frontiers in microbiology, 9:2597.

Celiac disease (CD) is an autoimmune disorder of the small intestine, caused by gluten induced inflammation in some individuals susceptible to genetic and environmental influences. To date, pathophysiology of CD in relation to intestinal microbiota is not known well. This review relies on contribution of intestinal microbiome and oral microbiome in pathogenesis of CD based on their interactions with gluten, thereby highlighting the role of upper gastrointestinal microbiota. It has been hypothesized that CD might be triggered by additive effects of immunotoxic gluten peptides and intestinal dysbiosis (microbial imbalance) in the people with or without genetic susceptibilities, where antibiotics may be deriving dysbiotic agents. In contrast to the intestinal dysbiosis, genetic factors even seem secondary in disease outcome thus suggesting the importance of interaction between microbes and dietary factors in immune regulation at intestinal mucosa. Moreover, association of imbalanced counts of some commensal microbes in intestine of CD patients suggests the scope for probiotic therapies. Lactobacilli and specific intestinal and oral bacteria are potent source of gluten degrading enzymes (glutenases) that may contribute to commercialization of a novel glutenase therapy. In this review, we shall discuss advantages and disadvantages of food based therapies along with probiotic therapies where probiotic therapies are expected to emerge as the safest biotherapies among other in-process therapies. In addition, this review emphasizes on differential targets of probiotics that make them suitable to manage CD as along with glutenase activity, they also exhibit immunomodulatory and intestinal microbiome modulatory properties.

RevDate: 2018-11-16

Vieira-Potter VJ, Cross TL, Swanson KS, et al (2018)

Soy-Induced Fecal Metabolome Changes in Ovariectomized and Intact Female Rats: Relationship with Cardiometabolic Health.

Scientific reports, 8(1):16896 pii:10.1038/s41598-018-35171-3.

Phytoestrogens are plant-derived compounds found in a variety of foods, most notably, soy. These compounds have been shown to improve immuno-metabolic health, yet mechanisms remain uncertain. We demonstrated previously that dietary phytoestrogen-rich soy (SOY) rescued metabolic dysfunction/inflammation following ovariectomy (OVX) in female rats; we also noted remarkable shifts in gut microbiota in SOY vs control diet-fed rats. Importantly, specific bacteria that significantly increased in those fed the SOY correlated positively with several favorable host metabolic parameters. One mechanism by which gut microbes might lead to such host effects is through production of bacterial metabolites. To test this possibility, we utilized non-targeted gas chromatography-mass spectrometry (GCMS) to assess the fecal metabolome in those previously studied animals. Partial least square discriminant analysis (PLSDA) revealed clear separation of fecal metabolomes based on diet and ovarian state. In particular, SOY-fed animals had greater fecal concentrations of the beneficial bacterial metabolite, S-equol, which was positively associated with several of the bacteria upregulated in the SOY group. S-equol was inversely correlated with important indicators of metabolic dysfunction and inflammation, suggesting that this metabolite might be a key mediator between SOY and gut microbiome-positive host health outcomes.

RevDate: 2018-11-16

Bor B, McLean JS, Foster KR, et al (2018)

Rapid evolution of decreased host susceptibility drives a stable relationship between ultrasmall parasite TM7x and its bacterial host.

Proceedings of the National Academy of Sciences of the United States of America pii:1810625115 [Epub ahead of print].

Around one-quarter of bacterial diversity comprises a single radiation with reduced genomes, known collectively as the Candidate Phyla Radiation. Recently, we coisolated TM7x, an ultrasmall strain of the Candidate Phyla Radiation phylum Saccharibacteria, with its bacterial host Actinomyces odontolyticus strain XH001 from human oral cavity and stably maintained as a coculture. Our current work demonstrates that within the coculture, TM7x cells establish a long-term parasitic association with host cells by infecting only a subset of the population, which stay viable yet exhibit severely inhibited cell division. In contrast, exposure of a naïve A. odontolyticus isolate, XH001n, to TM7x cells leads to high numbers of TM7x cells binding to each host cell, massive host cell death, and a host population crash. However, further passaging reveals that XH001n becomes less susceptible to TM7x over time and enters a long-term stable relationship similar to that of XH001. We show that this reduced susceptibility is driven by rapid host evolution that, in contrast to many forms of phage resistance, offers only partial protection. The result is a stalemate where infected hosts cannot shed their parasites; nevertheless, parasite load is sufficiently low that the host population persists. Finally, we show that TM7x can infect and form stable long-term relationships with other species in a single clade of Actinomyces, displaying a narrow host range. This system serves as a model to understand how parasitic bacteria with reduced genomes such as those of the Candidate Phyla Radiation have persisted with their hosts and ultimately expanded in their diversity.

RevDate: 2018-11-16

Nocera AL, Mueller SK, Stephan JR, et al (2018)

Exosome swarms eliminate airway pathogens and provide passive epithelial immunoprotection through nitric oxide.

The Journal of allergy and clinical immunology pii:S0091-6749(18)31351-4 [Epub ahead of print].

BACKGROUND: Nasal mucosa-derived exosomes (NMDEs) harbor immunodefensive proteins and are capable of rapid interepithelial protein transfer.

OBJECTIVES: We sought to determine whether mucosal exposure to inhaled pathogens stimulates a defensive swarm of microbiocidal exosomes, which also donate their antimicrobial cargo to adjacent epithelial cells.

METHODS: We performed an institutional review board-approved study of healthy NMDE secretion after Toll-like receptor (TLR) 4 stimulation by LPS (12.5 μg/mL) in the presence of TLR4 inhibitors. Interepithelial transfer of exosomal nitric oxide (NO) synthase and nitric oxide was measured by using ELISAs and NO activity assays. Exosomal antimicrobial assays were performed with Pseudomonas aeruginosa. Proteomic analyses were performed by using SOMAscan.

RESULTS: In vivo and in vitro LPS exposure induced a 2-fold increase in NMDE secretion along with a 2-fold increase in exosomal inducible nitric oxide synthase expression and function through TLR4 and inhibitor of nuclear factor κB kinase activation. LPS stimulation increased exosomal microbiocidal activity against P aeruginosa by almost 2 orders of magnitude. LPS-stimulated exosomes induced a 4-fold increase in NO production within autologous epithelial cells with protein transfer within 5 minutes of contact. Pathway analysis of the NMDE proteome revealed 44 additional proteins associated with NO signaling and innate immune function.

CONCLUSIONS: We provide direct in vivo evidence for a novel exosome-mediated innate immunosurveillance and defense mechanism of the human upper airway. These findings have implications for lower airway innate immunity, delivery of airway therapeutics, and host microbiome regulation.

RevDate: 2018-11-16

Laha T, Brindley PJ, Suyapoh W, et al (2018)

RNA Interference as an Approach to Functional Genomics Genetic Manipulation of Opisthorchis viverrini.

Advances in parasitology, 102:25-43.

The availability of genome and transcriptome data of the liver fluke Opisthorchis viverrini provides the foundation for exploration of gene function and its effect on host-parasite interactions and pathogenesis of O. viverrini-associated bile duct cancer. Functional genomics approaches address the function of DNA at levels of the gene, RNA transcript and protein product using informative manipulations of the genome, epigenome, transcriptome, proteome, microbiome and metabolome. Advances in functional genomics for O. viverrini have thus far focused on RNA interference. The flukes have been transfected with double-stranded RNAs aiming to silence target gene expression. In general, this approach for functional genomics investigation of this pathogen has been found to be tractable and efficient: suppression of messenger RNA expression in O. viverrini results in reduction of protein activity and phenotypic changes. Future perspectives for functional genomics of this liver fluke and close phylogenetic relatives are also discussed.

RevDate: 2018-11-16

Saltykova IV, Petrov VA, PJ Brindley (2018)

Opisthorchiasis and the Microbiome.

Advances in parasitology, 102:1-23.

The liver flukes Opisthorchis viverrini, O. felineus, and Clonorchis sinensis are closely related fish-borne trematodes endemic in East Asia, Eurasia, and Siberia. Following ingestion, the parasites locate to the biliary tree, where chronic infection frequently leads to cholangiocarcinoma (CCA). Infection with C. sinensis or O. viverrini is classified as a Group 1 carcinogen by the International Agency for Research on Cancer. Infection with O. felineus may also be carcinogenic. The mechanism(s) by which infection with these liver flukes culminates in CCA remain elusive, although they are likely to be multi-factorial. Not yet well studied is the influence of opisthorchiasis on the microbiome of the host despite reports that helminth parasites are capable of affecting the microbiome, potentially modulating gastrointestinal inflammation in response to the appearance of pathogenic strains of bacteria. Here, we review recent findings related to opisthorchiasis and the microbiome and related issues. In the hamster, a tractable model of infection with liver fluke and of infection-induced biliary morbidity and CCA, infection with O. viverrini perturbs the microbiome of the gastrointestinal tract, including increasing numbers of Lachnospiraceae, Ruminococcaceae, Lactobacillaceae, and others, while decreasing Porphyromonadaceae, Erysipelotrichaceae, and Eubacteriaceae. In addition, a complex microbial community associates with the parasites within the biliary tree, including Helicobacter pylori and related bacteria. Moreover, higher rates of infection with Helicobacter occur in Thailand in persons with opisthorchiasis in a liver fluke infection intensity-dependent manner. Experimental infection of hamsters with Opisthorchis felineus results in increased alpha diversity of the microbiota diversity in the biliary tract. In humans, infection with O. felineus modifies the composition of the biliary microbiome, with increasing numbers of species of Klebsiella, Aggregatibacter, Lactobacillus, Treponema, and others. Several phylotypes of Archaea occurred solely in bile from persons infected with O. felineus.

RevDate: 2018-11-16

Barnett JA, DL Gibson (2018)

H2Oh No! The importance of reporting your water source in your in vivo microbiome studies.

Gut microbes [Epub ahead of print].

Water is a fundamental part of any in vivo microbiome experiment however, it is also one of the most overlooked and underreported variables within the literature. Currently there is no established standard for drinking water quality set by the Canadian Council on Animal Care. Most water treatment methods focus on inhibiting bacterial growth within the water while prolonging the shelf-life of bottles once poured. When reviewing the literature, it is clear that some water treatment methods, such as water acidification, alter the gut microbiome of experimental animals resulting in dramatic differences in disease phenotype progression. Furthermore, The Jackson Lab, one of the world's leading animal vendors, provides acidified water to their in-house animals and is often cited in the literature as having a dramatically different gut microbiome than animals acquired from either Charles River or Taconic. While we recognize that it is impossible to standardize water across all animal facilities currently conducting microbiome research, we hope that by drawing attention to the issue in this commentary, researchers will consider water source as an experimental variable and report their own water sources to facilitate experimental reproducibility. Moreover, researchers should be cognisant of potential phenotypic differences observed between commercial animal vendors due to changes in the gut microbiome as a result of various sources of water used.

RevDate: 2018-11-16

Gao Z, Chen KY, Mueller O, et al (2018)

Microbiota of Inflammatory Bowel Disease Models.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2018:2374-2377.

Gut microbiome plays an important role in inflammatory bowel disease (IBD), a group of intestinal chronic inflammation conditions that affect a large population. The animal models of IBD have long been established on basis of pathological features, but their ability to recapitulate patient gut microbiota is unknown. We investigated and compared the composition and biodiversity of bacterial population in the fecal samples from rat models of the two IBD subtypes, and compared them with patient samples. Our analyses revealed that inflammation reduces overall microbiome diversity and increased variation between individuals. We identified specific microbial signatures associated with the two IBD subtypes that were consistent between the animal models and human IBD patients, suggesting that the animal models can partially recapitulate the microbiota in human diseases. Furthermore, metagenome prediction analysis suggested microbial functions that were likely altered by host-microbiota interactions in IBD models.

RevDate: 2018-11-15

Park CH, Lee AR, Lee YR, et al (2018)

Evaluation of gastric microbiome and metagenomic function in patients with intestinal metaplasia using 16S rRNA gene sequencing.

Helicobacter [Epub ahead of print].

BACKGROUND: Despite recent advances in studies on the gastric microbiome, the role of the non-Helicobacter pylori gastric microbiome in gastric carcinogenesis remains unclear. We evaluated the characteristics of the gastric microbiome and metagenomic functions in patients with IM.

METHODS: Participants were classified into six groups according to disease status (chronic superficial gastritis [CSG], intestinal metaplasia [IM], and cancer) and H. pylori- infection status (H. pylori-positive and H. pylori-negative). The gastric microbiome was analyzed in mucosal tissues at the gastric antrum by 16S rRNA gene sequencing. Moreover, we assessed the metagenome including the type IV secretion system (T4SS) gene, as T4SS proteins are essential for transferring CagA from H. pylori- into the human gastric epithelium.

RESULTS: Among the 138 included patients, 48, 9, 23, 14, 12, and 32 were classified into the H. pylori-negative CSG, H. pylori-negative IM, H. pylori-negative cancer, H. pylori-positive CSG, H. pylori-positive IM, and H. pylori-positive cancer groups, respectively. Cyanobacteria were predominant in the H. pylori-negative CSG group compared to in the H. pylori-negative IM and H. pylori-negative cancer groups (H. pylori-negative CSG vs H. pylori-negative IM vs H. pylori-negative cancer: 14.0% vs 4.2% vs 0.04%, P < 0.001). In contrast, Rhizobiales were commonly observed in the H. pylori-negative IM group (H. pylori-negative CSG vs H. pylori-negative IM vs H. pylori-negative cancer: 1.9% vs 15.4% vs 2.8%, P < 0.001). The relative abundance of Rhizobiales increased as H. pylori-infected stomachs progressed from gastritis to IM. In the H. pylori-negative IM group, genes encoding T4SS were prevalent among the metagenome. Additionally, after H. pylori- eradication therapy, the gastric microbiome was similar to the microbiome observed after spontaneous clearance of H. pylori-.

CONCLUSIONS: The relative abundance of Rhizobiales was higher in patients with H. pylori-negative IM than in those with H. pylori-negative CSG or cancer. Additionally, T4SS genes were highly observed in the metagenome of patients with IM. Highly abundant T4SS proteins in these patients may promote gastric carcinogenesis.

RevDate: 2018-11-15

Jha AR, Davenport ER, Gautam Y, et al (2018)

Gut microbiome transition across a lifestyle gradient in Himalaya.

PLoS biology, 16(11):e2005396 pii:pbio.2005396.

The composition of the gut microbiome in industrialized populations differs from those living traditional lifestyles. However, it has been difficult to separate the contributions of human genetic and geographic factors from lifestyle. Whether shifts away from the foraging lifestyle that characterize much of humanity's past influence the gut microbiome, and to what degree, remains unclear. Here, we characterize the stool bacterial composition of four Himalayan populations to investigate how the gut community changes in response to shifts in traditional human lifestyles. These groups led seminomadic hunting-gathering lifestyles until transitioning to varying levels of agricultural dependence upon farming. The Tharu began farming 250-300 years ago, the Raute and Raji transitioned 30-40 years ago, and the Chepang retain many aspects of a foraging lifestyle. We assess the contributions of dietary and environmental factors on their gut-associated microbes and find that differences in the lifestyles of Himalayan foragers and farmers are strongly correlated with microbial community variation. Furthermore, the gut microbiomes of all four traditional Himalayan populations are distinct from that of the Americans, indicating that industrialization may further exacerbate differences in the gut community. The Chepang foragers harbor an elevated abundance of taxa associated with foragers around the world. Conversely, the gut microbiomes of the populations that have transitioned to farming are more similar to those of Americans, with agricultural dependence and several associated lifestyle and environmental factors correlating with the extent of microbiome divergence from the foraging population. The gut microbiomes of Raute and Raji reveal an intermediate state between the Chepang and Tharu, indicating that divergence from a stereotypical foraging microbiome can occur within a single generation. Our results also show that environmental factors such as drinking water source and solid cooking fuel are significantly associated with the gut microbiome. Despite the pronounced differences in gut bacterial composition across populations, we found little differences in alpha diversity across lifestyles. These findings in genetically similar populations living in the same geographical region establish the key role of lifestyle in determining human gut microbiome composition and point to the next challenging steps of determining how large-scale gut microbiome reconfiguration impacts human biology.

RevDate: 2018-11-15

Berry D (2018)

Up-close-and-personal with the human microbiome.

Environmental microbiology reports [Epub ahead of print].

RevDate: 2018-11-15

Minakova E, BB Warner (2018)

Maternal immune activation, central nervous system development and behavioral phenotypes.

Birth defects research [Epub ahead of print].

Maternal immune activation (MIA) refers to a maternal immune system triggered by infectious or infectious-like stimuli. A cascade of cytokines and immunologic alterations are transmitted to the fetus, resulting in adverse phenotypes most notably in the central nervous system. Epidemiologic studies implicate maternal infections in a variety of neuropsychiatric disorders, most commonly autism spectrum disorders and schizophrenia. In animal models, MIA causes neurochemical and anatomic changes in the brain that correspond to those found in humans with the disorders. As our understanding of the interactions between environment, genetics, and immune system grows, the role of alternative, noninfectious risk factors, such as prenatal stress, obesity, and the gut microbiome also becomes clearer. This review considers how infectious and noninfectious etiologies activate the maternal immune system. Their impact on fetal programming and neuropsychiatric disorders in offspring is examined in the context of human and animal studies.

RevDate: 2018-11-15

Frew JW (2018)

Complement, Hidradenitis Suppurativa and Pathogen-Driven Positive Selection.

The precise pathogenesis of Hidradenitis Suppurativa (HS) remains unclear. Kanni et al1 provides novel data implicating C5a and the membrane attack complex in HS pathogenesis. This opens the possibility of therapeutic blockade of C5a for the treatment of HS, although the results do require replication in larger patient cohorts. The current HS pathogenic paradigm involves dysregulation of the Th17:T-reg axis with contribution from genetic polymorphisms, metabolic syndrome, the microbiome and smoking, so data implicating complement is somewhat unexpected, stimulating the need for reconsideration of the current pathogenic paradigm. This article is protected by copyright. All rights reserved.

RevDate: 2018-11-15

Schultz J, Schröttner P, Leupold S, et al (2018)

Conservative treatment of fingertip injuries in children - first experiences with a novel silicone finger cap that enables woundfluid analysis.

GMS Interdisciplinary plastic and reconstructive surgery DGPW, 7:Doc05 pii:Doc05.

Introduction: Human fingertips are able to regenerate soft tissue and skin after amputation injuries with excellent cosmetic and functional results when treated with semiocclusive dressings. Despite bacterial colonizations, proceeding infections are not reported with this management. The underlying mechanisms for this form of regenerative healing as well as for the resilience to infections are not known. Due to the lack of mechanical protection, the leakage of maloderous woundfluid and the sometimes challenging application, conventional film dressings have their problems, especially in treating young children. We therefore treated selected patients with a novel silicone finger cap with an integrated wound fluid reservoir that enables atraumatic routine wound fluid aspiration. Methods: We report on 34 patients in between 1 and 13 years with traumatic fingertip amputations primarily treated with occlusive dressings. 12 patients were treated with a novel silicone finger cap. We summarized clinical data for each patient. This included photographs and microbiological results from wound fluid analyses, whenever available. Results: The results of both, conventional film dressing and silicone finger cap treatment, were excellent with no hypersensitivity and no restrictions in sensibility and motility. Even larger pulp defects were rearranged in a round shape and good soft tissue coverage of the distal phalanx was achieved. Nail deformities were not observed. We detected a wide spectrum of both aerobic and anaerobic bacteria in the wound fluids but infections were not observed. Epithelialization times did not differ significantly and no severe complications were seen in all primarily conservatively treated patients. Conclusion: This study provides preliminary data demonstrating that the treatment with the silicone finger cap leads to excellent clinical results in wound healing. Interestingly, the wounds were colonized with a wide range of bacteria including species that may cause wound infections. However, we saw no proceeding inflammation and the regeneration was undisturbed. In the future, the efficacy of this new management should be evaluated in randomized, controlled clinical trials to confirm the results under standard conditions and get more insight into the role of the wound microbiome as well as other factors that may promote regeneration. The aspirable Reservoir of the finger cap will enable easy atraumatic sampling of wound fluids both for diagnostic and for research purposes as well as possibly allowing direct administration of pro-regenerative drugs in the future.

RevDate: 2018-11-15

Chen C, Huang X, Fang S, et al (2018)

Contribution of Host Genetics to the Variation of Microbial Composition of Cecum Lumen and Feces in Pigs.

Frontiers in microbiology, 9:2626.

Pigs are a perfect model for studying the interaction between host genetics and gut microbiome due to the high similarity of gastrointestine and digestive system with humans, and the easily controlled feeding conditions. In this study, two pig populations which were raised in uniformed farm conditions and provided with the same commercial formula diet were used as the experimental animals. A systematical investigation of host genetic effect on the gut microbial composition was separately performed in porcine cecum lumen and feces samples through the comparison of microbial composition among full-sibs, half-sibs and unrelated members, heritability estimate (h2), and genome-wide association study (GWAS). The results showed that full-sib members had a higher similarity of microbial composition than unrelated individuals. A significant correlation was observed between the microbial composition-based kinship and the host SNP-based kinship in both populations (P < 9.9 × 10-5). We identified 81 and 67 microbial taxa having h2 > 0.15 in fecal and cecum luminal samples, respectively, including 31 taxa with h2 > 0.15 in both types of samples. GWAS identified 40 and 34 significant associations between host genomic loci and the abundance or presence/absence of bacterial taxa in the fecal and cecum luminal samples. Functional classifications of host candidate genes related to microbial taxa are mainly associated with metabolism, immunity functions and response, and signal transduction. The high similarity of heritable taxa and functional categories of candidate genes among pig, human and mouse suggests the similar mechanism of the host genetic effect on gut microbiome across mammalian species. The results from this study provided another evidence that host genetics contributes significantly to the gut microbiome.

RevDate: 2018-11-15

Mas-Carrió E, Dini-Andreote F, Brossi MJL, et al (2018)

Organic Amendment Under Increasing Agricultural Intensification: Effects on Soil Bacterial Communities and Plant Productivity.

Frontiers in microbiology, 9:2612.

The soil microbiome is a complex living network that plays essential roles in agricultural systems, regardless of the level of intensification. However, the effects of agricultural management on the soil microbiome and the association with plant productivity remain largely unclear. Here, we studied the responses of three soil systems displaying distinct levels of agriculture intensiveness (i.e., natural, organic, and conventional soil management regimes) to experimentally manipulated organic farming amendments (i.e., dung and earthworms). We aimed at (i) identifying the effect on plant productivity and (ii) elucidating the degree of shifts in bacterial communities in response to the applied organic amendments. We found plant productivity to be lower with increasing agricultural intensification. Bacterial communities shifted distinctively for each soil management regime to the organic amendments applied. In brief, greater changes were observed in the Conventional management comparatively to the Organic and Natural management, an effect largely driven by dung addition. Moreover, we found evidence that the level of agricultural intensiveness also affects the timespan for these shifts. For instance, while the Natural system reached a relatively stable community composition before the end of the experiment, treatments on the conventional soil management regime did not. Random forest analyses further revealed an increasing impact of introduced taxa from dung addition aligned with increasing agricultural intensification. These analyses suggested that earthworms regulate the introduction of species from dung into the soil bacterial community. Collectively, our results contribute to a better understanding of the outcomes of organic amendments on soils under distinct levels of agriculture intensiveness, with implications for further development in soil restorations practices.

RevDate: 2018-11-15

Bruno A, Sandionigi A, Bernasconi M, et al (2018)

Changes in the Drinking Water Microbiome: Effects of Water Treatments Along the Flow of Two Drinking Water Treatment Plants in a Urbanized Area, Milan (Italy).

Frontiers in microbiology, 9:2557.

While safe and of high quality, drinking water can host an astounding biodiversity of microorganisms, dismantling the belief of its "biological simplicity." During the very few years, we are witnessing an exponential growth in scientific publications, exploring the ecology hidden in drinking water treatment plants (DWTPs) and drinking water distribution system (DWDS). We focused on what happens to the microbial communities from source water (groundwater) throughout the main steps of the potabilization process of a DWTP, located in an urbanized area in Northern Italy. Samples were processed by a stringent water filtration to retain even the smallest environmental bacteria and then analyzed with High-Throughput DNA Sequencing (HTS) techniques. We showed that carbon filters harbored a microbial community seeding and shaping water microbiota downstream, introducing a significant variation on incoming (groundwater) microbial community. Chlorination did not instantly affect the altered microbiota. We were also able to correctly predict (through machine learning analysis) samples belonging to groundwater (overall accuracy was 0.71), but the assignation was not reliable with carbon filter samples, which were incorrectly predicted as chlorination samples. The presence and abundance of specific microorganisms allowed us to hypothesize their role as indicators. In particular, Candidatus Adlerbacteria (Parcubacteria), together with microorganisms belonging to Alphaproteobacteria and Gammaproteobacteria, characterized treated water, but not raw water. An exception, confirming our hypothesis, is given by the samples downstream the filters renewal, which had a composition resembling groundwater. Volatility analysis illustrated how carbon filters represented an ecosystem that is stable over time, probably bearing the environmental conditions that promote the survival and growth of this peculiar microbial community.

RevDate: 2018-11-15

Kennedy EA, King KY, MT Baldridge (2018)

Mouse Microbiota Models: Comparing Germ-Free Mice and Antibiotics Treatment as Tools for Modifying Gut Bacteria.

Frontiers in physiology, 9:1534.

As the intestinal microbiota has become better appreciated as necessary for maintenance of physiologic homeostasis and also as a modulator of disease processes, there has been a corresponding increase in manipulation of the microbiota in mouse models. While germ-free mouse models are generally considered to be the gold standard for studies of the microbiota, many investigators turn to antibiotics treatment models as a rapid, inexpensive, and accessible alternative. Here we describe and compare these two approaches, detailing advantages and disadvantages to both. Further, we detail what is known about the effects of antibiotics treatment on cell populations, cytokines, and organs, and clarify how this compares to germ-free models. Finally, we briefly describe recent findings regarding microbiota regulation of infectious diseases and other immunologic challenges by the microbiota, and highlight important future directions and considerations for the use of antibiotics treatment in manipulation of the microbiota.

RevDate: 2018-11-15

Takeuchi K, Asakawa M, Hashiba T, et al (2018)

Effects of xylitol-containing chewing gum on the oral microbiota.

Journal of oral science [Epub ahead of print].

In this interventional study, a randomized controlled trial was used to evaluate the short-term effects of xylitol-containing chewing gum on the salivary microbiota. In total, 70 healthy adult men recruited from the Japan Ground Self Defense Force participated in the study during a 2-day training at Yamaguchi camp, Yamaguchi Prefecture, Japan. The men were randomly divided into two groups: one group chewed two pieces of xylitol-containing chewing gum 7 times/day for 2 days (n = 34) and the other did not (n = 36). Baseline and follow-up stimulated saliva samples were collected and the salivary microbial composition was assessed using the 16S rRNA gene next-generation sequencing analysis. The total salivary bacterial count was quantified using a quantitative real-time PCR system. No statistically significant difference was found between the two groups regarding any parameter analyzed in the baseline samples; however, the follow-up samples of the test group showed significantly lower total salivary bacterial count than those of the control group. Conversely, no significant difference was observed in the overall composition of the salivary microbiota between the baseline and follow-up samples of the two groups. These results indicate that xylitol-containing chewing gum inhibits the increase in total salivary bacteria over a short time during which the salivary microbial composition is not affected.

RevDate: 2018-11-15

Bodogai M, O'Connell J, Kim K, et al (2018)

Commensal bacteria contribute to insulin resistance in aging by activating innate B1a cells.

Science translational medicine, 10(467):.

Aging in humans is associated with increased hyperglycemia and insulin resistance (collectively termed IR) and dysregulation of the immune system. However, the causative factors underlying their association remain unknown. Here, using "healthy" aged mice and macaques, we found that IR was induced by activated innate 4-1BBL+ B1a cells. These cells (also known as 4BL cells) accumulated in aging in response to changes in gut commensals and a decrease in beneficial metabolites such as butyrate. We found evidence suggesting that loss of the commensal bacterium Akkermansia muciniphila impaired intestinal integrity, causing leakage of bacterial products such as endotoxin, which activated CCR2+ monocytes when butyrate was decreased. Upon infiltration into the omentum, CCR2+ monocytes converted B1a cells into 4BL cells, which, in turn, induced IR by expressing 4-1BBL, presumably to trigger 4-1BB receptor signaling as in obesity-induced metabolic disorders. This pathway and IR were reversible, as supplementation with either A. muciniphila or the antibiotic enrofloxacin, which increased the abundance of A. muciniphila, restored normal insulin response in aged mice and macaques. In addition, treatment with butyrate or antibodies that depleted CCR2+ monocytes or 4BL cells had the same effect on IR. These results underscore the pathological function of B1a cells and suggest that the microbiome-monocyte-B cell axis could potentially be targeted to reverse age-associated IR.

RevDate: 2018-11-15

Mahadik K, Yadav P, Bhatt B, et al (2018)

Deregulated AUF1 Assists BMP-EZH2-Mediated Delayed Wound Healing during Candida albicans Infection.

Journal of immunology (Baltimore, Md. : 1950) pii:jimmunol.1800688 [Epub ahead of print].

Tissue repair is a complex process that necessitates an interplay of cellular processes, now known to be dictated by epigenetics. Intriguingly, macrophages are testimony to a large repertoire of evolving functions in this process. We identified a role for BMP signaling in regulating macrophage responses to Candida albicans infection during wound repair in a murine model. In this study, the RNA binding protein, AU-rich element-binding factor 1, was posttranslationally destabilized to bring about ubiquitin ligase, NEDD4-directed activation of BMP signaling. Concomitantly, PI3K/PKCδ mobilized the rapid phosphorylation of BMP-responsive Smad1/5/8. Activated BMP pathway orchestrated the elevated recruitment of EZH2 at promoters of genes assisting timely wound closure. In vivo, the repressive H3K27 trimethylation was observed to persist, accompanied by a robust upregulation of BMP pathway upon infection with C. albicans, culminating in delayed wound healing. Altogether, we uncovered the signaling networks coordinated by fungal colonies that are now increasingly associated with the infected wound microbiome, resulting in altered wound fate.

RevDate: 2018-11-15

Limborg MT, P Heeb (2018)

Special Issue: Coevolution of Hosts and Their Microbiome.

Genes, 9(11): pii:genes9110549.

The evolution of life-history traits in plants and animals has taken place in the midst of complex microbial communities. [...].

RevDate: 2018-11-15

Tuncil YE, Thakkar RD, Arioglu-Tuncil S, et al (2018)

Fecal Microbiota Responses to Bran Particles Are Specific to Cereal Type and In Vitro Digestion Methods That Mimic Upper Gastrointestinal Tract Passage.

Journal of agricultural and food chemistry [Epub ahead of print].

Although in vitro studies to identify interactions between food components and the colonic microbiota employ distinct methods to mimic upper gastrointestinal (GI) tract digestion, the effects of differences in protocols on fermentation have not been rigorously addressed. Here, we compared two widely used upper GI tract digestion methods on four different cereal brans in fermentations by fecal microbiota to test the hypotheses that (1) different methods are varyingly efficient in removing accessible starches and proteins from dietary components and (2) these result in cereal-specific differences in fermentation by fecal microbiota. Our results supported both hypotheses, in that the methods differed significantly in bran starch and protein retention and that the effects were cereal-specific. Furthermore, these differences impacted fermentation by the fecal microbiota of healthy donors, altering both short-chain fatty acid production and microbial community composition. These data suggest that digestion methods should be standardized across laboratories for in vitro fiber fermentation studies.

RevDate: 2018-11-14

Brito TL, Campos AB, Bastiaan von Meijenfeldt FA, et al (2018)

The gill-associated microbiome is the main source of wood plant polysaccharide hydrolases and secondary metabolite gene clusters in the mangrove shipworm Neoteredo reynei.

PloS one, 13(11):e0200437 pii:PONE-D-18-18461.

Teredinidae are a family of highly adapted wood-feeding and wood-boring bivalves, commonly known as shipworms, whose evolution is linked to the acquisition of cellulolytic gammaproteobacterial symbionts harbored in bacteriocytes within the gills. In the present work we applied metagenomics to characterize microbiomes of the gills and digestive tract of Neoteredo reynei, a mangrove-adapted shipworm species found over a large range of the Brazilian coast. Comparative metagenomics grouped the gill symbiont community of different N. reynei specimens, indicating closely related bacterial types are shared. Similarly, the intestine and digestive gland communities were related, yet were more diverse than and showed no overlap with the gill community. Annotation of assembled metagenomic contigs revealed that the gill symbiotic community of N. reynei encodes a plethora of plant cell wall polysaccharides degrading glycoside hydrolase encoding genes, and Biosynthetic Gene Clusters (BGCs). In contrast, the digestive tract microbiomes seem to play little role in wood digestion and secondary metabolites biosynthesis. Metagenome binning recovered the nearly complete genome sequences of two symbiotic Teredinibacter strains from the gills, a representative of Teredinibacter turnerae "clade I" strain, and a yet to be cultivated Teredinibacter sp. type. These Teredinibacter genomes, as well as un-binned gill-derived gammaproteobacteria contigs, also include an endo-β-1,4-xylanase/acetylxylan esterase multi-catalytic carbohydrate-active enzyme, and a trans-acyltransferase polyketide synthase (trans-AT PKS) gene cluster with the gene cassette for generating β-branching on complex polyketides. Finally, we use multivariate analyses to show that the secondary metabolome from the genomes of Teredinibacter representatives, including genomes binned from N. reynei gills' metagenomes presented herein, stands out within the Cellvibrionaceae family by size, and enrichments for polyketide, nonribosomal peptide and hybrid BGCs. Results presented here add to the growing characterization of shipworm symbiotic microbiomes and indicate that the N. reynei gill gammaproteobacterial community is a prolific source of biotechnologically relevant enzymes for wood-digestion and bioactive compounds production.

RevDate: 2018-11-14

Ver Heul A, Planer J, AL Kau (2018)

The Human Microbiota and Asthma.

Clinical reviews in allergy & immunology pii:10.1007/s12016-018-8719-7 [Epub ahead of print].

Over the last few decades, advances in our understanding of microbial ecology have allowed us to appreciate the important role of microbial communities in maintaining human health. While much of this research has focused on gut microbes, microbial communities in other body sites and from the environment are increasingly recognized in human disease. Here, we discuss recent advances in our understanding of host-microbiota interactions in the development and manifestation of asthma focusing on three distinct microbial compartments. First, environmental microbes originating from house dust, pets, and farm animals have been linked to asthma pathogenesis, which is often connected to their production of bioactive molecules such as lipopolysaccharide. Second, respiratory microbial communities, including newly appreciated populations of microbes in the lung have been associated with allergic airway inflammation. Current evidence suggests that the presence of particular microbes, especially Streptococcus, Haemophilus, and Morexella species within the airway may shape local immune responses and alter the severity and manifestations of airway inflammation. Third, the gut microbiota has been implicated in both experimental models and clinical studies in predisposing to asthma. There appears to be a "critical window" of colonization that occurs during early infancy in which gut microbial communities shape immune maturation and confer susceptibility to allergic airway inflammation. The mechanisms by which gut microbial communities influence lung immune responses and physiology, the "gut-lung axis," are still being defined but include the altered differentiation of immune cell populations important in asthma and the local production of metabolites that affect distal sites. Together, these findings suggest an intimate association of microbial communities with host immune development and the development of allergic airway inflammation. Improved understanding of these relationships raises the possibility of microbiota-directed therapies to improve or prevent asthma.

RevDate: 2018-11-14

David Spence J (2018)

Advances in Stroke Prevention.

Journal of translational internal medicine, 6(3):105-114 pii:jtim-2018-0024.

There have been recent advances in stroke prevention in nutrition, blood pressure control, antiplatelet therapy, anticoagulation, identification of high-risk asymptomatic carotid stenosis, and percutaneous closure of patent foramen ovale. There is evidence that the Mediterranean diet significantly reduces the risk of stroke and that B vitamins lower homocysteine, thus preventing stroke. The benefit of B vitamins to lower homocysteine was masked by harm from cyanocobalamin among study participants with impaired renal function; we should be using methylcobalamin instead of cyanocobalamin. Blood pressure control can be markedly improved by individualized therapy based on phenotyping by plasma renin and aldosterone. Loss of function mutations of CYP2D19 impair activation of clopidogrel and limits its efficacy; ticagrelor can avoid this problem. New oral anticoagulants that are not significantly more likely than aspirin to cause severe bleeding, and prolonged monitoring for atrial fibrillation (AF), have revolutionized the prevention of cardioembolic stroke. Most patients (~90%) with asymptomatic carotid stenosis are better treated with intensive medical therapy; the few that could benefit from stenting or endarterectomy can be identified by a number of approaches, the best validated of which is transcranial Doppler (TCD) embolus detection. Percutaneous closure of patent foramen ovale has been shown to be efficacious but should only be implemented in selected patients; they can be identified by clinical clues to paradoxical embolism and by TCD estimation of shunt grade. "Treating arteries instead of treating risk factors," and recent findings related to the intestinal microbiome and atherosclerosis point the way to promising advances in future.

RevDate: 2018-11-14

Berger FK, Schwab N, Glanemann M, et al (2018)

Flavonifractor (Eubacterium) plautii bloodstream infection following acute cholecystitis.

IDCases, 14:e00461 pii:e00461.

Flavonifractor plautii (formerly Eubacterium plautii) is an anaerobic gram positive rod shaped bacterium belonging to the family of Clostridiales, and a common member of the human gut microbiome. However, it is very rarely isolated from clinical human specimens, so data about its clinical significance are scarce. Here we report of a bloodstream infection due to F. plautii following gangrenous cholecystitis in a 69 year old man. After cholecystectomy and empirical antimicrobial treatment with ceftriaxone and metronidazole the patient recovered. F. plautii was the only bacterium detected in blood culture, suggesting that it might have been causative for cholecystitis. Antimicrobial resistance testing identified decreased susceptibilities against linezolid and penicillin indicating that a targeted therapy might be necessary. F. plautii can be considered a potential pathogen for cholecystitis.

RevDate: 2018-11-14

Ornelas-García P, Pajares S, Sosa-Jiménez VM, et al (2018)

Microbiome differences between river-dwelling and cave-adapted populations of the fish Astyanax mexicanus (De Filippi, 1853).

PeerJ, 6:e5906 pii:5906.

Symbiotic relationships between host and microbiome can play a major role in local adaptation. Previous studies with freshwater organisms have shown that microbiome performs numerous important biochemical functions for the host, playing a key role in metabolism, physiology or health. Experimental studies in fish groups have found an effect of enzymatic activity of gut microbiota on a variety of metabolic processes. The goal of this study was to compare stomach microbiome from cave and surface Astyanax mexicanus, in order to evaluate the potential response of microbiota to contrasting environmental conditions and physiological adaptations of the host. Stomach microbiota was obtained from three different populations: Pachón cave, and two surface rivers (Rascón and Micos rivers). The stomach microbiome was analyzed using the Ion 16S Metagenomic kit considering seven variable regions: V2, V3, V4, V6-7, V8 and V9. A high diversity was observed across samples, including 16 phyla, 120 families and 178 genera. Gammaproteobacteria, Firmicutes, Bacteroidetes and Betaproteobacteria were the most abundant phyla across the samples. Although the relative abundance of the core OTUs at genus level were highly contrasting among populations, we did not recover differences in stomach microbiome between contrasting habitats (cave vs. surface rivers). Rather, we observed a consistent association between β-diversity and dissolved oxygen concentration in water. Therefore, and unexpectedly, the microbiota of A. mexicanus is not linked with the contrasting conditions of the habitat considered here but is related to water parameters.

RevDate: 2018-11-14

Ong J, Bath MF, Swift C, et al (2018)

Does colectomy affect the progression of primary sclerosing cholangitis? A systematic review and meta-analysis.

Gastroenterology and hepatology from bed to bench, 11(4):277-283.

Aim: The aim of this systematic review was to determine if the human colon, through the lower gut-liver axis, drives PSC activity by assessing the progression of the disease in patients with and without colectomy for colonic disease.

Background: The gut-liver axis is involved in the pathogenesis of liver disease. Abnormal immune-mediated responses to intestinal microbiome are implicated in primary sclerosing cholangitis (PSC) however the mechanisms remain poorly understood. Currently, no single animal model recapitulates all attributes of PSC in humans and this limits further studies of gut-liver interactions.

Methods: A systematic search of PubMed, Medline, and Scopus was performed for articles that contained the terms "colectomy" or "bowel resection" AND "primary sclerosing cholangitis" up to 15th April 2018. Articles were reviewed by 2 reviewers and raw data collated. A Forest plot was used to illustrate the effect of colectomy on subsequent liver transplantation for PSC. Linear regression was used to estimate mortality risk.

Results: Colectomy appeared to have no effect on PSC progression, although high-quality studies were lacking. Rates of liver transplantation or transjugular intrahepatic portosystemic shunt for PSC were not affected by colectomy (OR 0.59, 95% CI 0.14 - 2.53, p=0.48). Mortality risk following colectomy in patients with PSC is 2.11% per year (95% CI 0.03% - 4.18%, p=0.032, R2 = 0.722).

Conclusion: Current evidence is limited but suggests colectomy does not affect the progression of PSC in patients with colonic disease. Pathogenic micro-organisms or antigens that drive PSC may not be limited to the lower gut.

RevDate: 2018-11-14

Hubert J, Nesvorna M, Sopko B, et al (2018)

Two Populations of Mites (Tyrophagus putrescentiae) Differ in Response to Feeding on Feces-Containing Diets.

Frontiers in microbiology, 9:2590.

Background:Tyrophagus putrescentiae is a ubiquitous mite species in soil, stored products and house dust and infests food and causes allergies in people. T. putrescentiae populations harbor different bacterial communities, including intracellular symbionts and gut bacteria. The spread of microorganisms via the fecal pellets of T. putrescentiae is a possibility that has not been studied in detail but may be an important means by which gut bacteria colonize subsequent generations of mites. Feces in soil may be a vector for the spread of microorganisms. Methods: Extracts from used mite culture medium (i.e., residual food, mite feces, and dead mite bodies) were used as a source of feces-inhabiting microorganisms as food for the mites. Two T. putrescentiae populations (L and P) were used for experiments, and they hosted the intracellular bacteria Cardinium and Wolbachia, respectively. The effects of the fecal fraction on respiration in a mite microcosm, mite nutrient contents, population growth and microbiome composition were evaluated. Results: Feces from the P population comprised more than 90% Bartonella-like sequences. Feces from the L population feces hosted Staphylococcus, Virgibacillus, Brevibacterium, Enterobacteriaceae, and Bacillus. The mites from the P population, but not the L population, exhibited increased bacterial respiration in the microcosms in comparison to no-mite controls. Both L- and P-feces extracts had an inhibitory effect on the respiration of the microcosms, indicating antagonistic interactions within feces-associated bacteria. The mite microbiomes were resistant to the acquisition of new bacterial species from the feces, but their bacterial profiles were affected. Feeding of P mites on P-feces-enriched diets resulted in an increase in Bartonella abundance from 6 to 20% of the total bacterial sequences and a decrease in Bacillus abundance. The population growth was fivefold accelerated on P-feces extracts in comparison to the control. Conclusion: The mite microbiome, to a certain extent, resists the acquisition of new bacteria when mites are fed on feces of the same species. However, a Bartonella-like bacteria-feces-enriched diet seems to be beneficial for mite populations with symbiotic Bartonella-like bacteria. Coprophagy on the feces of its own population may be a mechanism of bacterial acquisition in T. putrescentiae.

RevDate: 2018-11-14

Fang X, Monk JM, Nurk S, et al (2018)

Metagenomics-Based, Strain-Level Analysis of Escherichia coli From a Time-Series of Microbiome Samples From a Crohn's Disease Patient.

Frontiers in microbiology, 9:2559.

Dysbiosis of the gut microbiome, including elevated abundance of putative leading bacterial triggers such as E. coli in inflammatory bowel disease (IBD) patients, is of great interest. To date, most E. coli studies in IBD patients are focused on clinical isolates, overlooking their relative abundances and turnover over time. Metagenomics-based studies, on the other hand, are less focused on strain-level investigations. Here, using recently developed bioinformatic tools, we analyzed the abundance and properties of specific E. coli strains in a Crohns disease (CD) patient longitudinally, while also considering the composition of the entire community over time. In this report, we conducted a pilot study on metagenomic-based, strain-level analysis of a time-series of E. coli strains in a left-sided CD patient, who exhibited sustained levels of E. coli greater than 100X healthy controls. We: (1) mapped out the composition of the gut microbiome over time, particularly the presence of E. coli strains, and found that the abundance and dominance of specific E. coli strains in the community varied over time; (2) performed strain-level de novo assemblies of seven dominant E. coli strains, and illustrated disparity between these strains in both phylogenetic origin and genomic content; (3) observed that strain ST1 (recovered during peak inflammation) is highly similar to known pathogenic AIEC strains NC101 and LF82 in both virulence factors and metabolic functions, while other strains (ST2-ST7) that were collected during more stable states displayed diverse characteristics; (4) isolated, sequenced, experimentally characterized ST1, and confirmed the accuracy of the de novo assembly; and (5) assessed growth capability of ST1 with a newly reconstructed genome-scale metabolic model of the strain, and showed its potential to use substrates found abundantly in the human gut to outcompete other microbes. In conclusion, inflammation status (assessed by the blood C-reactive protein and stool calprotectin) is likely correlated with the abundance of a subgroup of E. coli strains with specific traits. Therefore, strain-level time-series analysis of dominant E. coli strains in a CD patient is highly informative, and motivates a study of a larger cohort of IBD patients.

RevDate: 2018-11-14

Miller I (2018)

The gut-brain axis: historical reflections.

Microbial ecology in health and disease, 29(1):1542921 pii:1542921.

The gut-brain axis and the microbiome have recently acquired an important position in explaining a wide range of human behaviours and emotions. Researchers have typically presented developments in understandings of the microbiome as radical and new, offering huge potential for better understandings of our bodies and what it means to be human. Without refuting the value of this research, this article insists that, traditionally, doctors and patients acknowledged the complex interactions between their guts and emotions, although using alternative models often based on nerves or psychology. For example, nineteenth-century doctors and patients would have been well acquainted with the idea that their stomachs and minds were somehow connected, and that this interaction could produce positive or negative physical and mental health impacts. To demonstrate this, this article offers a snapshot of medical and public thought on (what we currently call) the gut-brain axis in the nineteenth and twentieth centuries, using Britain as a key case study due to the prevalence of gastric problems in that country. It commences by exploring how nineteenth-century doctors and patients took for granted the intimate relations between gut and mind and used their ideas on this to debate personal health, medical theory and social and political discourse. The article then moves on to argue that various medical sub-disciplines emerged (anatomy, physiology, surgery) that threatened to reduce the stomach to a physiologically complex organ but, in doing so, inadvertently began to erase ideas of a gut-mind connection. However, these new models proved unsatisfactory, allowing more holistic ideas of the body-mind relationship to continue to carry currency in twentieth-century psychological and medical thought. In the late century, pharmacological developments once again threatened to minimise the gut-brain axis, before it once again became popular in the early twenty-first century, now debated through a new language of microbiology.

RevDate: 2018-11-14

Hansen LBS, Roager HM, Søndertoft NB, et al (2018)

A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults.

Nature communications, 9(1):4630 pii:10.1038/s41467-018-07019-x.

Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.

RevDate: 2018-11-14

Su X, Jing G, McDonald D, et al (2018)

Identifying and Predicting Novelty in Microbiome Studies.

mBio, 9(6): pii:mBio.02099-18.

With the expansion of microbiome sequencing globally, a key challenge is to relate new microbiome samples to the existing space of microbiome samples. Here, we present Microbiome Search Engine (MSE), which enables the rapid search of query microbiome samples against a large, well-curated reference microbiome database organized by taxonomic similarity at the whole-microbiome level. Tracking the microbiome novelty score (MNS) over 8 years of microbiome depositions based on searching in more than 100,000 global 16S rRNA gene amplicon samples, we detected that the structural novelty of human microbiomes is approaching saturation and likely bounded, whereas that in environmental habitats remains 5 times higher. Via the microbiome focus index (MFI), which is derived from the MNS and microbiome attention score (MAS), we objectively track and compare the structural-novelty and attracted-attention scores of individual microbiome samples and projects, and we predict future trends in the field. For example, marine and indoor environments and mother-baby interactions are likely to receive disproportionate additional attention based on recent trends. Therefore, MNS, MAS, and MFI are proposed "alt-metrics" for evaluating a microbiome project or prospective developments in the microbiome field, both of which are done in the context of existing microbiome big data.IMPORTANCE We introduce two concepts to quantify the novelty of a microbiome. The first, the microbiome novelty score (MNS), allows identification of microbiomes that are especially different from what is already sequenced. The second, the microbiome attention score (MAS), allows identification of microbiomes that have many close neighbors, implying that considerable scientific attention is devoted to their study. By computing a microbiome focus index based on the MNS and MAS, we objectively track and compare the novelty and attention scores of individual microbiome samples and projects over time and predict future trends in the field; i.e., we work toward yielding fundamentally new microbiomes rather than filling in the details. Therefore, MNS, MAS, and MFI can serve as "alt-metrics" for evaluating a microbiome project or prospective developments in the microbiome field, both of which are done in the context of existing microbiome big data.

RevDate: 2018-11-14

Castillo-Álvarez F, ME Marzo-Sola (2018)

Disease of the holobiont, the example of multiple sclerosis.

Medicina clinica pii:S0025-7753(18)30568-2 [Epub ahead of print].

In recent years there has been a revolution regarding the role of the microbiota in different diseases, most of them within the spectrum of inflammatory and autoimmune diseases, associated with the development of metagenomics and the concept of holobiont, a large organism together with its microbiota. Specifically, in Multiple Sclerosis, multiple evidence points to the role of the microbiota in experimental autoimmune encephalomyelitis, animal model of the disease, and several articles have been published in recent years about differences in intestinal microbiota among patients with multiple sclerosis and control subjects. We review in this article the concept of holobiont and the gut microbiota functions, as well as the evidence accumulated about the role of the microbiota in experimental autoimmune encephalomyelitis and multiple sclerosis. Nowadays, there is a lot of evidence showing the role of the microbiota in the genesis, prevention and treatment of experimental autoimmune encephalomyelitis based mainly on three immunological pillars, the Th1-Th17 / Th2 balance, the Treg cells and the humoral immunity. It is also well documented that there are differences in the microbiota of patients with MS that are associated with a different expression of genes related to inflammation.

RevDate: 2018-11-14

Haney MM, Ericsson AC, TE Lever (2018)

Effects of Intraoperative Vagal Nerve Stimulation on the Gastrointestinal Microbiome in a Mouse Model of Amyotrophic Lateral Sclerosis.

Comparative medicine [Epub ahead of print].

The gastrointestinal microbiota (GM) plays a fundamental role in health and disease and contributes to the bidirectional signaling between the gastrointestinal system and brain. The direct line of communication between these organ systems is through the vagus nerve. Therefore, vagal nerve stimulation (VNS), a commonly used technique for multiple disorders, has potential to modulate the enteric microbiota, enabling investigation and possibly treatment of numerous neurologic disorders in which the microbiota has been linked with disease. Here we investigate the effect of VNS in a mouse model of amyotrophic lateral sclerosis (ALS). B6SJL-Tg(SOD1*G93A)dl1Gur (SOD1dl) and wildtype mice underwent ventral neck surgeryto access the vagus nerve. During surgery, the experimental group received 1 h of VNS, whereas the sham group underwent 1 h of sham treatment. The third (control) group did not undergo any surgical manipulation. Fecal samples were collected before surgery and at 8 d after the initial collection. Microbial DNA was sequenced to determine the GM profiles at both time points. GM profiles did not differ between genotypes at either the initial or end point. In addition, VNS did not alter GM populations, according to the parameters chosen in this study, indicating that this short intraoperative treatment is safeand has no lasting effects on the GM. Future studies are warranted to determine whether different stimulation parametersor chronic use of VNS affect GM profiles.

RevDate: 2018-11-14

Singh NK, Wood JM, Karouia F, et al (2018)

Succession and persistence of microbial communities and antimicrobial resistance genes associated with International Space Station environmental surfaces.

Microbiome, 6(1):204 pii:10.1186/s40168-018-0585-2.

BACKGROUND: The International Space Station (ISS) is an ideal test bed for studying the effects of microbial persistence and succession on a closed system during long space flight. Culture-based analyses, targeted gene-based amplicon sequencing (bacteriome, mycobiome, and resistome), and shotgun metagenomics approaches have previously been performed on ISS environmental sample sets using whole genome amplification (WGA). However, this is the first study reporting on the metagenomes sampled from ISS environmental surfaces without the use of WGA. Metagenome sequences generated from eight defined ISS environmental locations in three consecutive flights were analyzed to assess the succession and persistence of microbial communities, their antimicrobial resistance (AMR) profiles, and virulence properties. Metagenomic sequences were produced from the samples treated with propidium monoazide (PMA) to measure intact microorganisms.

RESULTS: The intact microbial communities detected in Flight 1 and Flight 2 samples were significantly more similar to each other than to Flight 3 samples. Among 318 microbial species detected, 46 species constituting 18 genera were common in all flight samples. Risk group or biosafety level 2 microorganisms that persisted among all three flights were Acinetobacter baumannii, Haemophilus influenzae, Klebsiella pneumoniae, Salmonella enterica, Shigella sonnei, Staphylococcus aureus, Yersinia frederiksenii, and Aspergillus lentulus. Even though Rhodotorula and Pantoea dominated the ISS microbiome, Pantoea exhibited succession and persistence. K. pneumoniae persisted in one location (US Node 1) of all three flights and might have spread to six out of the eight locations sampled on Flight 3. The AMR signatures associated with β-lactam, cationic antimicrobial peptide, and vancomycin were detected. Prominent virulence factors were cobalt-zinc-cadmium resistance and multidrug-resistance efflux pumps.

CONCLUSIONS: There was an increase in AMR and virulence gene factors detected over the period sampled, and metagenome sequences of human pathogens persisted over time. Comparative analysis of the microbial compositions of ISS with Earth analogs revealed that the ISS environmental surfaces were different in microbial composition. Metagenomics coupled with PMA treatment would help future space missions to estimate problematic risk group microbial pathogens. Cataloging AMR/virulence characteristics, succession, accumulation, and persistence of microorganisms would facilitate the development of suitable countermeasures to reduce their presence in the closed built environment.

RevDate: 2018-11-14

Kaliannan K, Robertson RC, Murphy K, et al (2018)

Estrogen-mediated gut microbiome alterations influence sexual dimorphism in metabolic syndrome in mice.

Microbiome, 6(1):205 pii:10.1186/s40168-018-0587-0.

BACKGROUND: Understanding the mechanism of the sexual dimorphism in susceptibility to obesity and metabolic syndrome (MS) is important for the development of effective interventions for MS.

RESULTS: Here we show that gut microbiome mediates the preventive effect of estrogen (17β-estradiol) on metabolic endotoxemia (ME) and low-grade chronic inflammation (LGCI), the underlying causes of MS and chronic diseases. The characteristic profiles of gut microbiome observed in female and 17β-estradiol-treated male and ovariectomized mice, such as decreased Proteobacteria and lipopolysaccharide biosynthesis, were associated with a lower susceptibility to ME, LGCI, and MS in these animals. Interestingly, fecal microbiota-transplant from male mice transferred the MS phenotype to female mice, while antibiotic treatment eliminated the sexual dimorphism in MS, suggesting a causative role of the gut microbiome in this condition. Moreover, estrogenic compounds such as isoflavones exerted microbiome-modulating effects similar to those of 17β-estradiol and reversed symptoms of MS in the male mice. Finally, both expression and activity of intestinal alkaline phosphatase (IAP), a gut microbiota-modifying non-classical anti-microbial peptide, were upregulated by 17β-estradiol and isoflavones, whereas inhibition of IAP induced ME and LGCI in female mice, indicating a critical role of IAP in mediating the effects of estrogen on these parameters.

CONCLUSIONS: In summary, we have identified a previously uncharacterized microbiome-based mechanism that sheds light upon sexual dimorphism in the incidence of MS and that suggests novel therapeutic targets and strategies for the management of obesity and MS in males and postmenopausal women.

RevDate: 2018-11-14

Sharaf LK, Sharma M, Chandel D, et al (2018)

Prophylactic intervention of probiotics (L.acidophilus, L.rhamnosus GG) and celecoxib modulate Bax-mediated apoptosis in 1,2-dimethylhydrazine-induced experimental colon carcinogenesis.

BMC cancer, 18(1):1111 pii:10.1186/s12885-018-4999-9.

BACKGROUND: Colorectal cancer has been found to be attenuated either with prophylactic manipulation of gut microbiome with probiotics or celecoxib, a non-steroidal anti-inflammatory drug mainly by suppressing early pro-carcinogenic markers in various experimental studies. Therefore, the present study was designed to assess the prophylactic potential of combinatorial administration of probiotics (Lactobacillus rhamnosus GG, Lactobacillus acidophilus) and celecoxib in experimental colon carcinogenesis.

METHODS: Six groups of Spraugue Dawely rats received probiotics L.rhamnosus GG or/and L.acidophilus in combination with celecoxib one week prior to the inducement of tumor by 1,2-dimethylhydrazine (DMH) and the treatment continued for 18 weeks. Prophylactic potentials of probiotics and celecoxib were determined by employing various methods such as tumor incidence, tumor burden, tumor multiplicity, apoptosis, caspase activity, expression of proto-oncogene K-ras and tumor suppressor p53 gene in colonic tumors.

RESULTS: Interestingly, it was found that one week prior supplementation of both probiotics and celecoxib reduced tumor burden, tumor multiplicity, down-regulated the expression of anti-apoptotic Bcl-2, proto-oncogene K-ras and up-regulated pro-apoptotic Bax as well as tumor suppressor p53 in L.rhamnosus GG + celecoxib+DMH animals compared with counter controls and DMH-treated.

CONCLUSIONS: It can be concluded that such combinatorial approach may be useful in reducing the burden and severity of disease in highly susceptible individuals but needs to be validated clinically.

RevDate: 2018-11-14

Teschke R (2018)

Alcoholic Liver Disease: Alcohol Metabolism, Cascade of Molecular Mechanisms, Cellular Targets, and Clinical Aspects.

Biomedicines, 6(4): pii:biomedicines6040106.

Alcoholic liver disease is the result of cascade events, which clinically first lead to alcoholic fatty liver, and then mostly via alcoholic steatohepatitis or alcoholic hepatitis potentially to cirrhosis and hepatocellular carcinoma. Pathogenetic events are linked to the metabolism of ethanol and acetaldehyde as its first oxidation product generated via hepatic alcohol dehydrogenase (ADH) and the microsomal ethanol-oxidizing system (MEOS), which depends on cytochrome P450 2E1 (CYP 2E1), and is inducible by chronic alcohol use. MEOS induction accelerates the metabolism of ethanol to acetaldehyde that facilitates organ injury including the liver, and it produces via CYP 2E1 many reactive oxygen species (ROS) such as ethoxy radical, hydroxyethyl radical, acetyl radical, singlet radical, superoxide radical, hydrogen peroxide, hydroxyl radical, alkoxyl radical, and peroxyl radical. These attack hepatocytes, Kupffer cells, stellate cells, and liver sinusoidal endothelial cells, and their signaling mediators such as interleukins, interferons, and growth factors, help to initiate liver injury including fibrosis and cirrhosis in susceptible individuals with specific risk factors. Through CYP 2E1-dependent ROS, more evidence is emerging that alcohol generates lipid peroxides and modifies the intestinal microbiome, thereby stimulating actions of endotoxins produced by intestinal bacteria; lipid peroxides and endotoxins are potential causes that are involved in alcoholic liver injury. Alcohol modifies SIRT1 (Sirtuin-1; derived from Silent mating type Information Regulation) and SIRT2, and most importantly, the innate and adapted immune systems, which may explain the individual differences of injury susceptibility. Metabolic pathways are also influenced by circadian rhythms, specific conditions known from living organisms including plants. Open for discussion is a 5-hit working hypothesis, attempting to define key elements involved in injury progression. In essence, although abundant biochemical mechanisms are proposed for the initiation and perpetuation of liver injury, patients with an alcohol problem benefit from permanent alcohol abstinence alone.

RevDate: 2018-11-14

Solano-Aguilar GI, Jang S, Lakshman S, et al (2018)

The Effect of Dietary Mushroom Agaricus bisporus on Intestinal Microbiota Composition and Host Immunological Function.

Nutrients, 10(11): pii:nu10111721.

A study was designed to determine the potential prebiotic effect of dietary mushrooms on the host immune response, and intestinal microbiota composition and function. Thirty-one six-week-old pigs were fed a pig grower diet alone or supplemented with either three or six servings of freeze-dried white button (WB)-mushrooms for six weeks. Host immune response was evaluated in peripheral blood mononuclear cells (PBMC), and alveolar macrophages (AM) after stimulation with Salmonella typhymurium-Lipopolysaccharide (LPS). Isolated DNA from fecal and proximal colon contents were used for 16S rDNA taxonomic analysis and linear discriminant analysis effect size (LEfSe) to determine bacterial abundance and metabolic function. Pigs gained weight with no difference in body composition or intestinal permeability. Feeding mushrooms reduced LPS-induced IL-1β gene expression in AM (P < 0.05) with no change in LPS-stimulated PBMC or the intestinal mucosa transcriptome. LEfSe indicated increases in Lachnospiraceae, Ruminococcaceae within the order Clostridiales with a shift in bacterial carbohydrate metabolism and biosynthesis of secondary metabolites in the mushroom-fed pigs. These results suggested that feeding WB mushrooms significantly reduced the LPS-induced inflammatory response in AM and positively modulated the host microbiota metabolism by increasing the abundance of Clostridiales taxa that are associated with improved intestinal health.

RevDate: 2018-11-14

Lee SH, Lee Y, Park JS, et al (2018)

Characterization of Microbiota in Bronchiectasis Patients with Different Disease Severities.

Journal of clinical medicine, 7(11): pii:jcm7110429.

The applications of the 16S rRNA gene pyrosequencing has expanded our knowledge of the respiratory tract microbiome originally obtained using conventional, culture-based methods. In this study, we employed DNA-based molecular techniques for examining the sputum microbiome in bronchiectasis patients, in relation to disease severity. Of the sixty-three study subjects, forty-two had mild and twenty-one had moderate or severe bronchiectasis, which was classified by calculating the FACED score, based on the FEV₁ (forced expiratory volume in 1 s, %) (F, 0⁻2 points), age (A, 0⁻2 points), chronic colonization by Pseudomonas aeruginosa (C, 0⁻1 point), radiographic extension (E, 0⁻1 point), and dyspnoea (D, 0⁻1 point). Bronchiectasis was defined as mild, at 0⁻2 points, moderate at 3⁻4 points, and severe at 5⁻7 points. The mean age was 68.0 ± 9.3 years; thirty-three patients were women. Haemophilus (p = 0.005) and Rothia (p = 0.043) were significantly more abundant in the mild bronchiectasis group, whereas Pseudomonas (p = 0.031) was significantly more abundant in the moderate or severe group. However, in terms of the alpha and beta diversity, the sputum microbiota of the two groups did not significantly differ, i.e., the same dominant genera were found in all samples. Further large-scale studies are needed to investigate the sputum microbiome in bronchiectasis.

RevDate: 2018-11-13

Cruz-Aguliar RM, Wantia N, Clavel T, et al (2018)

An Open-Labeled Study on Fecal Microbiota Transfer in Irritable Bowel Syndrome Patients Reveals Improvement in Abdominal Pain Associated with the Relative Abundance of Akkermansia Muciniphila.

Digestion pii:000494252 [Epub ahead of print].

BACKGROUND/AIMS: The gut microbiota is altered in irritable bowel syndrome (IBS), and microbiota manipulations by diet or antibiotics can reduce its symptoms. As fecal microbiota transfer (FMT) in IBS is still controversial, we investigated the clinical and side effects of FMT in a cohort of IBS patients with recurrent, treatment refractory symptoms, and studied gut microbiota signatures.

METHODS: Using an observational, prospective study design, we applied FMTs from one unrelated, healthy donor to 13 IBS patients. Fecal samples of patients and the donor were analyzed by 16S ribosomal RNA amplicon sequencing.

RESULTS: On a symptom level, primarily abdominal pain symptoms were reduced after FMT, and no adverse effects were observed. Studying the microbiome, we found an increase in alpha diversity and changes in the composition of the gut microbiota after FMT. Beta diversity changes after FMT were prominent in a subset of 7 patients with microbiota profiles coming very close to the donor. These patients also showed most pronounced visceral pain reduction. The relative abundance of Akkermansia muciniphila was inversely correlated with pain reduction in our cohort.

CONCLUSION: Although exploratory in nature and with a pilot character, this study highlights the potential role of microbiota manipulations in IBS and describes a novel association of intestinal Akkermansia and pain modulation.

RevDate: 2018-11-13

Okubo R, Koga M, Katsumata N, et al (2018)

Effect of bifidobacterium breve A-1 on anxiety and depressive symptoms in schizophrenia: A proof-of-concept study.

Journal of affective disorders, 245:377-385 pii:S0165-0327(18)31360-0 [Epub ahead of print].

BACKGROUND: Studies of probiotics have suggested they have a positive effect on anxiety and depressive symptoms in humans. This study investigated the effect of consuming the probiotic Bifidobacterium breve A-1 on anxiety and depressive symptoms in patients with schizophrenia and explored its effect on immune products such as cytokines and chemokines.

METHODS: In this open-label single-arm study, all participants received B. breve strain A-1 (1011 cfu/day) for 4 weeks followed by 4 weeks of observation. The primary outcome was the Hospital Anxiety and Depression Scale (HADS) score. Secondary outcomes were anxiety and depressive symptoms on the Positive and Negative Syndrome Scale (PANSS), blood test findings, and fecal microbiome composition.

RESULTS: Twenty-nine outpatients completed the study. HADS total score and PANSS anxiety/depression score were significantly improved at 4 weeks. Based on the criterion of a greater than 25% reduction in HADS total score at 4 weeks from baseline, there were 12 responders and 17 non-responders. Responders were found to have fewer negative symptoms, reduced intake of dairy products, and higher relative abundance of Parabacteroides in the gut microbiome than non-responders. Moreover, IL-22 and TRANCE expression was significantly increased at 4 weeks from baseline in responders but not in non-responders.

LIMITATIONS: This open-label, single-arm study cannot exclude a placebo effect.

CONCLUSIONS: The results suggest the potential effect of B. breve A-1 in improving anxiety and depressive symptoms in patients with schizophrenia. Further studies should investigate this effect in patients with other psychiatric conditions and assess dietary habits and the gut microbiome.

RevDate: 2018-11-13

García-Jiménez B, de la Rosa T, MD Wilkinson (2018)

MDPbiome: microbiome engineering through prescriptive perturbations.

Bioinformatics (Oxford, England), 34(17):i838-i847.

Motivation: Recent microbiome dynamics studies highlight the current inability to predict the effects of external perturbations on complex microbial populations. To do so would be particularly advantageous in fields such as medicine, bioremediation or industrial scenarios.

Results: MDPbiome statistically models longitudinal metagenomics samples undergoing perturbations as a Markov Decision Process (MDP). Given a starting microbial composition, our MDPbiome system suggests the sequence of external perturbation(s) that will engineer that microbiome to a goal state, for example, a healthier or more performant composition. It also estimates intermediate microbiome states along the path, thus making it possible to avoid particularly undesirable/unhealthy states. We demonstrate MDPbiome performance over three real and distinct datasets, proving its flexibility, and the reliability and universality of its output 'optimal perturbation policy'. For example, an MDP created using a vaginal microbiome time series, with a goal of recovering from bacterial vaginosis, suggested avoidance of perturbations such as lubricants or sex toys; while another MDP provided a quantitative explanation for why salmonella vaccine accelerates gut microbiome maturation in chicks. This novel analytical approach has clear applications in medicine, where it could suggest low-impact clinical interventions that will lead to achievement or maintenance of a healthy microbial population, or alternately, the sequence of interventions necessary to avoid strongly negative microbiome states.

Code (https://github.com/beatrizgj/MDPbiome) and result files (https://tomdelarosa.shinyapps.io/MDPbiome/) are available online.

Supplementary information: Supplementary data are available at Bioinformatics online.

RevDate: 2018-11-13

Frioux C, Fremy E, Trottier C, et al (2018)

Scalable and exhaustive screening of metabolic functions carried out by microbial consortia.

Bioinformatics (Oxford, England), 34(17):i934-i943.

Motivation: The selection of species exhibiting metabolic behaviors of interest is a challenging step when switching from the investigation of a large microbiota to the study of functions effectiveness. Approaches based on a compartmentalized framework are not scalable. The output of scalable approaches based on a non-compartmentalized modeling may be so large that it has neither been explored nor handled so far.

Results: We present the Miscoto tool to facilitate the selection of a community optimizing a desired function in a microbiome by reporting several possibilities which can be then sorted according to biological criteria. Communities are exhaustively identified using logical programming and by combining the non-compartmentalized and the compartmentalized frameworks. The benchmarking of 4.9 million metabolic functions associated with the Human Microbiome Project, shows that Miscoto is suited to screen and classify metabolic producibility in terms of feasibility, functional redundancy and cooperation processes involved. As an illustration of a host-microbial system, screening the Recon 2.2 human metabolism highlights the role of different consortia within a family of 773 intestinal bacteria.

Miscoto source code, instructions for use and examples are available at: https://github.com/cfrioux/miscoto.

RevDate: 2018-11-13

Shah A, Morrison M, GJ Holtmann (2018)

Gastroduodenal "Dysbiosis": a New Clinical Entity.

Current treatment options in gastroenterology pii:10.1007/s11938-018-0207-x [Epub ahead of print].

PURPOSE OF REVIEW: Like the rest of the gastrointestinal tract, the small intestine is colonised by microbes, but how this "microbiome" affects the immune system and digestive functions has largely been overlooked, especially in the "omics" era. Here, we present recent findings that show that the diversity, density and interactions of these microbes in the small intestine can play an important role in the pathogenesis of a number of gastrointestinal and extraintestinal disorders.

RECENT FINDINGS: Changes in the small intestinal mucosa-associated microbiota (SI-MAM) have been shown to occur with inflammatory bowel diseases, functional gastrointestinal disorders, metabolic disorders such as obesity and type 2 diabetes. More recently, there is emerging evidence that small intestinal dysbiosis can be a driver for the progression of chronic liver disease. Initially believed that small intestinal dysbiosis (e.g. SIBO) is mainly due to alterations of luminal conditions (e.g. after surgical resections of the ileocecal valve), there is now enough evidence to conclude that small intestinal dysbiosis can occur without underlying structural abnormalities. Alterations of the SI-MAM appear to play a key role for the manifestation and progression of inflammatory and metabolic disorders.

RevDate: 2018-11-13

Malfertheiner P, J Mayerle (2018)

[Gastrointestinal innovations].

MMW Fortschritte der Medizin, 160(Suppl 3):58-63.

RevDate: 2018-11-13

Macut D, Milutinović DV, Rašić-Marković A, et al (2018)

A decade in female reproduction: an endocrine view of the past and into the future.

Hormones (Athens, Greece) pii:10.1007/s42000-018-0073-x [Epub ahead of print].

Over the last decade, huge achievements have been made in the fields of neurophysiology, molecular endocrinology, and biochemistry, as well as in the successful translation of clinical research into diseases into clinical practice. As regards female reproduction, most of the advances made in this area were achieved in gonadal axis regulation, regulation of behavior through sex steroids, reproductive genetics, preservation of ovarian reproductive function, steroid profiling, and metabolic and overall reproductive outcomes. The coming years are expected to bring further understanding of the relationships between nutrition, energy metabolism, and reproductive function and to succeed in identifying new genetic markers linked to adverse metabolic and unfavorable cardiovascular outcomes in women. From our perspective, future research in the field of female reproduction should be directed toward doing research into genetic reproductive abnormalities and neuroendocrine diseases, pathophysiology, long-term health outcomes for oligo/amenorrhea, hyperandrogenism, and ovulatory dysfunction. It is additionally expected that a better understanding will be gained of the endocrinology of the placenta and of pregnancy, the role of the microbiome in female reproduction, the role of insulin sensitizers, anti-obesity and anti-diabetic drugs, and various advances in the prevention of ovarian damage caused by various oncology therapies, while new therapeutic options for the treatment of infertility, including kisspeptin, will be developed.

RevDate: 2018-11-13

Cortez RV, Taddei CR, Sparvoli LG, et al (2018)

Microbiome and its relation to gestational diabetes.

Endocrine pii:10.1007/s12020-018-1813-z [Epub ahead of print].

PURPOSE: Gestational diabetes mellitus (GDM), the major endocrine pathology in pregnancy, has been associated with the development of an intense inflammatory process and increased insulin resistance. The maternal microbiota is involved in several metabolic functions; however, its role in GDM physiopathology remains unclear. The aim of this study was to assess the composition of the microbiota at different sites and evaluate its relationship with the occurrence of GDM.

METHODS: This cross-sectional study recruited women in the third trimester of gestation with and without GDM. Oral, vaginal, and stool samples were evaluated using next-generation sequencing. We included 68 participants: 26 with and 42 without GDM.

RESULTS: The analysis of the oral microbiome did not show significant differences in phyla and genus among the studied groups. In contrast, GDM patients presented a specific vaginal and intestinal microbiome composition, which was less diverse than those found in the control group, showing genera related to dysbiosis.

CONCLUSIONS: Our findings suggest that changes in the composition of the vaginal and intestinal microbiome might be involved in the development of GDM. The follow-up of these patients in order to evaluate vaginal and intestinal samples after delivery may contribute to understanding the development of metabolic disease in women with previous GDM.

RevDate: 2018-11-13

López Nadal A, Peggs D, Wiegertjes GF, et al (2018)

Exposure to Antibiotics Affects Saponin Immersion-Induced Immune Stimulation and Shift in Microbial Composition in Zebrafish Larvae.

Frontiers in microbiology, 9:2588.

In the last decades, pollution of the environment by large scale use of antibiotics in agriculture and human medicine have led to increased antimicrobial resistance in both the environment and the host animal microbiome. Disturbances in the host microbiome can result in impaired immunity and reduced resilience of aquaculture species. Here, we investigated whether environmentally measured levels of the commonly used antibiotics ciprofloxacin and oxytetracycline influences the host microbiome and susceptibility toward saponin-induced immune stimulation in larval zebrafish. Firstly, neutrophil and macrophage reporter zebrafish larvae were exposed to different concentrations of soy saponin by immersion. A dose-dependent increase in neutrophil presence in the intestinal area was observed together with increased expression of immune genes il1b, tnfa, il22 and mmp9. To investigate the effect of antibiotics, larval zebrafish were immersed in ciprofloxacin or oxytetracycline in the presence or absence of a low dose of saponin. In vivo imaging revealed that antibiotic treatment did not reduce the number of neutrophils that were recruited to the intestinal area upon saponin exposure, although it did tend to lower pro-inflammatory cytokine levels. Microbial sequencing of whole larvae revealed that exposure to a low dose of saponin already shifted the microbial composition. The combination of oxytetracycline and saponin significantly increased α-diversity compared to the controls. In conclusion, the current study provides evidence that the combination of low levels of antibiotics with low levels of anti-nutritional factors (saponin) can induce inflammatory phenotypes and can modify the microbiota, which might lead to altered disease susceptibility.

RevDate: 2018-11-13

De Vrieze M, Germanier F, Vuille N, et al (2018)

Combining Different Potato-Associated Pseudomonas Strains for Improved Biocontrol of Phytophthora infestans.

Frontiers in microbiology, 9:2573.

Late blight caused by Phytophthora infestans is considered as the most devastating disease of potato and is a re-emerging problem worldwide. Current late blight control practices rely mostly on synthetic fungicides or copper-based products, but growing awareness of the negative impact of these compounds on the environment has led to the search for alternative control measures. A collection of Pseudomonas strains isolated from both the rhizosphere and the phyllosphere of potato was recently characterized for in vitro protective effects against P. infestans. In the present study, we used a leaf disk assay with three different potato cultivars to compare the disease inhibition capacity of nine selected Pseudomonas strains when applied alone or in all possible dual and triple combinations. Results showed a strong cultivar effect and identified strains previously thought to be inactive based on in vitro assays as the best biocontrol candidates. One strain was much more active alone than in combination with other strains, while two other strains provided significantly better protection in dual combination than when applied alone. A subset of five strains was then further selected to determine their mutual influence on each other's survival and growth, as well as to characterize their activity against P. infestans in more details. This revealed that the two strains whose dual combination was particularly efficient were only weakly interfering with each other's growth and had complementary modes of action. Our results highlight the potential to harness the crop's native rhizosphere and phyllosphere microbiome through re-assembling strains with differing modes of action into small communities, thereby providing more consistent protection than with the application of single strains. We consider this as a first step toward more elaborate microbiome management efforts, which shall be integrated into global strategies for sustainable control of potato late blight.

RevDate: 2018-11-13

Galand PE, Chapron L, Meistertzheim AL, et al (2018)

The Effect of Captivity on the Dynamics of Active Bacterial Communities Differs Between Two Deep-Sea Coral Species.

Frontiers in microbiology, 9:2565.

Microbes play a crucial role in sustaining the coral holobiont's functions and in particular under the pressure of environmental stressors. The effect of a changing environment on coral health is now a major branch of research that relies heavily on aquarium experiments. However, the effect of captivity on the coral microbiome remains poorly known. Here we show that different cold-water corals species have different microbiome responses to captivity. For both the DNA and the RNA fraction, Madrepora oculata bacterial communities were maintained for at least 6 months of aquarium rearing, while Lophelia pertusa bacteria changed within a day. Interestingly, bacteria from the genus Endozoicomonas, a ubiquitous symbiont of numerous marine hosts, were resilient and remained active in M. oculata for several months. Our results demonstrate that a good knowledge of the coral microbiome and an understanding of the ecological strategy of the holobiont is needed before designing aquarium experiments.

RevDate: 2018-11-13

Levy B, E Jami (2018)

Exploring the Prokaryotic Community Associated With the Rumen Ciliate Protozoa Population.

Frontiers in microbiology, 9:2526.

Ciliate protozoa are an integral part of the rumen microbiome and were found to exert a large effect on the rumen ecosystem itself as well as their host animal physiology. Part of these effects have been attributed to their ability to harbor a diverse ecto- and endo-symbiotic community of prokaryotic cells. Studies on the relationship between the protozoa population and their associated prokaryotic community in the rumen mainly focused on the methanogens, revealing that protozoa play a major role in enhancing methanogenesis potential. In contrast, little is known about the composition and function of the bacteria associated with rumen protozoa and the extent of this association. In this study, we characterize the prokaryotic communities associated with different protozoa populations and compare their structure to the free-living prokaryotic population residing in the cow rumen. We show that the overall protozoa associated prokaryotic community structure differs significantly compared to the free-living community in terms of richness and composition. The methanogens proportion was significantly higher in all protozoa populations compared to the free-living fraction, while the Lachnospiraceae was the most prevalent bacterial family in the protozoa associated bacterial communities. Several taxa not detected or detected in extremely low abundance in the free-living community were enriched in the protozoa associated bacterial community. These include members of the Endomicrobia class, previously identified as protozoa symbionts in the termite gut. Our results show that rumen protozoa harbor prokaryotic communities that are compositionally different from their surroundings, which may be the result of specific tropism between the prokaryotic community and protozoa.

RevDate: 2018-11-13

Li W, Yuan Y, Xia Y, et al (2018)

A Cross-Scale Neutral Theory Approach to the Influence of Obesity on Community Assembly of Human Gut Microbiome.

Frontiers in microbiology, 9:2320.

Background: The implications of gut microbiome to obesity have been extensively investigated in recent years although the exact mechanism is still unclear. The question whether or not obesity influences gut microbiome assembly has not been addressed. The question is significant because it is fundamental for investigating the diversity maintenance and stability of gut microbiome, and the latter should hold a key for understanding the etiological implications of gut microbiome to obesity. Methods: In this study, we adopt a dual neutral theory modeling strategy to address this question from both species and community perspectives, with both discrete and continuous neutral theory models. The first neutral theory model we apply is Hubbell's neutral theory of biodiversity that has been extensively tested in macro-ecology of plants and animals, and the second we apply is Sloan's neutral theory model that was developed particularly for microbial communities based on metagenomic sequencing data. Both the neutral models are complementary to each other and integrated together offering a comprehensive approach to more accurately revealing the possible influence of obesity on gut microbiome assembly. This is not only because the focus of both neutral theory models is different (community vs. species), but also because they adopted two different modeling strategies (discrete vs. continuous). Results: We test both the neutral theory models with datasets from Turnbaugh et al. (2009). Our tests showed that the species abundance distributions of more than ½ species (59-69%) in gut microbiome satisfied the prediction of Sloan's neutral theory, although at the community level, the number of communities satisfied the Hubbell's neutral theory was negligible (2 out of 278). Conclusion: The apparently contradictory findings above suggest that both stochastic neutral effects and deterministic environmental (host) factors play important roles in shaping the assembly and diversity of gut microbiome. Furthermore, obesity may just be one of the host factors, but its influence may not be strong enough to tip the balance between stochastic and deterministic forces that shape the community assembly. Finally, the apparent contradiction from both the neutral theories should not be surprising given that there are still near 30-40% species that do not obey the neutral law.

RevDate: 2018-11-13

Wang Y, Wiesnoski DH, Helmink BA, et al (2018)

Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis.

Nature medicine pii:10.1038/s41591-018-0238-9 [Epub ahead of print].

We report the first case series of immune checkpoint inhibitors (ICI)-associated colitis successfully treated with fecal microbiota transplantation, with reconstitution of the gut microbiome and a relative increase in the proportion of regulatory T-cells within the colonic mucosa. These preliminary data provide evidence that modulation of the gut microbiome may abrogate ICI-associated colitis.

RevDate: 2018-11-13

Yost S, Stashenko P, Choi Y, et al (2018)

Increased virulence of the oral microbiome in oral squamous cell carcinoma revealed by metatranscriptome analyses.

International journal of oral science, 10(4):32 pii:10.1038/s41368-018-0037-7.

Oral squamous cell carcinoma (OSCC) is the most prevalent and most commonly studied oral cancer. However, there is a void regarding the role that the oral microbiome may play in OSCC. Although the relationship between microbial community composition and OSCC has been thoroughly investigated, microbial profiles of the human microbiome in cancer are understudied. Here we performed a small pilot study of community-wide metatranscriptome analysis to profile mRNA expression in the entire oral microbiome in OSCC to reveal molecular functions associated with this disease. Fusobacteria showed a statistically significantly higher number of transcripts at tumour sites and tumour-adjacent sites of cancer patients compared to the healthy controls analysed. Regardless of the community composition, specific metabolic signatures were consistently found in disease. Activities such as iron ion transport, tryptophanase activity, peptidase activities and superoxide dismutase were over-represented in tumour and tumour-adjacent samples when compared to the healthy controls. The expression of putative virulence factors in the oral communities associated with OSCC showed that activities related to capsule biosynthesis, flagellum synthesis and assembly, chemotaxis, iron transport, haemolysins and adhesins were upregulated at tumour sites. Moreover, activities associated with protection against reactive nitrogen intermediates, chemotaxis, flagellar and capsule biosynthesis were also upregulated in non-tumour sites of cancer patients. Although they are preliminary, our results further suggest that Fusobacteria may be the leading phylogenetic group responsible for the increase in expression of virulence factors in the oral microbiome of OSCC patients.

RevDate: 2018-11-13

Gay MCL, Koleva PT, Slupsky CM, et al (2018)

Worldwide Variation in Human Milk Metabolome: Indicators of Breast Physiology and Maternal Lifestyle?.

Nutrients, 10(9): pii:nu10091151.

Human milk provides essential substrates for the optimal growth and development of a breastfed infant. Besides providing nutrients to the infant, human milk also contains metabolites which form an intricate system between maternal lifestyle, such as the mother's diet and the gut microbiome, and infant outcomes. This study investigates the variation of these human milk metabolites from five different countries. Human milk samples (n = 109) were collected one month postpartum from Australia, Japan, the USA, Norway, and South Africa and were analyzed by nuclear magnetic resonance. The partial least squares discriminant analysis (PLS-DA) showed separation between either maternal countries of origin or ethnicities. Variation between countries in concentration of metabolites, such as 2-oxoglutarate, creatine, and glutamine, in human milk, between countries, could provide insights into problems, such as mastitis and/or impaired functions of the mammary glands. Several important markers of milk production, such as lactose, betaine, creatine, glutamate, and glutamine, showed good correlation between each metabolite. This work highlights the importance of milk metabolites with respect to maternal lifestyle and the environment, and also provides the framework for future breastfeeding and microbiome studies in a global context.

RevDate: 2018-11-13

Cáliz J, Triadó-Margarit X, Camarero L, et al (2018)

A long-term survey unveils strong seasonal patterns in the airborne microbiome coupled to general and regional atmospheric circulations.

Proceedings of the National Academy of Sciences of the United States of America pii:1812826115 [Epub ahead of print].

Airborne microbes (bacteria, archaea, protists, and fungi) were surveyed over a 7-y period via high-throughput massive sequencing of 16S and 18S rRNA genes in rain and snow samples collected fortnightly at a high-elevation mountain Long-Term Ecological Research (LTER) Network site (LTER-Aigüestortes, Central Pyrenees, Spain). This survey constitutes the most comprehensive mountain-top aerobiology study reported to date. The air mass origins were tracked through modeled back-trajectories and analysis of rain water chemical composition. Consistent microbial seasonal patterns were observed with highly divergent summer and winter communities recurrent in time. Indicative microbial taxa were unveiled as a forensic signature, and ubiquitous taxa were observed as common atmosphere inhabitants, highlighting aerosols as a potentially successful mechanism for global microbial dispersal. Source-tracking analyses identified freshwater, cropland, and urban biomes as the most important sources for airborne bacteria in summer, while marine and forest biomes prevailed in winter, in agreement with air mass retrotrajectories and the prevailing general and regional atmospheric circulation.

RevDate: 2018-11-13

de Souza Moraes B, Mary Dos Santos G, Palladino Delforno T, et al (2018)

Enriched microbial consortia for dark fermentation of sugarcane vinasse towards value-added short-chain organic acids and alcohol production.

Journal of bioscience and bioengineering pii:S1389-1723(18)30567-X [Epub ahead of print].

The role of sugarcane vinasse as a nutrient source and the impacts of different inoculum pretreatment methods (acid-thermal and thermal treatment) were assessed in acidogenic systems aiming to produce value-added short-chain organic acids (SCOA) and alcohols. In-depth microbiome characterization was also conducted by high-throughput sequencing of the 16S rRNA gene using the Miseq Illumina platform. SCOA production was 47.3 % higher in vinasse-fed reactors, with isobutyric (up to 10.3 g L-1) and butyric (up to 10.6 g L-1) acids as the primary metabolites most likely resulting from lactate conversion. Ethanol comprised the main product from solventogenic pathways in all conditions, with values ranging between 2.7 and 5.2 g L-1, whereas no butanol was detected. Microbial analyses revealed high relative abundance values for the Clostridium, Lactobacillus, Bacillus and Ruminococcus genera, with the predominance of the Clostridium genus (17%) in acid-thermal treatment reactors and the Lactobacillus genus (37%) in thermal treatment reactors. Overall, vinasse proved to be a suitable substrate for value-added SCOA production, which characterizes a potential management approach to this wastewater stream. In this sense, the biochemical production of butyrate from vinasse could diversify the product portfolio of sugarcane biorefineries, also minimizing bioenergy losses by converting residual carbon fractions.

RevDate: 2018-11-13

Lamprecht P, Fischer N, Huang J, et al (2018)

Changes in the composition of the upper respiratory tract microbial community in granulomatosis with polyangiitis.

Journal of autoimmunity pii:S0896-8411(18)30460-8 [Epub ahead of print].

Dysbiosis¸ i.e. changes in microbial composition at a mucosal interface, is implicated in the pathogenesis of many chronic inflammatory and autoimmune diseases. To assess the composition of the microbial upper respiratory tract (URT) community in patients with granulomatosis with polyangiitis (GPA), we used culture-independent high-throughput methods. In this prospective clinical study, nasal swabs were collected from patients with GPA, patients with rheumatoid arthritis (RA, disease control), and healthy controls. Nasal bacterial taxa were assessed using V3-V4 region 16S rRNA amplicon sequencing. Staphylococcus aureus, Haemophilus influenza, and entero- and rhinoviruses were detected using qPCR. Unbiased metagenomic RNA sequencing (UMERS) was performed in a subset of samples to determine the relative abundance of bacterial, fungal, and viral species. A trend toward reduced microbiome diversity was detected in GPA samples compared with healthy controls. The abundance of bacterial taxa and microbial richness were significantly decreased in GPA samples compared with RA samples. The relative abundance of bacterial families shifted, with increased Planococcaceae and decreased Moraxellaceae, Tissierellaceae, Staphylococcaceae, and Propionibacteriaceae in GPA and RA. Further, decreased abundance of Corynebacteriaceae, and Aerococcaceae was observed in GPA samples. Significantly more colonization of S. aureus was seen in the nasal microbiome of GPA compared with RA and healthy control samples. H. influenzae colonization was also observed in GPA samples. UMERS detected the presence of rhinoviral sequences in some GPA samples. Thus, our study uncovered changes in the URT microbial composition in patients with GPA and RA, suggesting that both immunosuppression and disease background affect the URT microbiome. Complex alterations of host-microbiome interactions in the URT could influence chronic endonasal inflammation in GPA.

RevDate: 2018-11-13

Frugé AD, Van der Pol W, Rogers LQ, et al (2018)

Fecal Akkermansia muciniphila Is Associated with Body Composition and Microbiota Diversity in Overweight and Obese Women with Breast Cancer Participating in a Presurgical Weight Loss Trial.

Journal of the Academy of Nutrition and Dietetics pii:S2212-2672(18)30279-X [Epub ahead of print].

BACKGROUND: Akkermansia muciniphila (AM) is a gram-negative, mucin-degrading bacteria inhabiting the gastrointestinal tract associated with host phenotypes and disease states.

OBJECTIVE: Explore characteristics of overweight and obese female early-stage (0 to II) breast cancer patients with low AM relative abundance (LAM) vs high (HAM) enrolled in a presurgical weight-loss trial.

DESIGN: Secondary analysis of pooled participants in a randomized controlled trial (NCT02224807).

PARTICIPANTS/SETTING: During the period from 2014 to 2017, 32 female patients with breast cancer were randomized to weight-loss or attention-control arms from time of diagnosis-to-lumpectomy (mean=30±9 days).

INTERVENTION: All were instructed to correct nutrient deficiencies via food sources and on upper-body exercises. The weight-loss group received additional guidance to promote 0.5 to 1 kg/wk weight-loss via energy restriction and aerobic exercise.

MAIN OUTCOME MEASURES: At baseline and follow-up, sera, fecal samples, two-24 hour dietary recalls and dual x-ray absorptiometry were obtained. Bacterial DNA was isolated from feces and polymerase chain reaction (16S) amplified. Inflammatory cytokines were measured in sera.

Differences between LAM and HAM participants were analyzed using t tests and nonparametric tests. Spearman correlations explored relationships between continuous variables.

RESULTS: Participants were aged 61±9 years with body mass index 34.8±6. Mean AM relative abundance was 0.02% (0.007% to 0.06%) and 1.59% (0.59% to 13.57%) for LAM and HAM participants, respectively. At baseline, women with HAM vs LAM had lower fat mass (38.9±11.2 kg vs 46.4±9.0 kg; P=0.044). Alpha diversity (ie, species richness) was higher in women with HAM (360.8±84.8 vs 282.4±69.6; P=0.008) at baseline, but attenuated after weight-loss (P=0.058). At baseline, interleukin-6 level was associated with species richness (ρ=-0.471, P=0.008) and fat mass (ρ=0.529, P=0.002), but not AM. Change in total dietary fiber was positively associated with AM in LAM (ρ=0.626, P=0.002), but not HAM (ρ=0.436, P=0.180) participants.

CONCLUSIONS: Among women with early-stage breast cancer, body composition is associated with AM, microbiota diversity, and interleukin-6 level. AM may mediate the effects of dietary fiber in improving microbiota composition.

RevDate: 2018-11-13

Silverman JD, Durand HK, Bloom RJ, et al (2018)

Dynamic linear models guide design and analysis of microbiota studies within artificial human guts.

Microbiome, 6(1):202 pii:10.1186/s40168-018-0584-3.

BACKGROUND: Artificial gut models provide unique opportunities to study human-associated microbiota. Outstanding questions for these models' fundamental biology include the timescales on which microbiota vary and the factors that drive such change. Answering these questions though requires overcoming analytical obstacles like estimating the effects of technical variation on observed microbiota dynamics, as well as the lack of appropriate benchmark datasets.

RESULTS: To address these obstacles, we created a modeling framework based on multinomial logistic-normal dynamic linear models (MALLARDs) and performed dense longitudinal sampling of four replicate artificial human guts over the course of 1 month. The resulting analyses revealed how the ratio of biological variation to technical variation from sample processing depends on sampling frequency. In particular, we find that at hourly sampling frequencies, 76% of observed variation could be ascribed to technical sources, which could also skew the observed covariation between taxa. We also found that the artificial guts demonstrated replicable trajectories even after a recovery from a transient feed disruption. Additionally, we observed irregular sub-daily oscillatory dynamics associated with the bacterial family Enterobacteriaceae within all four replicate vessels.

CONCLUSIONS: Our analyses suggest that, beyond variation due to sequence counting, technical variation from sample processing can obscure temporal variation from biological sources in artificial gut studies. Our analyses also supported hypotheses that human gut microbiota fluctuates on sub-daily timescales in the absence of a host and that microbiota can follow replicable trajectories in the presence of environmental driving forces. Finally, multiple aspects of our approach are generalizable and could ultimately be used to facilitate the design and analysis of longitudinal microbiota studies in vivo.

RevDate: 2018-11-03

Fatkhullina AR, Peshkova IO, Dzutsev A, et al (2018)

An Interleukin-23-Interleukin-22 Axis Regulates Intestinal Microbial Homeostasis to Protect from Diet-Induced Atherosclerosis.

Immunity pii:S1074-7613(18)30426-6 [Epub ahead of print].

Although commensal flora is involved in the regulation of immunity, the interplay between cytokine signaling and microbiota in atherosclerosis remains unknown. We found that interleukin (IL)-23 and its downstream target IL-22 restricted atherosclerosis by repressing pro-atherogenic microbiota. Inactivation of IL-23-IL-22 signaling led to deterioration of the intestinal barrier, dysbiosis, and expansion of pathogenic bacteria with distinct biosynthetic and metabolic properties, causing systemic increase in pro-atherogenic metabolites such as lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO). Augmented disease in the absence of the IL-23-IL-22 pathway was mediated in part by pro-atherogenic osteopontin, controlled by microbial metabolites. Microbiota transfer from IL-23-deficient mice accelerated atherosclerosis, whereas microbial depletion or IL-22 supplementation reduced inflammation and ameliorated disease. Our work uncovers the IL-23-IL-22 signaling as a regulator of atherosclerosis that restrains expansion of pro-atherogenic microbiota and argues for informed use of cytokine blockers to avoid cardiovascular side effects driven by microbiota and inflammation.

RevDate: 2018-11-12

Stallmach A, Reuken PA, N Teich (2018)

[Advances in the diagnosis and treatment of Clostridioides [Clostridium] difficile infections in inflammatory bowel disease].

Zeitschrift fur Gastroenterologie, 56(11):1369-1377.

Patients with chronic inflammatory bowel disease (IBD) have a significantly increased risk of clinically relevant clostridial infection (CDI). In turn, CDI can increase IBD activity. Therefore, rapid diagnosis and therapy is required. Many diagnostic and treatment studies on patients with CDI without inflammatory bowel disease are not congruent with IBD patients. This overview summarizes the everyday data of recent years and condenses these into four guiding principles. 1) patients with IBD present a risk population for a CDI. A CDI not only worsens the disease activity in the short term, but also causes increased morbidity and mortality in the long term. 2) If a CDI is suspected, glutamate-dehydrogenase (GDH) detection should be carried out quickly. If this is positive, and the disease activity is high, a therapy against C. difficile already may be initiated and-if necessary-terminated in cases of negative confirmation tests. 3) IBD patients with a proven CDI should be treated primarily with vancomycin. 4) In a relapsing CDI, fecal microbiome transfer is an effective therapeutic measure. However, activation of the IBD must be expected in about 15 % of cases. Consistent adherence to these guidelines may help treat a CDI in IBD patients.

RevDate: 2018-11-12

Salazar AM, Resnik-Docampo M, Ulgherait M, et al (2018)

Intestinal Snakeskin Limits Microbial Dysbiosis during Aging and Promotes Longevity.

iScience, 9:229-243 pii:S2589-0042(18)30181-0 [Epub ahead of print].

Intestinal barrier dysfunction is an evolutionarily conserved hallmark of aging, which has been linked to microbial dysbiosis, altered expression of occluding junction proteins, and impending mortality. However, the interplay between intestinal junction proteins, age-onset dysbiosis, and lifespan determination remains unclear. Here, we show that altered expression of Snakeskin (Ssk), a septate junction-specific protein, can modulate intestinal homeostasis, microbial dynamics, immune activity, and lifespan in Drosophila. Loss of Ssk leads to rapid and reversible intestinal barrier dysfunction, altered gut morphology, dysbiosis, and dramatically reduced lifespan. Remarkably, restoration of Ssk expression in flies showing intestinal barrier dysfunction rescues each of these phenotypes previously linked to aging. Intestinal up-regulation of Ssk protects against microbial translocation following oral infection with pathogenic bacteria. Furthermore, intestinal up-regulation of Ssk improves intestinal barrier function during aging, limits dysbiosis, and extends lifespan. Our findings indicate that intestinal occluding junctions may represent prolongevity targets in mammals.

RevDate: 2018-11-12

Ventura Spagnolo E, Stassi C, Mondello C, et al (2018)

Forensic microbiology applications: A systematic review.

Legal medicine (Tokyo, Japan), 36:73-80 pii:S1344-6223(18)30153-6 [Epub ahead of print].

According to the Human Microbiome Project (HMP), a healthy human body contains ten times more microbes than human cells. Microbial communities colonize different organs of the body, playing fundamental roles both in human health and disease. Despite the vast scientific knowledge of the role of microbial communities in a living body, little is known at present about microbial changes occurring after death, thus leading many authors to investigate the composition of the thanatomicrobiome and its potential applications in the forensic field. The aim of the following review is to provide a general overview of the advances of postmortem microbiology research, mainly focusing on the role of microbiological investigations carried out on internal organs and fluids. To this end, a total of 19 studies have been sistematically reviewed, each one chosen according to specific inclusion/exclusion criteria. The selected studies assess the contribution of contamination, postmortem transmigration and agonal spread to microbial isolation from dead body samples, and shed light on the role of postmortem microbiological investigations in several forensic fields, such as cause of death or PMI determination.

RevDate: 2018-11-12

Zhuo C, Yao Y, Xu Y, et al (2018)

Schizophrenia and gut-flora related epigenetic factors.

Progress in neuro-psychopharmacology & biological psychiatry pii:S0278-5846(18)30519-0 [Epub ahead of print].

BACKGROUND: Schizophrenia (SZ) is a complex psychiatric disorder and the exact mechanisms that underpin SZ remain poorly understood despite decades of research. Genetic, epigenetic, and environmental factors are all considered to play a role. The importance of gut flora and its influence on the central nervous system has been recognized in recent years. We hypothesize that gut flora may be a converging point where environmental factors interact with epigenetic factors and contribute to SZ pathogenesis.

AIM: To summarize the current understanding of genetic and epigenetic factors and the possible involvement of gut flora in the pathogenesis of schizophrenia.

RESULTS: We searched PubMed and Medline with a combination of the key words schizophrenia, microbiome, epigenetic factors to identify studies of genetic and epigenetic factors in the pathogenesis of schizophrenia. Numerous genes that encode key proteins in neuronal signaling pathways have been linked to SZ. Epigenetic modifications, particularly, methylation and acetylation profiles, have been found to differ in individuals that present with SZ from those that don't. Gut flora may affect epigenetic modifications by regulation of key metabolic pathway molecules, including methionine, florate, biotin, and metabolites that are acetyl group donors. Despite a lack of direct studies on the subject, it is possible that gut flora may influence genetic and epigenetic expression and thereby contribute to the pathogenesis of SZ.

CONCLUSION: Gut flora is sensitive to both internal and environmental stimuli and the synthesis of some key molecules that participate in the epigenetic modulation of gene expression. Therefore, it is possible that gut flora is a converging point where environmental factors interact with genetic and epigenetic factors in the pathogenesis of SZ.

RevDate: 2018-11-12

Hellauer K, Uhl J, Lucio M, et al (2018)

Microbiome triggered transformations of trace organic chemicals in the presence of effluent organic matter in managed aquifer recharge (MAR) systems.

Environmental science & technology [Epub ahead of print].

It is widely assumed that biodegradation of trace organic chemicals (TOrCs) in managed aquifer recharge (MAR) systems occurs via a co-metabolic transformation with dissolved organic carbon serving as primary substrate. Hence, the composition facilitating bioavailability of the organic matter seems to have a great impact on TOrCs transformation in MAR systems. The aim of this study was to elucidate the character of effluent organic matter present in the feed water of a simulated sequential MAR system throughout the infiltration by use of FT-ICR-MS analyses as well as spectroscopic methods. Furthermore, compositional changes were correlated with TOrCs targeted throughout the system as well as the abundance of different microbial phyla. Based on their behavior throughout the infiltration system in which different redox and substrate conditions prevailed, TOrCs were classified in four groups: easily degradable, redox insensitive, redox sensitive, and persistent. Masses correlating with persistent TOrCs were mainly comprised of CHNO containing molecules, but also of CHO which are known as carboxyl-rich alicyclic molecules, while CHOS and CHNOS can be neglected. Easily degradable TOrCs could be associated with CHNO, CHO and CHOS containing compounds. However, a shift of molecular compounds to mostly CHOS was observed for redox insensitive TOrCs. 338 masses correlated with removal of redox sensitive TOrCs, but no distinct clustering was identified.

RevDate: 2018-11-12

Compo NR, Gomez DE, Tapscott B, et al (2018)

Fecal bacterial microbiota of Canadian commercial mink (Neovison vison): Yearly, life stage, and seasonal comparisons.

PloS one, 13(11):e0207111 pii:PONE-D-17-29194.

The gastrointestinal microbiome is known to play a critical role in animal health but has been relatively poorly characterized in commercial mink, an obligate carnivore. Whether the microbiota can be manipulated in mink to improve pelt quality, health, and well-being is unknown. The objectives of this study were to characterize the fecal microbiota of commercial mink, and to evaluate potential changes due to year (2014 vs 2015), life stage (adult female vs weaned kit), season (summer vs winter), and between Canadian farms. Pooled fecal samples were collected from adult females and weaned kits in the summers of 2014 (n = 173) and 2015 (n = 168), and from females in the winter of 2016 (n = 39), a time when females undergo marked calorie restriction, from 49 mink farms in Ontario. Bacterial DNA was extracted and the V4 region of the 16S rRNA gene was amplified. Approximately 22 million sequences were identified following quality control filtering. A total of 31 bacterial phyla were identified; however, only 3 comprised >1% of the total sequences identified, with Firmicutes and Proteobacteria together comprising 95% of the total sequences. Comparisons were made by life stage, season and year; no differences were found in the relative abundance of any taxa between samples collected from adult females and weaned kits from the same year and the greatest number of differences at each taxonomic level were noted between 2014 and 2015. Significantly more operational taxonomic units (OTUs) were found in 2014 than 2015 or 2016 (p<0.05) and samples from 2014 were more even, but less diverse than in 2015 (p = 0.002 and 0.001, respectively). There were significant differences in community population and structure by year and season (all p-values <0.001). The predominant phyla and genera at the farm level were similar from year to year. Together, these indicate that mink environment, season, and time are important factors in the stability of gastrointestinal microbiota, once mink reach maturity.

RevDate: 2018-11-12

Meng X, Dunsmore G, Koleva P, et al (2018)

The profile of human milk metabolome, cytokines and antibodies in inflammatory bowel diseases versus healthy mothers and potential impact on the newborn.

Journal of Crohn's & colitis pii:5173481 [Epub ahead of print].

Background and Aims: For women with inflammatory bowel disease (IBD), it is not very well known how IBD or IBD treatment impacts their breastmilk components. We aimed to investigate whether breastmilk composition differs in healthy control (HC) versus IBD mothers in terms of antibodies, cytokines and metabolites to identify potential impact of IBD breastmilk on neonatal immune system.

Methods: Breastmilk specimens from HC (n=17) and IBD (n=31 for Crohn's disease (CD); n=41 for ulcerative colitis (UC)) were collected at 3 and 6 months post-partum (PP3) and (PP6), respectively. Fecal samples were also collected. Cytokines and immunoglobulins (IgA/IgG/IgE) were analyzed by multiplex Meso Scale Discovery (MSD) and commercial kits. Moreover, breastmilk metabolites were analyzed by 1H nuclear magnetic resonance (NMR).

Results: We found breastmilk from IBD mothers showed significantly lower levels of IgA, sugar metabolite (lactose) and 2-aminobutyrate. In contrast, we observed breastmilk from mothers with IBD had increased levels of pro-inflammatory cytokines and higher energy metabolites (lactate and succinate) than milk from healthy mothers. In addition, we noticed that the type of treatment (5-ASA versus Biologics) influenced the milk cytokines and metabolites profile.

Conclusions: The reduction in immunoprotective components of IBD breastmilk such as sIgA and lactose theoretically may modulate the potential protective effects of breastfeeding. On the other hand, presence of higher levels of pro-inflammatory cytokines, lactate and succinate may predispose the offspring to an inflammatory condition or impact the gut microbiome. Better understanding the role of succinate in infants and its potential effects on microbiome or mucosal immunity merits further investigations.

RevDate: 2018-11-12

Sams-Dodd J, F Sams-Dodd (2018)

Time to Abandon Antimicrobial Approaches in Wound Healing: A Paradigm Shift.

Wounds : a compendium of clinical research and practice, 30(11):345-352.

Antimicrobial approaches (eg, antibiotics and antiseptics) have been used for decades in the treatment of infected wounds, ulcers, and burns. However, an increasing number of meta-analyses have raised questions regarding the therapeutic value of these approaches. Newer findings show that the body actively hosts an ecosystem of bacteria, fungi, viruses, and mites on its outer surfaces, known as the microbiome, as part of its defense against pathogens. Antimicrobials would disrupt this system and thereby work against the strategy the body has chosen. Recently, a new technology, micropore particle technology (MPPT), has been identified; it is not an antimicrobial but instead acts as a passive immunotherapy that disrupts the weaponry bacteria and fungi use to inhibit the immune system, allowing the immune system to recover. Clinical findings show MPPT removes wound infections 60% quicker than antibiotics and antiseptics and promotes the healing of chronic wounds that have not responded to antimicrobials. These effects are achieved without antimicrobial action and, considering the limited therapeutic benefits of antibiotics and antiseptics for wound infections, it is valid to question the use of antimicrobial approaches in wound care and the dogma that a reduction in microbial burden will lead to a reduction in infection. Instead, it may be time to consider a paradigm shift in wound healing away from antimicrobials and towards therapies that support the immune system and the microbiome. This review covers the increasing evidence that infections on external surfaces have to be treated fundamentally differently to internal infections.

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RJR Experience and Expertise

Researcher

Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.

Educator

Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.

Administrator

Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.

Technologist

Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.

Publisher

While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.

Speaker

Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.

Facilitator

Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.

Designer

Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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