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1.
Statistics of correlated percolation in a bacterial community.
Zhai, X, Larkin, JW, Kikuchi, K, Redford, SE, Roy, U, Süel, GM, Mugler, A
PLoS computational biology. 2019;(12):e1007508
Abstract
Signal propagation over long distances is a ubiquitous feature of multicellular communities, but cell-to-cell variability can cause propagation to be highly heterogeneous. Simple models of signal propagation in heterogenous media, such as percolation theory, can potentially provide a quantitative understanding of these processes, but it is unclear whether these simple models properly capture the complexities of multicellular systems. We recently discovered that in biofilms of the bacterium Bacillus subtilis, the propagation of an electrical signal is statistically consistent with percolation theory, and yet it is reasonable to suspect that key features of this system go beyond the simple assumptions of basic percolation theory. Indeed, we find here that the probability for a cell to signal is not independent from other cells as assumed in percolation theory, but instead is correlated with its nearby neighbors. We develop a mechanistic model, in which correlated signaling emerges from cell division, phenotypic inheritance, and cell displacement, that reproduces the experimentally observed correlations. We find that the correlations do not significantly affect the spatial statistics, which we rationalize using a renormalization argument. Moreover, the fraction of signaling cells is not constant in space, as assumed in percolation theory, but instead varies within and across biofilms. We find that this feature lowers the fraction of signaling cells at which one observes the characteristic power-law statistics of cluster sizes, consistent with our experimental results. We validate the model using a mutant biofilm whose signaling probability decays along the propagation direction. Our results reveal key statistical features of a correlated signaling process in a multicellular community. More broadly, our results identify extensions to percolation theory that do or do not alter its predictions and may be more appropriate for biological systems.
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2.
Importance of the intestinal microbiota in ocular inflammatory diseases: A review.
Lin, P
Clinical & experimental ophthalmology. 2019;(3):418-422
Abstract
The purpose of this article is to review the literature on relationships between the intestinal microbiota and ocular inflammatory disease, specifically non-infectious uveitis and age-related macular degeneration. The importance of the intestinal microbiota in uveitis pathogenesis has been shown by multiple groups demonstrating that alterations in the microbiota induced by certain oral antibiotics results in reduced uveitis severity, and another group demonstrating that a commensal intestinal bacterial antigen activates retina-specific autoreactive T cells, potentially indicating a commensal trigger for uveitis. Additionally, commensal intestinal bacterial metabolite short chain fatty acids can be utilized to suppress autoimmune uveitis. Age-related macular degeneration is associated with intestinal dysbiosis, which is partially influenced by genetic risk alleles and AREDS supplementation. Strategies for therapeutically targeting the intestinal microbiota might involve several approaches, including the use of antibiotics, dietary changes, drugs that supplement beneficial bacterial metabolites or target causative bacterial strains, dietary strategies or faecal microbial transplantation. In summary, the intestinal microbiota are at the cross-roads of genetic and environmental factors that can promote ocular conditions such as non-infectious uveitis and age-related macular degeneration, partially via its dynamic influence on mucosal and systemic immunity. The intestinal microbiome thus represents a salient potential target for therapeutic modulation to treat these potentially blinding conditions.
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3.
Lactulose: Patient- and dose-dependent prebiotic properties in humans.
Ruszkowski, J, Witkowski, JM
Anaerobe. 2019;:100-106
Abstract
Lactulose is a disaccharide used in clinical practice since 1957 and has since been tested in the treatment of many human disorders, including chronic constipation, hepatic encephalopathy, and chronic kidney disease. Its mode of action is based on the lactulose fermentation by intestinal microbiota. Based on in silico, in vitro and in vivo studies we comprehensively review here the impact of lactulose on human gut/fecal and vaginal microbiota composition and both fecal and blood metabolomes. However, both in vitro and in vivo studies summarized in this review have revealed that the effects of lactulose on human microbiota composition are both patient- and dose-dependent. This highlights the need of heterogeneity indication in clinical trials.
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4.
The effect of the octenidine-based oral antiseptic on the structure of microbial communities and periodontal status in patients with fixed orthodontic treatments.
Vidović, B, Gušić, I, Tamaš, I, Mihajlović, D, Mitić, V, Obradović, R, Radovanović, M, Brkić, S
European review for medical and pharmacological sciences. 2019;(19):8598-8605
Abstract
OBJECTIVE To evaluate the effect of an octenidine (OCT)-based antiseptic on the gingival inflammation and microbial composition of subgingival dental plaque in patients with fixed orthodontic appliances. PATIENTS AND METHODS Thirty-three orthodontic patients were randomized into 2 groups. The control group patients were given standard oral hygiene and dietary advice, while the experimental group patients used an OCT-based antiseptic together with standard oral hygiene and dietary recommendations. The periodontal status was evaluated using the following indices: the plaque index (PI), the gingival index (GI), the papilla bleeding index (PBI) and the probing pocket depth (PD). Next Generation Sequencing of the 16S rRNA amplicons was performed in order to assess the subgingival microbiome. RESULTS The PD values obtained were significantly lower in the experimental group after one month, as well as PBI. The microbiological analysis showed a significant increase in the occurrence of the genus Prevotella in the control group, while the number of other periodontopathogens remained stable in both groups. The changes in the abundance of the bacteria not directly associated with periodontal disease were also observed. CONCLUSIONS The use of an OCT-based antiseptic has a positive effect on the prevention of gingival inflammation. Additionally, it also prevents a likely increase in numbers of periodontopathogens of the subgingival dental plaque in the first three months of fixed orthodontic treatment.
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5.
Integration of microbiology, molecular pathology, and epidemiology: a new paradigm to explore the pathogenesis of microbiome-driven neoplasms.
Hamada, T, Nowak, JA, Milner, DA, Song, M, Ogino, S
The Journal of pathology. 2019;(5):615-628
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Abstract
Molecular pathological epidemiology (MPE) is an integrative transdisciplinary field that addresses heterogeneous effects of exogenous and endogenous factors (collectively termed 'exposures'), including microorganisms, on disease occurrence and consequences, utilising molecular pathological signatures of the disease. In parallel with the paradigm of precision medicine, findings from MPE research can provide aetiological insights into tailored strategies of disease prevention and treatment. Due to the availability of molecular pathological tests on tumours, the MPE approach has been utilised predominantly in research on cancers including breast, lung, prostate, and colorectal carcinomas. Mounting evidence indicates that the microbiome (inclusive of viruses, bacteria, fungi, and parasites) plays an important role in a variety of human diseases including neoplasms. An alteration of the microbiome may be not only a cause of neoplasia but also an informative biomarker that indicates or mediates the association of an epidemiological exposure with health conditions and outcomes. To adequately educate and train investigators in this emerging area, we herein propose the integration of microbiology into the MPE model (termed 'microbiology-MPE'), which could improve our understanding of the complex interactions of environment, tumour cells, the immune system, and microbes in the tumour microenvironment during the carcinogenic process. Using this approach, we can examine how lifestyle factors, dietary patterns, medications, environmental exposures, and germline genetics influence cancer development and progression through impacting the microbial communities in the human body. Further integration of other disciplines (e.g. pharmacology, immunology, nutrition) into microbiology-MPE would expand this developing research frontier. With the advent of high-throughput next-generation sequencing technologies, researchers now have increasing access to large-scale metagenomics as well as other omics data (e.g. genomics, epigenomics, proteomics, and metabolomics) in population-based research. The integrative field of microbiology-MPE will open new opportunities for personalised medicine and public health. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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6.
The effect of antibiotics on the composition of the intestinal microbiota - a systematic review.
Zimmermann, P, Curtis, N
The Journal of infection. 2019;(6):471-489
Abstract
OBJECTIVE Antibiotics change the composition of the intestinal microbiota. The magnitude of the effect of antibiotics on the microbiota and whether the effects are short-term or persist long-term remain uncertain. In this review, we summarise studies that have investigated the effect of antibiotics on the composition of the human intestinal microbiota. METHODS A systematic search was done to identify original studies that have investigated the effect of systemic antibiotics on the intestinal microbiota in humans. RESULTS We identified 129 studies investigating 2076 participants and 301 controls. Many studies reported a decrease in bacterial diversity with antibiotic treatment. Penicillin only had minor effects on the intestinal microbiota. Amoxicillin, amoxcillin/clavulanate, cephalosporins, lipopolyglycopeptides, macrolides, ketolides, clindamycin, tigecycline, quinolones and fosfomycin all increased abundance of Enterobacteriaea other than E. coli (mainly Citrobacter spp., Enterobacter spp. and Klebsiella spp.). Amoxcillin, cephalosporins, macrolides, clindamycin, quinolones and sulphonamides decreased abundance of E. coli, while amoxcillin/clavulante, in contrast to other penicillins, increased abundance of E. coli. Amoxicllin, piperacillin and ticarcillin, cephalosporins (except fifth generation cephalosporins), carbapenems and lipoglycopeptides were associated with increased abundance of Enterococcus spp., while macrolides and doxycycline decreased its abundance. Piperacillin and ticarcillin, carbapenems, macrolides, clindamycin and quinolones strongly decreased the abundance of anaerobic bacteria. In the studies that investigated persistence, the longest duration of changes was reported after treatment with ciprofloxacin (one year), clindamycin (two years) and clarithromycin plus metronidazole (four years). Many antibiotics were associated with a decrease in butyrate or butryrate-producing bacteria. CONCLUSION Antibiotics have profound and sometimes persisting effects on the intestinal microbiota, characterised by diminished abundance of beneficial commensals and increased abundance of potentially detrimental microorganisms. Understanding these effects will help tailor antibiotic treatment and the use of probiotics to minimise this 'collateral damage'.
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7.
Environmental structure drives resistance to phages and antibiotics during phage therapy and to invading lysogens during colonisation.
Sousa, JAM, Rocha, EPC
Scientific reports. 2019;(1):3149
Abstract
Microbial communities are shaped by bacteriophages through predation and lysogeny. A better understanding of the interactions between these processes across different types of environments is key to elucidate how phages mediate microbial competition and to design efficient phage therapies. We introduce an individual-based model (eVIVALDI) to investigate the role of environmental structure in the elimination of a population with a combined treatment of antibiotics and virulent phages, and in the invasion of a population of phage-sensitive bacteria by lysogens. We show that structured environments facilitate the emergence of double resistance, to antibiotics and phages, due to limited diffusion of phage particles and increased nutrient availability from dead cells. They also hinder phage amplification, thus decreasing the generation of phage genetic diversity and increasing the unpredictability of phage-bacteria arms-races. We used a machine learning approach to determine the variables most important for the invasion of sensitive populations by lysogens. They revealed that phage-associated traits and environmental structure are the key drivers of the process. Structured environments hinder invasions, and accounting for their existence improves the fit of the model to published in vivo experimental data. Our results underline environmental structure as key to understand in vivo phage-bacteria interactions.
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8.
Interaction between the nasal microbiota and S. pneumoniae in the context of live-attenuated influenza vaccine.
de Steenhuijsen Piters, WAA, Jochems, SP, Mitsi, E, Rylance, J, Pojar, S, Nikolaou, E, German, EL, Holloway, M, Carniel, BF, Chu, MLJN, et al
Nature communications. 2019;(1):2981
Abstract
Streptococcus pneumoniae is the main bacterial pathogen involved in pneumonia. Pneumococcal acquisition and colonization density is probably affected by viral co-infections, the local microbiome composition and mucosal immunity. Here, we report the interactions between live-attenuated influenza vaccine (LAIV), successive pneumococcal challenge, and the healthy adult nasal microbiota and mucosal immunity using an experimental human challenge model. Nasal microbiota profiles at baseline are associated with consecutive pneumococcal carriage outcome (non-carrier, low-dense and high-dense pneumococcal carriage), independent of LAIV co-administration. Corynebacterium/Dolosigranulum-dominated profiles are associated with low-density colonization. Lowest rates of natural viral co-infection at baseline and post-LAIV influenza replication are detected in the low-density carriers. Also, we detected the fewest microbiota perturbations and mucosal cytokine responses in the low-density carriers compared to non-carriers or high-density carriers. These results indicate that the complete respiratory ecosystem affects pneumococcal behaviour following challenge, with low-density carriage representing the most stable ecological state.
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9.
An integrated metagenomic/metaproteomic investigation of microbiota in dajiang-meju, a traditional fermented soybean product in Northeast China.
Xie, M, Wu, J, An, F, Yue, X, Tao, D, Wu, R, Lee, Y
Food research international (Ottawa, Ont.). 2019;:414-424
Abstract
Dajiang-meju have been used as major ingredients for the preparation of traditional spontaneously fermented soybean paste in Northeast China. In this work, we sequenced and analyzed the metagenome of 12 dajiang-meju samples. To complement the metagenome analysis, we analyzed the taxonomic and functional diversity of the microbiota by metaproteomics (LC-MS/MS). The analysis of metagenomic data revealed that the communities were primarily dominated by Enterobacter, Enterococcus, Leuconostoc, Lactobacillus, Citrobacter and Leclercia. Moreover, changes in the functional levels were monitored, and metaproteomic analysis revealed that most of the proteins were mainly expressed by members of Rhizopus, Penicillium and Geotrichum. The number of sequences allocated to fungi in the fermentation process decreased, whereas the number of sequences assigned to bacteria increased with time of fermentation. In addition, functional metagenomic profiling indicated that a series of sequences related to carbohydrates and amino acids metabolism were enriched. Additionally, enzymes associated with glycolysis metabolic pathways were presumed to contribute to the generation of flavor in dajiang-meju. Proteins from different dajiang-meju samples involved in global and overview maps, carbohydrate metabolism, nucleic acid metabolism and energy metabolism were differentially expressed. This information improves the understanding of microbial metabolic patterns with respect to the metaproteomes of dajiang-meju and provides a powerful tool for studying the fermentation process of soybean products.
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10.
Supporting a Healthy Microbiome for the Primary Prevention of Eczema.
Szari, S, Quinn, JA
Clinical reviews in allergy & immunology. 2019;(2):286-293
Abstract
Eczema is increasing worldwide with associated increases in health costs and decreases in quality of life. There are many factors that are speculated to interact in the development of eczema including genetics and environmental exposures. Prevention of the development of eczema may prevent the further development of food allergies and asthma. This concept has prompted a variety of research into the area of primary prevention of eczema in infants. This exploration includes a growing body of research examining infants supplemented with probiotics, prebiotics, or both (synbiotics) often compared with their breastfed counterparts. The goal of this paper is to examine the evidence for manipulating the microbiome in the prevention of eczema. Several strains of probiotics, compositions of prebiotics, and varied combinations of both are commercially available. Evidence supports altering the microbiome in infants at high risk of atopy who are not able to breastfeed with Lactobacillus strains when given both prenatally followed by prolonged use (greater than 6 months) postnatally for the primary prevention of eczema. Prebiotics have also been shown beneficial for primary prevention of eczema in formula-fed infants with prolonged use greater than 6 months. These findings are in keeping with the World Allergy Organization (WAO) recommendations that support interventions to manipulate the microbiome with both probiotics and prebiotics.