scholarly journals Strain-level Screening of Human Gut Microbes Identifies Blautia Producta as a Novel Anti-hyperlipidemic Probiotic Via the Production of 12-methylmyristic Acid

2021 ◽  
Author(s):  
Chongming Wu ◽  
Wenyi Xu ◽  
Jiaqi Yu ◽  
Zhuanyu Li ◽  
Yinghui Zhang ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
High Throughput Screening ◽  
Large Scale ◽  
Bacterial Species ◽  
Strain Level ◽  
Bacterial Strains ◽  
Human Gut ◽  
Strain Specificity ◽  
Gut Microbes

Abstract Background: Compelling evidence has linked the commensal gut microbiota to human metabolic syndromes and provided new therapeutic potentials against diseases, such as hyperlipidemia. However, the precise regulatory effect of each bacterial species on human lipid homeostasis remains largely unknown.Results: We set up a cell-based high-throughput screening platform and screened 2250 human gut bacterial strains from 186 species for the lipid-decreasing activity in HepG2 cells, in which 388 strains steadily inhibited lipid accumulation. Different strains in the same species usually displayed distinct lipid-modulatory actions, revealing an obvious strain-specificity. Blautia producta, Lactobacillus gasseri, and Bifidobacterium pseudolongum contained a much higher portion of hypolipidemic strains. Among all the tested strains, the mucosal bacterium Blautia producta exhibited the most potency to suppress lipid accumulation, and gavage of live Bl. producta effectively ameliorated hyperlipidemia in mice. 12-Methylmyristic acid (12-MMA) was identified as an important active metabolite of Bl. producta by pan-genomics and comparative metabolomics, which exerted potent anti-hyperlipidemic effect in vivo and activated G protein-coupled receptor 120 (GPR120), thus stimulating white adipose tissue browning.Conclusions: Together, these data reveal a previously unreported large-scale lipid-modulatory profile of gut microbes at the strain level, and raise the possibility of developing therapeutics based on Bl. producta and microbial metabolite 12-MMA to treat hyperlipidemia.

scholarly journals MetaBMF: a scalable binning algorithm for large-scale reference-free metagenomic studies

2019 ◽  
Vol 36 (2) ◽  
pp. 356-363 ◽  
Author(s):  
Terry Ma ◽  
Di Xiao ◽  
Xin Xing
Keyword(s):  
Large Scale ◽  
Empirical Studies ◽  
Nonnegative Matrix ◽  
Rapid Identification ◽  
Strain Level ◽  
Bacterial Strains ◽  
Binary Matrix ◽  
Next Generation Sequencing Technology ◽  
Microbial Species ◽  
Reference Genomes

Abstract Motivation Metagenomics studies microbial genomes in an ecosystem such as the gastrointestinal tract of a human. Identification of novel microbial species and quantification of their distributional variations among different samples that are sequenced using next-generation-sequencing technology hold the key to the success of most metagenomic studies. To achieve these goals, we propose a simple yet powerful metagenomic binning method, MetaBMF. The method does not require prior knowledge of reference genomes and produces highly accurate results, even at a strain level. Thus, it can be broadly used to identify disease-related microbial organisms that are not well-studied. Results Mathematically, we count the number of mapped reads on each assembled genomic fragment cross different samples as our input matrix and propose a scalable stratified angle regression algorithm to factorize this count matrix into a product of a binary matrix and a nonnegative matrix. The binary matrix can be used to separate microbial species and the nonnegative matrix quantifies the species distributions in different samples. In simulation and empirical studies, we demonstrate that MetaBMF has a high binning accuracy. It can not only bin DNA fragments accurately at a species level but also at a strain level. As shown in our example, we can accurately identify the Shiga-toxigenic Escherichia coli O104: H4 strain which led to the 2011 German E.coli outbreak. Our efforts in these areas should lead to (i) fundamental advances in metagenomic binning, (ii) development and refinement of technology for the rapid identification and quantification of microbial distributions and (iii) finding of potential probiotics or reliable pathogenic bacterial strains. Availability and implementation The software is available at https://github.com/didi10384/MetaBMF.

scholarly journals Caenorhabditis elegans, a Host to Investigate the Probiotic Properties of Beneficial Microorganisms

2020 ◽  
Vol 7 ◽  
Author(s):  
Cyril Poupet ◽  
Christophe Chassard ◽  
Adrien Nivoliez ◽  
Stéphanie Bornes
Keyword(s):  
Caenorhabditis Elegans ◽  
High Throughput Screening ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Probiotic Properties ◽  
C Elegans ◽  
Probiotic Potential ◽  
Challenges And Opportunities ◽  
Future Challenges

Caenorhabditis elegans, a non-parasitic nematode emerges as a relevant and powerful candidate as an in vivo model for microorganisms-microorganisms and microorganisms-host interactions studies. Experiments have demonstrated the probiotic potential of bacteria since they can provide to the worm a longer lifespan, an increased resistance to pathogens and to oxidative or heat stresses. Probiotics are used to prevent or treat microbiota dysbiosis and associated pathologies but the molecular mechanisms underlying their capacities are still unknown. Beyond safety and healthy aspects of probiotics, C. elegans represents a powerful way to design large-scale studies to explore transkingdom interactions and to solve questioning about the molecular aspect of these interactions. Future challenges and opportunities would be to validate C. elegans as an in vivo tool for high-throughput screening of microorganisms for their potential probiotic use on human health and to enlarge the panels of microorganisms studied as well as the human diseases investigated.

scholarly journals Tumor-Targeting Bacteria: As Vectors, Immunotherapeutic Agents And Tumor-Targeting Probes For Cancer Detection And Therapy

2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Lihini Ranesha Weerakkody ◽  
Сhamindri Witharana
Keyword(s):  
Anticancer Agents ◽  
Tumor Targeting ◽  
Bacterial Species ◽  
Bifidobacterium Longum ◽  
Anticancer Therapy ◽  
Genetically Engineered ◽  
Treatment Modalities ◽  
Bacterial Strains ◽  
Angiogenic Proteins

Cancer is the world's second leading cause of death in humans. Conventional anticancer therapies are often associated with lack of tumor specificity, failure to detect small metastases, increased resistance of tumors to anticancer drugs, and unintended adverse effects. Numerous alternative and better strategies in cancer treatment have been developed to overcome the negative effects of traditional cancer therapies. More than a century ago, William Coley, the father of cancer immounotherapy, laid the groundwork for bacterial anticancer therapy. Bacterial immunotherapy has been emerging as a potential anticancer therapy. Moreover, certain obligate and facultative anaerobic bacterial species are exploited as vectors for gene delivery to treat cancer. These genes encode for anticancer agents, cytokines, cytotoxic peptides, anti-angiogenic proteins, therapeutic molecules and prodrug-converting enzymes. Genetically engineered bacterial strains of Salmonella, Bifidobacterium, Clostridium and Listeria are widely used to deliver genes in anticancer therapy since they can selectively accumulate in solid tumors with a hypoxic/necrotic core in vivo, providing appealing delivery systems to target therapeutic agents and immunomodulatory molecules to the site of tumor. Certain genetically modified bacterial species such as Bifidobacterium longum and Bacillus licheniformis have been effectively used for the enzyme/prodrug therapy for cancer. Furthermore, certain anaerobic bacteria are emerging as potential tumor markers due to the increased mobility and the selectivity in germinating and multiplying in hypoxic/anoxic environments. Many of these novel developments have been studied extensively in different experimental models of cancer and certain clinical trials are ongoing for some treatment modalities. Although favourable results have shown so far, further studies and technological innovations are required to ensure the efficacy of bacterial anticancer therapy.

scholarly journals A high-resolution pipeline for 16S-sequencing identifies bacterial strains in human microbiome

2019 ◽  
Author(s):  
Igor Segota ◽  
Tao Long
Keyword(s):  
Bacterial Species ◽  
Human Microbiome ◽  
Amplicon Sequencing ◽  
R Package ◽  
Strain Level ◽  
Sequencing Data ◽  
Bacterial Strains ◽  
16S Sequencing ◽  
16S Amplicon Sequencing ◽  
Sequencing Data Analysis

We developed a High-resolution Microbial Analysis Pipeline (HiMAP) for 16S amplicon sequencing data analysis, aiming at bacterial species or strain-level identification from human microbiome to enable experimental validation for causal effects of the associated bacterial strains on health and diseases. HiMAP achieved higher accuracy in identifying species in human microbiome mock community than other pipelines. HiMAP identified majority of the species, with strain-level resolution wherever possible, as detected by whole genome shotgun sequencing using MetaPhlAn2 and reported comparable relative abundances. HiMAP is an open-source R package available at https://github.com/taolonglab/himap.

scholarly journals Positive Synergistic Effects of Quercetin and Rice Bran on Human Gut Microbiota Reduces Enterobacteriaceae Family Abundance and Elevates Propionate in a Bioreactor Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Sudeep Ghimire ◽  
Supapit Wongkuna ◽  
Ranjini Sankaranarayanan ◽  
Elizabeth P. Ryan ◽  
G. Jayarama Bhat ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Rice Bran ◽  
Synergistic Effects ◽  
Bacterial Species ◽  
Positive Influence ◽  
Human Gut ◽  
Fatty Acid Production ◽  
Microbiome Composition ◽  
Human Gut Microbiota

Dietary fiber and flavonoids have substantial influence on the human gut microbiota composition that significantly impact health. Recent studies with dietary supplements such as quercetin and rice bran have shown beneficial impacts on the host alongside a positive influence of the gut microbiota. The specific bacterial species impacted by quercetin or rice bran in the diet is not well understood. In this study, we used a minibioreactor array system as a model to determine the effect of quercetin and rice bran individually, as well as in combination, on gut microbiota without the confounding host factors. We found that rice bran exerts higher shift in gut microbiome composition when compared to quercetin. At the species level, Acidaminococcus intestini was the only significantly enriched taxa when quercetin was supplemented, while 15 species were enriched in rice bran supplementation and 13 were enriched when quercetin and rice bran were supplemented in combination. When comparing the short chain fatty acid production, quercetin supplementation increased isobutyrate production while propionate dominated the quercetin and rice bran combined group. Higher levels of propionate were highly correlated to the lower abundance of the potentially pathogenic Enterobacteriaceae family. These findings suggest that the combination of quercetin and rice bran serve to enrich beneficial bacteria and reduce potential opportunistic pathogens. In vivo studies are necessary to determine how this synergy of quercetin and rice bran on microbiota impact host health.

scholarly journals Bacteriocins, Potent Antimicrobial Peptides and the Fight against Multi Drug Resistant Species: Resistance Is Futile?

Antibiotics ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 32 ◽  
Author(s):  
Meade ◽  
Slattery ◽  
Garvey
Keyword(s):  
Large Scale ◽  
Proteolytic Enzymes ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
Food Preservation ◽  
Scale Production ◽  
Major Drawback ◽  
Resistant Species ◽  
Medical Sector

Despite highly specialized international interventions and policies in place today, the rapid emergence and dissemination of resistant bacterial species continue to occur globally, threatening the longevity of antibiotics in the medical sector. In particular, problematic nosocomial infections caused by multidrug resistant Gram-negative pathogens present as a major burden to both patients and healthcare systems, with annual mortality rates incrementally rising. Bacteriocins, peptidic toxins produced by bacteria, offer promising potential as substitutes or conjugates to current therapeutic compounds. These non-toxic peptides exhibit significant potency against certain bacteria (including multidrug-resistant species), while producer strains remain insusceptible to the bactericidal peptides. The selectivity and safety profile of bacteriocins have been highlighted as superior advantages over traditional antibiotics; however, many aspects regarding their efficacy are still unknown. Although active at low concentrations, bacteriocins typically have low in vivo stability, being susceptible to degradation by proteolytic enzymes. Another major drawback lies in the feasibility of large-scale production, with these key features collectively limiting their current clinical application. Though such limitations require extensive research, the concept of expanding bacteriocins from food preservation to human health opens many fascinating doors, including novel drug delivery systems and anticancer treatment applications.

scholarly journals In vitro Assays and Imaging Methods for Drug Discovery for Cardiac Fibrosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Giorgia Palano ◽  
Ariana Foinquinos ◽  
Erik Müllers
Keyword(s):  
Image Analysis ◽  
Drug Discovery ◽  
High Throughput Screening ◽  
Large Scale ◽  
Cardiac Fibrosis ◽  
3D Models ◽  
In Vitro Assays ◽  
Stress Injury

As a result of stress, injury, or aging, cardiac fibrosis is characterized by excessive deposition of extracellular matrix (ECM) components resulting in pathological remodeling, tissue stiffening, ventricular dilatation, and cardiac dysfunction that contribute to heart failure (HF) and eventually death. Currently, there are no effective therapies specifically targeting cardiac fibrosis, partially due to limited understanding of the pathological mechanisms and the lack of predictive in vitro models for high-throughput screening of antifibrotic compounds. The use of more relevant cell models, three-dimensional (3D) models, and coculture systems, together with high-content imaging (HCI) and machine learning (ML)-based image analysis, is expected to improve predictivity and throughput of in vitro models for cardiac fibrosis. In this review, we present an overview of available in vitro assays for cardiac fibrosis. We highlight the potential of more physiological 3D cardiac organoids and coculture systems and discuss HCI and automated artificial intelligence (AI)-based image analysis as key methods able to capture the complexity of cardiac fibrosis in vitro. As 3D and coculture models will soon be sufficiently mature for application in large-scale preclinical drug discovery, we expect the combination of more relevant models and high-content analysis to greatly increase translation from in vitro to in vivo models and facilitate the discovery of novel targets and drugs against cardiac fibrosis.

scholarly journals Massive expansion of human gut bacteriophage diversity

2020 ◽  
Author(s):  
Luis F. Camarillo-Guerrero ◽  
Alexandre Almeida ◽  
Guillermo Rangel-Pineros ◽  
Robert D. Finn ◽  
Trevor D. Lawley
Keyword(s):  
Gene Flow ◽  
Large Scale ◽  
Bacterial Species ◽  
Single Species ◽  
Viral Diversity ◽  
Evolutionary Analysis ◽  
Flow Networks ◽  
Human Gut ◽  
Viral Genomes ◽  
Globally Distributed

SUMMARYBacteriophages drive evolutionary change in bacterial communities by creating gene flow networks that fuel ecological adaptions. However, the extent of viral diversity and prevalence in the human gut remains largely unknown. Here, we introduce the Gut Phage Database (GPD), a collection of ∼142,000 non-redundant viral genomes (>10 kb) obtained by mining a dataset of 28,060 globally distributed human gut metagenomes and 2,898 reference genomes of cultured gut bacteria. Host assignment revealed that viral diversity is highest in the Firmicutes phyla and that ∼36% of viral clusters (VCs) are not restricted to a single species, creating gene flow networks across phylogenetically distinct bacterial species. Epidemiological analysis uncovered 280 globally distributed VCs found in at least 5 continents and a highly prevalent novel phage clade with features reminiscent of p-crAssphage. This high-quality, large-scale catalogue of phage genomes will improve future virome studies and enable ecological and evolutionary analysis of human gut bacteriophages.

scholarly journals Enlightening the Taxonomy Darkness of Human Gut Microbiomes With Cultured Biobank

2020 ◽  
Author(s):  
Chang Liu ◽  
Meng-Xuan Du ◽  
Rexiding Abuduaini ◽  
Hai-Ying Yu ◽  
Dan-Hua Li ◽  
...  
Keyword(s):  
New Species ◽  
Large Scale ◽  
Human Microbiome ◽  
Human Microbiome Project ◽  
Public Access ◽  
Rrna Gene ◽  
New Genera ◽  
Human Gut ◽  
Isolation And Identification ◽  
Gut Microbes

Abstract Background The cultivated gut microbial resource plays essential role in gut microbiome studies such as gut microbial function and their interactions with host. Though several major studies had been performed to understand the cultured human gut microbiota, up to 70% of the Unified Human Gastrointestinal Genome species remain uncultivated and their taxonomy is not clear. Large-scale gut microbial isolation and identification and their access to pubic are imperative for gut microbial studies and for understanding of the human gut microbial functions.Results Here, we report the construction of an human Gut Microbial Biobank (hGMB) (homepage: hgmb.nmdc.cn) by large-scale cultivation of 10,558 isolates from 239 feces of healthy Chinese volunteers, and deposited 1,170 strains representing 404 different species in International Depository Authority for long-term preservation and public access worldwidely. We discovered and denominated 107 new species, and proposed 28 new genera and 3 new families. The new species and their newly sequenced genomes uncovered 16 “most-wanted” or “medium priority” taxa proposed by the Human Microbiome Project and 42 previously-uncultured MAGs in IGGdb, respectively. The hGMB represented over 80% of the common and dominant human gut microbial genera or species of global human gut 16S rRNA gene amplicon data (n=11,647), and covered 70% of the known genes (KEGG Orthologys) and 10% of the functionally-unknown genes in the global human gut gene catalogs. Conclusions A publically accessible human Gut Microbial Biobank (hGMB) that contains 1,170 strains and represents 404 human gut microbial speces is estabolished. The hGMB expands the currently known, taxonomically-characterized gut microbial resources and genomic repository by adding 107 new species and 115 new genomes of human gut microbes. Based on the newly discovered species in this study, 28 new genera and 3 new families of human gut microbes were identified and proposed.

scholarly journals Systematic mapping of drug metabolism by the human gut microbiome

2019 ◽  
Author(s):  
Pranatchareeya Chankhamjon ◽  
Bahar Javdan ◽  
Jaime Lopez ◽  
Raphaella Hull ◽  
Seema Chatterjee ◽  
...  
Keyword(s):  
Drug Metabolism ◽  
Small Molecules ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Drug Bioavailability ◽  
Oral Drugs ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Comprehensive Framework

ABSTRACTThe human gut microbiome harbors hundreds of bacterial species with diverse biochemical capabilities, making it one of nature’s highest density, highest diversity bioreactors. Several drugs have been previously shown to be directly metabolized by the gut microbiome, but the extent of this phenomenon has not been systematically explored. Here, we develop a systematic screen for mapping the ability of the complex human gut microbiome to biochemically transform small molecules (MDM-Screen), and apply it to a library of 575 clinically used oral drugs. We show that 13% of the analyzed drugs, spanning 28 pharmacological classes, are metabolized by a single microbiome sample. In a proof-of-principle example, we show that microbiome-derived metabolism occursin vivo, identify the genes responsible for it, and provide a possible link between its consequences and clinically observed features of drug bioavailability and toxicity. Our findings reveal a previously underappreciated role for the gut microbiome in drug metabolism, and provide a comprehensive framework for characterizing this important class of drug-microbiome interactions.

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