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contents

July 2018, 20th
FEATURE STORY ● Metagenomic and clinical microbiology BASIC SCIENCE ● Establishing a mucosal gut microbial community in vitro using an artificial simulator ● Meanings, measurements, and musings on the significance of patterns in human microbiome variation DYSBIOSIS ● Microbiota-Host Crosstalk: A bridge between cardiovascular risk factors, diet, and cardiovascular disease ● Fecal microbiota transplantation for recurrent Clostridium difficile infection in patients with solid organ transplants ● The microbiota-inflammasome hypothesis of major depression ● Impaired autophagy in intestinal epithelial cells alters gut microbiota and host immune responses HOMEOSTASIS - THERAPY ● Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients ● The influence of the intestinal microbiome on vaccine responses INDUSTRIAL LANDSCAPE & AGREEMENTS ● CRISPR-Cas3 platform developer Locus Biosciences acquires EpiBiome phage technology

July 2018, 20th

FEATURE STORY

● Metagenomic and clinical microbiology

BASIC SCIENCE

● Establishing a mucosal gut microbial community in vitro using an artificial simulator
● Meanings, measurements, and musings on the significance of patterns in human microbiome variation

DYSBIOSIS

● Microbiota-Host Crosstalk: A bridge between cardiovascular risk factors, diet, and cardiovascular disease
● Fecal microbiota transplantation for recurrent Clostridium difficile infection in patients with solid organ transplants

● The microbiota-inflammasome hypothesis of major depression

● Impaired autophagy in intestinal epithelial cells alters gut microbiota and host immune responses

HOMEOSTASIS - THERAPY

● Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients
● The influence of the intestinal microbiome on vaccine responses

INDUSTRIAL LANDSCAPE & AGREEMENTS

● CRISPR-Cas3 platform developer Locus Biosciences acquires EpiBiome phage technology

FEATURE STORY

Metagenomic and clinical microbiology

As a result of Next Generation Sequencing methods, metagenomic studies have become increasingly widespread. After being first applied to microbiome description, metagenomics is currently proposed as a diagnostic tool in clinical microbiology, although this application remains confined to the field of research. In this review, In a recent review French researchers discuss the application of metagenomics to the detection of bacterial pathogens and demonstrate that the interpretation of the metagenomic results may fluctuate depending on the type of sample analyzed. However, they propose a view of metagenomic application to the evaluation of antimicrobial resistance, epidemic investigations and forensic medicine. Secondly, they present the many limits of metagenomic interpretation and application in routine clinical microbiology. From our perspective, metagenomics is not yet reliable enough for general use in clinical microbiology.
The review appears in the August issue of Hum Microbiome J .

Related Informations/Publications

- Front Genet . 2018 Jun 13;9:212. Microbiome Research Is Becoming the Key to Better Understanding Health and Nutrition. Hadrich D, European Commission, Innovative and Personalised Medicine Unit, Health Directorate, Directorate-General Research and Innovation, Brussels, Belgium
Link: Abstract – Full Text
- Nat Rev Microbiol. 2018 May 1. Culturing the human microbiota and culturomics. Lagier JC et al. AP-HM, MEPHI, IHU Méditerranée Infection, Marseille, France
Link: Abstract

BASIC SCIENCE

Establishing a mucosal gut microbial community in vitro using an artificial simulator

Variation of the human microbiome is a multidimensional value depending on the question of interest. Unlike traditional human genetics, which most often deals with variation at the level of genes or genetic sequences, microbiome variation may be most relevant at the functional level and can be interrogated a number of ways. Most common methods are marker gene metataxonomic surveys or shotgun metagenomic sequencing, however more direct indicators of microbial activity that are gaining popularity include metabolomic and metatranscriptomic surveys. With all these data and promise in human microbiome research, it requires that resaerchers reassess what is meant by variation of the human microbiome and how its significance impacts the ability of microbiome research to be informative on a range of topics from evolutionary theory to clinical outcomes.
The Review appeared in July 13th online issue of Curr Opin Genet Rev .

Related Informations / Publications

-Biostatistics . 2018 Jun 24. Zero-inflated generalized Dirichlet multinomial regression model for microbiome compositional data analysis. Tang ZZ & Chen G, Wisconsin Institute for Discovery, Madison, WI 53715, USA
Results / Comments: The advantages of the proposed methods are demonstrated through simulation studies and an analysis of a gut microbiome dataset
Link: Abstract

Meanings, measurements, and musings on the significance of patterns in human microbiome variation

The Twin Simulator of the Human Intestinal Microbial Ecosystem (TWINSHIME®) was initially developed to study the luminal gut microbiota of the ascending (AC), transverse (TC), and descending (DC) colon regions. Given the unique composition and potential importance of the mucosal microbiota for human health, the TWINSHIME was recently adapted to simulate the mucosal microbiota as well as the luminal community. It has been previously demonstrated that the luminal community in the TWINSHIME reaches a steady state within two weeks post inoculation, and is able to differentiate into region specific communities. However, less is known regarding the mucosal community structure and dynamics. During the current study, the luminal and mucosal communities in each region of the TWINSHIME were evaluated over the course of six weeks. Based on 16S rRNA gene sequencing and short chain fatty acid analysis, it was determined that both the luminal and mucosal communities reached stability 10-20 days after inoculation, and remained stable until the end of the experiment.
The results appeared in July 17th online issue of PloS One

Related Informations / Publications

-Bioinformatics . 2018 Jul 13. A parallel computational framework for ultra-large-scale sequence clustering analysis. Zheng W et al. University at Buffalo, The State University of New York, Buffalo, USA Link: Abstract

DYSBIOSIS

Microbiota-Host Crosstalk: A bridge between cardiovascular risk factors, diet, and cardiovascular disease

Cardiovascular disease is the leading cause of death and is also a major cause of disability worldwide. Indeed, even in well-treated patients for hypertension or dyslipidemia, there is still a high cardiovascular risk called residual risk. It is of utmost importance to identify the pathway leading from risk factors to cardiovascular disease to further improve stroke and myocardial infarction prevention. In a review, French investigators presented some of experimental and epidemiological evidences suggesting that microbiota-host crosstalk is involved in this pathway and bridges the gap between cardiovascular risk factors, diet, and cardiovascular residual risk.
The review appeared in July 16th online issue of Am J Hypertens

Related Informations / Publications

- Front Physiol. 2018 Jun 29;9:763. Physical Activity, Immune System, and the Microbiome in Cardiovascular Disease. Fernandez DM et al. Icahn School of Medicine at Mount Sinai, New York, NY, United States
Link: Abstract – Full Text
- Toxins (Basel). 2018 Jul 11;10(7). Gut Microbiota and Cardiovascular Uremic Toxicities. Velasquez MT et al. The George Washington University, Washington, DC 20037, USA
Link: Abstract - Full Text
- Curr Opin Cardiol. 2018 Jul 9. New biomarker strategies to enable precision cardiovascular medicine. Bede K & Tang WHW, the Cleveland Clinic Foundation, Cleveland, Ohio, USA
Link: Abstract

Fecal microbiota transplantation for recurrent Clostridium difficile infection in patients with solid organ transplants

Clostridium difficile , an anaerobic gram-positive, spore-forming bacillus, has become the most common cause of nosocomial infectious diarrhea, and is associated with increased mortality in all populations. Patients who have received solid organ transplants (SOT) are at increased risk of Clostridium difficile infection (CDI) and CDI recurrence (rCDI). This may be related to chronic immunosuppression, frequent antibiotic exposure, and increased or prolonged hospitalizations. Increased morbidity and mortality from CDI is well described in SOT patients. Conventional treatments for index and recurrent CDI include vancomycin and fidaxomicin. Fecal microbiota transplantation has emerged as an effective and safe alternative for treating rCDI in the general population. Reports of its safety in certain immunocompromised populations, such as those with inflammatory bowel disease, appear reassuring, but outcomes among SOT patients are less well known.
The review appeared in July 16th online issue of Transpl Infect dis

Related Informations / Publications

-J Hosp Infect . 2018 Jul 12. pii: S0195-6701(18)30369-4. Faecal microbiota transplantation with frozen capsules for relapsing Clostridium difficile infections: the first experience from 15 consecutive patients in France. Cheminet G et al. Hôpital Beaujon, Assistance-Publique Hôpitaux de Paris, 100 boulevard du Général-Leclerc, 92110 Clichy, France
Link: Abstract
- Antibiotics (Basel). 2018 Jun 30;7(3). Management of Primary and Recurrent Clostridium difficile Infection: An Update. Chai J & Lee CH, University of British Columbia Medical School, Vancouver, BC V6T 1Z3, Canada Results / Comments: This review summarizes current and emerging therapies in CDI management including antibiotics, fecal microbiota transplantation, monoclonal antibodies, spore-based therapies, and vaccinations
Link: Abstract – Full Text
- Front Microbiol. 2018 Jun 12;9:1242. Mechanistic Insights in the Success of Fecal Microbiota Transplants for the Treatment of Clostridium difficile Infections. Baktash A et al. Leiden University Medical Center, Leiden, Netherlands
Link: Abstract – Full Text

The microbiota-inflammasome hypothesis of major depression

In a recent publication, American and Australian researchers propose the "microbiota-inflammasome" hypothesis of major depressive disorder (MDD, a mental illness affecting the way a person feels and thinks, characterized by long-lasting feelings of sadness). Researchers hypothesize that pathological shifts in gut microbiota composition (dysbiosis) caused by stress and gut conditions result in the upregulation of pro-inflammatory pathways mediated by the Nod-like receptors family pyrin domain containing 3 (NLRP3) inflammasome (an intracellular platform involved in the activation of inflammatory processes). This upregulation exacerbates depressive symptomatology and further compounds gut dysbiosis. In this review investigators describe MDD/chronic stress-induced changes in: 1) NLRP3 inflammasome; 2) gut microbiota; and 3) metabolic pathways; and how inflammasome signaling may affect depressive-like behavior and gut microbiota composition.
The results appeared in July 13th online issue of Bioessays

Related Informations / Publications

- Trends Neurosci. 2018 Jul;41(7):413-414. Linking the Gut Microbiota to a Brain Neurotransmitter. Jameson KG & Hsiao EY, University of California at Los Angeles, Los Angeles, CA 90095, USA
Link : Abstract
- Psychiatr Danub . 2018 Jun;30(2):136-141. The Role of Microbiota in Depression - a brief review. Zalar B et al. University Psychiatric Clinic Ljubljana, Ljubljana, Slovenia
Link: Abstract – Full Text
- Int J Mol Sci . 2018 May 29;19(6). Recognizing Depression from the Microbiota⁻Gut⁻Brain Axis. Liang S et al. Chinese Academy of Sciences, Beijing 100101, China Results / Comments: Depression is closely related with the health condition of the brain⁻gut axis, and maintaining/restoring the normal condition of gut microbiota helps in the prevention/therapy of mental disorders
Link: Abstract - Full Text

Impaired autophagy in intestinal epithelial cells alters gut microbiota and host immune responses

Establishing and maintaining beneficial interactions between the host and associated gut microbiota are pivotal requirements for host health. Autophagy is an important catabolic recycling pathway that degrades long-lived proteins and some organelles by lysosome to maintain cellular homeostasis. Although impaired autophagy is thought to be closely correlated with Crohn's disease ( CD ), the functional role of autophagy in the maintenance of gut microbiota is poorly understood. As autophagy-related 5 (Atg5) is a key gene associated with the extension of the phagophoric membrane in autophagic vesicles, investigators established a gut-specific Atg5 knockout mouse model, and found that the disruption of autophagic flux in the intenstinal epithelium cells dramatically altered the composition of the gut microbiota and reduced alpha diversity. Differentially gene expression analysis revealed that two key genes, RORC and TBX21 involved in inflammatory bowels disease were up-regulated in Atg5-/- mice. The study suggests that Atg5 deficiency results in an imbalance of the host-microbe interaction and deterioration of the gut microenvironment.
The results appeared in July 13th online issue of Appl Environ Microbiol

Related Informations / Publications

-Front Microbiol . 2018 Jan 17;8:2705. Lactobacillus rhamnosus GG Affects Microbiota and Suppresses Autophagy in the Intestines of Pigs Challenged with Salmonella Infantis . Zhang W et al. College of Veterinary Medicine, China Agricultural University, Beijing, China
Results / Comments: LGG can restore the gut microbiota balance and preserve the autophagy-related intestinal epithelial barrier, thereby controlling infections
Link: Abstract – Full Text
- Microb Pathog . 2018 May;118:98-104. Gut microbiota and mTOR signaling: Insight on a new pathophysiological interaction. Noureldein MH & Eid AA, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon.
Link: Abstract

HOMEOSTASIS - THERAPY

Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients

Ulcerative colitis is a chronic inflammatory disease of the colon that carries a significant disease burden in children. Therefore, new therapeutic approaches are being explored to help children living with this disease. Fecal microbiota transplantation (FMT) has been successful in some children with ulcerative colitis. However, the mechanism of its therapeutic effect in this patient population is not well understood. To characterize changes in gut microbial and metabolomic profiles after FMT, American investigators performed 16S rRNA gene sequencing, shotgun metagenomic sequencing, virome analysis, and untargeted metabolomics by gas chromatography-time of flight-mass spectrometry on stool samples collected before and after FMT from four children with ulcerative colitis who responded to this treatment.
The results appeared in July 13th online issue of FEMS Microbiol Ecol

Related Informations / Publications

-Curr Opin Clin Nutr Metab Care . 2018 Jun 22. Fecal microbial transplantation: an update. Bouri S & Hart A. St Mark's Hospital, London, UK
Link: Abstract
- Internist (Berl). 2018 Jun 5. Inflammatory bowel diseases : Crohn's disease and ulcerative colitis. Fischer S et al. Friedrich-Alexander-Universität Erlangen-Nürnberg, Ulmenweg 18, 91054, Erlangen, Germany
Link: Abstract
- Gastroenterol Res Pract. 2018 Apr 3;2018:5480961. The Value of Fecal Microbiota Transplantation in the Treatment of Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis. Cao Y et al. The Third Affiliated Hospital of Xinxiang Medical University, Hua Lan Avenue, Xinxiang, Henan Province 453003, China
Results / Comments: FMT treatment had a higher efficacy and shorter time-point of early assessment of effectiveness on UC patients compared to traditional therapies
Link: Abstract – Full Text

The influence of the intestinal microbiome on vaccine responses

There is substantial variation between individuals in the immune response to vaccinations. The intestinal microbiome plays a crucial rule in the development and regulation of the immune system and therefore its composition might affect how individuals respond to vaccinations. In a recent review, Swiss and Australian researchers summarize studies that investigated the influence of the intestinal microbiome on humoral and cellular vaccine responses. To date, only four studies (three in infants and one in adults) have investigated the influence of the intestinal microbiome on vaccine responses. All found an association between the intestinal microbiome and vaccine responses. Despite the heterogeneity in study designs (including different vaccines, schedules, timing of collection of stool and blood samples, analysis methods and reporting of results on different taxonomic levels), findings across studies were consistent: a higher relative abundance of the phylum Actinobacteria (oral and parenteral vaccines) and Firmicutes (oral vaccines) was associated with both higher humoral and higher cellular vaccine responses, while a higher relative abundance of the phylum Proteobacteria (oral and parenteral vaccines) and Bacteroidetes (oral vaccines) was associated with lower responses.
The review appeared in the July issue of Vaccines

Related Informations / Publications

- Drugs . 2018 Jun 26. The Significance of the Intestinal Microbiome for Vaccinology: From Correlations to Therapeutic Applications. Harris VC, Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam, The Netherlands
Link: Abstract
-Pathogens. 2018 Jun 21;7(3). The Mammalian Intestinal Microbiome: Composition, Interaction with the Immune System, Significance for Vaccine Efficacy, and Potential for Disease Therapy. Desselberger U, University of Cambridge, Cambridge CB2 0QQ, UK
Results / Comments: Some gut bacteria, which have a beneficial effect on increasing immune responses or by overgrowing intestinal pathogens, are considered to act as probiotics and can be used for therapeutic purposes (as in the case of fecal microbiome transplantation).
Link: Abstract – Full Text

INDUSTRIAL LANDSCAPE
& agreements

CRISPR-Cas3 platform developer Locus Biosciences acquires EpiBiome phage technology

Locus Biosciences of Research Triangle Park, N.C., said on July 17th that it has acquired Union City, Calif.-based Epibiome ’s high-throughput bacteriophage discovery platform. The pairing of its phage isolation and characterization capability with Locus’s CRISPR-based synthetic biology platform and clinical development team creates a combined entity that will focus on developing products to treat antibiotic-resistant bacterial infections and precisely edit the microbiome, the company said. Terms of the deal were not disclosed.
For further information

Related Informations / Publications

-JAN 2018 : Locus Biosciences and IDbyDNA Partner to Develop Companion Diagnostic Test for Pseudomonas aeruginosa Infection Link: Press Release
-NOV 2017 : Locus Biosciences Closes $19 Million Series A Led by ARTIS Ventures for CRISPR-Cas3 Antimicrobials Link: Press Release

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