Golden
Cluster: Microbiome and gut health

Cluster: Microbiome and gut health

A cluster of topics related to microbiome and gut health.

Microbiome analysis methods

Several methods are used to analyse microbiota and identify and quantify the members of a microbial community. Analysis can be done at the DNA, RNA, protein and metabolite level.



There are several methods/ techniques for DNA sequencing and RNA sequencing of microbiota and individual microorganisms present in the human microbiome. Next-generation sequencing (NGS) applied to DNA in human feces samples is the predominant method and there are several strategies for NGS of the microbiome.

Metagenomics sequencing using next-generation sequencing (NGS)

Sequencing of microbiomes is sometimes referred to as metagenomics or metagenomic sequencing. The term metagenomics refers to gene-level and genome-level characterization of communities and their members using genomics methods and other “omics” methods that do not require cultivation of organisms.



NGS platforms sequence millions of small DNA fragments in parallel. Bioinformatics uses sequence maps to figure out where the sequenced fragments fit. NGS can sequence entire genomes or target specific regions. Amplicon sequencing targets specific regions by PCR which are then sequenced with NGS.

Ampicon sequencing with NGS

  • 16S rRNA. The highly conserved region of the genome that codes for 16S ribosomal RNA in bacteria and archaea is amplified by PCR and sequenced. Specific sequence differences correspond to a taxa at an operational taxonomic unit (OTU). OTUs correspond to organisms at the phyla and genera level and can be less precise at the species level.
  • 18S rRNA. Similar to 16S rRNA region used for bacterial and archaea.
  • Internal transcribed sequence (ITS). ITS sequences ITS1 and ITS2 are used for amplicon sequencing and identification of fungal DNA.

Whole genome sequencing with NGS

  • Whole genome shotgun sequencing (wgs) also called metagenomic shotgun sequencing. All genes in all organisms within the sample are sequenced. Random primers are used to sequence regions of the genome in overlapping reads which are assembled by computers. Using WGS, taxa can be defined at the species level. WGS is more expensive than 16S rRNA amplicon sequencing.

Metagenomics sequencing companies

Metagenomics computational analysis

RNA-based approaches

Metatranscriptomic analysis is concerned with transcribed genes, which provides a snapshot of active genes within a microbial community.

  • meta-total RNA sequencing (MeTRS). MeTRS requires a reverse transcription reaction step to convert it into cDNA for sequencing. 
  • RNA-Seq with NGS. Conversion of mRNA to cDNA is followed by NGS.
  • SSU rRNA-based RNA-seq. The target is small subunit rRNA. 

Protein-based approaches

The investigation of all proteins in one organism is termed proteomics or metaproteomics when multiple organisms are analysed.

  • MALDI-TOF mass spectrometry. Matrix assisted laser desorption ionization (MALDI) is a form of mass spectrometry that is used to generate a protein mass fingerprint (PMF) which is compared to a database. Mass spectrometry is a technique that uses ionization to categorize chemical compounds based on their mass to charge ratio. Microbial applications usually use time of flight (TOF) analyzers to measure mass.
  • LC‐MS/MS (liquid chromatography combined with mass spectrometry)
  • Shotgun metaproteomics

Metaproteomics sofware tools

Metabolite-based approaches

Metabolomic research is concerned with the metabolic profile including identification and classification of metabolites produced by microbes and deducing the biochemical pathways of those metabolites. The main technologies used in metabolomics are mass spectrometry and nuclear magnetic resonance spectroscopy. Metametabolomics is the analysis of metabolites in a community of microbes. 

  • GC-MS (Gas Chromatography Mass Spectrometry)

Metabolite Databases

Human gut microbiome components

Bacteria, archaea, yeast, fungi, protists, helminths and viruses are all found in the human gut.

  • Many commensal and pathogenic gut bacteria possess invertons which help them colonize and/or contribute to persistance of antibiotic resistance

Gut microbiome catalogs and standards

  • MetaHIT (Metagenomics of the Human Intestinal Tract)
  • International Human Microbiome Standards (IHMS) project
  • The Microbiome Quality Control project

Probiotics

Probiotics are a live microbe. Some probiotics are classified as medical foods.

Prebiotics

Pharmabiotics

A drug, not a food, that is mined from host–microbe–dietary interactions in the gut. 

Testing tools

Healthcare

These companies are using gut health and microbiome science to diagnosis, treat, or cure disease.

Animal Health

Neurological Health

Gastrointestinal Health

Infant gut health

Skincare

Therapeutics

Phage Therapy

The use of bacteriophages or phages therapeutically as antimicrobial treatments against bacteria.

Agriculture

Projects



Venture capital and accelerators

Other



Timeline

People

Name
Role
Related Golden topics

Chris Kresser





David Perlmutter





Elizabeth Bik

Science Editor

uBiome

Jessica Richman

Co-founder and CEO

uBiome

Mark Pimentel

Executive Director

Medically Associated Science and Technology program

Mary Shenouda





Rhonda Patrick





Roshini Raj





Susan Lynch



Further reading

Title
Author
Link
Type

'Ridiculously healthy' elderly have the same gut microbiome as healthy 30-year-olds





Computational methods for high-throughput comparative analyses of natural microbial communities.

Preheim SP , et al.



Exercise changes gut microbial composition independent of diet, team reports





Gut Bacteria in Health and Disease





Gut bug enzyme turns blood into type-O



Article

Gut microbiota are related to Parkinson's disease and clinical phenotype.

Scheperjans F , et al.



How Your Gut Microbiota Can Make You Fat (or thin)





Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial.

Paramsothy S , et al.



Natural compound coupled with specific gut microbes may prevent severe flu: Mouse study reveals how gut microbes fight influenza





Penn researchers single out bacterial enzyme behind gut microbiome imbalance linked to Crohn's disease





Personalized Nutrition by Prediction of Glycemic Responses





Pre-treatment microbial Prevotella-to-Bacteroides ratio, determines body fat loss success during a 6-month randomized controlled diet intervention

Israeli D, da Silva IT, Ward TL, Hjorth MF, Tolhurst G, Zhao L, Knights D, Chen T, Zmora N, Ana D, Long W, Kovatcheva-Datchary P, Juan José A, Ko G, Langin D, Mayer EA, Lim MY, Saris WHM, Blaak EE, Gonzalez A, Zeevi D, Lee K, Almeida-Pititto B, Gomes EP, Akrami R



Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota

Edgar, R. C., Tiedje, J. M., Matziouridou, C., DeSantis, T. Z., Bercik, P., Gill, K. D., M. Jucker, Jeffery, I. B., Cattaneo, A., Garrity, G. M., Berer, K., Taylor, V. H., Hooper, L. V., Bienenstock, J., V. Cheatham, Nguyen, T. D., Ishibashi, K., Love, S., Ishiwata, K., K. D. Mc Coy, Leal, M. C., Mahdi, A. A., Morelli, L., Klipper-Aurbach, Y., T. Harach



Successful Resolution of Recurrent Clostridium difficile Infection using Freeze-Dried, Encapsulated Fecal Microbiota; Pragmatic Cohort Study.

Staley C , et al.



The Big List of Microbiome Companies and Investors



Web

Documentaries, videos and podcasts

Title
Date
Link





Companies

Company
CEO
Location
Products/Services

Barry Kiely

Ireland

Probiotic, Pharmabiotic

AM Pharma





Healthcare



Oakland, CA

Pet Products





Healthcare





Infant gut health

Avaxia Biologics



USA

Healthcare





Healthcare

Azitra



Farmington, CT

Skin care

Bezoar Laboratories





Probiotic



San Francisco, CA



BioResource International



USA

Agriculture



USA

Probiotic



Marina del Rey, CA

Healthcare

Carbiotix







CosmosID



Rockville, MD



DayTwo



Israel

Nutrition

Dermbiont





Skin care

Eatrics



London, U.K.

Healthcare



Paris, France

Healthcare





Healthcare

Epibiome



Union City, CA

Agriculture



Cambridge, Massachusetts

Healthcare



Davis, CA

Infant gut health



Somerville, MA

Gut microbiome



Canada



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References