Human microbiota associated-rodent models

I came across brilliant review by Jens Walter et al. that resonates with my thoughts in microbiome field. I also work in the same field doing similar experiments, but sometimes it is better to stop and look back what you have been doing. This review has discussed some important points on the transmissibility of human diseases in human microbiota-associated mouse models. They acknowledge the importance of human microbiota-associated mouse models as valuable resource in the microbiome field. However, through systematic review they demonstrate that according to current literature it is easily possible to transfer (any!) human disease in mice through microbiota transplant. The inflated positivity and hype around these experiments must be criticized. Most importantly, they talk about the relevance of negative transplant studies, which are seldom published, and urge to use rigorous statistics to improve the data interpretation. Following are some excerpts from the review, though reading full review is highly recommended.

The problem with the concept:

“Because a “normal” or “healthy” microbiome has not been defined yet, we use the term dysbiosis to refer solely to an altered microbiome associated with a specific disease or condition as compared to a control. Whether such “dysbiotic” microbiomes are the cause or consequence of disease, or whether both are caused by a third factor, is, in most instances, unproven.”

“There are two well-documented diseases in the microbiome field that link a microbial biomarker with causation in disease: Helicobacter pylori-associated peptic ulceration and gastric cancer, and Clostridium (or Clostridioides) difficile infection-associated diarrhea. However, causal inferences between complex microbiomes and other inflammatory, metabolic, neoplastic, and neuro-behavioral disorders have been neither compelling nor conclusive.”

“A substantial proportion of the taxa that comprise the human gut microbiome fail to colonize in the recipient animals. Most importantly, the ecological factors (such as diet, lifestyle, disease phenotype, and human genotype) that have driven the dysbiosis in humans in the first place are absent in the recipient rodents, making it unlikely that disease-associated alterations are replicated. Taxa that colonize at sufficient levels may not engage in the EVOLUTIONARY routed host-microbe interactions that they establish with their native host.”

“Consider H. pylori and C. difficile, two members of the human microbiome with established causality in human disease, neither of which exhibit sufficient colonization to cause reliable pathology in conventional murine models.”

Results from systematic review:

“Of 38 studies meeting the inclusion criteria, all but two (36/38; 95%) concluded that fecal transfer from diseased donors resulted in at least one phenotype of the human disease being greater in the recipient mice when compared with transfers from healthy donors.”

Of all the studies, 63% (24/38) of the studies tested for a dysbiosis in the original human donor samples, and only 29% (11/38) confirmed that at least some aspect (reduced diversity, ecosystem processes/services, loss or bloom of specific taxa, or shifts in metabolic capacity) of the “human dysbiosis” was replicated in the recipient animals. Consequently, the majority of studies did not attempt to identify the “causal component” of the microbiome. Only a few studies (34%; 13/38) identified potential underlying mechanisms linking the dysbiotic microbiome with disease.”

Issues with statistics 

“Often, a small number (1–5) of human donors is used per human disease and control group, and these “donor microbiomes” are then replicated in a larger number of individual mice, which are then often used for statistical inference.”

“The result is “pseudoreplication,” which artificially inflates the sample size, the chance for “false positive” findings, and the evidence for a scientific claim. This problem is amplified if donor samples are pooled before the inoculation of groups of rodents, which is common practice for both the “diseased” and healthy control samples. We found that 84% (32/38) of the published studies on HMA murine models used the individual animals as the statistical inference, although animal numbers were much higher than the number of human donors and therefore inflated. Only 16% of studies (6/38) were clear in their use of the individual human donor samples as the “N” for statistical inferences or used the same number of rodents as donors.”

“When virtually all reports are positive, as in our systematic review, the greater the doubt will be and the more justified the scrutiny should be.”

Suggestions for alternative experimental approach

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Why is it important to change?

“Specifically, the correction of altered microbiomes, be it by FMT, live biotherapeutics, or microbial products, will be beneficial only if the alterations are causal or contributory to the disease rather than a bystander response. Causal claims in the microbiome field are often overstated and disproportional to the experimental evidence from which they are derived, and it has become difficult to identify a disease state in which the microbiome has not been implicated in the scientific literature, a notion amplified in the popular press.”

“Sadly, most researchers and reviewers in the microbiome field, and almost all editors of high-impact journals, seem to regard acceptance of the null hypothesis as a failure. As with all scientific endeavor, our field would be served better if editorial policies of higher tier journals and guidelines of funding agencies discouraged any discrimination against negative data, replications, validations of experimental designs, and statistical analyses.”

January 27, 2020

In today’s Monday morning post – establishing causality for gut microbiome using human microbiota associated rodents, gut microbiota profiling in pregnant women after bariatric surgery, proteomics changes in bacteria, discovery of core microbiome of common bean rhizosphere and many more.

General Microbiome

Establishing or Exaggerating Causality for the Gut Microbiome: Lessons from Human Microbiota-Associated Rodents – Jens Walter – Cell

Microbial Genomics and Metagenomics in India: Explorations and Perspectives– Princy Hira – Proceedings of Indian National Science Academy

Human Microbiome

Longitudinal metabolic and gut bacterial profiling of pregnant women with previous bariatric surgery – Kiana Ashley West – Gut

Identifying determinants of bacterial fitness in a model of human gut microbial succession – Lihui Feng – PNAS

16S rDNA microbiome composition pattern analysis as a diagnostic biomarker for biliary tract cancer – Huisong Lee – World Journal of Surgical Oncology

Faecal microbiota transplantations and urinary tract infections – Jean Christophe Lagier – Lancet

Animal Microbiome

Influences of a Prolific Gut Fungus (Zancudomyces culisetae) on Larval and Adult Mosquito (Aedes aegypti)-Associated Microbiota – Jonas Frankel-Bricker – Applied and Environmental Microbiology

Functional dynamics of bacterial species in the mouse gut microbiome revealed by metagenomic and metatranscriptomic analyses – Youn Wook Chung – PlosOne

Early life microbiome perturbation alters pulmonary responses to ozone in male mice – Traci A. Brown – Physiological Reports

Evolution and maintenance of microbe-mediated protection under occasional pathogen attack – Anke Kloock – BioRxiv

Plant, root and soil microbiome

Community sequencing on a natural experiment reveals little influence of host species and timing but a strong influence of compartment on the composition of root endophytes in three annual Brassicaceae – Jose G Macia-Vicente – BioRxiv

Discovery of a spatially and temporally persistent core microbiome of the common bean rhizosphere – Nejc Stopnisek – BioRxiv

Resident and phytometer plants host comparable rhizosphere fungal communities in managed grassland ecosystems – Ricardo Schöps – Scientific Reports

Evaluation of fatty acid derivatives in the remediation of aged PAH-contaminated soil and microbial community and degradation gene response – Qingling Wang – Chemosphere

Techniques

Proteomic changes in bacteria caused by exposure to environmental conditions can be detected by Matrix-Assisted Laser Desorption/Ionization – Time of Flight (MALDI-ToF) Mass Spectrometry – Denise Chac – BioRxiv

Probiotics, prebiotics

Beneficial bile acid metabolism from Lactobacillus plantarum of food origin – Roberta Prete – Scientific Reports

Microbes in the news

Could a kid’s microbiome alter their behaviour? – Health24

Microbiome Therapeutics Market Report Forecast by Capital Investment, Industry Outlook, Opportunities & Trends 2024 – Fusion Science Academy

January 11, 2020

Science doesn’t rest! Today’s Digest brings you several seminal papers and many news pieces. Highlights include a mouse study probing the mechanism behind maternally provisioned immunity for infants, a major effect to characterize mouse gut microbiota, a study on the diversity of the uncultured viruses of bacteria and archaea, and last but not least, a DIY method to deplete ribosomal RNA from your total RNA!

General microbiology

Preprint: Detection of phylogenetic core groups in diverse microbial ecosystems – Marcos Parras-Moltó & Daniel Aguirre de Cárcer – bioRxiv

Antimicrobial resistance

Preprint: Investigating the impact of combination phage and antibiotic therapy: a modeling study – Selenne Banuelos et al. – bioRxiv

Human liver microbiome

Intrahepatic bacterial metataxonomic signature in non-alcoholic fatty liver disease – Silvia Sookoian et al. – Gut

Cancer microbiome

Review: Roles of microbiota in response to cancer immunotherapy – Kentaro Inamura – Seminars in Cancer Biology

Animal experiments

Butyrate attenuated fat gain through gut microbiota modulation in db/db mice following dapagliflozin treatment – Tae Jung Oh et al. – Scientific Reports

Microvesicles from Lactobacillus reuteri (DSM-17938) completely reproduce modulation of gut motility by bacteria in mice – Christine L. West et al. – PLoS One

** Mouse: Microbiota-targeted maternal antibodies protect neonates from enteric infection – Wen Zheng et al. – Nature

Press: Maternal Microbiome Protects Newborns from Deadly Diarrheal Infections – Genengnews

Animal microbiome

** The Mouse Gut Microbial Biobank expands the coverage of cultured bacteria – Chang Liu et al. – Nature Communications

Energy conservation involving 2 respiratory circuits – Marie Charlotte Schoelmerich et al. – PNAS

Press: New metabolic pathway discovered in rumen microbiome – EurekAlert

Plant, root and soil microbiome

Soil bacterial diversity mediated by microscale aqueous-phase processes across biomes – Samuel Bickel & Dani Or – Nature Communications

Fungal community assembly in drought-stressed sorghum shows stochasticity, selection, and universal ecological dynamics – Cheng Gao et al. – Nature Communications

Phages and viruses

** Charting the diversity of uncultured viruses of Archaea and Bacteria – F. H. Coutinho, R. A. Edwards & F. Rodríguez-Valera – BMC Biology

Technology

** Preprint: A simple, cost-effective, and robust method for rRNA depletion in RNA-sequencing studies – Peter H. Culviner et al. – bioRxiv

Microbes in the news

Gut Microbiomes Are Linked To Diet And Evolution—Except In Flying Animals – Linh Anh Cat – Forbes

7 Effects of Greasy Food on Your Body – Elise Mandl – Healthline

Gut microbes may improve stroke recovery – University of Kentucky – EurekAlert

Surprising Ways A Virus Can Be A Man’s Best Friend – Mishal Shaheen et al. – The Health Mania

Twin Studies Examine Cohabiting Affect on Gut Microbiome – Technology Networks

Microbes on the market

Shoreline Biome expands presence in Asia to include Japan – Yahoo! Finance

Synthetic Biologics Receives FDA Guidance at Type C Meeting for SYN-004 (ribaxamase) Phase 1b/2a Clinical Trial in Allogeneic HCT Recipients – Synthetic Biologics – PR Newswire

Johnson & Johnson To Collaborate With Microbiome Biotech On Childhood Allergies – Taylor Carmichael – The Motley Fool

Kaleido Bio teams up with J&J to identify microbiome metabolic candidates – Douglas W. House – Seeking Alpha

Finch Therapeutics Completes Enrollment in Potentially Pivotal Trial of CP101, an Investigational Oral Full-Spectrum Microbiota® Therapy for the Prevention of Recurrent C. difficile Infection – The Tullahoma News

January 10, 2020

In today’s weekend post- maternal antibodies targeting microbiota protect mice from neonatal infection, exercise improves gestational diabetes in rodent models, bacterial signature in NAFLD and TMAO as negative predictor of human embryo quality. Happy reading and a nice weekend!

General microbiome

Adolescence and aging: impact of adolescence inflammatory stress and microbiota alterations on brain development, aging and neurodegeneration – Nour Yahfoufi – The Journal of Geronotology

Preclinical and clinical relevance of probiotics and synbiotics in colorectal carcinogenesis: a systematic review – Bruna C.S. Cruz – Nutrition Reviews

Gut microbiota: a new piece in understanding hepatocarcinogenesis – An Zhou – Cancer Letters

Gut Microbiota, Diet, and Chronic Diseases: The Role Played by Oxidative Stress – Elisardo C. Vasquez – Oxidative Medicine and Cellular Longevity

New insights on the colonization of the human gut by health-promoting bacteria – Sinead T. Morrin – Applied Microbiology and Biotechnology

Human microbiome

Salivary microbiota and inflammation‐related proteins in patients with psoriasis – Daniel Belstrøm – Oral Diseases

Oral butyrate does not affect innate immunity and islet autoimmunity in individuals with longstanding type 1 diabetes: a randomised controlled trial – Pieter F. de Groot – Diabetologia

Fusobacterium nucleatum in the colorectum, and its association with cancer risk and survival: a systematic review and meta-analysis – Christian Gethings-Behncke – Cancer Epidemiology Biomarkers and Prevention

Potential impact of removing metronidazole from treatment armamentarium of mild acute Clostridioides difficile infection – Shani Zilberman-Itskovich – Future Medicine

Intrahepatic bacterial metataxonomic signature in non-alcoholic fatty liver disease Silvia Sookoian – Gut

Microbial imbalance in inflammatory bowel disease patients at different taxonomic levels – Mohammad Tauqeer Alam – Gut Pathogens

Early life microbiota

Antibiotic Resistance Genes in the Gut Microbiota of Children with Autistic Spectrum Disorder as Possible Predictors of the Disease – Alexey S. Kovtun – Microbial Drug Resistance

Trimethylamine-N-oxide is present in human follicular fluid and is a negative predictor of embryo quality – R.A.Nagy – Human Reproduction

Animal experiments

Microbiota-targeted maternal antibodies protect neonates from enteric infection – Wen Zheng – Nature

Characterization of metabolic and inflammatory profiles of transition dairy cows fed an energy-restricted diet – Giulia Esposito – Journal of Animal Science

Microbiota dependent production of butyrate is required for the bone anabolic activity of PTH – Jau-Yi Li – Journal of Clinical Investigation

Betaine addition as a potent ruminal fermentation modulator under hyperthermal and hyperosmotic conditions in vitro – Mubarik Mahmood – Journal of the Science of Food and Agriculture

Investigating temporal microbial dynamics in the rumen of beef calves raised on two farms during early life – Eóin O’Hara – FEMS Microbial Ecology

Dietary Xanthan Gum Alters Antibiotic Efficacy against the Murine Gut Microbiota and Attenuates Clostridioides difficile Colonization – Matthew K. Schnizlein – mSphere

Post‐natal co‐development of the microbiota and gut barrier function follows different paths in the small and large intestine in piglets – Alexis Pierre Arnaud – Faseb Journal

Phellinus linteus polysaccharide extract improves insulin resistance by regulating gut microbiota composition – Yangyang Liu – Faseb Journal

Exercise improves metabolic function and alters the microbiome in rats with gestational diabetes – Dayana Mahizir – Faseb Journal

Microbial reconstitution reverses early female puberty induced by maternal high-fat diet during lactation – Mengjie Wang – Endocrinology

Fecal microbiota as a noninvasive biomarker to predict the tissue iron accumulation in intestine epithelial cells and liver – Bingdong Liu – Faseb Journal

Techniques

Systematic Analysis of Impact of Sampling Regions and Storage Methods on Fecal Gut Microbiome and Metabolome Profiles – Yali Liang – mSphere

December 20, 2019

This may be our last edition of the Microbiome Digest before the holidays kick in. A rich and dynamic Digest brings you all things microbiome (apologies for the tight formatting). An encouraging report on how we can reduce antimicrobial resistance organically, an amazing recovery of a human genome and an oral microbiome from chewed birch pitch thousands of years ago, and a network analysis reveals four levels of hierarchical trophic interactions in the human gut microbiome. Enjoy Reading and Happy Holidays!
Events
BMC Medicine’s upcoming collection, New Frontiers in Diagnosis, Treatment and Management of Neuromuscular Disorders, is soliciting submissions.
Current Issue of The ISME Journal
The 9th Gut Microbiota for Health World Summit – March 7 and 8 2020 in Madrid, Spain
General microbiology
High-order interactions distort the functional landscape of microbial consortia – Sanchez-Gorostiaga & Bajić et al. – PLoS Biology
Antimicrobial resistance
Human skin microbiome
Human oral microbiome
** A 5700 year-old human genome and oral microbiome from chewed birch pitch – Theis Z. T. Jensen et al. – Nature Communications
Press: Ancient “Chewing Gum” Reveals a 5,700-Year-Old Microbiome – Jim Daley – Scientific American
Human respiratory microbiome
Press: Child asthma flare-ups coincide with microbiome changes – JULIA EVANGELOU STRAIT-WUSTL – Futurity
Human gut microbiome
Human vaginal microbiome
Human gut-microbiota-brain axis
Review: Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain – Kan Gao et al. – Advances in Nutrition
Cancer microbiome
Metabolomics
The total microbiome functions in bacteria and fungi – Robert Starke et al. – Journal of Proteomics
Animal experiments
Animal microbiome
Plant, root and soil microbiome
Root microbiomes as indicators of seagrass health – Belinda C Martin et al. – FEMS Microbiology Ecology
Water and extremophile microbiome
Phages and viruses
Technology
Manipulating rod-shaped bacteria with optical tweezers – Zheng Zhang et al. – Scientific Reports
Bioinformatics
** Evidence for a multi-level trophic organization of the human gut microbiome – Tong Wang et al. – PLoS Computational Biology
Microbes in the news
The microbiome is fundamental to both health and disease – Fabian Brockotter – Poultry World
Low FODMAP Diet Helps IDB Patients – Kenny Walter – MDMAG
Oral Health: Caring for the Other Microbiome – Julia Peterman – Whole Foods Magazine
Non-microbiology pick

 

December 6, 2019

Today’s post is about metabolic networks of the human gut microbiota with host, how aging affects microbial world in humans, microbiome in honey bee and lifestyle dependent gut microbiota gradients in diverse Indian population. Have a nice weekend!

General microbiome

Review: Metabolic networks of the human gut microbiota – Susannah Selber-Hnatiw – Microbiology

Review: Cannabinoids and the Microbiota‐Gut‐Brain‐Axis: Emerging Effects of Cannabidiol and Potential Applications to Alcohol Use Disorders – Hollis C. Karoly – Alcoholism Clinical and Experimental Research

Review: The Unexplored World of Human Virome, Mycobiome, and Archaeome in Aging – Oscar Salvador Barrera-Vázquez – Journal of Gerontology

Review: Nanotechnology intervention of the microbiome for cancer therapy – Wantong Song – Nature Nanotechnology

Commentary: Gut microbiome influences exercise response – Claire Greenhill – Nature Reviews Endocrinology

Human microbiome

Bacterial DNA induces the formation of heat-resistant disease-associated proteins in human plasma – Victor Tetz – Scientific Reports

Lifestyle induced microbial gradients: An Indian perspective – Rashmi Singh – Frontiers in Microbiology

Microbiota, type 2 diabetes and non-alcoholic fatty liver disease: protocol of an observational study – Benedetta M. Motta – Journal of Translational Medicine

Antibiotic exposure and the risk of colorectal adenoma and carcinoma: systematic review and meta‐analysis of observational studies – Leigh N. Sanyaolu – Colorectal Disease

Higher frequency of vertebrate‐infecting viruses in the gut of infants born to mothers with type 1 diabetes – Ki Wook Kim – Pediatric Diabetes

Animal experiments

Integrative analysis of the gut microbiota and metabolome in rats treated with rice straw biochar by 16S rRNA gene sequencing and LC/MS-based metabolomics – Jie Han – Scientific Reports

Division of labor in honey bee gut microbiota for plant polysaccharide digestion – Hao Zheng – PNAS

The effect of carbohydrate sources: Sucrose, invert sugar and components of mānuka honey, on core bacteria in the digestive tract of adult honey bees (Apis mellifera) – Michelle A. Taylor – PlosOne

Seven-day Green Tea Supplementation Revamps Gut Microbiome and Caecum/Skin Metabolome in Mice from Stress – Eun Sung Jung – Scientific Reports

Cattle intestinal microbiota shifts following Escherichia coli O157:H7 vaccination and colonization travel – Raies A. Mir – PlosOne

Characterization of the cecal microbiome composition of Wenchang chickens before and after fattening – Zhen Tan – PlosOne

SOD1 deficiency alters gastrointestinal microbiota and metabolites in mice – Haruka Sagi – Experimental Gerontology

Plant, soil, root microbiome

Host-mediated microbiome engineering (HMME) of drought tolerance in the wheat rhizosphere – Michael D. Jochum – PlosOne

Arctic tundra soil bacterial communities active at subzero temperatures detected by stable isotope probing – Preshita S. Gadkari – FEMS Microbiology Ecology

Techniques

Comparison of extraction methods for recovering ancient microbial DNA from paleofeces – Richard W. Hagan – American Journal of Physical Anthropology

Microbes in the news

How Microbiomes Affect Fear – Quanta Magazine

Rainforest Dwellers and Urbanites Have Consistently Different Microbiomes – Scientific American

Human Microbiome Modulators Market is Furbishing worldwide with Bayer, BioGaia, Chr. Hansen Holding, DowDuPont – News Description

December 4, 2019

Highlights: Microbiome of human milk, AMON to integrate microbiome and metabolome data, soil microbiomes, skin microbiome based news and many more!

General microbiome

The fight for glycans in reproductive tract microbial ecology – MIH Pishchany – AJOG

Microbiota, a Third Player in the Host–Plasmodium Affair – D Mukherjee – Trends in Parasitology

Pregnancy and early life

Baby’s First Microbes: The Microbiome of Human Milk – MC Collado – How Fermented Foods Feed a Healthy Gut Microbiota

Human respiratory microbiome

Anterior Nares Diversity and Pathobionts Represent Sinus Microbiome in Chronic Rhinosinusitis – ID Boeck – mSphere

Animal microbiome 

Next generation sequencing reveals significant variations in bacterial compositions across the gastrointestinal tracts of the Indian major carps, rohu (Labeo rohita), catla (Catla catla) and mrigal (Cirrhinus cirrhosis) – MJ Foysal – Letters in Applied Microbiology

Plant, root, and soil microbiome

Rewetting of three drained peatlands drives congruent compositional changes in pro- and eukaryotic microbiomes through environmental filtering – M Weil – bioRxiv

The influence of substrate concentration on the culturability of heterotrophic soil microbes isolated by high-throughput dilution-to-extinction cultivation –  R Bartelme – bioRxiv

Rhizosphere: a home for human pathogens – R Sharma – Plant Biotic Interactions

Amplicon sequencing and imputed metagenomic analysis of waste soil and sediment microbiome reveals unique bacterial communities and their functional attributes – SD Mandal – Environmental Monitoring and Assessment

Soil bacterial and fungal communities exhibit distinct long-term responses to disturbance in temperate forests – ED Osburn – Frontiers in Microbiology

Decomposition of mixtures of cover crop residues increases microbial functional diversity – SM Drost – Geoderma

Techniques

AMON: annotation of metabolite origins via networks to integrate microbiome and metabolome data – M Shaffer – BMC Bioinformatics

Identification and quantitation of clinically relevant microbes in patient samples: Comparison of three k-mer based classifiers for speed, accuracy, and sensitivity – GS Watts – PLoS Computational Biology

Extracting the GEMs: Genotype, Environment and Microbiome interactions shaping host phenotypes – BO Oyserman – bioRxiv

Microbes in the news

Korean beauty makers join the rush towards new skin gold mine of microbiome – Pulse

Mode of Delivery May Alter Microbiome, But Study Finds No Link to Later GI Issues – Gastro Endo News

Smart Skin care – Cosmetics Design Europe

The Dynamic Microbiome – Gen Eng News

microRNA Found in Gut Microbiome May Unlock Future Therapeutic Approach for MS – Multiple Sclerosis News Today

A Matchmaker for Microbiomes – Identifying Relationships of Microbes and Metabolites – Scitech Daily