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 25, 2020

In today’s microbiome digest various interesting aspects of microbiome research has been covered such as 1) a summary report by Marc G. Chevrette on one of my favorite research of the decade – “A metagenomic strategy for harnessing the chemical repertoire of the human microbiome”, 2) Oral administration of hydrogels promoted intestinal barrier function, suppressed the pro-inflammatory mRNA expression, 3) Association of low fiber intake in chronic heart failure, and several other interesting articles! Enjoy reading! Happy Weekend!

General microbiome

From Metagenomes to Molecules: Innovations in Functional Metagenomics Unlock Hidden Chemistry in the Human Microbiome – Marc G. Chevrette – Biochemistry

A systematic review of economic evaluation in fecal microbiota transplantation – Thomas Stalder – Infection Control & Hospital Epidemiology

Review: Microbial Contribution to the Human Metabolome: Implications for Health and Disease – William Van Treuren – Annual Review of Pathology

Human gut microbiome

Low fibre intake is associated with gut microbiota alterations in chronic heart failure – Cristiane C.K. Mayerhofer – ESC Heart Fail

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

Compositional flux within the intestinal microbiota and risk for bloodstream infection with gram-negative bacteria – Igor Stoma – Clinical Infectious Diseases

Comparative Analysis of Gut Microbiota Following Changes in Training Volume Among Swimmers– Jarrad Timothy Hampton-Marcell – International Journal of Sports Medicine

Diversity, compositional and functional differences between gut microbiota of children and adults – Djawad Radjabzadeh – Scientific Reports

Environmental and intrinsic factors shaping gut microbiota composition and diversity and its relation to metabolic health in children and early adolescents: A population-based study – Sofia Moran-Ramos – Gut Microbes

Human skin microbiome

Impact of the early-life skin microbiota on the development of canine atopic dermatitis in a high-risk breed birth cohort– S. Rodriguez-Campos – Scientific Reports

Human respiratory microbiome

The lung microbiota: role in maintaining pulmonary immune homeostasis and its implications in cancer development and therapy – Michele Sommariva – Cellular and Molecular Life Sciences

Lung Microbiota Predict Clinical Outcomes in Critically Ill Patients – Robert P. Dickson – American Journal of Respiratory and Critical Care Medicine

Animal microbiome / Animal experiments

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

Effect of Lactobacillus acidophilus D2/CSL (CECT 4529) supplementation in drinking water on chicken crop and caeca microbiome– De Cesare A – PLOSE ONE

Differential effects of synthetic psychoactive cathinones and amphetamine stimulants on the gut microbiome in mice – Angoa-Pérez M – PLOSE ONE

Modulation of inflammatory response and gut microbiota in ankylosing spondylitis mouse model by bioactive peptide IQW – Gang Liu – Journal of Applied Microbiology

Effect of cereal soaking and carbohydrase supplementation on growth, nutrient digestibility and intestinal microbiota in liquid-fed grow-finishing pigs – Alberto Torres-Pitarch – Scientific Reports

Anesthesia and surgery induce age-dependent changes in behaviors and microbiota – Ning Liufu – Aging

Amyloid–Polyphenol Hybrid Nanofilaments Mitigate Colitis and Regulate Gut Microbial Dysbiosis – Bing Hu – ACS Nano

Clostridium butyricum Modulates the Microbiome to Protect Intestinal Barrier Function in Mice with Antibiotic-Induced Dysbiosis – Mao Hagihara – iScience

Microbes in news

Can our microbiome accurately identify diseases … and predict death?

January 18, 2020

Check out today’s digest which includes very diverse microbiome research. I would like to highlight specifically these three 1) Indole-3-carbinol in the prevention of colitis and associated microbial dysbiosis, 2) A rapid and convenient derivatization method for the quantitation of short‐chain fatty acids in human feces, and 3) Role of complex microbiome human in vitro fertilization procedure. There are several other interesting articles in every section! Enjoy reading!

General microbiome

Review: Whole Food–Based Approaches to Modulating Gut Microbiota and Associated Diseases – Han Y –  Annual Review of Food Science and Technology

Microbiome signatures in neonatal central line associated bloodstream infections – Mohan Pammi – PLOS ONE

Human gut microbiome

Gut Microbiota Compositional and Functional Fingerprint in Patients with Alcohol Use Disorder and Alcohol Associated Liver Disease – Giovanni Addolorato – Liver INTERNATIONAL

Parkinson disease, levodopa and the gut microbiota‐when microbiology meets pharmacology – Harald Brüssow – Environmental Microbiology

Short chain fatty acids and methylamines produced by gut microbiota as mediators and markers in the circulatory system – Maksymilian Onyszkiewicz – Experimental Biology and Medicine

Prospective study reveals a microbiome signature that predicts the occurrence of post-operative enterocolitis in Hirschsprung disease (HSCR) patients– Weibing Tang – Gut Microbes

Review: Systematic review of human gut resistome studies revealed variable definitions and approaches – Jeferry Ho – Gut Microbes

Indole-3-carbinol prevents colitis and associated microbial dysbiosis in an IL-22–dependent manner – Philip B. Busbee – JCI Insight

The biotransformation of Bupleuri Radix by human gut microbiota – Cui Tang – Xenobiotica

Human oral microbiome

Signatures of oral microbiome in HIV-infected individuals with oral Kaposi’s sarcoma and cell-associated KSHV DNA – Marion Gruffaz – PLOS PATHOGENS

Review: A Systematic Review of the Root Canal Microbiota Associated with Apical Periodontitis: Lessons from Next‐Generation Sequencing – Daniel Manoil – Proteomics Clinical Applications

The influence and impact of smoking on red blood cell morphology and buccal microflora: A case‐control study – Khalid Hadi Aldosari – Journal of Clinical Laboratory Analysis

Human reproductive microbiome

The complex microbiome from native semen to embryo culture environment in human in vitro fertilization procedure – Jelena Štšepetova – Reproductive Biology and Endocrinology

Understanding the terms we use: support for using ‘sexually shared microbiota’ (SSM)
David Taylor-Robinson – International Journal of STD and AIDs

Human respiratory microbiome

Pharyngeal microbiome alterations during Neisseria gonorrhoeae infection – Antonella Marangoni – PLOS ONE

Animal microbiome / Animal experiments

Camellia Sinensis and Litsea Coreana Ameliorate Intestinal Inflammation and Modulate Gut Microbiota in Dextran Sulfate Sodium‐Induced Colitis Mice – Yan Liu

Improving Alzheimer’s disease by altering Gut Microbiota in tree shrews with ginsenoside Rg1 – Limei Wang – FEMS MICROBIOLOGY LETTERS

The composition of the perinatal intestinal microbiota in horse – A. Husso – Scientific Reports

Plant microbiome

The influence of host‐plant connectivity on fungal assemblages in the root microbiota of Brachypodium pinnatum – C. Mony – Ecology

Methods

A rapid and convenient derivatization method for quantitation of short‐chain fatty acids in human feces by ultra‐performance liquid chromatography‐tandem mass spectrometry – Huan Fu – Rapid communications in Mass Spectrometry

Microbiome news

It takes more than two to tango: Microbial communities influence animal sex and reproduction

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 29, 2019

Have a nice sunday!  Today we have papers about the microbiome in martial arts athletes, more research about Fusobacterium and colorectal cancer, the effect of light in atopic dermatitis and the effect of alcohol binge in a mouse model, among other papers.  

Human and General Microbiome

Review: The Gut-Liver-Kidney axis: novel regulator of fatty liver associated chronic kidney disease – Desh Raj – Pharmacological Research

Characteristics of the gut microbiota in professional martial arts athletes: A comparison between different competition levels – Ru Liang – PLoS One

The balance between breast cancer and the immune system: challenges for prognosis and clinical benefit from immunotherapies – Constantin N. Baxevanis – Seminars in Cancer Biology

Review: Host- and Microbiota-Derived Extracellular Vesicles, Immune Function, and Disease Development – Laurence Macia – International Journal of Molecular Sciences

Recent advances in understanding the natural history of the otitis media microbiome and its response to environmental pressures – Robyn L. Marsh – International Journal of Pediatric Otorhinolaryngology

Association of autophagy status with amount of Fusobacterium nucleatum in colorectal cancer – Koichiro Haruki – The Journal of Pathology

Effects of 308 nm excimer light treatment on the skin microbiome of atopic dermatitis patients – Yuko Kurosaki – Photodermatology, Photoimmunology and Photomedicine

Rapid Multiplex Real-Time PCR Method for the Detection and Quantification of Selected Cariogenic and Periodontal Bacteria – Jan Lochman – Diagnostics

Review: Biomarkers of a Healthy Nordic Diet-From Dietary Exposure Biomarkers to Microbiota Signatures in the Metabolome – Rikard Landberg – Nutrients

 

Animal Microbiome

Gut microbiota of provisioned and wild rhesus macaques (Macaca mulatta) living in a limestone forest in southwest Guangxi, China – Ting Chen – MicrobiologyOpen

The Diversity of the Endobiotic Bacterial Communities in the Four Jellyfish Species – Qing Liu – Polish Journal of Microbiology

Switching to a Healthy Diet Prevents the Detrimental Effects of Western Diet in a Colitis-Associated Colorectal Cancer Model – Charlotte Gröschel – Nutrients

The Effect of Thermal Stress on the Bacterial Microbiome of Exaiptasia diaphana – Leon M. Hartman – Microorganisms

Pretreatment with Yeast-Derived Complex Dietary Polysaccharides Suppresses Gut Inflammation, Alters the Microbiota Composition, and Increases Immune Regulatory Short-Chain Fatty Acid Production in C57BL/6 Mice – Radhika Gudi – The Journal of Nutrition

Long-lasting microbial dysbiosis and altered enteric neurotransmitters in adult rats following adolescent binge ethanol exposure – Ryan P. Vetreno – Addiction Biology

 

Beneficial Microbes and Compounds

Minireview: Use of Synbiotics for Ulcerative Colitis Treatment – Marianna Roselli –  Current Clinical Pharmacology

The Structure Features and Improving Effects of Polysaccharide from Astragalus membranaceus on Antibiotic-Associated Diarrhea – Shanshan Ll – Antibiotics

Deep-Fried Atractylodis Rhizoma Protects against Spleen Deficiency-Induced Diarrhea through Regulating Intestinal Inflammatory Response and Gut Microbiota – Kun Shi – International Journal of Molecular Sciences

Hafnia alvei HA4597 Strain Reduces Food Intake and Body Weight Gain and Improves Body Composition, Glucose, and Lipid Metabolism in a Mouse Model of Hyperphagic Obesity – Nicolas Lucas – Microorganisms

 

Wastewater Microbiome

Microbiome changes and oxidative capability of an anaerobic PCB dechlorinating enrichment culture after oxygen exposure – Bruna Matturro – New Biotechnology

 

Plant Microbiome

Tomato RNA-seq Data Mining Reveals the Taxonomic and Functional Diversity of Root-Associated Microbiota – Bruna Matturro – Microorganisms

Metagenome sequencing of fingermillet-associated microbial consortia provides insights into structural and functional diversity of endophytes – M. K. Prasannakumari – 3 Biotech 

Resilience to multiple stressors in an aquatic plant and its microbiome – Anna M. O’Brien – American Journal of Botany

 

Techniques

Scalable and cost-effective ribonuclease-based rRNA depletion for transcriptomics – Yiming Huang – Nucleic Acids Research