A detailed database of transcriptomic data from over 100,000 individual cells taken from the mouse model organism Mus musculus, titled Tabula Muris, is now available for use by biomedical researchers around the world. This work, completed by the The Tabula Muris Consortium, was a project funded by the Chan Zuckerberg Biohub.
This database is the first concise and detailed collection of mouse single cell transcriptomic data from this important model organism. It reveals the individual gene expression levels of the cells from 20 different organs and tissues and is a first draft for an organism-wide representation of cellular diversity. This now-publicly-available resource will aid in the discovery of new cell types and of novel gene expression patterns, while also serving as a reference for healthy organs and tissues, making it an important baseline for future disease models. The team also made all of the data, scripts, and protocols publicly available along with an interactive data browser. The aim is to allow future groups to carry out further in depth-analysis and exact replications of their work.
In order to complete such an ambitious project, the consortium assembled expertise from several groups. Consortium members included researchers from Chan Zuckerberg Biohub, multiple faculty at Stanford University, and experts from the Palo Alto Healthcare System. Each group specialised in a tissue type (e.g. kidneys or lungs), or had specific experience (e.g. pathology or flow cytometry). A breadth of knowledge was required because the over 100,000 individual cells needed to be individually isolated. For mammalian cells, two methods were used: fluorescence-activated cell sorting and the microfluidic droplet technique. From here, DNA and RNA were extracted and sequenced. In tandem, fecal samples were collected for functional analysis of the microbiota. It was at this stage that Microbiome Insights provided their expertise by performing a customized suite of DNA extraction and library preparation services to contribute to the overall results.
“Working closely with Microbiome Insights to quickly analyze the data was critical to our ability to integrate microbiota information with the rest of the Cell Atlas project,” said KC Huang, a Stanford professor involved in the project. The sheer number of cell types and subsequent genomic information to be processed required an enormous feat of coordination—making this a remarkable example of research collaboration.
The strength of this single cell and organ approach is that it will allow researchers working with a single organ, for example, to see the changes that occur throughout the entire body. It provides a whole-body view of disease and development. This could aid in studies on prevention and potentially even cures for many important diseases such as diabetes, heart disease, and cancer. The Chan Zuckerberg group is now supporting a similar project, The Human Cell Atlas, which according to their website, is aimed at building “a collection of maps that will describe and define the cellular basis of health and disease”.
https://microbiomeinsights.com/wp-content/uploads/2018/12/shutterstock_668875504-e1544644253416.jpg4851000Bradley van Paridonhttps://microbiomeinsights.com/wp-content/uploads/2018/11/logo-new-1030x999.pngBradley van Paridon2018-12-09 13:55:272018-12-12 11:52:29Stanford group draws wide expertise from Microbiome Insights & others to complete Chan Zuckerberg Biohub’s Tabula Muris project
Microbiome Insights was a proud founding partner of the Microbiome Skin Health and Dermatology conference, a part of the Hanson Wade Microbiome Movement Series—held September 10th to 12th, 2018. The aim of this event was to explore ways of understanding the mechanisms underlying microbial interactions with skin health, and to discuss standardization of metagenomics research and how to develop effective products. Over 100 leaders in the skin microbiome field were on site at this exciting event.
We’re pleased to present a summary of the highlights from both the pre-conference workshop and the two-day main event.
The September 10th workshop, called “Harnessing the gut-skin-brain axis in health and disease”, was led by Lionel Breton, L’Oreal Advanced Research, Scientific Director. Breton spoke about what we know today regarding the connections between the skin microbiota, gut microbiota, and neurological disorders. Scientists are puzzling through these links, on the path to developing commercially viable therapeutics for skin health and brain health.
Day 1 summary
The first day of the conference began with opening remarks by Larry Weiss of Persona Biome: he acknowledged that the skin microbiome represents an exciting therapeutic frontier in dermatology, but encouraged the audience to be cautious and exercise humility—because after all, “we still don’t know what we don’t know”.
Richard Gallo of UCSD then spoke about “Targeted Design of Microbial Biotherapy for Skin Disease”. Gallo began with an overview of how microbes relate to human health in general: he argued that researchers need to look at the ‘hologenome’, as it takes into account that human functions are based on genes that are expressed via microbes and the environment.
Gallo turned specifically to the microbial life surrounding hair follicles on the skin. He noted that human follicles greatly increase the surface area of the skin; when the microbes in follicles were analyzed using 16S DNA sequencing, it appeared that most of the microbial DNA did not exist on the surface, but rather, it existed deep down in the follicle. A very small percentage of the microbes were further down, penetrating the fat and tissues under the follicle. The composition of the microbes in the fat was similar to that found on the surface.
Gallo emphasized the capacity for systemic interactions linked to the skin microbiome, as the blood vessels on the skin can have extensive communication with, and impact on, the rest of the body. He gave the example of atopic dermatitis: not only do people with this condition have a higher abundance of Gram-positive bacteria (S. aureus) than other people, but Gallo’s work showed that they also have an immune abnormality that inhibited the development of antimicrobial peptides to fight the disease. The presence of S. aureus drives a Th2 immune response, which further decreases the antimicrobial peptides and amplifies the disease. So what appears to be a skin disease is actually a complex condition with systemic influences.
Next up was a talk by Curtis Huttenhower of the Harvard TH Chan School of Public Health, a member of the Microbiome Insights Scientific Advisory Board. He presented on “Structure, Function and Diversity of the Healthy Human Microbiome”. Huttenhower began by explaining the phases of the Human Microbiome Project (HMP): while HMP 1 had the goal of identifying the baseline microbiota of a healthy cohort of individuals, HMP 2 included more multi-omics analyses, and had a longitudinal focus, aiming to uncover interactions in disease. HMP1-II was a recent follow-up on the HMP 2 data; it involved 300 people (half men, half women). Huttenhower noted that the field has seen great advancements since the kick-off of HMP 1, and argued that we are getting to the point where scientists can do meta-analyses to see which methods are more reproducible and reliable.
Specifically related to the skin microbiome, Huttenhower said we have a long way to go—not only in characterizing the ‘healthy’ skin microbiome, but also in defining its biochemistry. Novel functionality is associated with certain strains. Ongoing work is looking at how the skin microbiome may be acquired in the first place, by examining mother-infant pairs. Initial analyses indicate the strains of most bugs on the infant do not originate from the mother.
Julia Oh of The Jackson Laboratory spoke next, on “The Human Skin Microbiome: From Metagenomes to Therapeutics”. Oh emphasized the differences in composition of the skin microbiome, depending on body site: oily sites, for example, are very different from dry sites.
She advised that when looking at therapeutics, skin microbiome researchers should consider factors like site specificity, diversity of the microbiome, and stability of the community. For instance, in those with atopic dermatitis, the skin microbiome looks different depending on whether you measure it at baseline, during a disease flare (when relative abundance of S. aureus increases), and post-flare.
Oh offered some general criteria for what organisms to focus on in the development of new skin therapeutics:
An organism that grows well on the skin—that is, on a graph of time versus growth, an organism that has a U-shaped trajectory (rather than flat).
An organism that is beneficial to the immune system. Their group looked at T cells and measured the rate of MAIT activation with 4000 different species.
An organism that is innate. Most skin sites are stable over time, so the challenge is integrating a foreign species into a community. Previous experiments show it’s difficult to get something to colonize on the skin.
The set of talks was rounded out by Microbiome Insights CEO Malcolm Kendall, on the topic: “From Swab to Data: Considerations for Designing Skin Microbiome Studies.” He emphasized looking at skin microbiome studies from many angles: study design (including the power), collection, stabilization, transport, sequencing, and analysis.
He noted the in-house work of Microbiome Insights that investigated the total DNA as well as the microbial content while using swabs versus tape for a skin microbiome sample. Results showed little difference in total DNA content across systems, but higher microbial content (less host content) on premoistened swabs. Of course, this approach is useful for skin surface microbiome but may not be the best method to look at the follicle microbiome.
Kendall says he has noticed a lot of debate surrounding the variable region that will provide the most fruitful information for skin microbiome analysis using 16S. Microbiome Insights has done some internal R&D work to address this issue: the outcome of which is a new ‘V4_skin’ primer that provides better species-level identification of skin taxa while maintaining low error.
An intriguing panel discussion was held later that morning: “Where will the Skin Microbiome Need Standardization to Advance Science & Future Products?” It was led by Huttenhower, joined by Amanda Nelson of PennState.
Participants emphasized the problem of contamination, since skin microbiome samples have a low microbial biomass; researchers need to include positive and negative controls for ‘human’ and body site. The panelists covered the relative advantages of different collection techniques, sequencing techniques, and culture libraries. For bacteria and skin fungi, libraries are improving, but viruses change so quickly that they won’t be covered in reference libraries. Integrating different data (using multi-omics analyses) will lead to better insights.
In the afternoon of day one, participants heard from Huiying Li of UCLA, on “The Human Skin Microbiome in Health and Disease”. Li spoke about acne in particular: they found individuals with acne and those with healthy skin had significant differences in the facial microbiome at the strain level; there are genes that are differentially expressed.
Later, Pieter Dorrestein of UCSD moved the topic to metabolomics—he spoke about “Microbial Metabolites of the Skin Microbiome – Identifying Skin Chemistry to Search for Function.” He described how his group is taking several hundred swabs from the bodies of two individuals and translating the mass spectrometry data onto a 3D model—with the ultimate aim being to find the origin of the molecules. A combined metabolomics and 16S analysis showed no changes when the face and arms were treated with certain personal care products; however, there appeared to be a deodorant-dependent change in the armpit skin. In general, it appears that the profile is resilient, but that certain lifestyle factors can indeed impact the skin.
Day 2 summary
The second day of the Skin Health & Dermatology meeting featured another great lineup of speakers addressing different aspects of the skin microbiome. Amitabha Majumdar, Senior Research Scientist at Unilever, presented on “Commercializing Microbiome-based Beauty & Personal Care Products”.
Majumdar spoke about some of the major challenges in microbiome-focused product development:
Finding the right target: In looking for the cause of malodour, the company found certain microbes, molecules, and pathways that were responsible; when they had the right target, they developed products (like Dove deodorant) to address the problem.
Hitting a target better: In terms of acne, Majumdar says they found that lesions were reduced after a particular 3-week treatment that included natural oils. The company then took two natural oils that were part of this treatment and added them to two facial products already on the market.
‘Rebalancing’ the microbiota: One of the company’s toothpaste products were studied clinically—and they found that after 14 weeks, some of the bacteria associated with oral health were altered.
Majumdar’s talk was followed by one from Alex Goddard, VP, Research & Development at AOBiome: “Using Ammonia Oxidizing Bacteria to Restore Healthy Skin”. Goddard started with the premise that we are being deprived of certain metabolites because of the nature of our hygiene practices, and this may be altering our overall immune system and general health. He reported that David Whitlock, one of the company founders, noticed animals like horses roll in the soil to relieve an itch on the skin. This led to an investigation of whether the soil somehow had a therapeutic effect—and to the potential of ammonia oxidizing bacteria. These bacteria produce nitric oxide (which is anti-microbial and anti-inflammatory).
The company’s general approach is to discover new environmental bacteria that can be used on the skin. Goddard cited some of the challenges in developing new therapeutics: determining mechanism of action (whether direct or indirect); dosing; and variability in patients (from a physiological and microbial standpoint).
Then, Livia Zaramela, postdoc at UCSD, spoke on “The Role of the active Microbiome in Skin: Emphasis on Atopic Dermatitis”. Zaramela addressed the connection between food allergy and atopic dermatitis, as about one third of children with atopic dermatitis have food allergy. Their group uses a multi-omics approach to identify whether food allergies are intrinsically linked to atopic dermatitis or not.
Zaramela discussed how to overcome the challenges of low biomass samples for metatrascriptomics analysis: they maximize collection, extraction, and mRNA enrichment, and they work to minimize contamination. In terms of contamination, it’s necessary to reduce human content in the samples, but also reagent contamination.
Another speaker in the morning session was Magali Moreau, Associate Principal Scientist, Open Research at L’Oreal. She spoke on “Human Skin Microbiome: Opportunities for Healthy Skin with Aging.”
Moreau described how the company is looking at the skin microbiomes of women of all ages. At four different skin sites across two age groups, the distribution of Staphylococcus appeared to change significantly, while the proportion of Cutibacterium at each site decreased with age. Diversity was higher in the older group, across all sites. Thus, the trend with aging seems to involve a decrease in sebum and an increase in skin microbiome diversity, with some oral bacteria increasing on the skin.
She then addressed how to translate this growing microbiome knowledge into products. Approaches include fostering the growth of beneficial bacteria, controlling the community metabolites to bring back ‘equilibrium’, or perhaps using the virome for precision modulation.
Stephen France, Business Development at SkinBioTherapeutics, was the next speaker, on “Harnessing the Power of the Microbiome for Skin Health.” He focused particularly on some interesting observations on lysates (i.e. fluids containing the contents of lysed cells). They found lysates could inhibit pathogens and change the skin barrier; pretreatment of the skin with lysates protected against S. aureus invasion.
A talk from Greg Hillebrand, Senior Principal Scientist at Amway, capped off the morning sessions: “Changes in the Facial Skin Microbiome: A One-Year Longitudinal Study in Normal Healthy Men and Women.”
Hillebrand began by describing the company’s investigations into the meaning of skin health, with input from 70 individuals. The resulting points were: “it has to perform, but needs to be resilient when stressed; it needs to look even color-toned, and fairly unremarkable (you don’t notice your skin)”.
Hillebrand described the company’s ‘Cinco de mayo’ study, done in collaboration with Microbiome Insights. Skin samples from the forehead and cheek were taken from 150 Amway employees (aged 20 to 60) in 2017, with a repeated measure on 137 of the individuals in 2018. They measured other parameters like elasticity. Microbiome analysis using 16S V4 and V1-V3 revealed overlap in the microbial communities of the forehead and cheek, with some differences. Individuals’ skin microbiomes were relatively stable, and the individuals who had low diversity of their skin microbiome in 2017 also had low diversity the following year.
Barrier function was stronger with a more diverse skin microbiome; as water loss went up, barrier function went down. The other striking finding was that bacteria from the genus Corynebacterium increased with age. Amway is looking to build on these findings, with Microbiome Insights acting as an external R&D arm, to rapidly develop microbiome-focused solutions for skin health.
https://microbiomeinsights.com/wp-content/uploads/2018/09/Hillebrand-photo.jpg22684032Karl Moranhttps://microbiomeinsights.com/wp-content/uploads/2018/11/logo-new-1030x999.pngKarl Moran2018-09-18 12:36:322019-10-18 13:33:38Microbiome Movement Skin Health & Dermatology Conference Summary: Days 1 & 2
Microbiome Insights, Inc. is planning to move operations into a new laboratory space in UBC’s Pharmaceutical Sciences building — and to mark the occasion, they will host a champagne reception with a poster competition open to local microbiome researchers.
Poster competition details:
The competition is open to all researchers and research assistants affiliated with UBC. Participants may bring any poster related to microbiome data collected within the past five years — up to 3 posters per participant may be entered.
Posters previously presented at academic conferences are encouraged! Most standard poster sizes can be accommodated.
Posters will be judged on both scientific content and presentation. Judges will award first, second, and third prizes as well as a “crowd favourite”.
Participants should bring their poster for setup between 1:00 and 3:30 on May 28th. Winners will be announced during the champagne reception at 5:30.
Prizes are as follows:
First place: 50 free samples of amplicon sequencing ($5,500 value)
Second place: 30 free samples of amplicon sequencing ($3,300 value)
Third place: 20 free samples of amplicon sequencing ($2,200 value)
Crowd favourite: Cash prize of $250
RSVP for the poster competition to Jen Bower: firstname.lastname@example.org
Only the first 30 entries can be accepted, so email now!
https://microbiomeinsights.com/wp-content/uploads/2018/11/logo-new-1030x999.png00Malcolm Kendallhttps://microbiomeinsights.com/wp-content/uploads/2018/11/logo-new-1030x999.pngMalcolm Kendall2018-05-14 17:33:132018-05-17 06:15:05Microbiome Insights to mark opening of new lab space with champagne reception and microbiome poster competition
This year, 2017, will go down in Microbiome Insights history as the year the company hit its stride and established itself as a leader in the microbiome testing field. The challenging work our team has been doing since we were founded in 2015 clearly paid off—as evidenced by our expanding client list, our strong financial position, and our team’s awards and recognitions.
In the past twelve months we have had to more than double the size of our Vancouver-based team, hiring some of the best technicians, scientists, and bioinformaticians to meet the needs of our clients.
Here are some highlights of our company’s 2017, by the numbers:
Number of conferences Microbiome Insights attended as exhibitors or sponsors. Our team enjoyed meeting new and existing clients at important academic and industry conferences in all corners of North America—from ASM Microbe 2017 in New Orleans to the Microbiome R&D and Business Collaboration Forum in San Diego. We also trailblazed as one of the first microbiome-centered companies to attend two genomics events: ASHG 2017 in Orlando and the 3rd annual Understand your Genome conference in Boston.
British Columbia (BC) life sciences companies (including Microbiome Insights) on the ‘Ready to Rocket’ 2017 Life Science Emerging Rocket List—a business recognition program that profiles technology companies in BC with the greatest potential for revenue growth. These “Emerging Rocket” companies are recognized as having a clear business model and go-to-market strategy that will prove attractive to investors.
Number of microbiome studies our team supported this year—across a broad range of human, animal, agricultural, and environmental applications. We are very proud that many of these were repeat clients.
Number of dollars invested in our company by Genome BC, following successful equity financing. In combination with funds from the company’s recent round of equity funding, this will help build out our new CLIA-certified lab facility, grow our team and capabilities, and develop and launch new services and tests in 2018.
Here are some of the technical insights from our team this year:
The staying power of amplicon-based analyses: For studies whose primary objective is to get a comprehensive picture of the bacteria in an environment, or to build models of disease classification (for many diseases) data derived from 16S genes is as good as it gets
The power of multi-omics integration: Although it still poses technical challenges, integration of multiomics datasets can reveal things far beyond what each technology can show separately
And finally, here are our team’s picks for the hot areas to watch in microbiome science in the coming year:
The contribution of microbes to “inflammaging”—the progressive increase in pro-inflammatory status that occurs with age
Progress toward microbiome therapies that modulate the brain through the gut-brain axis
Larger and longer studies on the skin microbiome, looking at lifestyle factors and making more definitive associations between skin microbes (composition and function) and healthy skin
Tracking the presence of viruses in the gut microbiome and gaining insights about health implications
A very happy 2018, from our team to you!
https://microbiomeinsights.com/wp-content/uploads/2018/02/microbiome-insights-conference.jpg1200900Malcolm Kendallhttps://microbiomeinsights.com/wp-content/uploads/2018/11/logo-new-1030x999.pngMalcolm Kendall2017-12-21 00:00:002018-12-10 10:30:36Microbiome Insights’ Year in Review: 2017 by the numbers
Debate exists about how soon knowledge about the gut-brain axis will bear fruit. Yet the microbiome-gut-brain axis is a hot topic of scientific investigation and several companies around the globe are actively pursuing gut microbiome therapies that focus on brain-related conditions.
Here’s a quick overview from our lab scientists on various areas of brain health and the evidence linking each one to the gut microbiota.
General early life neurodevelopment
Dozens of human studies and mechanistic animal studies support the relevance of gut microbiota to normal behaviour and neurodevelopment; however, these studies are not always specific to neurological development, and the observed effects could be confounded by many other factors that affect the early life microbiome.
Autism spectrum disorders
Although there are known genetic contributors to autism spectrum disorders, both human and animal studies show a connection between gut microbiota and both gastrointestinal symptoms and social deficits in these individuals.
A moderate level of evidence links anorexia with gut microbiota; no mechanistic studies have been completed to date.
Attention deficit hyperactivity disorder (ADHD)
A low level of evidence implicates gut microbiota in ADHD; this disorder may also be linked to diet, but much more research needs to be undertaken.
A growing number of human studies as well as mechanistic animal studies have found the gut microbiota has immunomodulatory effects that may affect multiple sclerosis (MS) disease progression. Transfer of the microbiota from a human with MS to a mouse increases MS-like symptoms.
Post-traumatic stress disorder (PTSD)
Moderate evidence and one human study connects the gut microbiota with PTSD; further research may explore the mechanistic role of chronic inflammation as well as cortisol and dopamine regulation.
A high level of evidence links gut microbiota with depressive symptoms; probiotics may improve depression in both humans and animals.
While the studies on anxiety overlap with those on depression, some reports in both animals and humans show potential of microbiota modulation — for example, through probiotics — for improving symptoms of anxiety.
Extreme fatigue may also be linked with the gut microbiota, although diet appears to be a major confounding factor and more research is required.
Many studies in humans link Parkinson’s disease (PD) with the gut, but chronic constipation in those with PD is a possible confounding factor. Mechanistic evidence to back these findings is just beginning to emerge.
Emerging evidence shows the Alzheimer’s-gut connection: in mice, Alzheimer’s-like symptoms are altered by microbiome manipulation.
A round table discussion at the Global Engage Microbiome R&D and Business Collaboration Forum on Thursday, November 2nd, led by CEO Malcolm Kendall, will explore what we know about the gut-brain axis and how soon it could yield breakthrough therapies.
CEO Malcolm Kendall
https://microbiomeinsights.com/wp-content/uploads/2017/10/DNA-samples-96-well-plate.jpg10801920Malcolm Kendallhttps://microbiomeinsights.com/wp-content/uploads/2018/11/logo-new-1030x999.pngMalcolm Kendall2017-11-02 00:00:002018-12-17 21:07:34How close are microbiome-modulating therapies that target the brain? A quick overview of the evidence