Global Engage 6th Microbiome R&D and Business Collaboration Forum Summary: Days 1 & 2

Leaders in the microbiome industry met in San Diego (USA) for two days, on October 29th and 30th, 2018, to dive into the advancements in research and product development that have occurred to date. Microbiome Insights was an exhibitor at this event—The 6th Microbiome R&D and Business Collaboration Forum–one of the largest annual microbiome-related gatherings in the US, with 300 attendees coming from North America and Europe.

The conference talks were divided into three tracks: microbiome therapeutics, skin microbiome, and probiotics. Here, we present highlights from each of the tracks in this two-day event:

Day 1

Probiotics

Jennifer Spinler of Baylor College of Medicine spoke on “Targeting Antibiotic-Associated Digestive Diseases Using Next-Generation Probiotics”. She started by outlining the need for new therapies to prevent antibiotic-associated diarrhea. Clostridium difficile infection is one of the leading reasons for antibiotic administration, and a 2017 Cochrane Review showed probiotics can prevent Clostridium difficile-associated diarrhea in adults and children. Spinler’s approach is to explore a probiotic strategy for preventing Clostridium difficile infection in the first place by looking at how host bacteria are normally able to protect against C. difficile. She focused on Lactobacillus reuteri, which has anti-inflammatory effects and activity against Gram positive and Gram negative bacteria. She found that L. reuteri alone didn’t prevent the growth of C. difficile, but L. reuteri plus glycerol knocked down C. diff growth in the system—with an accompanying shift in the overall microbial community.

Brunella Gonzalez Cautela of Lallemand gave a talk on “Probio’Stick and the brain-gut axis: Focus on recent clinical findings”. She noted that the etiology of depression is obscure, but one contributor under consideration is immune-mediated inflammation. She thus posed the question: can probiotics be used for depression? A pilot study by the company, in collaboration with researchers from Queen’s University, focused on patients who were depressed but never treated before. In addition to completing a survey, the subjects were tested for inflammatory markers in the blood, serotonin levels, and fecal microbiome composition. Those who received ProbioStick for 8 weeks showed significant improvement in mood-related symptoms compared to those who received a placebo.

Microbiome

Kathy McCoy of University of Calgary presented on “Impact of the gut microbiome in shaping innate immunity: Defining Mechanisms”, going over several examples of using gnotobiotics to define mechanisms underlying microbiome and host interactions. In one example, researchers studied microbial impact on T Cells in a non-obese diabetic mouse model of type 1 diabetes. They looked at the ability of the bacteria to bring the integrase-specific T cells to the gut, and found that microbial antigens had a dramatic protective effect against colitis.

Jessica Schneider of Takeda Pharmaceuticals spoke about the company’s growing microbiome drug portfolio, and how gastrointestinal indications are paving the way for future indications (gut-brain axis and others). She explained the company’s interest in commensal bacterial co-occurrence networks in various disease states, and deriving effective therapeutics from these. Takeda is driven by the hypothesized mechanism of disease: either bugs as drugs, or (in the case of their collaboration with Enterome), drugs for/from bugs. She listed approaches in the industry, in increasing order of R&D complexity: fecal microbiota transplantation, bacteriophage engineering, bacterial consortia, engineered bacteria, single strain commensal bacteria, and small molecules.

Morten Isaksen of Bio-Me spoke on “Positioning microbiome analysis for use in precision medicine”. The company has developed a platform that does precision microbiome profiling (species/strain level) and direct quantification reads in less than a day. Isaksen described a demonstration study on diet: subjects consumed their normal diet for 4 weeks, then changed their diet in some way for the next 4 weeks—for example, consuming more fiber or changing sugar consumption. Bio-Me carried out daily sampling of fecal microbiota and found, interestingly, that after an initial microbiome change (after 3-5 days) there tended to be a rebound to pre-intervention levels of bacteria. Follow-up work will try to uncover the cause of this phenomenon.

Skin microbiome

Kausar Malik of Amway Corporation presented “The Cinco de Mayo Study: A one-year longitudinal study of the facial skin microbiome in normal healthy adults”—a project done in collaboration with the Microbiome Insights team. Malik described how bacterial species on the skin vary depending on the environment (e.g. moist or dry); the study aimed to find out the stability of the skin microbiome in a large population of healthy individuals over time, in order to begin identifying biomarkers of skin aging. In addition to skin swabs, they looked at red spots, wrinkles, brown spots, skin elasticity, barrier function, and surface pH. They found no significant change in alpha diversity over time, although some individuals showed a change in microbiome diversity on the cheek. Corynebacterium increased with age, and was also correlated with higher redness (in line with other published work).

Day 2

Microbiome

Eric Pamer of Memorial Sloan Kettering Cancer Center gave a keynote address on “Microbiota-mediated defense against intestinal infection”. His research focused on patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT): these patients receive antibiotics, chemotherapy, and radiation, and mortality is high in the case of bloodstream infection caused by vancomycin-resistant enterococcus (VRE). Given that the microbiome normally eliminates persistent VRE, the question is whether there’s a way to eliminate VRE in allo-HSCT patients. Pamer and colleagues showed that with a fecal transplant in these patients they re-established almost all the normal microbiome components—but which bugs were causing clearance of VRE? The researchers used particular bacteria and did a dilution test to examine the clearance of VRE. Blautia producta were the only bacteria that caused complete inhibition. When they looked into what Blautia producta expresses that none of the others do, they found it encodes a lantibiotic operon; these lantibiotics can also be expressed by anaerobes living in the colon.

Peter Spanogiannopoulos of UCSF was next up, with “The metabolism of fluoropyrimidine anticancer drugs by the human gut microbiome”. He cited work showing that Proteobacteria can inactivate 5FU—and noted that, fortunately, there is a lot about Proteobacteria in literature. He and his colleagues in the Turnbaugh lab are looking to answer the question: can probiotics rescue toxicity? One day they hope to sequence someone’s microbiome before administering anticancer drugs, in order to assess the pharmacokinetics.

Pierre Belichard of Enterome spoke on “Building the leading microbiome-derived immunotherapy company”. He explained that Enterome, a spin-out of MetaGenoPolis in France, is focused on determining function of the microbiome in cancer and inflammatory bowel disease. They are developing everything except ‘live biotics’—and their multiple programs are currently in various stages: for instance, glioblastoma and solid tumors (phase 1); Crohn’s disease (phase 2). They work on epitope mimicry to trigger an anti-tumor T-cell response, ‘waking up’ existing dormant T-cells in the gut lining to activate the biggest group of T cells in the human body. Their work in animal models has established this and they are now carrying it through in clinical trials with humans.

The next event in the microbiome track was a panel discussion led by Microbiome Insights CEO Malcolm Kendall: “Where the money is going and where the money will be made: The unique perspective of venture capitalists”. On the panel were Asish Xavier of J&J Innovation and Denise Kelly of Seventure. In response to an audience question, the panelists emphasized that they look carefully at every company that comes through the door; sometimes they ask for more information or progress and a company comes back later having secured a better position. Kendall asked the panelists the key things they look for in a company, and Kelly responded that the number one factor is top-notch science: validated and preferably peer-reviewed. Then comes intellectual property: who else is competing, and what makes the company different? Third is the business team and the research team. Xavier agreed, adding that the science may be very interesting but the key is whether it is translatable.

Timing is another factor: Xavier says he has seen companies take 20 years to bring something to market. He said timing is critical for a company—so sometimes he explores whether they can build a small product to bring to market while working on a larger one.

Kendall asked the panelists how they think microbiome science is progressing. Xavier acknowledged a lot of good science emerging—with an exponential number of publications—but not all of the ideas can be translated into a drug. The science only has potential as a company if you can get to phase 3 and beyond. Most times the drugs will be advanced by a bigger company because of regulatory challenges so the start-ups will have to partner at some point in their existence. Kelly agreed, and noted that over the past five years we have seen a massive capitalization of the scientific progress.

For more on the conference talks, see #MicrobiomeProbioticsForum on Twitter.

Microbiome Movement Skin Health & Dermatology Conference Summary: Days 1 & 2

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.

Pre-conference workshop

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:

  1. 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).
  2. 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.
  3. 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:

  1. 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.
  2. 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.
  3. ‘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.

Highlights of the Microbiome Drug Development Summit 2018 in Boston

Development and commercialization of microbiome-based therapeutics was the focus of a recent event in Boston (USA): the Microbiome Drug Development Summit 2018, organized by Hanson Wade. The Microbiome Insights team was in attendance – and here we share some of the highlights from this exciting event:

DAY 1

Jennifer Wortman, Senior Director, Bioinformatics, Seres Therapeutics

Unraveling Microbiome Signatures for Drug Design

Seres Therapeutics, one of the top 5 microbiome biotechnology companies in the world by funding, has a robust microbiome development pipeline. Their approach for addressing disease is to supply bacterial species that are associated with health in an attempt to change disease course.

Wortman explained the company has an extensive strain library isolated from healthy donors. They design consortia for their treatments using in silico design models (e.g. species and functions to reduce inflammation and increase epithelial barrier integrity) and by looking at species that are naturally co-occurring.

One product, SER-287, is an orally delivered community of purified Firmicutes spores associated with gastrointestinal health; it has efficacy in mild to moderate ulcerative colitis and is currently in phase 2B clinical trials. No serious drug-related adverse effects were noted in the trials. Research on SER-287 looks at engraftment: which species were absent at baseline but present after treatment? In all groups, they have seen engraftment of the spore-forming species following treatment: 19 species were more prevalent in patients achieving clinical remission; 13 species were more prevalent in patients not achieving remission.

Julia Cope, Director Scientific Operations, Diversigen

Microbiome Tools and Trends for the Pharmaceutical Industry

Cope spoke about the process for developing drugs to address various microbiome-linked diseases, including obesity, IBD, and cancer. To treat a disease, you need to know what to target. She cautioned that not all targets are likely to be bacterial in origin; researchers should also pay attention to viruses or fungal members of the microbiota.

Cope gave an example of four different studies that revealed four different microbiome-disease associations: taxonomy was similar but the specific biomarkers were different. She advised integrating as many cohorts as possible in order to prevent confounds.

Cathryn Nagler, President ClostraBio & Professor, University of Chicago

The Gut Microbiome, Immunity, and Allergic Disease

Nagler’s central question was whether we’ll be able to develop new microbiota-based strategies to regulate or prevent food allergies. She explained that certain populations of bacteria (classified as clostridia) make barrier-protective cytokines; they also stimulate the production of mucus, antibacterial peptides, etc.

Nagler’s data showed that lactobacilli were depleted in infants allergic to cow’s milk, with an increase in microbes that typically characterize an adult microbiome. Treatment with LGG increased tolerance of cow’s milk in these infants, and increased fecal butyrate. ClostraBio is engineering synthetic drugs to mimic the protective function of the health-associated bacteria.

Mark Smith, CEO Finch Therapeutics Group

Leveraging Reverse Translation to Develop Microbial Therapies

Smith described how broad-spectrum microbial interventions (i.e. fecal microbiota transplantation, or FMT) have good safety profiles in different therapeutic areas. Finch is using data from FMT trials to identify the bacteria linked with positive clinical outcomes, and then making these into bacterial cocktails for the treatment of disease. Smith described their product FIN-524 (developed with Takeda)–noting the challenges in understanding which organisms are driving the response.

An afternoon panel discussion, called Clinical Development of Microbiome-Based Therapeutics, covered a range of questions: clinical trial design in the development of microbiome-based therapeutics; key learnings from existing clinical programs for these therapeutics; and the relative importance of clinical efficacy and mechanism of action.

The panel discussed ‘hype’ in the media: some outlets inflate the importance of the scientific results, but companies need to temper the enthusiasm and stay focused on robust science. As for health professionals, they may be aware of this area but they are uncomfortable talking to patients about it until new products are approved and released into the market.

Regulation was another topic of interest: in particular, the need for flexibility in regulating new microbiome-related drugs. Panelists noted that there’s very little guidance in both the US and Europe, and it might make sense to develop guidelines or have guidance to expedite the development of some of these products. The Parallel Scientific Review is one mechanism that could help.

DAY 2           

Evgueni Doukhanine, R&D Scientist, Microbiome, DNA Genotek

Establishing Techniques for Reproducible and Insightful Microbiome Studies

Doukhanine discussed the necessary steps to design microbiome studies for scalability and innovative analysis. Many people pay attention to the sequencing technology—but the bioinformatics pipeline is also a very important factor. For 16S, they have seen that depending on the bioinformatic pipeline, the relative abundance recovery is quite different. DNA Genotek has moved from collection kits into study design consultation.

Phil Strandwitz, Co-founder & CEO, Holobiome

GABA-Modulating Bacteria of the Human Gut Microbiota

Strandwitz gave an overview of the microbiota-gut-brain axis and described the identification of a bacterium from the human microbiota that’s completely dependent on GABA for growth; Holobiome is using it to identify and culture a panel of diverse GABA-producing bacteria with the hopes that they can modulate levels of this important neurotransmitter.

4th Annual Translational Microbiome Conference: Day One Summary

The Microbiome Insights team is pleased to be exhibiting at the 4th Annual Translational Microbiome Conference in Boston! The first day of the main program was filled with talks that covered an excellent breadth of topics having to do with the microbiome field.

Beyond sequencing

A highlight of the morning was a lecture by Peter Christey (Co-Founder and CEO of General Automation Lab Technologies, or GALT) on “Going Beyond Sequencing – New Research Tools in the Era of the Microbiome”. Christey explained that next-generation sequencing provides an amazing window into the microbiome, but it does have its limitations. Comparing cultures with culture-independent techniques on the same sample shows that adding a small cultivation step in the process allows observation of many more OTUs per sample. Christey argued that for the best insights, a mix of old and new techniques is necessary—both next-generation sequencing and wet lab techniques.

Precision medicine

Morten L. Isaksen (CEO of Bio-Me AS) then spoke about “A Microbiome-based Approach to Precision Medicine and Personalized Nutrition”. Isaksen described GutCheck—a gut health test that can be combined with data from biobanks that are available. The company links a person’s profile with several medical databases to gain insights on how the microbiome relates to drug consumption and other factors.

Main track: Skin microbiome & cancer immunotherapies

From there, the sessions separated into two tracks: a main track and a consumer track. In the main track, audience members heard from Travis Whitfill (Co-Founder and CSO of Azitra, Inc) on “Translational Challenges in the Skin Microbiome”. Whitfill emphasized the need to eliminate the idea of ‘good’ bacteria and ‘bad’ bacteria, arguing the importance of knowing bacterial strain characteristics.

Vancheswaran Gopalakrishnan ( Translational Scientist, Computational & Analytics Support, & MD at Anderson Cancer Center, The University of Texas Health Science Center at Houston) spoke about a hot area: “Impact of Microbiome on Immunotherapy Response”. Gopalakrishnan is working with Seres Therapeutics to identify whether fecal microbiota transplantation, compared to probiotics or lifestyle changes, is the best way of shifting the microbiome into a state associated with a favorable response to cancer immunotherapies. This talk was followed by a panel with Gopalakrishnan and others on immunotherapies and the microbiome, moderated by Take Ogawa (Director, Business Development, Second Genome). Panelists discussed the need to find out what is happening mechanistically in the individuals who respond favorably to immunotherapies. Bernat Olle (CEO, Vedanta Biosciences) outlined the need for harmonizing the observations on which microbe communities might drive the response.

Gut microbiome modulation

Continuing after the lunch break, the talks in the main track turned to microbiome modulation. Mark Smith (CEO, Finch Therapeutics) presented on “Reverse Translation for Therapeutic Development in the Human Microbiome”. He described the dual approach of delivering entire microbial communities to individuals in order to have immediate efficacy, and then working to modulate the microbiome over time.

Next, Assaf Oron (CBO, BiomX) spoke about “A Novel Therapeutic Approach To IBD Through Microbiome Modulation”. Oron explained some individuals with IBD have bacteria residing in the body that bring about flare-ups. So when they come into the clinic they are asked to take a fecal sample; the company tests the pro-inflammatory bacteria and then introduce a phage to eradicate them. They take into account geography, microbiome, and clinical phenotype. At present, a topical gel containing a customized phage cocktail to modulate the skin microbiome is going through clinical trials.

Later in the day, David Kyle (CSO, Evolve Biosystems) spoke about going “From Dysbiosis to Recovery in the Infant Gut Microbiome”. He covered the differences observed in the microbiomes of infants today as compared to previous decades, and how the company is developing solutions to help human milk oligosaccharides (HMOs) be digested by bacteria in the infant digestive tract, thereby elevating the beneficial short-chain fatty acids acetate and lactate in the i

Banff Keystone Symposia on Gut Microbiota: Day Three Summary

Wednesday was the third day of the joint Keystone Symposia in Banff, Canada: (1) “Manipulation of the Gut Microbiota for Metabolic Health” and (2) “Microbiome, Host Resistance and Disease”, and the great talks kept on coming!

One track opened the day with a group of lectures on nutrition and gut microbiota. Jens Walter (a local, from University of Alberta) talked about modulation of the human gut microbiota with non-digestible carbohydrates—taking an ecological perspective. Then Nathalie Delzenne (Université catholique de Louvain) spoke about the links between prebiotics, gut microbiota, and human health, describing her intervention study on increasing inulin-rich vegetables in the diet. On the mechanism side, André Marette (Université Laval) described mouse work on the interaction between dietary polyphenols—for example, arctic fruit extracts—and the gut microbiota to alleviate obesity-related diseases. And regarding the early life period in humans, Maria Carmen Collado gave an apt overview of what we know about how the maternal microbiome (in breast milk especially) affects the infant gut microbiome and health. Meanwhile, in the other track, the account by Kerwyn Casey Huang (Stanford) of how the gut microbiota can be resilient to perturbations proved popular.

At 5:00 pm the action continued with a track on xenobiotics-microbiota interactions in metabolic diseases and another on disease tolerance, pathology, and the microbiome. In the latter, Yasmine Belkaid (NIAID, NIH) spoke about her extensive work on control of skin tissue immunity and repair by the microbiota, discussing how homeostatic immunity to the skin microbiota occurs through diverse mechanisms that may or may not involve inflammation. Janelle S. Ayres (Salk Institute) then talked about what she has learned about host-microbe interactions (and adaptations); she described her mouse model findings on how micronutrients—for example, iron—mediate healthy host-pathogen interactions.

Thursday will be the last day of these joint conferences! But don’t forget—you can still re-live the action on Twitter by searching the conference hashtags, #KSmicrobiome and #KSgut.

Banff Keystone Symposia on Gut Microbiota: Day Two Summary

March 6, 2018 marked the second day of the joint Keystone Symposia in Banff, Canada: (1) “Manipulation of the Gut Microbiota for Metabolic Health” and (2) “Microbiome, Host Resistance and Disease”.

Morning sessions were split into two tracks. The first track covered microbiota and metabolic disorders, with two initial talks by François Leulier (Institut de Génomique Fonctionnelle de Lyon) on gut microbiota and host mutualism in chronic undernutrition, and Emily P. Balskus (Harvard University) on microbiota-drug interactions.

The complex development of early life gut microbiota and immune function was the topic covered by the second track. Maria Gloria Dominguez-Bello (Rutgers University) gave an overview of what we know about how C-section birth is linked with later-life disease through the gut microbiota, showing the associations that exist in human populations and the causal evidence that exists in mouse models. Andrew J. S. Macpherson (University of Bern) then gave a detailed account of early postnatal innate immune development, showing how the site of microbe administration shapes distinct repertoires of IgA and IgG antibodies from mature B cells, and how these antibodies are found in several sites through the host. Subsequent talks branched out to other immune-related topics linked to skin commensals, and also the gut-brain axis (i.e. a gut bacterial metabolite that causes behavioural abnormalities related to anxiety and autism spectrum disorder).

The evening’s sessions were divided into one track on gut barrier alterations and host metabolic disorders, and one on mechanistic microbiome function in physiology and aging. A highlight of the evening was the account given by Lora Hooper (University of Texas Southwestern Medical Center) of mechanisms linking circadian rhythm with adipose tissue development: in mouse models, she found a conventional microbiota drives immune system regulation of circadian rhythms, resulting in more long-chain fatty acid uptake on a high-fat diet, and ultimately an increase in adipose tissue. Participants in the evening session also heard a talk by Michiel Kleerebezem focusing on the microbiota of the small intestine and how a robotic capsule can be used to track the effects of a dietary intervention.

We’ll be tweeting again on Wednesday! Look for the conference hashtags, #KSmicrobiome and #KSgut.

Banff Keystone Symposia on Gut Microbiota: Day One Summary

Gut microbiota researchers from across the globe gathered in Banff, Canada for two joint conferences: (1) “Manipulation of the Gut Microbiota for Metabolic Health” and (2) “Microbiome, Host Resistance and Disease”. On day one of the conference—March 5, 2018—all sessions were held concurrently.

For several human diseases, observed differences in gut microbiota composition between disease populations and healthy controls are well known. What’s of greater interest is mechanism: the steps causally involved in disease pathogenesis or maintenance. On March 5th, to a packed room, the presenters delved deep into the gut-microbiome mechanisms responsible for human disease states ranging from obesity and diabetes to cardiovascular disease.

The morning sessions focused on the mechanisms of pathogen infection as well as obesity and type 2 diabetes. In the keynote address, Andreas J. Bäumler (University of California, Davis) gave a detailed account of something that could be a driver of gut dysbioses: oxygen becoming available to gut pathogens. Then Fredrik Bäckhed (University of Gothenburg) described how a bacterial metabolite—imidazole propionate—may be related to type 2 diabetes, and Liping Zhao (Shanghai Jiao Tong University & Rutgers University) delivered a talk on various aspects of the gut microbiota in obesity, underscoring the necessity of considering microbial ecology.

After an afternoon workshop by Microbiome Insights’ Scientific Advisory Member Curtis Huttenhower (Harvard), which gave an overview of different microbial community analysis workflows, the afternoon sessions focused in on the gut microbiota’s role in the control of fat metabolism. The wide-ranging topics covered how the gut microbiota may be involved in liver disease pathogenesis; how cold temperatures transform fat (a process called “browning”) in order to use more energy and decrease adiposity; and extensive work from the lab of Patrice D. Cani on the endocannabinoid system and how intestinal NAPE-PLD appears to be a key sensor controlling food intake and energy metabolism upon fat exposure.

Follow our Twitter feed tomorrow — and don’t forget to check out the hashtags #KSmicrobiome and #KSgut for more of the action from the Banff Keystone Symposia!