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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.

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

How close are microbiome-modulating therapies that target the brain? A quick overview of the evidence

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.

Anorexia nervosa

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.

Multiple sclerosis

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.

Depression

A high level of evidence links gut microbiota with depressive symptoms; probiotics may improve depression in both humans and animals.

Anxiety

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.

Fatigue

Extreme fatigue may also be linked with the gut microbiota, although diet appears to be a major confounding factor and more research is required.

Parkinson’s disease

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.

Alzheimer’s disease

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.

microbiome insights CEO

CEO Malcolm Kendall

About the company

Microbiome Insights provides state-of-the art microbiome analysis and bioinformatics.

Our end-to-end service starts with experimental design and sample collection and extends to data analysis and bioinformatics interpretation.

Microbiome Insights is focused on providing our clients with a deeper understanding of functions and interactions of microbial communities across a range of human, animal, agricultural, and environmental research applications. Our team of experts and testing methods combine to provide fast, dependable, cost-effective results with highly comprehensive, publication quality bioinformatics. To learn more, see here.