New publication from Mohn Lab shows diversity and significance of steroid-degrading bacteria is largely underestimated

Steroids in the environment accumulate from both natural and anthropogenic sources. Cholesterol, for example, is an essential part of cellular membranes and a natural source of steroids in the environment. Anthropogenic sources include steroid hormones associated with birth control pills. Regardless of where they originate, however, steroids have been found to accumulate in soil, wastewater treatment plants, and aquatic environments, where even at low concentrations they have negative impacts on animals—including humans. So far, only a few types of bacteria are known to degrade steroids in the environment and these species will play a big role in regulating steroidal pollution and its impacts.

To better understand the distribution and ecological significance of these steroid degraders, researchers from the Canadian universities of British Columbia and Waterloo, along with collaborators from Georgetown University in Washington, set out to apply a metagenomics approach to studying these bacteria. This approach uses DNA sequencing to find genes from the 9, 10-seco pathway responsible for steroid degradation in environmental samples and not the bacteria itself. The team then builds phylogenies to find the bacteria according to the phyla in which these genes occur.

The results of this paper supported earlier work showing that bacteria using the 9, 10-seco pathway belong to the Actinobacteria and Proteobacteria phyla. Members of both phyla coexist in wastewater, while species of Actinobacteria alone are found in soil and rhizospheres. While the complete set of genes used in this pathway were not assigned to any other phylum, evidence for steroid degradation ability was found for the first time in the alphaproteobacterial lineages Hyphomonadaceae, Rhizobiales, and Rhodobacteraceae, as well as the gammaproteobacterial lineages Spongiibacteraceae and Halieaceae. Actniobacterial degraders were found in the deep ocean samples while alpha- and gammaproteobacterial degraders were found in other marine samples, including sponges. Furthermore, the authors confirmed that the steroid-degrading bacteria from sponges, Spongiibacteraceae and Halieaceae, catabolize steroids.

The metagenomics approach is a useful one because many bacterial species cannot be cultured and identified directly. However, the techniques involved in DNA extraction and sequencing have inherent biases that cannot be avoided. It is therefore important to note that the absence of steroid degradation proteins from a sample does not definitely mean that the bacteria are not present. Despite this potential underestimation, this study is, according to researchers, “the first analysis of aerobic steroid degradation in diverse natural, engineered, and host-associated environments via bioinformatic analysis of an extensive metagenome data set.” Not only does this confirm the usefulness of the technique; it also demonstrates that the ecological significance and taxonomic and biochemical diversity of these bacteria have been largely underestimated.

Holert J, Cardenas E, Bergstrand LH, et al. Metagenomes reveal global distribution of bacterial steroid catabolism in natural, engineered, and host environments. MBio. 2018; 9: e02345-17.

Why and how do scientists study the microbiome? Highlighting the Microbiomes in Transition Initiative [VIDEO]

Microbiome Insights co-founder Dr. Bill Mohn chairs the Advisory Board to the Microbiomes in Transition (MinT) program at the Department of Energy’s Pacific Northwest National Laboratory (PNNL). In this video, our Scientific Advisory Board member Janet Jansson, Senior Microbial Scientist at PNNL, discusses how microbes affect human and environmental health.

Microbiomes exist everywhere, both in nature and within and on humans. The microbiomes of every human or ecosystem play a significant role in maintaining their proper function. Now, due to recent technological breakthroughs in sequencing and computing we are able to begin to characterise these organisms and their impacts.

Soil, for example, is one of the most diverse microbial communities on the planet and has traditionally been difficult to characterise. Understanding the microbial make-up of different soils like the permafrost, which currently has trapped within it vast amounts of carbon, will be crucial to understanding how, with warming temperatures, microbes will begin to degrade this carbon and release CO2. Within humans too, understanding the newfound correlations between the microbiome, diet, and certain diseases could constitute a huge step towards better health. To process all of this information strong analytic systems and supercomputing devices are required.

 

Publication from Mohn Lab assesses genetic potential of the forest soil microbiome post-harvesting

Harvesting trees from forests, even when replanting efforts are made, has a huge impact on the long-term functioning of the soil microbiome. The unique microbial community in the soil performs essential tasks like decomposing plant material, which recycles nutrients for new plants to use. Plus, these microbes play vital roles in nutrient cycling such as the carbon and nitrogen cycles. To better understand the effects that removing organic matter (harvesting) has on the capacity of the soil microbiome to perform these duties, researchers from the University of British Colombia and the Georgia Institute of Technology assessed the genetic potential of soil communities for biomass decomposition and nitrogen cycling in harvested sites across North America, each representing a unique ecozone.

Using study sites and designs from the Long Term Soil Productivity Study, established during the 1980s, the researchers used shotgun metagenomic sequencing to quantify the diversity and abundance of genes essential to the microbial community’s decomposition and nutrient cycling functions. Harvesting and replanting occurred roughly ten years prior, with three different levels of organic material being taken at each site: stem-only harvesting, whole-tree harvesting, and whole-tree harvesting plus forest floor removal.

Harvesting overall played a role in altering the soil gene profiles, but the level of organic matter harvested did not. Researchers observed a reduced relative abundance of carbohydrate active enzymes genes—which are important for decomposition—and an increase in the abundance of nitrogen cycling genes. However, the increase in nitrogen cycling genes did vary by ecozone, suggesting ecozone-specific nutrient availability plays a role in the sensitivity of the carbon and nitrogen cycles to harvesting.

This was the first large-scale metagenomics study looking at the effects of harvesting on the potential for soil communities to perform some of their natural functions. The team believes that these changes could have an affect on forest productivity as trees grow and their nutrient demand increases, and may also alter a forest’s ability to resist future perturbations. According to the researchers, “our results suggest a mechanism by which harvesting can exacerbate nitrogen losses at sites predisposed to such losses, potentially lowering plant productivity and increasing greenhouse gas emissions.”

Cardenas E, Orellana LH, Konstantinidis KT, Mohn W. Effects of timber harvesting on the genetic potential for carbon and nitrogen cycling in five North American forest ecozones. Sci Rep. 2018; 8: 3142.

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.

Rethinking germs: Healthy living with our microbes [VIDEO]

In this series of videos, Microbiome Insights co-founder Dr. Brett Finlay, along with Dr. Jennifer Gardy, answers questions about the microbiome and its role in human health and development—making a case for rethinking what it means to live a healthy lifestyle.

Rethinking germs: Healthy living with our microbes Part 1 Q&A

https://www.youtube.com/watch?v=OzOHeyq53FU

Topics addressed in Part 1 of the Q&A session include:

  • How clean should we be? Finlay says we don’t need antibacterial soaps, nor do we need to sterilize our homes. In general, just keeping the numbers of microbes in your home down is enough. In certain cases, more cleaning is necessary: when getting rid of mold or when cooking raw meat, for example.
  • How do we receive our first dose of microbes? From our mothers during birth. This initial microbial community has effects on early life development.
  • Is coffee bad for the microbiome? And how does diet affect the microbiome?
  • How is inflammation related to health and aging? Finlay gives an example of how Parkinson’s disease may actually originate in the gut.

Rethinking germs: Healthy living with our microbes Part 2 Q&A

https://www.youtube.com/watch?v=ldIuwecaKGU&t=32s

In Part 2 Finlay discusses:

  • How do early life microbes influence allergies and asthma? He explains that they shape the immune system; he describes some early results of research into timing of exposure to common allergens like peanuts.
  • Should we let kids be dirty? Finlay talks about the importance of kids’ exposure to the world and its microbial environments, a topic that’s detailed in the book he co-authored, “Let Them Eat Dirt”.
  • Probiotics and prebiotics—what are they and what do we know?
  • How important is diet for maintaining a healthy microbiome? Hint—the white sugar and white flour diet is not ideal.
  • What will be the focus of personalized medicine in future?
  • What threat do antibiotics pose?

Rethinking germs: Healthy living with our microbes Part 3 Final Thoughts

https://www.youtube.com/watch?v=jZ6rGcR1x9g

Finlay gives a final bit of advice on taking care of our microbiomes: it’s really important to make sure our hygiene practices and products like antibacterial soaps are used appropriately: for example, in cases where infection control is required or when dealing with vulnerable groups like seniors.

He advises not be alarmed by the microbial world—but rather, to recognise and respect the organisms living on and in you because they are part of what makes you who you are.

PRESS RELEASE: Rebiotix and Microbiome Insights collaborate on a microbiome IBD tool for clinical development

Recent study provides proof of concept for using novel scoring system to define IBD-related changes in microbiome

With a growing body of science linking gut microbiota to inflammatory bowel disease (IBD), a need exists in clinical settings to understand changes in the gut microbial community as they relate to IBD and its management.
Two leading microbiome companies, Rebiotix (part of the Ferring Pharmaceuticals Group) and Microbiome Insights, are collaborating to validate one such tool: a proprietary analysis to determine how closely a patient’s microbiome resembles that of someone with IBD. Microbiome Insights’ bioinformaticians developed an IBD Microbiome Score, based on a vast dataset of over 1600 individuals with IBD and healthy controls. The metric combines the latest understandings of the gut microbiome as a complex ecosystem with information on hundreds of taxa in the bacterial community, rather than the presence or absence of specific taxa. Based on fecal microbial characterization by sequencing, the IBD Microbiome Score can be assigned for each individual patient at diagnosis and at different times throughout treatment, making the Score practical for clinical use. Leveraging Rebiotix’s proprietary Microbiota Restoration Therapy™ (MRT) drug development platform, the Score is being evaluated in active clinical trials to treat IBD.

“The microbiome field is enormously complex,” says Dr. Ken Blount, Rebiotix’s Chief Scientific Officer. “With the use of the first-in-class Rebiotix MRT platform continuing to expand into complex conditions such as IBD, it is critical to have strong, scientifically-validated tools to understand the dynamics of the microbiomes changes within our patients. We’ve seen first-hand how the novel platform and expertise of Microbiome Insights has the potential to rapidly advance not only our understanding of the impact of MRT on patients, but also to uncover valuable microbiome findings for the entire industry.”

“Our scientific team has consulted with leading gastroenterologists to explore ways of leveraging the science on the microbiome and IBD in the clinical setting,” says Microbiome Insights CEO Malcolm Kendall. “Now we have developed the first scientifically robust tool for tracking the microbiome of people with IBD and understanding its link to clinical outcomes. The ability to work with Rebiotix on this path to discovery underscores the future utility of our platform in the clinical setting.”

The companies are continuing to explore applications of Rebiotix interventions and Microbiome Insights’ personal health platform in other microbiome-related diseases.

About Rebiotix
Rebiotix Inc., part of the Ferring Pharmaceuticals Group, is a late-stage clinical microbiome company focused on harnessing the power of the human microbiome to revolutionize the treatment of debilitating diseases using drug products built on its pioneering Microbiota Restoration Therapy™ (MRT) platform. The MRT platform is a standardized, stabilized drug technology that is designed to rehabilitate the human microbiome by delivering a broad consortium of live microbes into a patient’s intestinal tract via a ready-to-use and easy-to-administer format. For more information on Rebiotix and its pipeline of human microbiome-directed therapies, visit www.rebiotix.com.

About Microbiome Insights
Microbiome Insights, Inc. is a global leader providing end-to-end services for microbiome DNA sequencing, including state-of-the-art bioinformatic analysis. Based in Vancouver, Canada, the company’s customized suite of services enables researchers and clinicians to easily and effectively include microbiome analysis in studies across a range of human, animal, agricultural and environmental applications. The multidisciplinary team of researchers and knowledge leaders at the company provide access to decades of expertise in traditional sciences such as ecology, microbiology, infectious diseases, and genetics. Microbiome Insights’ award-winning team is committed to providing clients with fast, dependable, cost-effective results.

See the original Business Wire press release here.