Today, I live tweeted from the 4th Annual North American Microbiome Congress, in Washington DC. Here are my tweets, nicely bundled for you, per talk.
In about 30 min, I will start live tweeting from the 4th Kisaco North American Microbiome Congress in Washington DC. @MBCongress @KisacoRes
Get your coffee ready and hear about the latest in Microbiome Research!
While I am going to grab a coffee, get ready for the morning session at the DC Microbiome Congress @KisacoRes with Jo Handelsman @Jo_Microbe and Jeff Leach.
Opening remarks by David Kyle, Evolve Biosystems
David Kyle of @EvolveBio will be the chair of this morning, and welcomes us all. He reminds us about all the great research that came out in the last decade.
David Kyle: The gut microbiome is sort of a complex organ that needs to be fed well. We sometimes damage it by antibiotics – which we should not eliminate, because they save lives! How can we return it to its original state after the use of antibiotics?
David Kyle: The first 100 days of life are fascinating. Immune system is learning what is self or not, microbiome is forming – infant nutrition is important.
David Kyle: In this congress we will hear about the impact of the microbiome on many aspects of physiology, skin, gut, brain. The microbiome has in impact on our whole body, this is a multidisciplinary field.
David Kyle: Let’s recognize that we are all students. We are all here to learn about this rapidly changing field. Please engage in questions! And make sure to network, and challenge each other. Let’s make this a melting pot of thoughts.
Jo Handelsman, Wisconsin Institute for Discovery – Welcome Address
Next up is Jo Handelsman @Jo_Microbe @jo44atWID @WIDiscovery who starts off with some remarkable words: “The most valuable citizen of the Earth was the microbe” – written by Mark Twain in “My 3000 Years with the Microbes”
Jo Handelsman: Catching up with Mark Twain: The number of microbiome publications and investment has increased incredibly. The White House Microbiome Initiative from 2016 played a big role.
Jo Handelsman: Microbes are connected to many different diseases, either being protective or associated. For example, work from the Jeff Gordon lab doing microbiome transfers from obese humans to germ-free mice.
Jo Handelsman: The microbiome plays roles in most chronic diseases. Most stunningly and un-anticipated, there are associations between the microbiome and the brain. Depression, autism, Alzheimers, have all been linked to microbiome composition.
Jo Handelsman: These diseases can e.g. be transferred by fecal transplants to mice. Extensive research going on in all these fields.
Jo Handelsman: One of the challenges is that the microbiome is very hard to change. It is resilient. Metchnikoff consumed liters of yogurt and found Lactobacillus, but it disappeared after he stopped eating yogurt.
Jo Handelsman: There are of course ways to change the microbiome, such as fecal transplants, phages, probiotics, prebiotics. But we don’t yet understand the basis for community robustness, the resistance to change, or resilience (change but then snap back).
Jo Handelsman: We launched the White House National MIcrobiome Initiative in 2016 under the Obama administration, to fund basic research on the microbiome.
Jo Handelsman: The White House Microbiome Initiative evolved around two basic questions:
1. What is a healthy microbiome? Is a change after a perturbation good or bad? Parallels with changes in water microbes in Gulf of Mexico after Deepwater Horizon oil spill.
Jo Handelsman: 2. How do we change a microbiome? Can we restore a microbiome after a perturbation? Can we change it in a directional and predictable way?
Jo Handelsman: National Microbiome Initiative goals: interdisciplinary research on fundamental questions about diverse microbiomes, different environments, but we all have the same questions. Also, to develop new platforms and tools to probe microbiomes.
Jo Handelsman: Of course, we hoped for practical outcomes to improve the health of humans, animals, agriculture and environmental habitats.
Jo Handelsman: We need to understand how to alter microbiome predictably and reliably, understand robustness, and develop predictive models for microbiome behavior.
Jo Handelsman: Do not only look at human microbiome studies, we need to broaden our view to other fields (plant, animal, environmental) to learn about the principles that govern microbiome composition and robustness.
Keynote lecture by Jeff Leach, Human Food Project
Next up: Jeff Leach, founder of the Human Food Project. @humanfoodproj with “Re-becoming Human”.
Jeff Leach: I got interested in the microbiome, and asked the question: why is no one working in Africa? We started a project on hunter gatherers. We are going to talk about poop today (shows image of elephant pooping).
Jeff Leach: The Hadza in Tanzania are hunter gatherers. Women gather tubers, men hunt for zebras etc. They are connected to nature in a way no one else is anymore. They live like humans lived for millions of years.
Jeff Leach: The Hadza eat a lot of birds, honey, baobab, berry and tubers. Depending on the season, they might eat honey for days in a row, and fiberfull berries.
Jeff Leach: They might eat 10-15 pounds of meat in a sitting, or 1000s of calories of honey. It can be very monotonous, and not what your nutritionist would recommend.
Jeff Leach: The women dig up tubers all day, every day. They taste like a sweet potato. (shows lots of pictures of Hadza and their food).
Jeff Leach: The vast majority of their calories comes from one type of food, lots of fiber. The kids’ bellies are swollen because of fermentation; they eat >100 gram of fiber (age matched kids in the US eat 10 grams).
Jeff Leach: We wanted to see what the Hadza microbiomes looked like. So we took lots of samples: 14,000 samples from skin and gut, but also of their food/environment. We freeze in the field in liquid nitrogen. Very difficult.
Jeff Leach: I spent many months there, not showering, drinking water from puddles, eating with the Hadza, but I never got sick. I sampled myself before/after these trips.
Jeff Leach: Our original question was to find out how seasonal changes affect the Hadza microbiomes. During wet season, their microbiome diversity drops, because they eat less meat (less contact with animal droppings).
Jeff Leach: Certain bacteria are coming and going, seasonably, but they are missing from western microbiomes.
Jeff Leach: Treponema, Akkermansia, Prevotella are much more common in non-industrialized communities.
Jeff Leach: The Hadza are connected to nature. They kill an animal, take out the colon, squeeze out the poop, and eat it. They don’t wash their hands, and then touch their children.
Jeff Leach: Their skin microbiome changes all the time because they touch and butcher and don’t wash their hands.
Jeff Leach: The average life expectancy of the Hadza is 36 years, mainly because of child mortality, but also of falling out of trees, shooting each other with poison arrows, and infections. But not because of obesity or poor nutrition.
Jeff Leach: The Hadza stand at the microbial highway of Africa. They come into contact with all microbes in their environment. Where do you stand, here in DC? Most of us spend >80% of our lives indoors.
Jeff Leach: Hadza men eat a lot more honey and meat than the women, but their microbiomes largely overlap. Most of their BMIs are around 20.
Jeff Leach showing the many differences between Hadza lifestyle and Western lifestyle.
Jeff Leach: The Hadza have twice the microbial diversity as most of us (except me). Their microbiome bounces back within 48h after antibiotic treatment. Very resistant and resilient microbiomes.
Jeff Leach goes way over time, but seems unstoppable.
Jeff Leach: We need new nutrition and health advice that does not focus on our food input but on our filters – our environment. We need more connections with nature.
Next up: Panel discussion: Pharmaceutical investment in microbiome therapeutics and strategizing ways to overcome the valley of death.
Daniel Couto @VedantaBio – moderator
James Brown @GSK
Dirk Gevers @dirk_gevers @JanssenGlobal
Arpita Maiti @pfizer
Arpita Maiti: At @Pfizer we look at the microbiome in a broad context – the data is not yet robust enough for us to make big investments. But this could quickly change in the next 12 months.
Dirk Gevers: @JanssenGlobal At the Janssen Human Microbiome Institute we invested in lots of research and partnerships – we have a very broad portfolio.
James Brown @gsk It is great to be looking at one particular small molecule but we probably need to focus more on consortia.
Question from the audience: Why aren’t there more physicians at these conferences? Or on panels?
Arpita Maiti @pfizer – we might still be very compartmentalized – the microbiome spans many disciplines.
Dirk Gevers @JanssenGlobal – many physicians are very involved. Scientists and physicians are including the microbiome in increasing number of clinical trials.
James Brown @GSK Most of our work is on clinical populations, not on animals. We need more interventional studies.
David Kyle, Evolve Biosystems
David Kyle: Breast milk is an important source of nutrition for babies. 85% of the nutrients in milk go into infant growth, 15% of the nutrients are HMO’s – this is the food for their microbiome.
David Kyle: Bifidobacterium infantis is the sole consumer of these HMOs (Human Milk Oligosaccharides). It converts indigestible HMOs into usable fuels: lactate and acetate. These reduce the fecal pH.
David Kyle: HMO + B. infantis provides pathogen colonization resistance to baby. In those first 100 days, the immune system is educated, so does not work properly. Breastmilk helps protect the baby, it is full of protective factors (IgA etc).
David Kyle: Most babies nowadays have highly variable microbiotas. Disrupted by c-section, antibiotics, formula feeding. How did baby poop look like 100 years ago?
David Kyle: There is a 1913 publication (W.R. Logan, J Path Bacteriol) that described almost pure culture of Gram-positive bacilli – which we believe were Bifidobacteria.
David Kyle: Several studies have described high amounts of Bifidobacteria in Bangladesh, Gambia, etc (80%). Much lower in western countries, and often not B. infantis.
David Kyle: Gut pH of infant stool in 1920s was 5.0. Now the pH is 6.1. Steady increase of pH in stools might be associated with the loss of B. infantis in baby stool.
David Kyle: The vaginal microbiome does not contain B. infantis, but mom’s stool might contain low amounts. This symbiosis is disrupted by formula feeding (no HMOs), C-section, antibiotics (B infantis is very sensitive to that).
David Kyle: IMPRINT trial (Smilowitz, Frese): B. infantis for 21 days in first weeks after birth. These babies got high levels of B. infantis, even after stopping the probiotics.
Persistence of Supplemented Bifidobacterium longum subsp. infantis EVC001 in Breastfed Infants
David Kyle: Significant different in stool composition (high Bifido, lower Klebsiella / Escherichia/ Clostridium/ Streptococcus) and HMO utilization between infants who did or did not receive the B. infantis.
David Kyle: Escherichia/Klebsiella/Clostridia break down mucin glycans (they eat it). B. infantis EVC001 binds to the mucin glycans, but don’t break it down, protecting the breakdown of the gut barrier.
David Kyle: Control babies (no B. infantis) showed higher inflammatory markers, such as calprotectin (high calprotectin can predict atopy/asthma at later age).
David Kyle: Are we remodeling the gut? Or “unremodeling”? Just restoring it to where it was 100 years ago?
Maxim Seferovic, Baylor College of Medicine
Next up is Maxim Daniel Seferovic @MaximSeferovic, Baylor College of Medicine, with “Our earliest microbial encounters and the developmental origins of disease”.
Maxim Seferovic: What are the long term consequences of early exposures to microbes? Genomic variation and epigenomics only partially explain diversity of human phenotypes.
Maxim Seferovic: Do microbial metagenomes contribute to our phenotypic diversity? Which factors, including maternal factors, determine microbial exposure early in life?
Maxim Seferovic: The vaginal microbiome is different during pregnancy – diversity is temporarily diminished during pregnancy (Pace, revised submission).
Maxim Seferovic: There is a mismatch of microbial taxa between the gut of newborns (first days of life) and vaginal bacteria. Are babies exposed to bacteria before birth?
Maxim Seferovic: The uterus (womb) is not sterile; it is open to the vagina. There might be microbial exposure to the developing fetus. Placenta functions as a conduit for microbial communication between mother and fetus.
Maxim Seferovic: We did in situ hybridization (amplified FISH) labeling of placental tissue. We found bacteria in roughly half of the placentas in cesarean, term, healthy pregnancies. Not in all tissues, though.
Maxim Seferovic: Meconium is different, while mouth/gut/nose of newborns look very similar. At 6 weeks old, microbiomes of newborns are diversified / differentiated.
Maxim Seferovic: We did not find any effect of cesarean delivery on community. See Chu 2017:
Maturation of the infant microbiome community structure and function https://www.nature.com/articles/nm.4272
Maxim Seferovic: Directly after delivery, neonates are seeded with maternal strains. These are gone after 6 weeks.
Maxim Seferovic: We confirmed in animal studies that placental sequences were different than those found in kit reagents. These are not contaminants.
Maxim Seferovic: Animal experiments: maternal high-fat diet alters the offspring gut microbiome from fetal life, onto adult life (in monkeys). Maternal factors (diet, breastfeeding) influence early exposures.
Amir Bein, Wyss Institue
I switched to Track 2 but the talk started too early so I missed half of it 😦
Amir Bein – Human intestine chip colonized with complex gut microbiome for in vitro disease modeling and drug testing
Actually, his talk is already finished. I only saw the last 2 slides. That is too bad – I had hoped to see more of it. 😦
OK, all of us from the other rooms complained, and Amir Bein is kind enough to give his talk again – Yay!
Amir Bein: Challenges in drug development: it costs a lot of money to do studies, and animal studies are difficult and not always good models for human disease.
Amir Bein: We built a microfluidic device with a membrane, that mimics a human lung, with different cells and media on different sides of the membrane. We can use this to study e.g. adherence of certain immune cells, and measure this with a microscope.
Amir Bein: shows videos of cells flowing over the chip, or adhering to it.
Amir Bein: We took this technique further to develop “organ on a chip” modules, such as the “gut on a chip”. Epithelial cells are seeded on a membrane, and fed with liquid flow. These develop vili-like structures.
Amir Bein: Mechanical cues are important. But we can also co-culture with microbes. We see that bacterial exposure increases the barrier functions. They change the morphology as well: higher villi.
Amir Bein: Inflammatory bowel disease model (Kim 2015, PNAS). We can also study protective effect of probiotic therapy. We can grow anaerobic bacterial communities on these chips too.
Amir Bein: We also developed a primary human small intestine chip, with beautiful villi. Transcriptomic analysis: it really resembles the duodenum much better than older models.
Amir Bein: We use this chip to study Environmental enteric dysfunction: stunted growth because of recurrent infections and poor nutrition.
Amir Bein: Doing all these complex studies would be very hard in most in vitro models, but this chip allows to study and measure many variants.
Amir Bein: It takes about 3-4 weeks to grow the complete organ/chip model. Thanks to the amazing team at the @wyssinstitute and the @gatesfoundation.
Nur Hasan, Cosmos ID
There are three parallel sessions to choose from but I will be live tweeting the talk by Nur Hasan, CSO of @CosmosID with “Unlocking the microbiome with bias-free, affordable, metagenomic sequencing and best-in-class cloud bioinformatics”
Nur Hasan: The microbiome is broadly implicated with health and disease. Therefore, it is a target for many diagnostic and therapeutic approaches. Interpretation of cause and effect, and understanding pathways all are still not well established.
Nur Hasan: You need to have high resolution strain-level data for better functional insight. A strain is the clinically informative and actionable unit, not a species.
Nur Hasan: Different Lactobacillus casei strains are used for making Wisconsin cheese, chardonnay wine, or yogurt. Same species, very different strains.
Nur Hasan: We offer end-to-end sequencing and analysis services, as well as bioinformatics analysis and visualization, even for people with little bioinformatics background.
Nur Hasan: There are several different next-generation sequencing methods – which method for which purpose?
Amplicon sequencing has served us well, but has limitations. Shotgun sequencing adds to specificity. Need good reference databases.
Nur Hasan: Within shotgun metagenomics, choice of sequencing depth depends on e.g. % host DNA, diversity in your sample, desired information, and purpose.
Nur Hasan: We have done lots of probiotics studies, which are very strain-specific.
Nur Hasan: We have developed large curated strain-level databases @CosmosID , and I invite everyone to try our tools online at app.cosmosid.com
Johan van Hylckama Vlieg, Chr Hansen
The second talk of this session will be by Johan van Hylckama Vlieg, @vanHylckama, VP of Microbiome & Human Health Innovation, @Chr_Hansen with “The microbiome as a source of next-generation probiotics and therapeutic microbes”
Johan van Hylckama Vlieg: I changed my title to “Microbes Matter – More than Ever”. I work for @Chr_Hansen, a company in Denmark, the largest producer of live bacterial cultures – for over 140 years!
Johan van Hylckama Vlieg: Food cultures and enzymes (mainly dairy cultures), health & nutrition, and therapeutics. We ship trillions of bacteria every day!
Johan van Hylckama Vlieg: Industrial production of bacterial cultures involves huge fermentors! Everything gets big at this scale. We also know a lot about dosage forms and stability e.g. at room temperature.
Johan van Hylckama Vlieg: More than 100y ago, Elie Metchnikoff postulated that supplementation of diet with lactic acid bacteria has health benefits, even if you cannot consume dairy products.
Johan van Hylckama Vlieg: Lactobacillus rhamnosus LGG was isolated from human gut in 1983, used worldwide for more than 20 years. Tested eg. in preterm infants, pregnant women, elderly. Prevents infections in children, and promising results in other fields.
Johan van Hylckama Vlieg: LGG produces pili important for mucus adhesion. However, genomic locus for these pili is absent in some strains – see:
Genome Instability in Lactobacillus rhamnosus GG
Luckily, in our production chain, the pili locus is present throughout. 🙂
Johan van Hylckama Vlieg: Given homology of LGG pili to Vancomycin-Resistant Enterococci (VRE) pili, it might be helpful in eradication of VRE infection. aem.asm.org/cgi/pmidlookup…
Johan van Hylckama Vlieg: The small intestine is a highly attractive target for probiotic interventions – much lower bacterial density.
Johan van Hylckama Vlieg: Much interest for the role of gut barrier function in maintaining health – and many in vitro models to study this. We are currently studying the effect of probiotics on aspirin-induced damage (ulcers).
Johan van Hylckama Vlieg: New probiotics (other than Lactobacillus and Bifidobacterium spp) are being investigated: Clostridium, Eubacterium, Faecalibacterium, Akkermansia, Christensenella spp.
Johan van Hylckama Vlieg: After the hype: more realism and managing expectations.
The Zmora 2019 paper gives an excellent overview on food as a modulator of the human gut microbiome.
Johan van Hylckama Vlieg: Dobzhansky 1973 said: “Nothing in biology makes sense except in the light of evolution”
Let me end by giving you a variant of that statement:
“Nothing in probiotics makes sense except in the light of the microbiome”
Christopher Mason, Weill Cornell Medicine
Christopher Mason @WeillCornell with “Modern methods for deliniating metagenomic complexity: defining clinical quality genome measurements and editing for the microbiome space”
Christopher Mason: We work on standardization of 16S and metagenomic analysis: Genome in a bottle (GIAB): extensive, public and un-embargoed data.
Ratios of 16S derived taxa vary a lot with primer choice.
Zymo has a good set of standards to monitor extraction.
Christopher Mason: IMMSA-Home – IMMSA http://MicrobialStandards.org
lists many approaches, and our 2017 paper has suggestions for methods to use:
Comprehensive benchmarking and ensemble approaches for metagenomic classifiers
Christopher Mason: How many species do I have? Each metagenomic tool gives a completely different number.
Christopher Mason: We have an ongoing project in our lab to sample the public environment, e.g. the subways of major cities #MetaSUB
Homepage – MetaSUB: http://metasub.org/
Christopher Mason: This way we are building genetic maps of public transportation systems and expanding the number of microbial taxa that are known. Which city has the most mystery taxa? Tokyo has the most novel peptides, Santiago has many novelty as well.
Christopher Mason: We are also mapping the antibiotic resistance gene abundance per city. Highly correlated with use of over-the-counter antibiotic use.
Christopher Mason: What can be learned from a surface? Skin bacterial communities (“microbial fingerprints”) were some of the earliest application. Small molecules on your phones and shoes reveal differences between people.
Christopher Mason: We swabbed phones at JPMorgan, metagenomics sequencing, and used MetaGenScope, a basic pipeline for taxonomy and functional profiles.
Christopher Mason: We mapped DNA from phones to corn, apple, salads, orange, leather purse, often what people ate just before swabbing. But also skin microbes. Engineers had urogenital bacteria on their phones. We can predict who has cats or dogs.
Christopher Mason: Twin astronauts study – Firmicutes/Bacteroidetes ratio switched while in space. Can we sequence in space? Nanopore was tested by Kate Rubins and it worked well.
Dan Knights – University of Minnesota
The next speaker is @KnightsDan with “New methods for affordable and high-resolution shotgun sequencing”
Dan Knights: There is a big need for cheap tools (like 16S) that have a high level of information content (like WGS). We started to develop affordable methods of the whole workflow.
Dan Knights: How can we automate the lab work? How can we do shallower sequencing to save some money? See our publication here:
Evaluating the Information Content of Shallow Shotgun Metagenomics
Dan Knights: With moderate depth shotgun sequencing, you get much better information than 16S. Even with 5000 reads (shotgun) you can almost get the same signal (betadiv ordination plot) as with 50 million reads.
Dan Knights: 10K gives alpha/beta diversity, 500k gives strains, 2M ($99) gives strains at 0.01%, 20-50M ($500) reads allows assembly of new genomes. Big step between these last 2. You can start by 2M reads, then follow up by deep shotgun sequencing on subset.
Dan Knights: Using this approach we sequenced gut microbiome of 34 people over time, correlated that with diet. Most folks have stable gut communities, despite super variable dietary intake.
Dan Knights: In two people who followed a (super stable) soylent diet, there was as much variation in gut microbiome as in regular, variable diets.
Dan Knights: We found that microbiome pairs with food groups (e.g. vegetables, eggs), not with nutrients (kale vs spinach). But every person responds differently to each food group.
Kiran Krishnan, Microbiome Labs
I hopped rooms again, for Kiran Krishnan, CSO of Microbiome Labs, with “Intelligent microbiota modulation”
Kiran Krishnan: We can define dysbiosis associated with disease as low amounts of keystone strains. E.g. amounts of Akkermansia, Faecalibacterium, and Bifidobacterium sp. are negatively associated with several health conditions.
Kiran Krishnan: Low amounts of these keystone species: disrupted mucosa, higher immune response, dysfunctional gut barrier, leaky gut.
Kiran Krishnan: Bacillus subtilis HU58 results in higher amounts of butyrate production and less ammonium. Synbiotic increased butyrate production even more.
Kiran Krishnan: We published a paper last year about effect of a probiotic on post-prandial dietary endotoxin, triglycerides, and disease risk biomarkers.
Oral spore-based probiotic supplementation was associated with reduced incidence of post-prandial dietary endotoxin, triglycerides, and disease risk biomarkers
That concludes all the talks of today. There were 3 parallel sessions, so I could not report on all the talks, but I hope you enjoyed my reporting.