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Working with Athletes to Determine if Algae Can Improve Gut Health

January 31st, 2017
By Embriette Hyde with Dave Schroeder of Triton Algae Innovations


When a baby is born, it receives its first source of nutrients in the form of colostrum. Colostrum is the very first milk produced by a mother’s mammary glands, and it chock full of antibodies and antioxidants. Colostrum is critical for the health and protection of the new baby, as it provides a rich source of immunity that will protect the baby until its own immune system matures (which of course is dependent on the gut microbiome).

Recently, there has been widespread interest in using colostrum proteins to improve health and immune function not in babies, but in adults! Triton Algae Innovations (tritonai.com) is a company in the Knight lab’s backyard-a start-up spun out of UC San Diego in 2013-that is particularly interested in the healthy properties conferred by colostrum proteins. Triton Algae Innovations produces high-value colostrum proteins from a platform of eukaryotic green algae, a well-known and comprehensively studied wild-type algae strain called Chlamydomonas reinhardtii.

If you’ve spent any time in a lab, you know that accidental discoveries not only happen, but can often prove more significant that the original hypothesis. Triton Algae Innovations made such a discovery in the course of refining the algae production platform for these colostrum proteins and running a series of safety trials in animal models using the wild-type algae (i.e., the normal, non colostrum-producing algae). These trials, performed across different animal models, revealed that the wild type algae was almost as effective as the colostrum proteins in reducing diarrhea and gastrointestinal inflammation!

This algae, which has been proven safe for human consumption by other groups, features an abundance of natural, healthy, and nutritionally impactful components, including:


  • high levels of easily digested protein;
  • excellent source of Omega fatty acids and oils;
  • rich in Vitamin A, B-carotene, chlorophyll and iron

Given the statistically significant and compelling results observed in their animal studies, Triton is eager to better understand whether similar positive effects of this algae can be realized in the gut microbiome of humans, and recently approached the Knight lab-and the American Gut Project-with a compelling idea. We of course listened with eager ears, given our intimate work with the gut microbiome and its relationship with human health and disease, and our goal to research as many different topics in the field as we can.

Dave Schroeder explained to us that Triton is planning a consumption study of this algae in two human cohorts that have been of great interest to the Knight lab and the American Gut Project-athletes, and people with a history of IBS/IBD-type symptoms. As Triton’s major goal is to assess the effects of the algae on human gut health, a microbiome assessment is naturally a major aim of the study.  Participants will consume a small serving of this algae once a day for 30 days. Samples of the individual microbiomes will be collected before starting the trial, on the seventh day of the trial, and at the end of the trial. Dave indicated that he would love to work with the Knight lab to sequence the stool samples collected from trial participants, and enthusiastically accepted our suggestion to allow these samples to enter the American Gut Project cohort. Specifically, we see this project as a great way to further our existing collaboration with UCSD athletics. Through this study, not only will Triton be able to determine if the algae has positive effects on athletes’ gut health, but American Gut will be able to collect even more microbiome data on athletes, growing an already existing, exciting cohort.

We are in the process of writing protocols for institutional review board approval and hope to begin collecting samples in March or April of this year.

If you are interested in hearing more about this trial or think you might be interested in participating in this trial, please contact Dave Schroeder at dave@tritonai.com.

A Veterinary Perspective on American Gut Project: Man’s Best Friend

October 19th, 2016
By Julia Honneffer, DVM
Julia Honneffer is a veterinarian and PhD student in the lab of Jan Suchodolski at Texas A&M University, studying gastrointestinal diseases of the dog.


Similar to the work being performed through the American Gut Project to elucidate relationships between human diseases and the gastrointestinal microbiota, efforts are being made to explore health status and the gut microbiota of man’s best friend, the dog. Many people do not realize that dogs naturally develop many of the same diseases that people do, including inflammatory bowel disease (IBD), which is a major focus of researchers in the Gastrointestinal Laboratory in the Small Animal Clinical Sciences department at Texas A&M University. The GI Lab receives samples from all over the United States and beyond, often through collaborations with veterinary researchers throughout the world. These samples come from client-owned patients, and unlike rodent models of human disease, these pets share environmental exposures with their owners, from the water they drink to the air they breathe, often even sleeping in the same bed.

Among aspects studied by the Knight lab, dog ownership was shown to influence the human microbiome. Simply being a dog owner alters the microbiome compared to people who do not own dogs, and within households that have a dog, a greater degree of similarity was observed between human members of the household. But rather than focusing on the human microbiome, what about the dog’s microbiome?

By employing some of the same molecular tools used in the American Gut Project, we see both similarities and differences across host species. From an evolutionary perspective, this makes sense. As diverse as the class Mammalia is, each species has developed a blueprint that is compatible with life in its normal environment, efficiently filling a niche with the assistance of the microbiota that co-evolved with them. In veterinary species, as in humans, we are still learning and trying to understand the wide range of functions and influences that are credited to the microbiota.

My personal favorite tool for exploring these functional effects is metabolomics, which is broadly analyzing a sample (serum, urine, feces, saliva, tears, tissue homogenates, etc.) for the metabolites it contains. Interestingly, some of the metabolites found in feces are thought to be produced exclusively by the microbiota, some only by the host, and still others that may be produced by either. A given metabolite might be produced by many different bacterial groups, and the metabolic activity of the bacteria might depend upon available substrates or interactions with other bacteria in the environment. In other words, the metabolome and microbiome are intensely interdependent, yet also can change independently to an extent. This greatly complicates interpretation of the etiology of differences of biochemical composition between fecal samples of healthy and diseased dogs. However, becoming aware of disease-associated alterations in metabolite profiles might help guide us towards therapeutic strategies, or finding non-invasive biomarkers for gastrointestinal disease, even if we don’t completely understand the underlying mechanism driving the change.

While the microbiome and metabolome of the dog are certainly not the same as those of the human, ultimately they are far more similar than different. Extrapolations across host species about characteristics of health versus disease may require caution, but the “rules” that govern host-microbiota interactions are likely more universal. Thus the work being done by the American Gut Project is an asset to our understanding of any mammalian gut microbiome.

Cheese Microbes-Your Cheese Doesn’t Stand Alone!

August 8th, 2016
By Emily Pierce, PhD Student

 

One of my favorite parts of working in Rachel Dutton’s lab (besides having my boss bring cheese into the office on a regular basis) is getting to see people react to the statement “I’m doing research with cheese.”

This reaction usually occurs in three phases.  First is the initial surprise, followed by a momentary doubt that this is a legitimate scientific endeavor, and finally there is the exclamation of “That’s really cool!”  I couldn’t agree more; it is cool, and when you think about it, cheese is a great system for studying microbiology.  Cheese, like other fermented foods and like our gut, is home to a diverse community of bacteria and fungi.  Using cheese as a model, we are able to study both the mechanisms that drive the formation of these communities and the interactions between community members.  For me, this research is the perfect pairing of my love of food and my love of interesting biology, and although it may sound cheesy, I feel like it was fer-meant to be.

Microbial rinds form on the surface of cheese during the aging process.  The microbes that make up these rinds can come from intentionally added starter cultures, the milk or containers used, or from the surrounding environment.  By altering characteristics of the cheese such as salt, pH, and moisture, cheesemakers can shape the microbial communities that form.  The amazing diversity that you see when drooling over the cheese case at your local grocery store is largely a result of the various microbes that give each cheese its unique character.  These microbes influence not only the appearance of the rind, but also the flavor of the cheese.  Enzymes produced by microbes help to digest components of the cheese curds into smaller compounds that have distinct sensory properties.  For example, Penicillium roqueforti, a fungus added to blue cheeses, produces a molecule called 2-heptanone that gives these cheeses their recognizable “blue” aroma.  These microbial rinds also help to maintain a protective barrier that prevents pathogens from colonizing the cheese.



Left: This is a cross-section of an aged cheese showing a microbial rind biofilm on the surface. Image from Wolfe, et al. Cell 158.2 (2014): 422-433. Right: Here you see some examples of microbes isolated from cheese that can be cultured in the lab.


Using some of the same tools that are used by the American Gut project to look at the human microbiome, our lab has been able to characterize the microbial diversity of cheese rinds from all over the world.  Interestingly, these studies showed that worldwide there are 24 genera of bacteria and fungi that consistently dominate cheese.  Luckily for us, we are able to grow representatives of these genera in the lab, which means that we can reconstruct their communities and study how these microbes interact in the context of their natural environments.


This figure shows the results of a study looking at microbial diversity present in 137 different cheeses based on sequencing of bacterial 16S rRNA and fungal ITS markers. Each column in this figure represents an individual cheese. The bacteria and fungi listed at the bottom are frequent cheese inhabitants. For more information, see Wolfe, et al. Cell 158.2 (2014): 422-433.

This figure shows the results of a study looking at microbial diversity present in 137 different cheeses based on sequencing of bacterial 16S rRNA and fungal ITS markers. Each column in this figure represents an individual cheese. The bacteria and fungi listed at the bottom are frequent cheese inhabitants. For more information, see Wolfe, et al. Cell 158.2 (2014): 422-433.


One of the other interesting findings of this study was that there is a reproducible pattern of microbial succession on the surface of the cheese.  As the cheese ages, new microbes establish themselves and replace the original pioneers in a systematic way.  This makes cheese a good system for investigating how microbial communities initially form.

Cheese is therefore not only rich in flavor, but also rich in opportunities for studying microbial life.  Although I am a relative newcomer to the field, this is certainly an exciting time to be involved in researching microbial communities.  Through our collaboration with the Knight lab and the American Gut project, we hope to gain a better understanding of the microbial diversity present in fermented foods and to start to make connections between these microbes and our health.  This spring, I was able to join the American Gut project at the Santa Barbara Earth Day Festival and was inspired by the interest that fermentation enthusiasts showed in the science behind these foods.  I’m looking forward to the Santa Barbara Fermentation Festival in September as another opportunity to learn from the fermentation community and to encourage their involvement in the American Gut project.


The Dutton lab. Blog author Emily Pierce is second from right. The Dutton lab. Blog author Emily Pierce is second from right.


Emily Pierce is a second-year PhD student in Rachel Dutton’s lab, in the Division of Biological Sciences at the University of California San Diego.

Fermentation and Microbiome Research: Ancient Cultural Practices Meet Cutting Edge Genetic Analyses

August 1st, 2016
By Sandor Ellix Katz


I call myself a fermentation revivalist.

It began twenty-some years ago as a personal obsession with all things fermented, starting with sauerkraut (my gateway) and continuing through yogurt, sourdough, and country wines into researching fermentation traditions around the world, and years of kitchen experimentation. I was drawn to the compelling flavors, the practical benefit of preservation, and the probiotic promise of live-culture foods. My obsession became a reputation, and led to an invitation to teach, and in that first workshop in 1998 I learned that for many people the prospect of cultivating bacteria on food is terrifying. Demystifying fermentation and showing people how easy, safe, fun, and delicious it is became a mission for me. Workshops led to books: Wild Fermentation, initially self-published in 2001, then expanded into a book and published by Chelsea Green in 2003, and about to be released in a revised and updated edition later this summer (2016); and the Art of Fermentation, much more in-depth, published in 2012.  The workshops have never stopped. I have not kept count, but there have been many hundreds of them, in nearly every state, and increasingly abroad.

There is great interest in fermentation, everywhere. People are interested in connecting with food, and cultural traditions, and agrarian practicality. And of course, most people love the flavors of fermentation. But more than anything, people are drawn to fermented foods and beverages for their perceived health benefits. Live culture foods such as yogurt and sauerkraut can improve digestion and overall immune function and contribute to well-being in myriad other ways, but in fact we know very little about how, and specifically about the interaction between the microbial communities of the fermented foods and the more complex microbial communities of our intestines.

I am not a scientist and have no formal background in biology (nor in food science or culinary arts). But via my interest in fermentation, I have become very interested in microbiology. The cultural practices of fermentation arose everywhere long before the science of microbiology (or for that matter the written word). But microbiology, and the new methods of genetic analysis, give us new insights into what is happening, and what we are learning is so exciting. Bacteria and other microscopic life forms are everywhere. They are in us and on us and everything we eat. They exist in elaborate communities with complexity we are just beginning to recognize and little comprehend.

I have followed microbiome research with great interest. I supported the initial American Gut Project crowdfunding, and submitted a sample for analysis. I have followed the work of Rob Knight, and we had a great conversation when we met at the San Diego Fermentation Festival in 2015. And I have visited Rachel Dutton’s lab and greatly admire her research on cheese. So when they approached me about testing foods I was fermenting, and the students fermenting them with me, I jumped at the chance.

In addition to all the workshops I travel to teach, I host residency programs at my home in Tennessee. These are intensive immersions into fermentation with 12-15 people, each of whom have at least some fermentation experience, over 5-6 days. Together we make and eat krauts and kimchis, yogurt, kefir, alcoholic beverages, lightly fermented soft drinks, koji (a Japanese starter culture), miso, tempeh, sourdoughs, dosas and idlis, injera, and more.



Sandor with students at Walnut Ridge.


One of these workshops was coming up just a few weeks after Rob and Rachel emailed me about collaborating. This was a great opportunity to test lots of varied fermented foods and beverages, at different stages of development, as well as people before, while, and after eating them intensively. The lab sent boxes of swabs, instructions, and we were off!

Each participant took three samples on arrival: stool, mouth, and (dominant) hand; then another three on departure day, and a third set a week later, which they mailed in. As the workshop progressed, we swabbed raw ingredients, starters, and the ferments once they got going. I did more swabbing after everyone left, then mailed all the samples back to the lab.


Student Lauren Rhoades making kimchi.
Student Lauren Rhoades making kimchi.

Fermented daikon radish black-eyed pea natto, and other fermented delicacies served with lunch at Walnut Ridge.
Fermented daikon radish black-eyed pea natto, and other fermented delicacies served with lunch at Walnut Ridge.


I have not yet seen any results of our testing, but I am hoping it can help us better understand the distinctive microbial communities of different traditional fermented foods and how, and how community composition develops over time. And I hope that the testing of the students can help us better understand how eating these microbe-rich foods impacts upon our own microbiomes. I look forward to further collaboration with the American Gut Project, and to better understanding complex microbial communities and the interactions among them.


Sandor Ellix Katz is a fermentation revivalist. His books Wild Fermentation (2003) and the Art of Fermentation (2012), along with the hundreds of fermentation workshops he has taught around the world, have helped to catalyze a broad revival of the fermentation arts. A self ­taught experimentalist who lives in rural Tennessee, the New York Times calls him “one of the unlikely rock stars of the American food scene.” Sandor is the recipient of a James Beard award and many other honors. For more information, check out his website.