My co-first author paper with Gabi Fragiadakis was published in Cell last week and was trending #1 on PubMed for a few days! This is the seminal paper of my PhD career and I am incredibly proud of the final product. The village of researchers that worked on this paper is immense and I feel so grateful to have been able to work on it during my time in Sonnenburg Lab.
I wanted to write a little breakdown of what went into this study and how to interpret the main findings for people who may not have spent as much time steeped into the fields of microbiome, immune system, or data analysis.
What goes into a study like this?
This study was the brain child of Justin Sonnenburg and Christopher Gardner who had a vision to run the most comprehensive human dietary intervention and understand how diet can influence both the microbiome and immune system. Justin is a professor at Stanford in the Microbiology and Immunology department. Christopher is a professor at Stanford in the Prevention Research Center.
The study itself was actually largely funded by donors interested in diet driven changes to the microbiome. The participants were recruited from the Bay Area because they needed to come into the lab for blood draws and sample drop off every other week. The largest demographic of participants were white women, however this was the first human intervention study jointly run by the Sonnenburg and Gardner lab and studies in the future have a more diverse demographics pool.
Fun fact, we call the study FeFiFo as a shorthand for Fermented, Fiber Foods study. I originally used this term as a joke during lab meeting because it is such a GIANT study (like from Jack and the Bean Stalk, get it?).
What is a dietary intervention?
The participants worked with dieticians in Gardner lab to change their diet over a period of 10 weeks. A key highlight of this study is the vision Christopher Gardner and his group have in how dietary changes need to be implemented into people’s existing lifestyle. While some dietary studies control the foods people eat by providing them with boxed meals, this study opted to allow people to integrate the dietary change into their existing lifestyle.
Being able to go to the store and pick out the foods you like makes it much more likely that you’ll stick with it even after the study ends.
Before the intervention, participants ate around 20 g fiber/day and 0-1 servings of fermented foods/day. Participants in each diet group slowly increased their intake during the “ramp phase” and had their highest consumption during the “maintenance phase” at over 40 g fiber/day and 6 servings of fermented foods/day! This is quite a lot!
All participants made dietary changes after extensive education from a crew of the best dieticians at Stanford. The participants also consulted the dieticians multiple times during the course of the study.
What does it mean to study the microbiome and immune system?
We studied the participants’ microbiome through their poop. The gut microbiome resides in your intestines and we can study a snapshot of what microbes are in there by sequencing the bacterial DNA in your stool. We can also measure the proteins and small molecules the microbes produce by measuring them in your stool.
We studied the participants’ immune system through their blood. Our immune system is a complex network of proteins, cholesterol, hormones, etc. that are constantly circulating around in your body. While there is no singular measure for how healthy your immune system is, we can paint a picture of it’s general state by measuring the levels of inflammatory proteins and immune cells signaling in your blood. In broad strokes, lower inflammation is better for the average person.
Why fiber? Why fermented foods?
Plant-based fiber cannot be broken down by the human body, so we rely on our gut microbes to do it for us. There have been a number of studies that show diets high in fiber lead to lower mortality, higher microbiome diversity, and improvements of other health markers.
Fermented foods include products like yogurt, kombucha, sauerkraut, and kimchi. They have a community of microbes that are ingested when we eat them. Fermented foods have also been associated with health benefits and changes to the microbiome. Check out the paper for more information and references on this.
What is microbiome diversity and why does it matter?
Microbiome diversity can refer to a number of things, but most commonly, it is describing the number of unique species in your gut. It’s better to have a high diversity because it means your gut community is more resilient to perturbations like eating spoiled food or licking your hand after touching a gross doorknob at the airport. The direct impact a high diversity microbiome has on human health is undefined, but healthy people have higher diversity than those with obesity, diabetes, or chronic diseases.
What is immune status and why does it matter?
Immune status is broadly referring to the health of your immune system. As mentioned above, there is no “one” measurement for how healthy your immune system is, which is why we opted in this study to measure everything we could (over 200 immune system parameters!). This gives us the most comprehensive picture possible so instead of focusing on one specific immune measurement that could lead to immunology rabbit holes, we could discern broad trends that point to a cohesive narrative. Think of it as looking at the forest instead of the trees.
What are the main takeaways from the study?
A diet rich in plant-based fiber leads to a personalized immune response that corresponds with a person’s baseline microbiome diversity. The higher a person’s microbiome diversity was before the high fiber intervention, the better their immune status was by the end of study. While the microbiome diversity as a whole did not change throughout the intervention, the capacity their microbes had to digest fiber increased. In other words, as people ate more fiber, their microbial capacity to digest it increased.
A diet rich in fermented foods reproducibly increases microbiome diversity, remodels microbiome composition, and decreases markers of chronic inflammation. It is incredible that a simple dietary change like eating fermented foods can actually decrease the amount of baseline inflammation a person has!
What’s next?
More human dietary intervention studies!! This paper stands as a landmark to show that marked changes can be seen in the microbiome and immune system in a study like this. People didn’t think we would be able to show any detectable changes if participants weren’t locked in a room and fed the exact same foods. The possibility for microbiome-targeted interventions is endless and hopefully more will be funded, run, and deeply analyzed by Sonnenburg and Gardner labs, as well as labs across the world.
More fermented foods! The finding that fermented foods can lead to measurable improvement of immune status is exciting. Even more exciting than this is that fermented foods, especially vegetable ferments like sauerkraut and kimchi, are cheap and can be made at home. I’ve seen fermented foods rise in popularity over the past few years (hopefully even more now that the paper is published), but they do not have to be a boutique item. Fermentation can be an accessible avenue for people to make healthier foods at home and share with others (starter cultures make great gifts).
Thanks for reading – hope you are convinced to add more fermented foods to your diet (and fiber, both is probably the best…study in the works to see if there’s a synergistic effect)!