Gut check: Benioffs donate $35 million to further study of microbiome at UCSF, Stanford

The human microbiome is a complex ecosystem of trillions of foreign organisms that live in and on every person’s body, and it’s closely connected to almost every facet of health — from immune function and metabolism to illnesses like allergies, multiple sclerosis and inflammatory bowel disease.

On Tuesday, both UCSF and Stanford are introducing new research programs to study and harness the microbiome with $35 million in grants from Marc and Lynne Benioff — $25 million to UCSF and $10 million to Stanford. The Stanford grant is the Benioffs’ first donation to the university; the couple have given about $350 million to UCSF previously.

The funding represents an important financial but also symbolic investment in microbiome research, which is still in its earliest stages, said the scientists leading both campus initiatives. They hope the funding will lead toward development of some of the first microbiome-based therapies to treat and prevent disease.

“We’ve reached a point where there’s enough evidence that the microbiome really matters for human health that people are ready to support and accelerate the field of study,” said Susan Lynch, director of the newly opened UCSF Benioff Center for Microbiome Medicine.

“We know these microbes and their products shape host health,” Lynch said. “Now the task is understanding which microbial products at which stages of life really matter for human health, and leveraging that information. We’re at a watershed moment.”

The microbiome is made up of non-human microbes that take up permanent residence in the body, mostly in the gut and on the skin. It functions as an ecosystem much the same way that a marshland or forest does, with the individual units — whether it’s trees, grass and insects or bacteria, viruses and fungi — working together and separately to create a unified environment that’s constantly evolving.

The microbiome works with a person’s own cells and tissue to metabolize chemicals — not unlike the function of a liver — and even fend off certain diseases. Scientists believe that the growth of the microbiome, beginning even before birth, is closely connected to immune system development.

For example, early exposure to dogs and cats is related to lower rates of asthma and allergies in older children. Further studies — including some led by Lynch — have found that the microbiomes of children raised with pets differ from children who don’t grow up around animals, and that some of those differences are tied to immune function and allergic responses.

The UCSF team is focused on understanding that early evolution of the microbiome and the long-term health consequences.

Elze Rackaityte looks through a box of cryovials as she works with bacterial isolates from the human microbiome in the Lynch Lab. The UCSF team is studying the early evolution of the human microbiome and the long-term health consequences.

Photo: Lea Suzuki / The Chronicle

“My project is determining what the earliest colonizers for the human intestine are,” said Elze Rackaityte, a sixth-year doctoral student who works in Lynch’s lab and is studying the microbiome of infants. “We think they have an impact on the whole ecosystem development. So we’re looking at what these early colonizers are, when they start to colonize, and what their impact is on the immune system.”

At Stanford, researchers are building synthetic microbiomes from scratch. The Stanford program is being funded with $7 million from Mark and Debra Leslie in addition to the Benioff gift.

The lab-made microbiomes are meant to replicate natural human ones, and could be used someday to replace faulty microbiomes that are causing chronic illness. Similar work is already happening in hospitals, where patients can get fecal transplants to treat certain stubborn bacterial infections. The donor fecal matter, which contains all the components of a healthy person’s microbiome, essentially reseeds the sick person’s microbiome and helps wipe out the infection.

Synthetic microbiomes also could be used for study — either for testing possible drug therapies or for understanding how adding or removing specific pathogens affects the entire microbiome.

Building a microbiome in a lab is an incredibly complicated endeavor, said Michael Fischbach, director of the Stanford Microbiome Therapies Initiative. Just determining which microbes are in a given microbiome, and the proportions of each one, is a massive undertaking. He said scientists have likened it to putting together a jigsaw puzzle — only instead of one puzzle it’s several hundred, all of the pieces jumbled together, and there’s no box cover to tell them what the finished product should look like.

Fischbach’s team essentially has the final image, but they have to grow all of the pieces — or organisms — and put them together in exactly the right concentrations. It’s a task for engineers as well as microbiologists.

“A scientist would look at the microbiome and say, ‘Wow, that’s really complicated. Just to observe it is going to be a decades-long challenge.’ Whereas an engineer would say you need to be able to build it and take it apart and replace it piece by piece,” Fischbach said. “And that’s what we’re doing.”

Marc Benioff said he was eager to bring the Stanford and UCSF teams together to “create one of the larger microbiome institutes in the world.”

“This is an area that still is in need of a lot more core, very basic research,” he said. He and his wife learned from previous gifts to UCSF that donations are helpful not only in funding important research, but in spotlighting the work so that other donors will support it too.

“We’ve done a tremendous amount of funding at UCSF. And as we’ve done that funding, we’ve come in contact with a lot of exciting, pioneering research, some of which doesn’t get the attention it deserves,” he said. “We want to make the microbiome part of that effort. We strongly believe the microbiome is a critical part of the future longevity of human beings.”