San Francisco Chronicle

Benioffs’ gifts to boost study of microbiome

- By Erin Allday

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 finan

cial 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 nonhuman 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 longterm health consequenc­es.

“My project is determinin­g what the earliest colonizers for the human intestine are,” said Elze Rackaityte, a sixthyear 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 labmade 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 decadeslon­g 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.”

 ?? Photos by Lea Suzuki / The Chronicle ?? Doctoral student Elze Rackaityte studies infant microbiome­s, determinin­g which microbes first colonize the intestine. “We think they have an impact on the whole ecosystem developmen­t.”
Photos by Lea Suzuki / The Chronicle Doctoral student Elze Rackaityte studies infant microbiome­s, determinin­g which microbes first colonize the intestine. “We think they have an impact on the whole ecosystem developmen­t.”
 ??  ?? Vials containing microbiome material sit on dry ice at the newly opened UCSF Benioff Center for Microbiome Medicine.
Vials containing microbiome material sit on dry ice at the newly opened UCSF Benioff Center for Microbiome Medicine.

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