Your body is composed of about 10 trillion human cells. It’s also home to about 100 trillion tiny microbes, mainly bacteria, that wield astonishing power over your health.

Many influences, from genetics, to diet and stress, contribute to the makeup of your microbiome — the collective community of microbes as personal as a fingerprint.

Understanding, manipulating and balancing the microbiome could play an increasing role in preventing and curing diseases.

In 2018, about 2,400 clinical trials tested therapies based on microbiome science. Israel is one of the countries experiencing rapid growth in microbiome research and entrepreneurship.

“In terms of discovery and publication rate, Israelis are at the global forefront,” says Dr. Eran Elinav, an international pioneer of microbiome research.

Head of the Weizmann Institute of Science’s Host-Microbiome Interaction Research Group, Elinav and Weizmann colleague Prof. Eran Segal made headlines in November 2015 with results of the first phase of their groundbreaking Personalized Nutrition Project.

The main takeaway message: Because of that very individualized gut microbiome, the same foods affect each person’s blood-sugar levels differently. Several large studies, including at the Mayo Clinic, later validated the Israeli findings.

“This was a big paradigm shift,” Elinav tells ISRAEL21c. “Diet advice used to be based on quantifying or grading food to determine which is good and which is not. We showed that rather than scoring food we should score people because people react uniquely.”

Their labs developed algorithms to quantify the gut microbiome and apply machine learning to predict what food spikes blood sugar for each individual.

“We are now engaged in ongoing trials utilizing the personalized nutrition approach with people with pre-diabetes to see if we can slow or reverse the tendency of this huge population to develop diabetes,” Elinav says. “The study is in Israel, but it’s become interesting to the global scientific community.”

Papers published by Elinav and Segal’s teams also reveal that artificial sweeteners impact gut microbes in a way that drives obesity; gut microbes may directly affect the course of the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS); and probiotics are not one-size-fits-all.

“We have a group of 40 researchers looking at the effect of the microbiome on many different diseases,” says Elinav.

His lab participated in a recently published groundbreaking study with Hadassah-Hebrew University Medical Center researchers showing that a new treatment approach, vaginal microbiome transplantation, is effective against chronic bacterial vaginosis.

Microbes and mothers

The maternal (or pregnancy) microbiome is an area of increasing interest: How do the microbiomes in the birth canal, gut and breastmilk affect mother and baby pre- and postpartum? Are infants delivered via C-section missing beneficial immunity effects of the vaginal microbiome?

This is one focus of Omry Koren, head of the Microbiome Research Lab at Bar-Ilan University’s medical school in Safed. He’ll be the keynote speaker at the international microbiome research conference on pregnancy, birth and infancy, October 31 in Milan.

Koren’s lab discovered that the pregnancy hormone progesterone regulates the mother’s gut microbiome to help the fetus develop.

In a recently published study in Gut, Koren explains why pregnancy for women with IBD is not only safe but even potentially beneficial: the hormonal effects steadily improve the diversity of the mother’s gut microbiome until it reaches a normal level.

“We are now trying to understand if we can use the microbiome to predict pregnancy complications and treat them, and how these complications affect the newborn,” Koren tells ISRAEL21c.

His lab also explores how bacteria and behavior influence one another. Perhaps, Koren explains, changing the balance of gut microbes could treat brain disorders such as depression.

Koren’s lab is involved in clinical trials on fecal transplantation, a method used to restore the bacterial balance in a patient’s gut using stool from healthy donors.

One such study, in collaboration with Sheba Medical Center, is investigating whether this method may help cancer patients who currently do not respond to immunotherapy.

Another collaboration with Sheba is examining the role of the microbiome in graft vs. host disease, where transplanted bone marrow attacks the recipient. Fecal transplants potentially could restore the microbiome and immune system.

Koren believes microbiome research will affect predicting, diagnosing and treating a wide range of conditions and diseases.

Illustrating the prominence of Israeli scientists in this field, Koren organized a Microbiome Israel Workshop at Bar-Ilan last year. To his surprise, more than 300 people came to hear the 15 presenters and he was asked to make it an annual event.

The next workshop is scheduled for December 12, featuring experts from Bar-Ilan, Weizmann, Hebrew University, Ariel University, Tel Aviv University, Ben-Gurion University, Technion-Israel Institute of Technology, Assaf Harofe Medical Center and Migal-Galilee Research Institute.

DayTwo: Food as medicine

Israeli microbiome research is feeding the startup engine.

Elinav and Segal’s research forms the basis for two Israeli companies: DayTwo of Tel Aviv and San Francisco, and BiomX of Ness Ziona.

DayTwo uses microbiome analysis to personalize nutrition for optimal health. CEO Lihi Segal (no relation to Eran) tells ISRAEL21c that tens of thousands of clients in Israel and America use DayTwo’s home test kit and app to choose, log, and track foods that best balance their blood sugar.

“Our scoring system rates thousands of different foods and food combinations based on your biometrics, gut microbiome analysis, lifestyle factors and health questionnaire,” says Segal. “Our algorithm continues to develop and validate itself based on user data, which means that the scoring system has become even more precise over time.”

In the competitive landscape of personalized nutrition programs, diabetes management and gut microbiome testing, only DayTwo combines all three.

Segal describes DayTwo as “an actionable solution, based on cutting-edge science, which allows users to enjoy a food-as-medicine approach to balancing blood-sugar levels and, ultimately, to battle chronic metabolic disease without relying on drugs.”

Among DayTwo’s users and investors is Israeli basketball star Omri Casspi.

Having raised $48 million, DayTwo is mining its microbiome sequencing database to research solutions for irritable bowel syndrome/disease (IBS/IBD) and intestinal cancers.

“Research tells us that the microbiome plays a role in a myriad of conditions including obesity, diabetes, malnutrition, asthma, allergies, inflammation, Crohn’s and colitis, IBS, rheumatoid arthritis, Parkinson’s, autism, C. Diff [a bacterium that causes diarrhea and colitis], colon cancer, lactose intolerance, and more,” says Segal.

Digital health advances are making it easier to test individuals’ gut microbiome and provide personalized patient experiences, she points out.

“Currently, the role of the microbiome in treating disease is primarily used in fields such as functional medicine and not necessarily part of the standard of care. As the science evolves, with more evidence supporting the microbiome as a key indicator in health and disease, we believe that it will become a pivotal component in diagnosing and treating disease.”

BiomX: A hammer in search of nails

BiomX focuses on phage therapy using natural and synthetic bacteriophages — viruses that infect and destroy bacteria.

This approach is based on Weizmann Institute and Massachusetts Institute of Technology research suggesting phage “cocktails” could target specific harmful bacteria without disturbing other residents of the microbiome as antibiotics do.

Phages were discovered 100 years ago but fell out of favor as a therapy once antibiotics were invented. Thanks to research by the Weizmann’s Rotem Sorek and others, it is now understood how bacteria defend themselves and how phage therapy can get around that defense system.

BiomX is working on its first product, to treat acne, in collaboration with an international cosmetics company. The next indication will be IBD followed by orphan liver disease and oncology.

“We’re holding a hammer and looking for the nails,” CEO Jonathan Solomon tells ISRAEL21c. “Not every disease can be explained by a specific type of bacteria. But we will find more, and we will have the precision tools to go after them.”

BiomX currently is developing diagnostic biomarkers to predict who will best respond to one of investor Johnson & Johnson’s key drugs for IBD. This is made possible in part by “fantastic computational tools” invented by Segal and further developed by RondinX, an Israeli company BiomX acquired in 2017.

“One day, you could have your microbiome analyzed from a small stool sample to find out what drug will work best for you, or the doctor could prescribe phages to manage IBD and control the inflammatory response,” saysBiomX chief business officer Assaf Oron.

“The jury is still out on how well these therapies work,” he adds. “But we believe phage therapy for certain indications will become standard in the future.”

MyBiotics

MyBiotics in Rehovot has developed a unique platform to grow beneficial bacteria, singly or in clusters, to compete with disease-promoting microbes in a patient’s gut and restore a healthy microbiome balance.

“We grow them in a way that protects the bacteria and allows them to colonize the gut in a better way than any probiotics,” says CEO and cofounder Didi Daboush.

The company is close to commercializing two initial products. The first will create a white powder from human donor feces to replace fecal transplantation with a safer, more controlled process. This will go to human clinical trials in 2020.

The second product is probiotics for nonclinical use such as food additives. MyBiotics has several collaborations with food and pharma companies to bring this to market.

The company works with academic institutes in Israel and abroad, and its staff of 15 also includes experts from Israel and abroad. A recently completed $8 million investment round with Israeli and Japanese participation takes the total raised since the company’s 2014 inception to $9 million.