In its efforts to stay at the forefront of the quickly emerging field of research into the human microbiome, the Mayo Clinic is adding to a growing list of collaborations with cutting-edge startups focused on understanding what the teeming microorganisms essential to digestion can tell us about a broad range of health issues. 
 
The Rochester nonprofit announced this month it established a formal collaboration with Cambridge, Mass.-based Evelo Biosciences, a new firm established last year after a $35 million investment from Flagship Ventures. That biotech-oriented fund has seen eight of its portfolio companies go public in recent years – four of them are currently worth at least $1 billion, according to the life sciences news site Xconomy. 
 
Evelo’s focus is on the relationship between the microbiome and the human immune system. Its goal is identifying how certain strains of bacteria in the human gut can “activate” the immune system against cancer and “down-regulate” it in the treatment of autoimmune and inflammatory diseases. Evelo is developing drug candidates to manipulate the microbiome to produce the desired result.
 
Its deal with Mayo includes an agreement “to isolate and characterize cancer-associated bacteria from patient stool samples and tumor biopsies,” thus enabling the startup to build up a library of bacterial suspects. Evelo says this is essential for the development of drugs capable of targeting the right bacteria to stimulate the immune system against cancer.
 
The collaboration marks the fifth such partnership between Mayo and a microbiome-focused startup – a sign the clinic is going all-in on the promising field, which in May became the subject of a $121 million national research initiative launched by the Obama administration.
 
Mayo’s other microbiome collaborators include:

• Seres Therapeutics, Cambridge, Mass. The partnership between Mayo and Seres is focused on using micro-organisms as therapeutic agents for disease in clinical trials.
• Enterome, Paris. The collaboration the French startup focuses on discovery and validation of gut microbiome-based diagnostics to predict responses to nutritional interventions in overweight and obese patients.
• Second Genome, San Francisco. Mayo and Second Genome collaborate in areas such as irritable bowel disease; obesity/metabolic disease; and surgery in obese patients with and without type 2 diabetes.
• Whole Biome, San Francisco. Mayo and Whole Biome are collaborating to decrease rates of preterm birth and labor, the leading cause of infant mortality in the United States, through microbiome-based diagnostics and therapies.

 
Several of the collaborations involve some sort of financial interest between the clinic and the companies. For instance, Second Genome became a Mayo Clinic Ventures portfolio company in 2014 as part of a clinical research collaboration. Earlier this year it was announced Mayo extended its venture stake in the company as part of a $42.6 million Series B financing round led by big pharma giants Pfizer and Roche.
 
Seres, meanwhile, revealed it has a financial interest with Mayo as a result of a June 2014 research agreement wherein the clinic obtained a warrant to purchase shares of its common stock.
 
Likewise, a press release issued this month in connection with the Evelo collaboration indicated there was a financial or licensing element involved in the deal. However, a Mayo Clinic spokeswoman told TCB further details of the arrangement were not ready to be released.
 
Financial terms of the Enterome and Whole Biome collaborations, each struck in 2014, also remain confidential.   
 
Mayo researchers themselves are busy working on several fronts in the microbiome field. These include gluten sensitivity: They have found that altered composition of the intestinal microflora is linked to disorders of the gastrointestinal tract, including gluten sensitivity and the risk of irritable bowel syndrome-like symptoms.
 
Another promising avenue is the link between the microbiome and rheumatoid arthritis. Mayo scientists have found that alterations of a normal gut bacteria can affect the integrity of the intestinal mucosal barrier, which serves as the body’s first line of defense against pathogens. Studies are trying to determine which strains of bacteria are associated with this effect, and which can trigger systemic disturbances in the immune system.
 
Colon cancer is yet another subject of microbiome-related research. There, Mayo is looking into how dietary factors interact with the gut microbiome to create metabolites that can harm bowel cells and produce DNA damage, leading to cancer development.