Fecal microbiota transplantation can modify gut microbes and has shown promise in cancer and other conditions, but results are inconsistent and donor selection lacks clear standards. Now, researchers have found that the therapeutic success of microbiota transplants depends on individual bacterial strains, rather than overall gut diversity.

The findings, published in Cell Host & Microbe, suggest that targeting those specific strains can help develop effective microbiota therapies.

So far, studies linking gut bacteria to treatment success have yielded conflicting results, and current donor screening focuses on diversity and safety, but not on whether beneficial strains can successfully establish themselves in the recipients.

To understand why responses vary, researchers led by Kai Chen at Soochow University in Suzhou, China, examined people with advanced lung cancer and other conditions who received a fecal microbiota transplant.

Microbial transplants

The team combined chemotherapy and immunotherapy with capsules containing gut bacteria from healthy donors. Out of 10 participants who completed the treatment, six showed clear benefits, including tumor shrinkage and disease control.

The treatment was safe, with no severe side effects from the bacterial capsules. The overall mix of bacteria in the recipients’ guts didn’t fully explain who benefited: some closely related bacterial strains had opposite effects, and species-level analysis couldn’t predict response across different diseases. 

To track gut microbes in a detailed way, the researchers developed a new tool called ucgMLST. Using this method, they analyzed samples from people with lung cancer receiving fecal microbiota transplants and found nearly 49,000 unique microbial strains. Some species, such as Akkermansia muciniphila, easily established themselves and persisted in recipients, while others, such as Enterobacter kobei, rarely did so. 

Microbiota-based treatments

People who responded well to treatment had higher levels of donor strains establishing themselves and lower levels of their original strains. Colonizers that persist in the recipients’ guts tend to have genes that help them survive in the gut and interact with the immune system, while colonizers that don’t persist rely on quick growth, the researchers found.

People who successfully acquired and maintained health-associated strains experienced clinical benefits, while disease-associated strains were linked to poor response. The team also identified 38 clinically beneficial strains, such as Faecalibacterium prausnitzii, and created a score to predict treatment response and guide donor selection. 

“These findings establish a strain-function-efficacy paradigm, elucidating the mechanistic basis of variable outcomes and guiding next-generation microbiome drug development,” the authors say.