A dysbiotic microbiome can lead to health complications. One treatment may come through precision microbiome engineering, which could lead to the development of live biotherapeutic products that can modulate damaged gut microbiomes.
A new study demonstrates that a synbiotic comprising human milk sugars, called human milk oligosaccharides (HMOs), and a strain of bacteria found in the gut of nursing infants, Bifidobacterium infantis (B. infantis), can safely and predictably control the gut microbiome in adults.
This work is published in Cell Host & Microbe in the paper, “Precision modulation of dysbiotic adult microbiomes with a human milk-derived synbiotic reshapes gut microbial composition and metabolites.”
For the last decade, researchers have been working on methods to engineer the gut microbiome in patients, drawing inspiration from the success of fecal microbiome transplants for treating Clostridioides difficile infections. “While some of these attempts have been clinically successful, they have been quite crude and undefined, lacking in precision and reproducibility,” said Greg McKenzie, PhD, vice president of product innovation at Prolacta Bioscience. The company, established in 1999 and headquartered in Duarte, CA, specializes in providing nutrition in the neonatal intensive care unit (NICU) through developing human milk-based products for use in the hospital. In addition, Prolacta is exploring the therapeutic potential of human milk across a wide spectrum of diseases.
Human breast milk contains high concentrations of a collection of approximately 200 structurally diverse HMOs. Unlike the nutritional components of breast milk, HMOs are not metabolized as an energy source by the infant. Instead, HMOs serve to guide the growth of appropriate bacteria in the gut, which helps to train the infant’s immune system.
One species of bacteria in the infant gut is B. infantis, which utilizes the HMOs in human breast milk. After infants are weaned from human milk, B. infantis levels decline into adulthood.
In the current research, the findings suggest that HMOs support engraftment of B. infantis in healthy adults with a median observed abundance of 45.9% and up to 81% relative abundance in antibiotic-treated adults; no serious adverse events were observed.
The unblinded clinical study enrolled 56 healthy adult subjects. A control group completed a five-day course of antibiotics with no other intervention. A second group received the same course of antibiotics along with B. infantis for 14 days, and a third group additionally received HMOs for 28 days. Stool and blood were collected at set intervals for a total of 35 days. This trial built upon prior research from the same investigators published last year in the article, “Dosing a synbiotic of human milk oligosaccharides and B. infantis leads to reversible engraftment in healthy adult microbiomes without antibiotics,” also published in Cell Host & Microbe. This previous work suggested that dosing with a synbiotic of HMOs and B. infantis led to controllable, HMO-dependent engraftment of B. infantis in healthy adult subjects.
In the more recent study, microbiome structure and gut metabolite levels were altered in engrafted subjects. When B. infantis was present, other members of the microbiome that are not directly influenced by HMOs changed in a reproducible manner. One notable example was Veillonella which feeds on molecules produced by B. infantis and subsequently generates metabolites that are beneficial to human health.
“These findings are incredibly exciting, as we are starting to do ecology in the human microbiome,” said Julie Button, PhD, director, non-clinical development at Prolacta. “The reproducibility of cross-feeding Veillonella is really striking, as this magnitude of downstream effects are normally seen only when treating patients with antibiotics.”
“We expect that this human milk-based synbiotic will have the power to repair the microbiome of sick patients using the same biology that establishes a healthy microbiome in infants,” said Scott Elster, CEO of Prolacta. “We plan to demonstrate what is essentially ‘Nature’s Microbiome Starter Kit’ in extremely fragile stem cell transplant patients in a Phase IIa clinical trial starting in Q3 2023.”
