Prolacta Bioscience to test “precision microbiome engineering” of its synbiotic in stem cell trials

04 Sep 2023 --- Global life sciences company Prolacta Bioscience has made a synbiotic breakthrough using sugars from human milk oligosaccharides (HMOs), a bacterial strain found in nursing infants, to precision heal the adult gut microbiome.

Published in Cell Host & Microbe, the research was conducted in cooperation with Prolacta, the MD Anderson Cancer Center and the University of Texas Southwestern Medical Center.

“We are demonstrating that the same biology that develops a healthy infant gut can be applied to adults with disrupted gut microbiomes,” Dr. Gregory McKenzie, VP of product innovation at Prolacta Bioscience and study co-author, tells Nutrition Insight.

“We can leverage our understanding of how babies are naturally protected from infection and inflammatory disease and start to have an impact on adult patients with infectious and inflammatory diseases.”

“Precision microbiome engineering” opens the door for the development of live biotherapeutic products to reconstitute a damaged or out-of-balance microbiome, as is the case in many infectious, autoimmune and metabolic diseases.

Synbiotic of human milk sugars
The study demonstrates how the synbiotic composed of HMOs coupled with a strain of bacteria from the microbiome of infants, Bifidobacterium infantis (B. infantis), can regulate the microbiome of adults.

“Our next clinical trial is in adults undergoing allogeneic stem cell transplants, but we expect that this synbiotic will be applicable to a broad variety of infectious, autoimmune, and metabolic disorders,” explains McKenzie.

The researchers observed that the HMOs support the engraftment of B. infantis in healthy adults with a 46% abundance rate and up to 81% relative abundance in antibiotic-treated adults.Engraftment of Prolacta’s HMO-based synbiotic will be used in an Investigational New Drug trial for cancer patients. 

The structure of the microbiome and the gut metabolite levels were altered in engrafted patients. In the presence of B.infantis, several microbiome components that are not directly influenced by HMOs changed in a reproducible manner. 

A notable example was a microbe called Veillonella that feeds on molecules produced by B. infantis and generates metabolites that benefit human health. No serious adverse effects were observed.

 “Research at a variety of hospitals has demonstrated that patients undergoing stem cell transplants have poorer outcomes driven by damage to their microbiomes. We are going to try to repair that damage to their microbiomes using our human milk-based synbiotic approach,” McKenzie notes. 

In 2022, Prolacta Bioscience based a study that found that HMO nutritional products should not be homogenized until the process’s safety and efficacy have been established.

Meanwhile, the gut microbiome is pegged as the “black box” of nutrition research as diet-microbiome interactions are anticipated to contribute to the foundation of dietary physiological effects. 

According to researchers from the University of Alberta, Canada and the University College Cork, Ireland, dietary guidelines could be improved, modified and innovated based on data on diet-microbiome-host connections.

Clinical trials in the pipeline
The unblinded clinical study enrolled 56 healthy adult subjects. The control group completed a five-day course of antibiotics, known to disrupt gut bacteria, with no other intervention. A second group received the same course of antibiotics along with B. infantis for 14 days, and a third group received HMOs for 28 days. 

The trial built on previous research where it was observed that dosing with a synbiotic of HMOs and B. infantis led to controllable, HMO-dependent engraftment of B. infantis. 

“The reproducibility of cross-feeding Veillonella is striking, as this magnitude of downstream effects is normally seen only when treating patients with antibiotics,” says Dr. Julie Button, director of non-clinical development at Prolacta.

Prolacta will initiate a Phase 2a Investigational New Drug (IND) trial to investigate the synbiotic in patients undergoing stem cell transplants for blood cancers. These patients often have disruptions in their gut microbiome, including increased numbers of potentially disease-causing species of bacteria and an overall loss of diversity, which can lead to organ attack and death.

The study will measure how well the synbiotic drives the redevelopment of a healthy microbiome, which it does naturally in the newborn gut.

“Our phase 2a study will treat stem cell transplant patients with a synbiotic comprising HMO and B. infantis and look for improvements in their microbiomes, but also lower rates of fever, infection and Graft-vs-Host Disease,” explains McKenzie.

Previous research published in Cell Host & Microbe journal expands the interest in human breast milk and its therapeutic applications for the gut microbiome. The findings suggest potential therapeutic benefits for microbiome imbalances and other diseases.

By Inga de Jong