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Can microbiome engineering replace antibiotics?

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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 reveals that a synbiotic comprising human milk sugars, human milk oligosaccharides (HMOs), and a strain of bacteria found in the gut of nursing infants, Bifidobacterium infantis (B. infantis), can carefully and probably 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.”

The history of microbiome engineering

 For the last decade, scientists 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. Greg McKenzie, Ph.D., vice president of product innovation at Prolacta Bioscience says: “While some of these attempts have been clinically successful, they have been quite simple, lacking in precision and reproducibility”. Established in 1999, the company specializes in providing nutrition in the neonatal intensive care unit (NICU) by developing human milk-based products. In addition, Prolacta is discovering the therapeutic potential of human milk across a wide range of diseases.

HMOs

Human breast milk contains high concentrations of a collection of nearly 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, helping to develop the infant’s immune system.
B. infantis is one species of bacteria in the infant gut that utilizes the HMOs in human breast milk. After infants are weaned from human milk, B. infantis levels decline into adulthood.

The clinical study 

This trial was built upon prior research from the same investigators published last year. The previous work suggested that treating 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 were not directly influenced by HMOs altered 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.

The vision of the study

Julie Button, PhD, director, non-clinical development at Prolacta says: “These findings are incredibly exciting, as we are starting to do ecology in the human microbiome”. “The reproducibility of cross-feeding Veillonella is really striking, as this magnitude of downstream effects is 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 are to demonstrate what is fundamentally ‘Nature’s Microbiome Starter Kit’ in stem cell transplant patients in a Phase IIa clinical trial starting in Q3 2023.”

Reference:

https://www.genengnews.com/topics/translational-medicine/human-milk-based-synbiotic-may-repair-the-microbiome-of-sick-patients/
https://www.sciencedirect.com/science/article/pii/S1931312823003293?via%3Dihub

 

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