Human milk sugar and probiotic blend may help manipulate the gut microbiota

New research suggests that a combination of human milk-derived sugars and the probiotic Bifidobacterium infantis could help manipulate the gut microbiota in ways that may offer therapeutic benefits.
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What is already known on this topic
Fecal microbial transplants are a promising approach to treat imbalances in the gut microbiota by shifting the composition and activity of microbial communities. However, the efficacy of microbial transplants depends of the long-term persistence — or ‘engraftment’ — of bacterial strains in the recipient microbiota.

What this research adds
Researchers investigated the engraftment of the probiotic Bifidobacterium infantis into the human gut microbiota by giving six groups of about 10 healthy people either multiple doses of sugars derived from human milk, a commercially available B. infantis supplement, or both. People who received both the human milk-derived sugars and the B. infantis supplement showed high-level colonization with B. infantis without antibiotic treatment nor adverse effects. Human milk-derived sugars also promoted the engraftment with B. infantis of human microbiotas transplanted into germ-free mice. The combination of sugars and probiotic supplement increased the levels of the short-chain fatty acid butyrate in mice and in co-cultures with Firmicutes bacteria, and it inhibited the growth of bacteria that tend to cause gastrointestinal diseases.

Conclusions
The findings may help to develop microbial-based therapies that reinstate the balance of the gut microbiota when it has been damaged or altered, for example in conditions such as Crohn’s disease.

Fecal microbial transplants are a promising approach to treat imbalances in the gut microbiota, but their efficacy depends of the long-term persistence — or ‘engraftment’ — of bacterial strains in the recipient microbiota. New research suggests that a combination of human milk-derived sugars and the probiotic Bifidobacterium infantis could help manipulate the gut microbiota in ways that may offer therapeutic benefits.

The findings, published in Cell Host & Microbe, could help to develop microbial-based therapies that reinstate the balance of the gut microbiota when it has been damaged or altered, for example in conditions such as Crohn’s disease.

Recent research has shown that a blend of a single human milk oligosaccharide and Bifidobacterium pseudocatenulatum led to engraftment and beneficial effects in a mouse model of colitis. Human milk oligosaccharides (HMOs) are a family of sugars present in human breast milk that serve as a prebiotic to help establish the infant gut microbiota. 

B. infantis is a bacterial species often found in the infant gut that is able to use HMOs and has been shown to help the immune system and intestinal tract to mature. However, as children are weaned, B. infantis is overtaken by other species of bacteria. 

To assess the engraftment of B. infantis into the adult gut microbiota, Gregory McKenzie at Prolacta Bioscience and his colleagues enrolled 62 healthy people in a clinical study.

Testing engraftment

The study participants were divided in six groups of about 10 people and given either multiple doses of HMOs, a commercially available B. infantis supplement, or both. One group received daily doses of B. infantis alone for 7 days; a second group received twice daily doses of HMOs alone for 14 days; three other groups received both B. infantis and HMOs together for the first 7 days, followed by HMOs alone through day 14. None of the participants was given antibiotics before the treatment.

People who received both the human milk-derived sugars and the B. infantis supplement showed high-level colonization with B. infantis. No adverse effects were reported.

Engraftment of B. infantis also led to changes in the levels of several metabolites. Lactate levels were higher at day 15 in people with engrafted B. infantis, but no other short-chain fatty acids differed significantly between engrafted and non-engrafted people.

Beneficial effects

Further experiments showed that human milk-derived sugars promoted the engraftment with B. infantis of human gut microbes transplanted into germ-free mice. The combination of HMOs and probiotic supplement also increased the levels of the short-chain fatty acid butyrate in mice and in co-cultures with Firmicutes bacteria, and it inhibited the growth of bacteria that tend to cause gastrointestinal diseases.

Butyrate is known to have anti-inflammatory effects, and the boost of butyrate production may be a mechanism by which treatment with B. infantis and HMOs could benefit people with altered gut microbiota, the researchers say.
B. infantis may modulate the gut environment through the metabolism of HMO and production of metabolites that may both enhance beneficial butyrate production by commensal microbes and inhibit enteropathogens,” they add. “This study also opens the door to the development of predictable and controllable [live biotherapeutic product] for treatment of a broad variety of microbiome disorders.”