In his presentation at the conference in Barcelona on Feb 6th, he highlighted the significance of these findings in sparking the company’s renewed research efforts to understand the mechanism of action of such synbiotics and ‘precision synbiotics’, to enable their potential future production at Chr. Hansen.
“We are trying to build an understanding of how we can best use HMOs in the best possible way together with some of the bacteria we have at Christian Hansen. And we have already done this for Bifidobacterium infantis,” he explained.
“We want to understand if we can go beyond the infant for the HMOs, and that’s what we’re seeing. Can we make some situations in adults or the elderly where we can see there will be a use?
“Later in the year we will be presenting the work we will do; building on the science we already have from the probiotic strain and that we’re developing with the HMO team, and then putting these together. We believe we can make some synbiotics that will actually work and have science to back them,”
Significant synbiotics
Baker opened the talk by highlighting a recently completed clinical trial establishing the beneficial effects of B. infantis for infant health. It was observed that seeding the strain in the infant using oral administration directly to the infant was most successful, as opposed to when given to the mother, with significant improvements noted in stool frequency and inconsolable crying and fuzzing.
As the studied newborns were also being breastfed, providing human milk oligosaccharides (HMOs), the scientists noted the possible significance of a synbiotic effect.
“It is a strain known to be important for infants, and for its ability to use HMOs as well. Chr Hansen have been growing it at high quality in the factories, but we have also been sequencing the strain and conducting data analysis in the lab. We have been putting the strain together with HMOs to see how it could potentially work in vivo”, Baker explains.
With regards to this research, he continues: “We used a challenge model, where we challenged the epithelial to create the equivalent of inflammation. We then added the infantis with the HMOs to see what was happening, especially with immune responses directly reacting with placenta-derived multipotent cells (PDMCs) out of blood.”
He says the study results will be published very soon, emphasising a significant observation seen in the recovery from epithelial inflammation following administration of infantis and HMOs.
“We can’t just think of prebiotics as prebiotics, and probiotics as probiotics. This is a bidirectional consideration to have. The preliminary data is showing that B. infantis is performing in different ways when it is in the presence of certain HMOs,” he stresses.
Future ventures
Following these findings, Baker continued to discuss the current extensive genome screening being conducted at the Chr. Hansen labs to understand the mechanism of action of synbiotics.
“We took 147 different bacteria from the Christian Hansen bank and did full genome screening on these. This gave us nearly 2.4 million base pairs of sequence to work with. We then went into the labs and did growth screens on the top five most known HMOs, which gave us 95,000 data points.”
He highlights how the results have shown significant variation in the presence of the HMO degradation gene within B. infantis strains, suggesting specialisation and differentiation in the use of HMOs across the same species of bacteria.
“We are trying to understand more about this specialisation and preference, but this was in the lab environment. We need to know what happens when this is challenged and put into a small or large intestine.”
With regards to meeting this challenge, he explained: “We also use the artificial TIM models from the TIM company in the Netherlands. The TIM-2 is a colonic model with four compartments, set up for adults to study the colonic microbiota. We have also spent the last two years developing and validating an infant model.
“This allows us to study the microbiota as we develop, and as we add the HMOs to the faecal material. We can add in the bacteria and see if it is grafting well or not. But we can also study the SCFA production, and what is being used by the HMOs that we put in. We can study the metabolic output, and challenge some of the hypotheses we have about how lab studied bacteria interact in a faecal ecosystem.
“It can then be established if synbiotics actually work.”