Improved strain-specific use of HMOs identified in DuPont-backed study

By Will Chu

- Last updated on GMT

Improved bacterial's use of HMO identified in DuPont study
Probiotic strain specificity is crucial if the benefits of human milk oligosaccharides (HMOs) such as 2′-fucosyllactose are to be passed on to the infant, according to a DuPont-sponsored study.

Work carried out by the firm’s Nutrition & Biosciences arm, found one strain of Bifidobacterium infantis​, adopts a more efficient method to utilise 2’-FL as well as the other HMOs 3’-FL and difucosyllactose (DFL).

According to the team, B. infantis​ Bi-26’s use of these HMOs results in faster growth, unique metabolite production, and a distinct gene transcription response when compared to other B. infantis​ subspecies.

“We are excited to further the research on defining the individual strain’s role within the complex system of the microbiome,”​ says Bryan Zabel, study lead author and assistant scientist DuPont Nutrition & Biosciences.

“It is essential to understand the numerous interactions affecting our health throughout life which can eventually be used as a guide to develop products for supplementation.”

HMOs nutritional value for an infant is considered negligible, as intestinal human enzymes do not hydrolyse most of the glycosidic bonds found in these compounds.

However, HMOs act as a bioactive compound providing infant benefits that include development of the immune system.

HMOs also function as prebiotics for beneficial bacteria, enriching the populations capable of efficiently utilising these substrates in the developing infant colon, often dominated by bifidobacteria.

The genus Bifidobacterium​ is made up of 70 species and 10 subspecies, where only a few can utilise HMOs as their sole carbon source and are dominant in the gut microbiota of breastfed infants.

Typical gut species include B. breve, B. longum subsp. longum​ and B. bifidum​, with B. pseudocatenulatum​, B. longum subsp. infantis, B. longum subsp. suis​, and B. kashiwanohense​ occurring at lower frequency

Study details

The team used growth, transcriptomic, and metabolite analysis to characterise key differences in the utilisation of 2′FL, 3FL and DFL (FLs) between B. longum​ subsp. infantis​ Bi-26 (Bi-26) and B. longum ​subsp. infantis strain ATCC 15697 (type strain)

This included testing both strains for growth on glucose, lactose, 2′-fucosyllactose (2′FL), 3-fucosyllactose (3FL), di-fucosyllactose (DFL), or fucose as the sole source of carbon.

These growth experiments were conducted in triplicate in Hungate tubes with 5 millilitre (mL) of mBasal media supplemented with 2% (w/v) of each carbon source.

Results revealed that Bi-26 appeared to grow faster, produce unique metabolites, and had a distinct global gene transcription response to FLs compared to the type strain.

Taken together the team suggest the findings demonstrate strain specific adaptations in Bi-26 regarding the efficient utilisation of FLs.

“Our research helps us to further understand the interactions between probiotic strains and HMOs and allows us to develop targeted health products,”​ explains Dr Ratna Mukherjea, technical fellow and technology & innovation leader, specialized nutrition, DuPont Nutrition & Biosciences.

“This study marks a significant advancement in DuPont’s work in early life nutrition.”

In discussing the findings’ significance, the team referenced previous observations suggesting that Bi-26s approach could provide a “competitive advantage via rapidly depleting the preferred substrates (2′FL, 3FL, DFL) and preventing other bifidobacteria from accessing them.

“Additionally, through metabolism of small, fucosylated HMOs, Bi-26 creates a low pH environment that may exclude potential pathogens. Our findings support this conclusion.”

Pyruvate excretion

The team go on to discuss the excretion of pyruvate as another process characteristic of Bi-26, suggesting the action to be an adaptation to growing in the infant gut where acetate can accumulate in high concentrations.

Switching to pyruvate excretion as an additional fermentation end product under conditions, where there are high levels of acetate and lactate, which can affect bifidobacterial growth and function, could be a valuable strategy of energy generation.

“We hypothesise that the pyruvate and L-fucose excretion by B. infantis Bi-26 reported in this study may represent additional potentially important factors in the ecological role of bifidobacteria in infant gut,” ​the study concludes.

“[This bifidobacteria] acts directly on the human colon epithelial cells or through cross-feeding to yield the health benefits associated with infant gut microbiota if dominated by B. infantis.”

Source: Scientific Reports

Published online: doi.org/10.1038/s41598-020-72792-z

“Strain-specific strategies of 2′-fucosyllactose, 3-fucosyllactose, and difucosyllactose assimilation by Bifidobacterium longum subsp. infantis Bi-26 and ATCC 15697.”

Authors: Zabel et al.

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