Order matters: Bifidobacterium species with weak HMO-utilising ability can dominate gut if present at birth

08-Aug-2022 - Last updated on 08-Aug-2022 at 01:16 GMT

Bifidobacterium breve can dominate a baby's gut if present at birth. ©Getty Images

Bacteria species that can feed on a wide range of human milk oligosaccharides (HMOs) are known to grow and dominate an infant’s gut microbiota, but this is not always the case, with a new research showing how the order of bacteria exposure could be more important.

The research, conducted by Japanese dairy giant Morinaga Milk and several institutions, including Kyoto University and University College Cork, specifically studied the Bifidobacterium species.

Bifidobacteria are among the first colonisers of the infant gut, commonly representing 70 per cent of the total gut microbial community in a breastfed infant.

The conventional understanding is that Bifidobacterium species with strong ability to utilise HMOs – which is found in mothers’ breastmilk – are able to grow and dominate an infant’s gut microbiota.

However, this particular research has shown that certain Bifidobacterium species with limited ability to feed on HMOs, in this case B. breve, can outgrow species with strong HMOs-feeding ability – if it was present in the infants’ gut within 24 hours after birth.

Findings published in The ISME Journal showed that B. breve is able to dominate against species that can better utilise HMOs, such as B. bifidum and B. longum subsp. infantis (B. infantis) in an in vitro setting.

“When B. breve was first (inoculated), priority effects and substantial growth were observed, as it dominated and drove B. bifidum to near extinction despite its limited HMO-consumption ability and low growth in HMO-supplemented medium during monoculture,” the researchers highlighted.

This is because of B. breve’s ability to utilise fucose – an HMO degradant produced by B. bifidum and B. infantis and not utilised by the other Bifidobacterium species.

This is also why B. breve growth remained low until B. bifidum and B. infantis were introduced, showing that both have a “facilitative” effect on B. breve growth.

Research method

The research was conducted in-vitro using mediums containing the HMOs 2’-fucosyllactose (2’-FL), 3-fucosyllactose (3-FL), lactodifucotetraose (LDFT), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-fucopentaose (LNFP) I, LNFP II/III, and lacto-N-difucohexaose (LNDFH) I.

This was followed by analysing in vivo faecal metagenomics data from a cohort of European infant-mother pairs. Infants who were at least partially breastfed at four months were chosen for the analysis.

Results show that if B. breve was present in the infant gut microbiota at birth, it was more likely to dominate in the community at four months of age – which displayed trends consistent with the in-vitro experiment.

“We found that the presence of B. breve at birth (40 out of 73 infants) was associated with its dominance at four months (p=0.029), while such patterns were not observed for B. bifidum or the B. longum group.”

The findings have shed light on the circumstances in how certain Bifidobacterium species come to dominate an infant’s gut, the researchers pointed out.

“Our results provide insight into previously unexplained B. breve abundance in breastfed infants. Despite certain limitations, we demonstrate the prevalence of priority effects in bifidobacterial communities, particularly for B. breve, and found that early introduction by just a few taxa has the potential to divert the maturational trajectory of the microbial community,” said the researchers.

Ranking the species

According to the in vitro monoculture experiment, the researchers found that B. bifidum and B. infantis showed substantial growth and have the greatest potential in dominating an infant’s gut due to their ability to utilise a variety of HMOs.

Their usage of the HMOs in turn deplete resources for later arriving Bifidobacterium species.

Specifically, B. bifidum and B. infantis were found to consume all HMOs, B. longum consumed LNT and fucosylated HMOs, namely 2’-FL, 3-FL, LDFT, and LNFP I.

On the other hand, B. breve only utilised LNT and LNnT.

As such, B. longum subsp. longum (B. longum) showed moderate growth, while B. breve showed limited growth.

Taking a step further, the researchers then assessed if timing matters by adding these four strains to the HMO culture medium in different orders.

When B. infantis was added to the medium followed by B. bifidum, it was found that B. bifidum was a stronger competitor and dominated the culture.

“Priority effects were stronger for B. bifidum, and it was a stronger competitor overall as it dominated in simultaneous culture and also maintained a stable population even when B. infantis was first.”

However, when comparing between B. bifidum and B. longum, the latter was able to dominate the culture when it was added first, possibly because it was able to utilise the HMO-degradants produced by B. bifidum.

Source: The ISME Journal

Priority effects shape the structure of infant-type Bifidobacterium communities on human milk oligosaccharides

https://doi.org/10.1038/s41396-022-01270-3

Authors: Ojima, M.N., Jiang, L., Arzamasov, A.A. et al.