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Babies who have a strong immune reaction in the first week of life seem to have triple the risk of developing an allergy or eczema by age 1, compared with those who don’t. But the long-term impact of this early immune response, now defined for the first time, seems to be modulated by the microbiome and how babies are fed.

“If you ask 100 immunologists, they would say that immune development begins at birth and continuously develops over time, without discrete phases,” says Petter Brodin at Imperial College London.

But at a talk at an immune conference in London earlier this month, Brodin challenged this idea. He revealed that he and his colleagues have found that if a baby has a strong immune response in the first week of life, this seems to have an oversized impact on how the infant’s immune system subsequently develops. “That’s a novel concept,” he said during the talk.

In ongoing research, Brodin and his colleagues have been studying nearly 600 infants in Sweden, collecting and analysing blood and stool samples from the infants throughout their first year of life. The analysis revealed that about half the babies had what the researchers termed a strong “seeding” immune reaction during the first week of life, marked by high levels of inflammatory molecules such as interferon gamma, which activates immune cells. The remaining infants had lower levels of these inflammatory molecules during the first week, which the team called a weak seeding reaction.

Further analysis revealed that babies with a strong seeding reaction had substantially more Bacteroides bacteria in their gut than those who had a weak reaction. “A high abundance of Bacteroides bacteria seems to drive seeding reactions to be very strong,” says Brodin – although it is also possible that the variation in levels of the bacteria actually resulted from differences in the severity of the seeding reaction. Babies can pick up these bacteria via interactions with their mother and family members, he says.

The researchers think the effects of the seeding reaction last for only about a week at the beginning of life because that is when the gut is especially leaky, enabling bacteria like Bacteroides to enter the bloodstream and activate immune cells. “Healthy infants are born with a leaky gut that closes up after about a week,” says Brodin.

But the seeding reaction may have lasting effects: by sifting through the infants’ medical records, the researchers found that 39 per cent of those with a strong seeding reaction developed either eczema or a food allergy by age 1. In contrast, just 12 per cent of infants with a weak seeding reaction developed at least one of these conditions, which are caused by excessive inflammation. “What we ideally want is a weak seeding reaction,” says Brodin.

Further analysis revealed that the infants with a strong reaction then followed one of three immune trajectories linked to two main factors: whether they were primarily fed breast or formula milk, and the abundance of bifidobacteria in their gut.

For instance, 50 per cent of babies who had a strong seeding reaction and were breastfed – but had low levels of bifidobacteria – developed eczema or food allergies. Breastfed infants who had a strong seeding reaction and had high bifidobacteria levels were less likely to develop eczema or food allergies, with 25 per cent of them doing so.

The researchers also found that 33 per cent of infants who had a strong seeding reaction and were fed formula milk developed eczema or an allergy by age 1. In the work presented at the conference, the team didn’t give details of bifidobacteria levels in the guts of these formula-fed babies.

Brodin says the bifidobacteria may be important because they break down certain sugars in breast milk, known as human milk oligosaccharides (HMOs), to produce anti-inflammatory molecules called short-chain fatty acids. In turn, these can prevent the immune system from overreacting, he says. The researchers plan to explore why exactly the other links may have emerged in future research, says Brodin.

“This is a really important piece of work. Only a few studies have looked at immune development during the first week after birth,” says Lucy Crouch at the University of Birmingham in the UK. The research could reveal ways to develop personalised medicine for infants, she says.

For instance, you could imagine measuring whether a baby has a strong or weak seeding reaction, then, depending on whether they are breastfed or not and their levels of bifidobacteria, you could give them a probiotic that boosts these microbes to cut their allergy or eczema risk, she says.

But further research is needed to establish whether the seeding reaction has effects beyond the first year, says Crouch. Studies should also explore whether the links made in the study really are causal, she says, which could be done by tracking how immune cells within gut organoids – clumps of lab-grown cells that are used to mimic the intestines – react to bacteria in the presence or absence of HMOs.

“The reported differences in allergy and eczema risk are striking, but they show associations rather than demonstrating that particular microbes or immune responses directly cause the later outcomes,” says Lindsay Hall, also at the University of Birmingham.

For now, parents shouldn’t alter how they feed or interact with their infants based on the results. “It is much too early to suggest that the findings should change advice to parents,” says Hall.

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