Friendly Gut Bacteria and the Premature Baby's Brain: What a Dutch Study Found, and What It Has Not Yet Shown

A family-friendly guide to a study from the NutriBrain trial (Voulgari-Kokota et al., Gut Microbes 2026) of a daily "synbiotic" supplement for babies born before 30 weeks

Doctors have long wondered whether the bacteria that settle in a premature baby's gut could affect how the baby's brain develops. In a Dutch trial of 99 babies born before 30 weeks, a daily supplement of a friendly bacterium, prebiotic fibres and glutamine quickly helped healthy bacteria take hold, but brain scans showed no difference in injury between the groups. A link between certain gut bacteria and brain development is promising, not yet proof.

Why a baby's gut and brain might be connected

About 11 in every 100 babies worldwide are born too early [1], and in roughly two out of three cases there is no obvious reason why [2]. Babies born very early arrive while their brain is still building its "wiring": the white matter, the bundles of nerve fibres that carry messages between different parts of the brain. Over the past twenty years, brain scans taken around a premature baby's original due date have shown that changes in this white matter are common, especially in the smallest babies, and that infections around the time of birth are among the things that make them more likely [3]. Doctors developed a scoring system, called the Kidokoro score, to describe these changes on scans, and it confirmed that the white matter is the part of the brain most often affected [4]. Experts now describe the effects of early birth on the brain as a recognised condition in its own right [5], yet there is still no medicine that protects the white matter. Good nutrition seems to help, but researchers have said that carefully controlled studies are needed [6].

At the same time, scientists were learning about the gut "microbiome", the community of bacteria living in the intestines. In premature babies, these bacteria arrive in a fairly predictable order over the first weeks [7]. Studies then noticed patterns: in a large French study, babies whose gut was dominated by certain bacteria (called Enterococcus and Staphylococcus) in their fourth week were more likely to have a poorer outcome at age two (death or delayed development) [8], and in a smaller study in Vienna, an overgrowth of a bacterium called Klebsiella went along with brain damage in extremely premature babies [9]. These studies could only show that things happened together, not that one caused the other.

Many neonatal units already give probiotics, which are supplements of live friendly bacteria, mainly to prevent a serious bowel illness called necrotising enterocolitis and blood infections. The results depend heavily on which bacterium is used: a large review of 51 studies found that only some products helped [10], and a big English study of one Bifidobacterium breve strain, the Probiotics in Preterm Infants Study (PiPS), carried out in 24 hospitals in southeast England, found no benefit [11]. The ingredients chosen for the Dutch study each had some earlier support. The bacterium B. breve M-16V settled well in babies' guts without causing harm in an Australian study [12]; glutamine, a building block of protein, was linked to fewer serious infections [13]; and prebiotic fibres, which act as food for friendly bacteria, appeared safe [14]. Nobody had yet tested all three together in premature babies, or asked whether they might help a premature baby's brain [15].

How the study worked

The study was part of the NutriBrain trial (a study of a nutritional supplement designed to support brain development in very premature babies) [15]. It was run from the neonatal intensive care unit of University Medical Center Utrecht in the Netherlands, and babies who moved to one of seven regional Dutch hospitals kept receiving their supplement there [1]. Between October 2018 and May 2022, 99 babies born between 24 and 30 weeks of pregnancy took part. By chance, like a coin toss, 50 were given the real supplement and 49 a look-alike dummy powder, called a placebo, with similar calories. Neither parents nor staff knew which babies received which.

The supplement is called a "synbiotic" because it combines a probiotic (the friendly bacterium B. breve M-16V) with prebiotic fibres that feed it, plus glutamine. Babies received it every day, with the bacterium given by feeding tube or syringe and the fibres and glutamine added to their milk, from two to three days after birth until they reached the equivalent of 36 weeks of pregnancy or went home. The researchers read the bacterial DNA in repeated nappy samples, like taking a census of who lives in the gut, and looked at each baby's brain with an MRI scan, a detailed picture taken with magnets rather than X-rays, around the original due date. Gut data were available for 84 babies, and both gut data and a brain score for 76. Of the 84 babies with gut data, about 72 out of every 100 in each group were fed mainly their mother's milk.

What happened in the babies' guts

The supplement worked quickly at its first job. At one week of age, the friendly bacterium was found in about 97 out of every 100 supplemented babies, compared with about 9 out of every 100 babies on the placebo [1]. Supplemented babies had more Bifidobacterium, the group of bacteria typical of healthy breastfed babies, and fewer Staphylococcus and Enterococcus in the early weeks. Their gut bacteria also carried more genes for making protein building blocks and for producing acetate and lactate, natural substances made when bacteria ferment sugars. The differences in gut bacteria faded after about six weeks, and the differences in bacterial genes after about three weeks; babies in both groups gained weight similarly.

Interestingly, by three weeks the friendly bacterium had also turned up in about 44 out of every 100 babies on the placebo. Bacteria can pass between babies in the same unit, something also seen in another neonatal unit during an earlier probiotic study [16].

What the researchers found about the brain

This is the most important part to read carefully. When the brain scans were scored, the babies who got the supplement and the babies who got the placebo did not differ in signs of brain injury [1].

The researchers then looked at all the babies together, regardless of group. Of 65 babies with gut samples at three weeks and a brain score, 20 showed slower development of myelin, the protective coating that helps nerve fibres send signals quickly. Those 20 babies had had fewer bacterial genes for making acetate and lactate at three weeks, the same genes the supplement had boosted. The researchers think these substances might calm inflammation and support the developing brain, an idea supported by studies in mice showing that bacterial products help immune cells in the brain mature [17]. A similar pattern appeared for a second scan feature. Eleven babies had a thinner corpus callosum, the thick bridge of nerve fibres joining the two halves of the brain, and their gut bacteria at one week looked different, with relatively more of a bacterium called Staphylococcus haemolyticus compared with B. breve. Other brain measurements showed no link with gut bacteria. But because this was an after-the-fact comparison, it shows that two things went together, not that the supplement improves the brain.

What this means for your baby

If your baby is in a neonatal unit today, this study does not mean you should ask for a probiotic to protect the brain. Decisions about probiotics are still based on their proven effects on bowel illness and infection, and those effects depend on the particular product [10]. If your unit already gives a probiotic, this study does not change that; it simply has not answered the brain question yet.

What families can take away is encouraging: a baby's gut bacteria can be gently shaped in the first weeks, and the bacteria that thrive there may matter for more than the gut. Your own breast milk remains valuable, and a review of earlier studies found that receiving more human milk was often linked with better white-matter development [6]. If you have questions about supplements, your baby's medical team is the best place to start. Useful questions include whether your unit gives a probiotic, which one it uses, and what it is meant to prevent.

Things to keep in mind

The study was fairly small and mainly based in one hospital, which may limit how well the results apply elsewhere. The supplement contained three ingredients, so no single one can be credited. The study was partly paid for by Danone Research & Innovation, and five of the researchers worked there, although the authors report that they were not involved in analysing the gut or brain data [1]. Another part of Danone supplied the study products [15]. The paper did not report information on side effects, so it cannot tell us about safety beyond weight gain.

What researchers are working on next

The NutriBrain team planned to measure the white-matter "wiring" in more detail on the brain scans and to check the children's development at two years of age [15]. We could not find any publication of those results yet; they will show whether the supplement makes a real difference. Researchers also want to measure the actual substances made by gut bacteria, and to compare different friendly bacteria. You can read more about how friendly bacteria products compare in preventing bowel illness at https://inneosight.org/en-US/articles/probiotics-nec-nma2025.

The bottom line

A daily supplement of a friendly bacterium, prebiotic fibres and glutamine quickly helped healthy bacteria settle in the guts of very premature babies in Utrecht [1]. Brain-injury scores were the same in both groups, and the link between gut bacteria and myelin development is a promising clue rather than proof. The trial's main brain results, still to come, will tell families and doctors much more.

References

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  2. Vogel JP, Chawanpaiboon S, Moller AB, Watananirun K, Bonet M, Lumbiganon P. The global epidemiology of preterm birth. Best Pract Res Clin Obstet Gynaecol. 2018;52:3-12. doi:10.1016/j.bpobgyn.2018.04.003 ↩
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  9. Seki D, Mayer M, Hausmann B, et al. Aberrant gut-microbiota-immune-brain axis development in premature neonates with brain damage. Cell Host Microbe. 2021;29(10):1558-1572.e6. doi:10.1016/j.chom.2021.08.004 ↩
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