Microbiota in preterm infants and cord blood: what a twin-pair study teaches us

What happens to the microbiota in preterm infants when a baby is given back its own cord blood cells at birth? A randomised study measured exactly that, using an unusual design: comparing monozygotic twins, one treated with their own cells, the other with saline. In the treated infants a more balanced immune profile and a more varied microbial flora emerge.

The study design: two identical twins compared

The hardest variable to keep under control in clinical research is variability between individuals: genetics, environment and clinical history can all blur the reading of the results. Working with monozygotic twin pairs — same genome, same pregnancy, same moment of birth — removes much of that background noise.

In each pair, one twin received an infusion of ACB-MNC, the mononuclear cells obtained from their own cord blood, while the other was given saline. The comparison therefore takes place between two organisms that are as closely equivalent as biology allows.

Microbiota in preterm infants: why it forms under abnormal conditions

A baby born well before term carries an immune system that is not yet mature. Two consequences follow, and they feed each other:

  • a poorly regulated inflammatory response, which can be at once too weak against infection and too aggressive towards the infant’s own tissue;
  • a microbiota — the population of microorganisms colonising the gut and airways — that establishes itself in an atypical setting, often in intensive care, amid antibiotics and non-physiological feeding.

The two levels hold together: the microbiota in preterm infants helps to “educate” the immune system in the first months of life, and an immune system out of balance in turn reshapes microbial composition.

What was observed in the immune system

In the infants who received their own cord blood cells, researchers recorded a consistent shift towards immune homeostasis, that is, towards balance:

  • a rise in regulatory T cells (Treg), the lymphocytes tasked with containing the immune response and preventing it from turning destructive;
  • a fall in pro-inflammatory cytokines, IL-6 and IL-17A in particular;
  • an increase in anti-inflammatory factors such as IL-10 and TGF-β, which shield tissue from inflammatory damage.

This is not the picture of immunosuppression but of regulation: the system is not switched off, it is steered back towards a steadier state.

Microbiota in preterm infants: greater diversity in lungs and gut

The infusion also left its mark on organ microecology: in the treated infants, the diversity of the pulmonary and intestinal microbiota was higher than in the controls.

Microbial variety is a recognised health indicator: a differentiated bacterial flora supports metabolism, competes with pathogens and accompanies the maturation of the mucosal barrier. In the very preterm infant, exposed to the risk of necrotising enterocolitis and respiratory infection, it is anything but a theoretical parameter.

The clinical benefits recorded

Alongside the laboratory data, the study noted differences on the clinical level too. Compared with the control twin, the treated infants showed:

  • a lower number of the complications typical of prematurity;
  • better linear growth — height and physical development — over time.

How to read these findings

The scientific reading is that cord blood cells work as an early regulatory signal: they do not replace missing tissue, but steer both immunity and the microbiota in preterm infants at a stage when each is still malleable.

The structural limitation of the design remains: twin-pair studies guarantee excellent control, but on necessarily small numbers. Verification in larger cohorts is indispensable.

Important note — The applications described belong to the field of clinical research and are not approved therapies in current practice. None of the information provided should be taken as medical advice.

Microbiota in preterm infants: why SSCB follows this research

One aspect makes this line of research especially pertinent to the question of storage: the cells used are the baby’s own and must be administered within the hours or days immediately following delivery. The sample therefore has to be collected at birth, processed properly and made available within a very tight window.

These are precisely the parameters governed by the FACT-NetCord standards: minimum thresholds for total nucleated cells and CD34+, cell viability, storage temperature, ISBT 128 traceability. SSCB is the only Swiss biobank accredited to this standard.

Want to know how collection at birth actually works? Contact the SSCB scientific team.

Source Ren Z, Nie C, Xu F, et al. Autologous Cord Blood Mononuclear Cells Modulate Immunity and the Microbiota in Very Preterm Twins: A Randomized Trial. Stem Cell Rev Rep. 2026.

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