Probiotics In The Prevention Of Necrotising Enterocolitis: Current Research And Recommendations
Published on: September 19, 2025
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GAYATRI MILIND SAUDI

Master of Pharmacy in Analytical Chemistry

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Menar Albesheir

Msc Physician Associate, SGUL

Introduction

Necrotising enterocolitis (NEC) is an extremely serious yet common gastrointestinal disease that usually affects newborn infants.  It is considered a medical emergency. 

The number of very low birth weight (VLBW) babies who survive is growing due to improved medical technology. However, about 7% of these babies still get NEC. A study showed that 9% of NEC cases in one children's hospital over 30 years were in full-term babies. Full-term babies with NEC usually have other health challenges too, such as cardiac issues or poor fetal growth well during pregnancy. NEC might affect full-term and preterm babies differently.1

In this article, we will explore the role of probiotics in preventing NEC and promoting the well-being of preterm infants. We will see how probiotics modulate the gut microbiome, reduce inflammation, and strengthen the intestinal barrier. Additionally, we will help you understand how probiotics can improve clinical outcomes and guide better neonatal care practices.

Understanding NEC and its pathophysiology

NEC is a serious condition that occurs when harmful bacteria invade the lining of a baby's intestine. This can lead to inflammation and damage to the intestinal tissue, making it difficult for the baby to digest food properly and absorb nutrients. In severe cases, the tissue may start to die, which can lead to serious complications if not treated promptly. This causes swelling and damage to the intestinal wall. If NEC isn’t caught and treated in time, it can cause a hole to form in the intestine. This allows the contents of the intestine to leak into the belly, which can lead to a serious infection known as peritonitis. We do not yet know exactly how or why the bacteria invade. In premature babies, the immature digestive system is thought to contribute to NEC.2

The intestinal wall in patients with NEC  becomes inflamed and invaded by bacteria. As the disease gets worse, the tissue loses blood supply, dies, and eventually tears. This tear can be small (microperforation) or large. Microperforation causes air to enter the intestinal wall. If a tear occurs, bacteria and bowel contents leak into the abdominal cavity, causing a serious infection called peritonitis.2

Recent advancements in the understanding of NEC indicate that the epithelial barrier, innate immunity, and the inflammatory response are critical in very preterm infants. Stress on the intestinal lining caused by things like feeding, harmful bacteria, or low blood flow can trigger inflammation, especially in premature babies whose bodies aren’t fully ready to defend or heal themselves. This chain reaction is the main process that leads to intestinal damage and the development of NEC.3

What Are Probiotics?

Probiotics are friendly live microbes that, when taken in the right amount, can promote gut health. These germs are mostly bacteria, but they can also be yeasts. You can find them in some fermented foods like yogurt, in certain food products, and as dietary supplements. But not all products labeled as probiotics are good for the gut. Probiotics are different from prebiotics, which are complex carbs that germs in your gut use for energy. Some products have both prebiotics and probiotics and are called synbiotics. Probiotics are also different from postbiotics, which are made of dead or broken germs and their byproducts that can still be good for your health.4

Probiotics are foods and health products that add helpful microbes to your gut and other parts of your body. They help keep the balance of good microbes in your microbiome. When they work, these microbes live in or on your body, joining the ones already there. Not all probiotics are the same. Different microbes work differently in your body, so some might be better for you than others. Probiotics are not checked by the Food and Drug Administration (FDA, US-based) so companies don't have to prove what's in their products. It's smart to talk to a healthcare provider to find out which probiotics might be best for you.5

Current Research Evidence

After birth, babies need to develop a normal mix of gut bacteria. This helps their immune system grow and keeps their intestines working well. If this normal gut bacteria mix is disturbed, it might lead to NEC in premature babies. Probiotics are live bacteria that can be good for health when taken in the right amounts. They can stop harmful bacteria from growing and help the immune system. Probiotics also help by preventing harmful bacteria from attaching to the walls of the gut. Giving probiotics by mouth is one way to prevent NEC by increasing good bacteria in the gut. Over the past 20 years, a lot of research has looked into whether giving probiotics to preterm babies can help lower the risk of NEC.6

A study shows that giving Bifidobacterium strains, like Bifidobacterium breve, to premature babies lowers the chances of NEC, sepsis, and death compared to a placebo. These probiotics help prevent infections and reduce complications associated with NEC.7

Safety and Regulatory Considerations

Concerns have been expressed by some with regards to the lack of side effects reporting with probiotic use.  But when it comes to preterm babies, most studies haven’t shown much difference in issues, such as bloating, diarrhea, vomiting, or feeding troubles when probiotics are used. Reviews of these trials show that probiotics help babies feed better and shorten hospital stays, The main risks of probiotics is sepsis from the probiotic itself and infections from contaminated products. Probiotic sepsis has been reported in common probiotics given to preterm babies, but it might be underestimated because it's hard to identify certain bacteria. Large studies looking for probiotic sepsis have not found cases. The drop in death rates and sepsis with probiotics suggests that probiotic sepsis is rare and that probiotics help reduce infections. In summary, probiotics have both risks and benefits. Doctors and parents must consider these when deciding to use probiotics for very preterm babies. The risks seem low and might be similar to or less than the risk of Cytomegalovirus infection from unpasteurised mother's milk.8

Future Directions

Preventing and treating NEC is very important for caring for very low birth weight preterm babies. Many neonatal intensive care units use probiotics, human milk, and antibiotics to stop NEC, but no one has done a detailed comparison of these methods. In this study, we found that preventing NEC changes the bacteria in the gut a lot. It also affects the fungi, archaea, and viruses in the gut in specific ways at different centers. This is important for archaea and viruses because NEC prevention methods do not directly target these parts of the microbiome.9

In the newer study, the VON is a group of over 1200 hospitals worldwide. They work together to compare outcomes and improve quality. The Vermont Oxford Network (VON) defines NEC as a diagnosis confirmed either during surgery, after death, or through clinical signs and X-ray findings, based on Bell staging criteria. Babies must show at least one of these signs: green vomit, swollen belly, or blood in stool (without a tear). They must also have one of these X-ray findings: air in the bowel wall, air in the liver area, or air in the abdominal cavity. If a baby has a bowel perforation found during surgery or after death, it is recorded as a different disease, not NEC. Recent studies show NEC cases in the US dropped from 7.1% in 2005 to 5.2% in 2014, using this definition.10

Today, more premature babies are surviving because of better technology and care. NEC is still a big problem for these babies. If we could find a way to diagnose NEC early and stop it with probiotics, it would change how we care for these babies. Current probiotics have not worked for everyone, so new ways to give probiotics might help prevent NEC.11

Summary

NEC is a severe and often life-threatening gastrointestinal condition that primarily affects premature infants. It occurs when bacteria invade the intestinal wall, leading to inflammation, tissue death, and potentially life-threatening infections like peritonitis. Despite advances in neonatal care that have improved survival rates among very low birth weight (VLBW) infants, NEC remains a significant concern, affecting around 7% of these babies.

Probiotics, which are live microorganisms that provide health benefits when taken in adequate amounts, have shown promise in preventing NEC. They work by promoting a healthy balance of gut bacteria, enhancing immune function, reducing inflammation, and preventing harmful bacteria from adhering to the gut lining. Research, including studies on specific strains like Bifidobacterium breve BBG-001, suggests that probiotics may play an important role in protecting preterm infants. These beneficial bacteria have been shown to help lower the chances of serious conditions such as NEC (a dangerous intestinal disease), sepsis (a life-threatening infection), and even reduce the risk of death in these vulnerable babies.

While probiotics are generally considered safe, there are concerns about rare cases of probiotic-induced sepsis and contamination of probiotic products. However, large-scale studies have not found significant evidence of such risks, and the overall benefits, such as improved feeding tolerance and reduced hospital stays, appear to outweigh the potential dangers.

Looking ahead, future research aims to compare different NEC prevention strategies, including the use of probiotics, human milk, and antibiotics. There is also a growing interest in understanding how these strategies affect the entire gut microbiome, including fungi and viruses. Additionally, developing new probiotic delivery methods and improving early diagnosis could transform the way NEC is managed in neonatal care. In summary, probiotics offer a promising and largely safe approach to preventing NEC and improving outcomes for premature infants.

FAQs

What is Necrotising Enterocolitis (NEC)?

NEC is a serious gastrointestinal disease that mostly affects premature infants. It occurs when bacteria invade the intestinal wall, causing inflammation, tissue damage, and, in severe cases, intestinal perforation and infection (peritonitis).

Who is most at risk for developing NEC?

Premature infants, especially those with very low birth weight (VLBW), are most at risk. However, NEC can also affect full-term babies, particularly those with other health issues like heart defects or poor intrauterine growth.

How do probiotics help in preventing NEC?

Probiotics help by:

  • Balancing gut bacteria
  • Enhancing immune function
  • Reducing gut inflammation
  • Preventing harmful bacteria from adhering to the intestinal wall

Which probiotic strains are effective against NEC?

Strains like Bifidobacterium breve BBG-001 have shown significant benefits in reducing NEC incidence, sepsis, and mortality in premature infants.

Are probiotics safe for preterm babies?

Generally, yes. Clinical trials have found few side effects, such as bloating or feeding issues. However, rare cases of probiotic-related sepsis have been reported, mostly from contamination or improper handling.

Are all probiotic products suitable for infants?

No. Not all probiotics are created equal. The effectiveness and safety of probiotics depend on the strain, dosage, and product quality. Always consult a neonatologist or pediatrician before using them.

What’s the difference between probiotics, prebiotics, and synbiotics?

  • Probiotics are live, beneficial microbes
  • Prebiotics are non-digestible food components that feed good bacteria
  • Synbiotics combine both probiotics and prebiotics

Is the use of probiotics regulated?

In most countries, probiotics are classified as dietary supplements, not drugs, meaning they are not strictly regulated by agencies like the FDA. Healthcare providers should guide their use.

Do probiotics completely prevent NEC?

Not completely. While they significantly reduce the risk, probiotics do not eliminate NEC in all infants. They are most effective when used as part of a broader care strategy.

What other methods are used to prevent NEC besides probiotics?

Other strategies include:

  • Feeding with human milk
  • Controlled use of antibiotics
  • Strict infection control practices in NICUs

What are researchers focusing on for the future of NEC prevention?

Future directions include:

  • Improved probiotic delivery methods
  • Early diagnosis tools for NEC
  • Comparing probiotics with other preventive strategies
  • Studying the gut’s full microbiome (including viruses and fungi)

What should parents consider before giving probiotics to their infant?

Parents should:

  • Consult their neonatologist
  • Understand the benefits and rare risks

Ensure the product is from a reputable source with proven strains and dosages

References

  1. How many infants are at risk for necrotizing enterocolitis (NEC)? | NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development [Internet]. 2024 [cited 2025 May 28]. Available from: http://www.nichd.nih.gov/health/topics/nec/conditioninfo/risk.
  2. Ginglen JG, Butki N. Necrotizing Enterocolitis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 May 28]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK513357/.
  3. Choi YY. Necrotizing enterocolitis in newborns: update in pathophysiology and newly emerging therapeutic strategies. Korean J Pediatr [Internet]. 2014 [cited 2025 May 30]; 57(12):505–13. Available from: http://www.e-cep.org/journal/view.php?doi=10.3345/kjp.2014.57.12.505.
  4. Office of Dietary Supplements - Probiotics  [Internet]. [cited 2025 May 28]. Available from: https://ods.od.nih.gov/factsheets/Probiotics-HealthProfessional/.
  5. What Are Probiotics & What Do They Do? Cleveland Clinic [Internet]. [cited 2025 May 30]. Available from: https://my.clevelandclinic.org/health/treatments/14598-probiotics.
  6. Jin Y-T, Duan Y, Deng X-K, Lin J. Prevention of necrotizing enterocolitis in premature infants – an updated review. World J Clin Pediatr [Internet]. 2019 [cited 2025 May 30]; 8(2):23–32. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477149/.
  7. Abdullahi AM, Zhao S, Xu Y. Efficacy of probiotic supplementation in preventing necrotizing enterocolitis in preterm infants: a systematic review and meta-analysis. The Journal of Maternal-Fetal & Neonatal Medicine [Internet]. 2025 [cited 2025 May 30]; 38(1):2485215. Available from: https://www.tandfonline.com/doi/full/10.1080/14767058.2025.2485215.
  8. Underwood MA, Arch EUM, Patel RM. Safety and Efficacy of Probiotic Administration to Preterm Infants: Ten Common Questions. Pediatr Res [Internet]. 2020 [cited 2025 May 30]; 88(Suppl 1):48–55. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210852/.
  9. Neumann CJ, Mahnert A, Kumpitsch C, Kiu R, Dalby MJ, Kujawska M, et al. Clinical NEC prevention practices drive different microbiome profiles and functional responses in the preterm intestine. Nat Commun [Internet]. 2023 [cited 2025 May 30]; 14(1):1349. Available from: https://www.nature.com/articles/s41467-023-36825-1.
  10. Patel RM, Ferguson J, McElroy SJ, Khashu M, Caplan MS. Defining Necrotizing Enterocolitis: Current Difficulties and Future Opportunities. Pediatr Res [Internet]. 2020 [cited 2025 May 30]; 88(Suppl 1):10–5. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096612/.
  11. Wala SJ, Ragan MV, Sajankila N, Volpe SG, Purayil N, Dumbauld Z, et al. Probiotics and novel probiotic delivery systems. Seminars in Pediatric Surgery [Internet]. 2023 [cited 2025 May 30]; 32(3):151307. Available from: https://www.sciencedirect.com/science/article/pii/S1055858623000549.
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GAYATRI MILIND SAUDI

Master of Pharmacy in Analytical Chemistry

I, Gayatri Saudi, a Master of Pharmacy with a strong foundation in pharmacology and clinical research, I bring precision and clarity to complex medical topics. I specialize in creating evidence-based, regulatory-compliant, and engaging content for healthcare professionals and patients alike.

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