Introduction

Necrotising Enterocolitis (NEC) is a dreadful condition that mostly affects premature babies. It occurs when a portion of the intestinal tissue becomes inflamed, begins to die, and may eventually detach. This impairment can create a hole in the intestinal wall, allowing harmful bacteria to pass into the abdomen or bloodstream. As a result, the baby can develop a severe infection that requires intense medical care. This whole scenario in the intestine is nothing but Necrotising Enterocolitis (NEC).¹

This disease affects premature neonates in particular and, according to studies, it has a mortality rate as high as 50% in infants. NEC is the most common lethal emergency affecting the gastrointestinal system of infants. It typically occurs in the second to third week of life. Case studies have already identified plenty of risk factors, but premature birth, low birth weight, and formula feeding have been identified as primary risks. Specifically, formulas with high osmotic strength have been pointed out as a risk factor. Genetic factors also play an important role.¹

Although gut bacteria play a vital role in human health by supplying the right nutrients in the bloodstream, changes in their composition as a result of gut environment (microbiota) changes can be harmful.²

In this article, we look into how an imbalance in the gut microbiota can play a vital role in causing necrotising enterocolitis (NEC), which is a serious condition in newborns, especially preemies. By exploring how the gut microbiota normally works and what happens when that balance is disturbed, we aim to better understand why NEC develops. Our goal is to shed light on the connection between gut health and this disease, and to open doors for finding ways to prevent or treat NEC more effectively in the future.

Overview of gut microbiota

Normal colonisation process in neonates

The developing immune system of infants undergoes major development during infancy and is highly related to the microbes that colonise the intestinal tract. It has been observed that different initial exposure depends on the mode of delivery (vaginal or cesarean). Today, the number of babies delivered via caesarean section is increasing. As such, the interplay between microbial gut ecology and the developing mucosal immune system gets compromised and studies show an emerging link between this and disease, such as autoimmune disease. Therefore, depending on whether a baby has been delivered vaginally or via caesarean, the baby may experience changes in long term colonisation of the gut and subsequent altering of the immune system.³

Another factor that decides the quality of gut bacteria in human health is breastfeeding versus formula feeding. Recent studies have found that infants who are exclusively breastfed tend to have less microbial diversity in their gut compared to formula-fed babies, whose gut microbiota is more varied and similar to older children.⁴

Functions of a healthy gut microbiota

Nowadays, there is a lot of awareness about the gut microbiome and how it is related to overall human health. Recent studies and research have shown that having a healthy balance of gut bacteria plays a big role in keeping the entire body healthy.⁵

Typically, the gut is home to a mix of different microorganisms, with two main types, Bacteroidetes and Firmicutes, making up the majority of this microbial community. The gut microbiota of infants, however, is quite random, only beginning to mimic the adult flora by the age of 3 years. Although the types of microbes in our digestive system can vary from one part to another, from the esophagus to the rectum, this variation is temporary and natural. These changes in microbial distribution are important because they help shape and support the body’s immune system.⁵

The gut bacteria help absorb various nutrients, such as vitamins, carbohydrates, short-chain fatty acids, and proteins. Each component’s absorption has different pathways. Research shows that microbiota has substantial capacity to metabolise phytochemicals, particularly polyphenols, by diverse, well-characterised pathways. There is extensive evidence that certain components’ metabolism differs from individual to individual and affects the overall composition of gut microbiota.⁶

Pathogenesis of NEC

Multifactorial nature of NEC

This fatal disease in infants can occur abruptly within a few hours or may be preceded by several days of feeding intolerance. In severe cases, NEC, which affects the gastrointestinal tract of infants, may have a profound systemic impact. The symptoms that occur at this stage may be subtle and can include feeding intolerance, bloody diarrhoea, temperature instability, lethargy, apnea, bradycardia, and many other complications related to respiration. Hence, NEC is a complex multifactorial disease.⁷

Risk factors

As we have seen, there are so many different angles to NEC, and as this disease majorly affects infants, the risk factors are very high. That’s why awareness of NEC is very much necessary to reduce NEC risk, including human milk feeding, the use of feeding guidelines, and the use of probiotics, needs to be followed to reduce the incidence of NEC.⁸

In this condition, part of the baby's intestine becomes swollen and damaged. If the damage worsens, the tissue can die and even break away. This may lead to a hole forming in the intestinal wall, giving bacteria a pathway to enter the bloodstream. When that happens, it can cause a serious infection that needs immediate medical attention to protect the baby’s health. By studying all these risk factors of NEC, there are various treatments based on them.⁸ 

Role of intestinal immaturity

When a human newborn is born, it has a small intestine that is morphologically more mature than a rodent. While human intestinal development occurs in the womb of the mother, that is the uterus, while rodents have developed a small intestine postnatally. Therefore, rodents serve as an effective model for studying the development of the small intestine in humans.⁹

It has been observed that immature characteristics of epithelial cell types in preterm infants make them more vulnerable to infectious diseases, which leads to NEC development. The damage to the immune system and epithelial barrier occurs when there is a reduction in the expression levels of MUC₂ (goblet cells) and lysozyme (Paneth cells). Reinforcing the development of intestinal cells, especially goblet cells, Paneth cells, and enterocytes, can help keep the gut healthy and protect it from inflammation and other gut-related issues, diseases like NEC, as well as prevent harmful pathogens from invading the gut.⁹

Gut microbiota in NEC

Changes in the composition and quality of gut microbiota is known as dysbiosis, which can disrupt the balance of the intestinal environment and contribute to NEC. Many factors are crucial in NEC, such as maternal and postnatal influences, antibiotic use, and formula feeding, which can also affect the gut microbiome and increase NEC risk. Hence, gut microbiota plays a vast role in NEC.¹⁰

Microbial differences observed in NEC infants

While there have been no direct studies on the diversity or composition of the microbiome specifically linked to NEC, many case studies have confirmed that the microbiome of infants with NEC differs in number and diversity from that of healthy infants.¹⁰

 It has been determined that a single microbial species is not the cause of NEC. Instead, a combination of various microbes is responsible for the development of the condition. Abnormal gut microbiota composition may be an important factor in the pathogenesis of NEC, however it is not the sole cause. Targeting the characteristics and functions of the gut microbiota may help us to further study and understand the exact cause of NEC.¹⁰

Mechanisms of injury

Research has focused on understanding the underlying causes of intestinal cell damage in premature infants with NEC.

Key factors such as excessive production of reactive oxygen species (ROS), oxidative stress, and inflammation have been identified as major contributors to cell death in the intestines. One specific factor, TNF-α, is produced mainly through lipopolysaccharide (LPS) stimulation and plays a role in damaging intestinal cells by affecting tight junction proteins, promoting autophagy, and inhibiting cell growth. Therefore, it is crucial to examine and understand the mechanisms behind intestinal injury, how they disrupt the balance of the gut, and how they increase intestinal permeability in NEC.¹¹

Potential preventive and therapeutic strategies

After years of research, scientists have explored new strategies to prevent NEC, such as avoiding premature deliveries with low birth weights and using probiotics to avoid dysbiosis, for which breast milk is the best option, which is rich in probiotics. Preventing infections and managing inflammation are both crucial steps in ensuring better health and recovery.¹³

The therapeutic strategies involve withholding of enteral feeds(stopping in-between feedings), which can give the bowel time to rest and also aid in its recovery. Providing intravenous fluids ensures proper hydration and maintains electrolyte balance. In some severe cases, oral antibiotics are also used to address the bacterial growth and infections. If NEC gets progressive, it is vital to remove the necrotic tissue and surgery is advisable. Additionally, there are emerging therapies that are based on immunological interventions.¹³

Considering these approaches, treatment and prevention of NEC is often personalised to the infant suffering with the condition, considering the specific needs and circumstances of the infant.¹³

FAQS

Why does NEC specifically affect premature babies?

Premature babies have underdeveloped guts and weaker immune systems. Their bodies are not fully ready to handle feeding, bacteria, or stress, which increases their risk of NEC.

What are the primary signs and symptoms of NEC?

Common signs include a swollen belly, trouble feeding, vomiting, bloody stools, low energy, and changes in breathing or heart rate. A doctor should be called right away if these appear.

How is NEC diagnosed?

Doctors use a combination of physical exams, blood tests, and X-rays of the baby’s belly to check for signs of infection, inflammation, or holes in the intestine.

How is NEC treated?

Treatment includes stopping feeds, giving fluids and antibiotics through an IV, and closely monitoring the baby. In severe cases, surgery may be needed to remove the damaged part of the intestine.

Can NEC be prevented?

Yes, to some extent. Breastfeeding, giving probiotics, reducing antibiotic use, and feeding babies slowly and carefully can help lower the risk. However, if your baby is at risk of NEC, your healthcare provider will advise you on the best course of preventative intervention.

Why is breastfeeding important in NEC prevention?

Breast milk contains helpful bacteria and nutrients that support gut and immune system development. It also protects against harmful bacteria that may cause NEC.

What role do gut bacteria play in NEC?

Healthy gut bacteria protect the baby’s intestine and help with digestion. An imbalance (too many harmful bacteria) can lead to inflammation and NEC.

Is NEC common?

It affects about 1 in 1,000 newborns, but the risk is much higher in premature babies, especially those born before 32 weeks of pregnancy.

What happens after a baby recovers from NEC?

Some babies recover fully, while others may have long-term issues like feeding problems or growth delays.

Summary

Necrotising enterocolitis (NEC) is a serious and often life-threatening condition that mostly affects premature and low birth weight babies. It causes swelling and damage in the baby’s intestines, sometimes creating holes in the gut wall, which can lead to dangerous infections. NEC is a life-threatening condition, and in severe cases, it can lead to death in as many as half of the affected infants.

NEC has been associated with multiple causes, such as underdeveloped intestines, gut bacteria imbalance, and how and what the baby is fed. Babies born early, fed formula (especially formulas with high osmotic strength), or delivered by cesarean section have a greater risk of developing NEC, since they miss early exposure to helpful bacteria and breast milk.

A healthy balance of gut bacteria is essential for building a baby’s immune system and helping with digestion. In babies with NEC, this balance is off, leading to the development of harmful bacteria, more inflammation, and tissue damage. When the body is under stress or experiencing inflammation, it can make the situation even more challenging, often worsening existing health issues.

To prevent NEC, breastfeeding, using probiotics, avoiding unnecessary antibiotics, and following careful feeding routines can help. Treatment may involve stopping feeds to let the gut rest, giving fluids and antibiotics, and sometimes surgery. Researchers are also looking at immune-based treatments. Understanding how gut health and immunity work together can help save lives.