Preterm birth defined as birth before 37 weeks of gestational age, is a leading cause of perinatal mortality and morbidity. The preterm birth rate has increased mostly in industrialised countries and is currently a global health challenge. Common reasons for preterm delivery include preeclampsia or eclampsia (pregnancy-related high blood pressure disorders) and intrauterine growth restrictions. Race, low maternal BMI and periodontal disease are some of the documented risk factors for preterm birth. Over the years, data from studies have shown a strong correlation between the gut microbiota in preterm infants and short and long-term health outcomes. The gut microbiota refers to the trillions of microorganisms in the gastrointestinal tract. The establishment of the gut microbiota during infancy is crucial and has been shown to have health implications not just in infancy but long-term implications in adulthood.

In early infancy, the gut microbiota plays a key role in the development and maturation of the gastrointestinal tract and the immune system, protection against pathogens and in nutrient absorption. In preterm neonates, the establishment of optimal gut microbiota is disrupted due to various factors, such as delivery mode (preterm infants are mostly delivered by C-section which leads to gut colonization by skin microbiota instead of the maternal vaginal and rectal microbiota), antibiotic use and prolonged hospitalization in neonatal intensive care units (NICUs). Even before birth, preterm infants are exposed to microbes through premature rupture of membranes and intra-amniotic infection.

Research has shown that the gut microbiota of healthy term infants is different from that of preterm infants. For instance, healthy commensals such as bifidobacteria are known to dominate the microbiota of healthy-term infants. These microbes can metabolize complex human milk oligosaccharides (HMOs) in breast milk. They are also producers of beneficial substances such as short-chain fatty acids (SCFA) amongst others. On the other hand, the gut microbiota of preterm infants is dominated by gram negative species belonging mostly to the Enterobacteriaceae and Enterococcaceae families and a higher abundance of pathogenic or harmful microbial species such as Clostridium species. These microbial groups are readily available in hospital environments and NICUs and rapidly colonize the gut of preterm infants. Furthermore, Preterm infants have been shown to have a reduced microbiota diversity. Gut microbiota diversity refers to the number and species of microbial groups present in the gut. A healthy microbiota is associated with a higher and balanced diversity (Eubiosis). This aberrant gut microbiota of preterm infants has been associated with an increased risk of necrotizing enterocolitis (NEC), sepsis, and other health problems.

Probiotics are live microorganisms that, when administered in adequate amounts, confer health benefits to the host. Emerging research suggests that probiotics can positively impact the health of preterm neonates by modulating the microbiota-gut axis. Firstly, strains of probiotics belonging to the Lactobacillus and Bifidobacterium species have been shown to positively influence the gut microbiota of preterm infants, promoting the growth of beneficial bacteria such as Bifidobacterium and reducing the colonization by pathogenic organisms. Also, probiotics have shown potential in reducing the incidence of sepsis and improving feeding tolerance in preterm neonates. Other probiotic-related benefits reported in studies include strengthening the gut barrier function, enhancing immune responses, and modulating inflammation.

Most importantly, probiotic administration in preterm neonates has been associated with a decreased risk of NEC, a severe inflammatory bowel disease that primarily affects preterm infants. 

Necrotizing enterocolitis (NEC) is a serious gastrointestinal condition primarily affecting premature infants. Although the precise cause of NEC remains unclear, it is widely believed to result from a combination of factors, with the immaturity of the infant’s digestive system playing a critical role.

In premature infants, several factors contribute to the development of NEC:

1. Immature Gastrointestinal Function: Premature infants have underdeveloped digestive systems that may struggle to break down and transport food efficiently. This dysfunction can lead to a buildup of harmful substances, which may injure the intestinal lining.
2. Disrupted Intestinal Microbiota: An imbalance in the gut's microbial population, known as dysbiosis, can promote the overgrowth of harmful bacteria. These bacteria can invade the intestinal lining, triggering inflammation and increasing the risk of infection.
3. Impaired Intestinal Barrier Function: The intestinal lining in premature infants is less capable of acting as a protective barrier. This underdevelopment, which typically improves after 26 weeks of gestation, allows harmful bacteria to cross into the intestinal tissue, causing inflammation and tissue damage.
4. Inadequate Blood Supply (Ischemia): Insufficient blood flow to the intestines can deprive tissues of oxygen and essential nutrients, weakening the gut’s ability to defend against bacteria and repair damaged cells.
5. Immature Immune Response: Premature infants may have an underdeveloped immune system, which can limit their ability to fight off infections effectively. This reduced defense mechanism increases the risk of inflammatory responses that can exacerbate intestinal injury.
6. Limited Production of Protective Secretions: The premature gut may produce insufficient amounts of protective substances, such as mucus and antimicrobial peptides, which normally help maintain a healthy balance of bacteria and protect the intestinal lining from harmful microorganisms.

The interplay of these factors makes premature infants particularly vulnerable to NEC. Early diagnosis and prompt management are essential to improve outcomes and reduce complications associated with this serious condition.

Symptoms of necrotizing enterocolitis (NEC) can vary from baby to baby but generally include diarrhea, lethargy (inactiveness), apnea (pauses in breathing), bradycardia (slowed heart rate), hypotension and constipation. A meta-analysis of 56 clinical trials and more than 10, 000 preterm infants showed that probiotic administration prevents NEC. The most used probiotics in the trials contained Bifidobacterium spp., Lactobacillus spp., Saccharomyces spp., and Streptococcus species as a single strain or a combination of strains. Currently, a large number of neonatal units in various countries across the world offer probiotics as standard of care for preterm infants at the risk of NEC following recommendations by health agencies. The European Society for Pediatric Gastroenterology Hepatology and Nutrition recommends that caregivers provide either Lactobacillus rhamnosus GG ATCC53103 or the combination of Bifidobacterium infantis Bb-02, Bifidobacterium lactis Bb-12, and Streptococcus thermophilus TH-4 to preterm infants to reduce NEC rate.

While probiotics have demonstrated potential benefits in preterm neonates, safety considerations should be of utmost importance. Answers to clinical questions such as the selection of probiotic strains, dosage, and timing of administration are still controversial and should be guided by evidence-based recommendations and clinical guidelines. Preterm infants have a delicate immune system and are susceptible to various infections that can be caused by organisms residing in the gut and as a result, caution must be exercised to ensure the safety of probiotic use. Adequate quality control measures should be in place to ensure the purity and viability of probiotic formulations before use.

In summary, the microbiota-gut axis plays a crucial role in the health and well-being of preterm neonates. Probiotics modulate the gut microbiota and improve the gastrointestinal health of preterm infants. However, further research is needed to establish optimal probiotic strains, dosages, and administration protocols. Collaborations between healthcare professionals, researchers, and regulatory bodies is essential to ensure the safe and effective use of probiotics in this vulnerable population. By harnessing the potential of probiotics, we can enhance the health outcomes of preterm babies and promote their overall well-being.