T Cells in Preterm Infants and the Influence of Milk Diet

Abstract

Preterm infants born before 32 weeks gestational age (GA) have high rates of late onset sepsis (LOS) and necrotizing enterocolitis (NEC) despite recent improvements in infection control and nutrition. Breast milk has a clear protective effect against both these outcomes likely due to multiple mechanisms which are not fully understood but may involve effects on both the infant's immune system and the developing gut microbiota. Congregating at the interface between the mucosal barrier and the microbiota, innate and adaptive T lymphocytes (T cells) participate in this interaction but few studies have explored their development after preterm delivery. We conducted a literature review of T cell development that focuses on fetal development, postnatal maturation and the influence of milk diet. The majority of circulating T cells in the preterm infant display a naïve phenotype but are still able to initiate functional responses similar to those seen in term infants. T cells from preterm infants display a skew toward a T-helper 2(T h 2) phenotype and have an increased population of regulatory cells (T reg s). There are significant gaps in knowledge in this area, particularly in regards to innate-like T cells, but work is emerging: transcriptomics and mass cytometry are currently being used to map out T cell development, whilst microbiomic approaches may help improve understanding of events at mucosal surfaces. A rapid rise in organoid models will allow robust exploration of host-microbe interactions and may support the development of interventions that modulate T-cell responses for improved infant health.

Chicory inulin enhances fermentation of 2′-fucosyllactose by infant fecal microbiota and differentially influences immature dendritic cell and T-cell cytokine responses under normal and Th2-polarizing conditions

“…21 Tailoring infant formula with new combinations of NDCs including HMOs might be of interest not only for babies with lower fermentability possibilities but also for example, for infants with different immune backgrounds, like preterm infants who have deviated T-lymphocyte (T-cell) responses. 22 Naïve T-cells play an important role in the defense against infections. After encountering antigen presenting cells like DCs, the naïve T-cells are activated and differentiate toward antigen specific T-cells.…”

“…In preterm infants naïve T-cells skew toward a T-helper 2 (Th2) phenotype, while they have a diminished T-helper 1 (Th1) response. 22 As newborns are exposed to many new antigens, this makes them more susceptible to infections by intracellular pathogens. 22 Dietary interventions are able to restore the balance between Th1 and Th2 responses.…”

“…22 As newborns are exposed to many new antigens, this makes them more susceptible to infections by intracellular pathogens. 22 Dietary interventions are able to restore the balance between Th1 and Th2 responses. For example, HMOs from preterm milk have been shown to promote Th1 responses and suppress Th2 responses in fetal in vitro organ cultures, 23 indicating that they contribute to healthier and more balanced T-cell responses.…”

Influence of Nutrition and Maternal Bonding on Postnatal Lung Development in the Newborn Pig

“…A number of factors contribute to adequate initial bacterial colonization in the newborn, including one important determinant, breast milk-based nutrition. Breast milk contains a variety of components that can affect intestinal mucosal immunity, as demonstrated in both humans and animal models of early life (46). The human lower airway microbiome forms within the first two postnatal months, and the mode of delivery determines the airway microbiota in preterm but not term births (12).…”

The Roles of Prebiotics on Impaired Immune System in Preterm Infants: A Narrative Literature Review

“…The study also found that weight gain was not significantly affected 25 . The stimulation of Bifidobacteria was found to be associated with a reduced presence of clinically relevant gut pathogens 33 .…”