410 - Probiotic Supplementation in Very Low Birthweight (VLBW) Infants: Effects on Systemic Immunity and Inflammation

Poster Number: 410
Publication Number: 410.334

Keisha D. Wolfe, Georgetown University School of Medicine, Alexandria, VA, United States; Elizabeth A. Reznikov, University of Washington/Seattle Childrens Hospital, Seattle, WA, United States; Michael Pippa, Medstar Washington Hospital Center, Arlington, VA, United States; Raymond K. Riley, Georgetown University School of Medicine, Alexandria, VA, United States; Lewis P. Rubin, Georgetown University Medical Center, Washington, DC, United States

Background: Trials and observational studies demonstrate that probiotics can reduce rates of necrotizing enterocolitis and late-onset sepsis in VLBW infants. Suspected mechanisms include decreased intestinal dysbiosis and immune system maturation. However, no studies have comprehensively interrogated serum pro-/anti-inflammatory and immunomodulatory profiles over time or probiotic effects on systemic innate and adaptive immunity.

Objective: Investigate effects of daily probiotics on longitudinal serum immune/inflammatory profiles in preterm infants enrolled in a randomized trial of ‘omics’ (microbiomic, metabolomic, proteomic) outcomes. A central hypothesis is probiotic administration will promote Th2 (T helper cell 2) and T regulatory (Treg) responses and suppress inflammatory Th1/Th17 polarization, thereby suppressing systemic inflammatory profiles.

Design/Methods: Following parental informed consent, infants ≤32 weeks gestation, birthweight (BW) ≤1500g were stratified by BW and randomized (probiotic vs no probiotic). The probiotic group received a daily multistrain preparation (B. lactis [BB-12], B. infantis [BB-02], S. thermophilus [H-4]; 0.5 g, 108 cfu/g) in milk from early feeding to 34 weeks post-menstrual age. Serum samples were obtained bimonthly during NICU hospitalization and analyzed for 17 cytokines/chemokines/biomarkers using customized multiplex magnetic bead antibody panels (Luminex). Analyte measurements were adjusted for BW and age (in weeks after birth). Comparisons between groups utilized mixed effects models for within-subject data including age and group-by-BW interactions. Model-adjusted means and regressions over age were plotted for each analyte.

Results: Longitudinal serum profiles (up to 7 samples/subject) and clinical data are available for 35 subjects (17 p</span>robiotics, 18 no probiotics). Analytes measured were: CRP, IFNγ, IL-1a, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12(p70), IL-13, IL-17A, IP-10, MCP-1, MIG, MIP-1a, sRAGE, and TNFα. Results were used to profile systemic pro-/anti-inflammatory marker polarization and inducers/products of circulating T cell and macrophage subsets. Probiotic treatment significantly decreased 8 inflammatory biomarkers over time compared to the ‘no probiotics’ subjects and suggested a model of Th2 and Treg polarization.

Conclusion(s):

Probiotic supplementation suppresses the chronic inflammatory state in VLBW infants. This is the first study comprehensively to profile circulating immune system/inflammatory mediators and biomarkers in infants over time. 

 

Abbott Nutrition, Tano Research Fund, Georgetown University Medical Center