Effects Of Early Probiotics Supplementation On Intestinal Symptoms And Immunity Of Preterm Infants

Objective Gut microbiota plays an important role in the establishment and maintance of health,especially probiotics,which are specific live microbial cultures which benefit the host by improving its intestinal microbial balance.Bifidobacteria and lactic acid bacteria are the dominant probiotic strains,which has attracted scientific interest after recent studies.Probiotics have been administrated to patients with diarrhea or constipation in clinical pratice.Many studies have demonstrated that probiotics have significant immunomodulatory properties,containing live or heat-inactivated probiotics, supematant fractions and pure genomic DNA.However,most of them have focused on cells in vitro or experimental animals.The effects on gastrointestinal functions and immunity of probiotics administration to preterm infants have not been recognized well.The immunity of neonates or preterm infants is different from that of adult.At present,it is thought that the immunocytes and immune organs of preterm infant are mature at birth.The immunoincompetence of preterm infant is the result of a shortage of stimulation from diverse antigens,no immune memory reaction.The relatively aseptic neonatal intensive care unit,lack of breastfeeding,use of antibiotics,and repeated invasive interventions contribute to delayed gut microbiota colonization with a limited number of bacterial species,especially probiotics. In this study,to recognize the effects of early probiotics supplementation on intestinal symptoms and immunity function of preterm infants in NICU,we used probiotics,recorded intestinal symptoms and detected levels of immunological indicators of peripheral blood.Methods According to the objective of this study and the clinical situation,we set a standard of subject enrollment.All the fifty preterm infants came from NICU of Shandong Provincial Hospital,which were divided into the control group and the probiotic group.The probiotic group received probiotics on day 0 to 14 after birth. The clinical symptoms were recorded,containing the numbers of warm brine enema and the incidence of diarrhea.The peripheral blood samples were collected on day 14～16 after birth.The erythrocyte immune function was checked with Guo's method;the T-lymphocyte subsets were detected with flow cytometry assay;the imrnunoturbidimetric assay was used to detected the level of immunoglobulin and complement;the interferon-gamma and interlukine-4 concentration was determined with enzyme-linked immunosorbent assay.Results1.Clinical symptoms:The numbers of warm brine enema of the probiotic group(0.36±0.70)was significantly lower than that of the control group(0.92±1.12)(P＜0.05);the incidence of diarrhea of the control group(1/25)and the probiotic group(0/25)had no statistically difference(P＞0.05).2.Immunological indicators of peripheral blood2.1 The erythrocyte immune function:In contrast to the control group, RBCC3b immune adherence inhibitor factor rosette(RFIR)was lower in the probiotic group(P＜0.05).RBC C3b receptor rosette(RBC-C3bRR),RBCC3b immune adherence enhance factor rosette(RFER)and RFER/RFIR were increased in the probiotic group(P＜0.05).There was no significant difference between RBC immune complex rosette(RBC-ICR)of two groups(P＞0.05).2.2 T-lymphocyte subsets:The proportion of CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes of the probiotic group were significantly higher than that of the control group(P＜0.05,P＜0.05).There was no significant difference between the proportion of CD3+ or CD8+ lymphocytes of the two groups respectively(P＞0.05).2.3 Immunoglobulin and complement:In contrast to the level of IgM of the control group,that of the probiotic group increased significantly(P＜0.05).The level of IgG,C3 and C4 of the two groups had no significant difference respectively (P＞0.05).2.4 Cytokines:The level of IFN-γand the ratio of IFN-γ/IL-4 of the probiotic group had no significant difference from that of the control group(P＞0.05).However, the level of IL-4 of the probiotic group was significantly higher than that of the control group(P＜0.05).Conclusions1.Early supplementation of probiotics can promote the movement of the intestine,promote defecation and decrease the numbers of the warm brine enema of the preterm infants in NICU.2.Early supplementation of probiotics have significant effects on immunological indicators of peripheral blood of the preterm infants in NICU.Early supplementation of probiotics can increase RBC-C3bRR,RFER,decrease RFIR, and increase the proportion of CD4+ lymphocytes,the level of immuglobulin M and interlukine-4.3.Early supplementation of probiotics is well tolerated.This study offered a theoretical basis for the probiotic administration to preterm infants and further clinical studies on the impact of probiotics on the immunity of preterm infants.