Effect Of Allogeneic Hematopoietic Stem Cell Transplantation On Intestinal Microflora Metabolism In Children With Leukemia

Objective:In vitro fermentation model and gas chromatography was used to determine the effects of oligosaccharides on the short chain fatty acids(SCFA)and gas production in children with leukemia in setting of allogeneic hematopoietic stem cell transplantation(allo-HSCT).The aims of current study are to explore the relationship between intestinal flora disturbance and their metabolism,in order to pruduce more beneficial SCFA by adjusting the dietary structure and improve the outcomes of children with leukemia undergoing allo-HSCT.Materials and Methods:We conducted a prospeotive observation study in patients with leukemia who undergoing allo-HSCT in hematology department,Children’s Hospital of Suzhou University from June to December 2017.Fresh stool specimens were collected at 4 time points from 15 individuals:before pretreatment(T1)、 during agranulocytosis after transplant(T2)、granulocyte engraftment after transplant(T3)、experiencing GI-a GVHD(T4).The concentration of short chain fatty acid(SCFA)in feces was detected.And then the fresh stool specimens were inoculated into the betch fermentation systems,which contained MOS,FOS,Inulin and xylitol as the sole carbon source,the gas production,SCFA concentration at 24 h were detected.In the end,SPASS 20.0 was used to analyze the data.Results:1.The level of total SCFA 、acetic acid、propionic acid、butyric acid showed such a trend in feces: it was hightest in T1,and then decreased in T2,had an upward trend in T3,and was lowest in T4.There were almost no differences in total acid,acetic acid,propionic acid,butyric acid,isobutyric acid,valeric acid and isovaleric acid production in feces among the four periods(P>0.05).2.The levels of all SCFA at 4 time points after fermentation with all tested oligosaccharides were increased at different degrees.Fermentation of MOS and INU,total acid,acetic acid,propionic acid in T1 was significantly higher than in T2(P<0.05);the level of propionic acid in T1 after FOS,XYI fermentation was significantly higher in comparison with T2(P <0.05);The level of butyric acid almost had no significantly differences after fermentation with all tested oligosaccharides.3.Comparison with YCFA:the level of total SCFA 、acetic acid、propionic acid、butyric acid in T1 and T4 had no significantly differences after fermentation with all tested oligosaccharides at the same time;the level of total SCFA 、acetic acid、propionic acid、butyric acid after MOS、FOS、INU fermentation was significantly lower in T2(P<0.05);in T3,total SCFA and three major SCFA had no significantly differences between fermentation of MOS and YCFA(P >0.05),the level of total SCFA、 acetic acid、butyric acid was significantly lower after FOS fermentation(P<0.05),and total SCFA was also significantly lower after INU fermentation(P<0.05).4.There were almost no differences in total acid,acetic acid,propionic acid,butyric acid production in feces between normal children and children undergoing allo-HSCT in T1(P>0.05);the level of acetic acid in T1 was significantly lower than normal children after FOS fermentation(P<0.05);the level of propionic acid was significantly lower than normal children after XYI、YCFA fermentation(P<0.05);There was no significantly differences in butyric acid production between normal children and children in T1 in all tested medium(P>0.05).5.The gas production after 24 h fermentation in most oligosaccharides containing medium in T1 and T3 was significantly higher than the basic medium that contained no any carbohydrates(P <0.05),while there were almost no differences in T2 and T4 between oligosaccharides containing medium and YCFA medium(P>0.05).Conclusion:1.The intestinal microbiota of children with leukemia undergoing allo-HSCT can use oligosaccharides to produce gases and SCFA which is beneficial to the host,suggesting that the bacteria in the feces are alive.Acetic acid is the highest amount of SCFA produced in four time points,followed by propionic acid and butyric acid,isobutyric acid,valeric acid and isovaleric acid production is very low.2.Allo-HSCT procedures disrupted intestinal microbiota.The amount of intestinal microbiota that can produce the acetic acid and propionic acid by MOS and INU was reduced in agranulocytosis after transplant(T2);When granulocyte engraftment(T3),the recovered gut microbiota can produce more total SCFA by MOS,but cannot produce more acetic acid and butyric acid by FOS.3.There was no significant difference in acid production between XYI medium and YCFA medium during the allo-HSCT,it was suggested that XYI and YCFA could act on similar gut microbiota.4.The pre-HSCT gut microbiota was found to be efficient in terms of short-chain fatty acid production.After fermentation by different oligosaccharides,acetic acid and propionic acid were lower than health children,suggesting that the pre-HSCT gut microbiota species were different from health children.5.The determination of SCFA level in the feces and application of the in vitro fermentation model for fermentation of oligosaccharides may be helpful to evaluate the degree of intestinal microbiota disturbance in children undergoing allo-HSCT,and may enable pediatrician to intelligently adjust the dietary structure in order to pruduce more beneficial SCFA...