Objective To analyze the changes of gut microbiota of short children before and after recombinant human growth hormone (rhGH) treatment by 16S rDNA high-throughput sequencing.

Methods Short children aged 3 to 14 years who were first treated with rhGH were selected as study objects, and were divided into long-acting group(n=16) and short-acting group (n=16) according to the dosage form of rhGH, and the long-acting group used polyethylen Glycol Recombinant Human Growth Hormone (PEG-rhGH). In the short-acting group, short-acting rhGH was used. A total of 83 fresh fecal specimens were collected from the two groups before treatment and 3 and 6 months after treatment, respectively. 16S rDNA high-throughput sequencing technology combined with bioinformation analysis technology were used to compare the differences in intestinal flora composition and abundance and explore their correlations with growth indicatorsinsulin-like growth factor-1 (IGF-1) and height standard deviation score (SDS)between the two groups at different time points.

Results The Chao1 and Pielou e indexes gradually increased in two groups before treatment, 3 months and 6 months after treatment, indicating consistently improvement of the richness and homogeneity of the gut microbiota. Chao1 index of the long-acting group was higher than that of the short-acting group at 3 months (P < 0.05). Per MANOVA unweighted-unifrac result showed F value was 3.425 and P value was 0.001, and Non-metric Multidimensional Scale (NMDS) analysis showed that Stress value was 0.17, suggesting that rhGH can regulate intestinal flora composition and structure in short children to a certain extent. With the extension of the use time of rhGH, the abundance of Bacteroidota and Bacteroides increased gradually in both groups, and the ratio of Bacteroidota/Firmicutes (B/F) increased gradually, while the abundance of the rest of the flora showed fluctuating changes, but the differences were not statistically significant (P>0.05). Correlation analysis showed that IGF-1 and height SDS were positively correlated with Bacteroidetes, Bacteroidetes and B/F in the long-acting group at 6 months; IGF-1 was positively correlated with Bacteroidetes, Bacteroidetes and B/F in the short-acting group at 6 months; IGF-1 and height SDS were positively correlated with Bifidobacterium in the short-acting group at 3 months. The functional prediction analysis showed that the gut microbiota of each group was mainly involved in carbohydrate metabolism and amino acid metabolism.

Conclusion The rhGH can improve the composition and abundance of gut microbiota in short children, and PEG-rhGH has an advantage in improving the abundance of gut microbiota in the short term compared with short-acting rhGH, and rhGH plays a synergistic role in growth promotion by increasing the abundance of beneficial bacteria.