CONFLICT OF INTEREST
digestive tract malformation, congenital heart disease, lower respiratory infections, diarrhea
RHEUMATOID HEART DISEASE, INFECTIVE ENDOCARDITIS, LOWER RESPIRATORY INFECTION, GROUP B
Qian Zhou, Wenkui Dai and Yanmin Bao contributed equally to this work.Dear Editor,Here, we report that baseline gut microbiome (GM) associate with the protection of probiotics against pediatric antibiotic‐associated diarrhea (AAD) via the double‐blind randomized control trial (RCT).Antibiotics are widely prescribed drugs in infancy and childhood.The inpatients with lower respiratory infections received antibiotic therapy for seven days, and Sample inclusion in this study. A total of 218 children who fulfilled the requirements of the inclusion criteria were recruited from four hospitals. Subjects were excluded if (1) had diarrhea in recent weeks before enrollment; (2) were hospitalized in intensive care units; (3) had digestive tract malformation, digestive tract surgery, congenital heart disease, artificial heart membrane surgery, rheumatoid heart disease, or infective endocarditis history; (4) receiving immunosuppressant therapy, probiotic or Chinese medicine in recent weeks before enrollment. One hundred seventy‐three children received the one‐week intervention. Forty provided qualified fecal samples, which were collected before and after the intervention.As measured by the Jensen‐Shannon distance,Inter‐individual structural variations for baseline gut microbiome (GM). (A) Principal coordinate analysis (PCoA) based on Jensen‐Shannon divergence as the distance measurement. (B) Distribution of phylum‐level GM compositions across three GM types. (C) Comparison of alpha‐diversity at genus level via the Shannon index. (D) Inter‐individual Bray‐Curtis distance for each type of GM. (E) Inter‐cluster Bray‐Curtis distance for three GM types. (F) Species‐level GM compositions for three GM types before clinical interventions and the colour in the heatmap represent log10 value of relative abundance. Wilcoxon rank‐sum test was applied to analyze the significance of inter‐cluster differences. **, ***, and **** represents adjusted Permutational multivariate analysis of variance indicated that baseline GM structures and probiotic supplementation contributed to genus‐ and species‐level dissimilarity notably (at genus level, Factors notably impacting gut microbiome (GM) dynamics following clinical interventions. (A) Permutational multivariate analysis of variance (PERMANOVA) to assess the effects of several indices on genus‐level GM structures: the contribution is larger if the point is located near the outer circle. Montmorillonite: yes or no; AAD: yes or no; Time: d1 or d7; Ara.amp: yes or no; Group: Group B (probiotics) or Group P (placebo); Cluster: baseline GM types (cluster_B, cluster_E, or cluster_P_B). (B) PERMANOVA to assess the effects of several indices on species_level GM structures. (C) PCoA based on the Bray‐Curtis distance between d1 and d7 microbial samples of each patient. GM changes for cluster_E and cluster_P_B are larger than those for cluster_B. (D) For patients with the baseline cluster_B GM type, PCoA based on the Bray‐Curtis distance between d1 and d7 microbial samples of each individual. The dissimilarity in Group P is slightly higher than that in Group B. (E) For patients with the baseline non‐Bacteroides‐dominated GM type, PCoA based on the Bray‐Curtis distance between d1 and d7 microbial samples of each individual. The dissimilarity in Group B is slightly higher than that in Group P.Changes in species‐level GM for individuals with different baseline gut microbiome (GM) structures. (A) Decreased alpha diversity for each GM type after clinical interventions. (B) Differences of inter‐individual Bray‐Curtis distance between d1 and d7 timepoints in each GM type. (C) Differences of inter‐group Bray‐Curtis distance between d1 and d7 timepoints. (D) Species‐level GM compositions for three GM types after clinical interventions and the colour in the heatmap represent the log10 value of relative abundance. (E) Species‐level GM structural changes for microbial samples with baseline Bacteroides‐dominated GM type and with placebo. The colour in the heatmap represents the log10 value of (d7 abundance/ d1 abundance) for each species. Wilcoxon rank‐sum test was applied to analyze the significance of inter‐group differences. ** and **** represent adjusted To better understand how GM changes differed with baseline GM structures and probiotic interventions, we applied penalized generalized estimating equationsNonetheless, notable structural GM variations also existed for subjects in cluster_B, including S1, S16, S21, S31, S38, and S39, who all received placebo supplementation (Figure The limitations of our study are the small sample size and non‐uniform antibiotics. It may bias statistical significance to the protective role of probiotics. Nonetheless, this study is the first double‐blind RCT to assess the role of probiotics in AAD prevention and observes the impact of pre‐existing GM structures on clinical efficacy of probiotics for Chinese children.In conclusion, this study suggests the impact of preexisting GM on the protection of probiotics against AAD and implies the necessity of considering preexisting GM structures when assessing clinical efficacy of probiotics in AAD prevention.The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.