Microbial imbalance in Chinese children with diarrhea or constipation

Abstract

Diarrhea and constipation are common health concerns in children. Numerous studies have identified strong association between gut microbiota and digestive-related diseases. But little is known about the gut microbiota that simultaneously affects both diarrhea and constipation or their potential regulatory mechanisms. Stool samples from 618 children (66 diarrhea, 138 constipation, 414 healthy controls) aged 0-3 years were collected to investigate gut microbiota changes using 16S rRNA sequencing. Compared with healthy, children with diarrhea exhibited a significant decrease in microbial diversity, while those with constipation showed a marked increase (p < 0.05). Significantly, our results firstly Ruminococcus increased in constipation (p = 0.03) and decreased in diarrhea (p < 0.01) compared to healthy controls. Pathway analysis revealed that Ruminococcus highly involved in the regulation of five common pathways (membrane transport, nervous system, energy metabolism, signal transduction and endocrine system pathways) between diarrhea and constipation, suggesting a potential shared regulatory mechanism. Our finding firstly reveals one core microorganisms that may affect the steady balance of the gut in children with diarrhea or constipation, providing an important reference for potential diagnosis and treatment of constipation and diarrhea.

Keywords: 16S rRNA sequencing; Childhood constipation; Childhood diarrhea; Cross-sectional study; Gut microbiota.

Figure 1

Comparison of gut microbial structure among the CC, CD and HC groups. (A) The structure of the gut microbiota at the genus level among the three groups. (B) Rank abundance curve showing the relative species abundance and evenness. (C) The Chao1 index of the CC group was significantly higher as compared with the HC group (p = 0.018), while that of CD group was significantly lower (p = 0.032). (D) The Shannon index of the CC group was significantly higher than that of HC (p < 0.001), while the Shannon index of CD group was lower although the difference was not significant (p = 0.113). (E) The Gini-Simpson index of the CC group was significantly higher than that of the HC (p < 0.001), while the Gini-Simpson index in the CD group was lower although the difference was not significant (p = 0.374). (F) Beta-diversity index (plots of NMDS) among the three groups.

Figure 2

Identification of potential biomarkers using LEfSe. (A) LDA score of enriched genera computed by LEfSe analysis between CC and HC groups (LDA score > 3, red, CC; green, HC). (B) LDA score of enriched genera computed by LEfSe analysis between CD and HC groups (LDA score > 3, red, CD; green, HC). (C) A cladogram made by LEfSe demonstrates different bacterial taxa between the CC and HC groups (red, CC; green, HC). (D) LEfSe cladogram of the gut bacterial community obtained from CD and HC groups (red, CD; green, HC).

Figure 3

Correlation analysis between significantly different genera and metabolic pathways. A Spearman correlation coefficient analysis was conducted to examine the correlation between the predicted 14 metabolic pathways and the identified genera in the diarrhea and constipation groups. The results are shown in red for positive correlation, blue for negative correlation, and light yellow for no significant correlation.