The Relative Balance of Ruminococcus and Clostridium Contributes to Gut Health in Chinese Children: A Cohort Study on Childhood Diarrhea and Constipation

Abstract

Abstract Diarrhea and constipation are common health concerns during childhood, with an estimated prevalence of 3% to 9% worldwide. Although numerous studies have identified strong association between gut microbiota and digestive-related diseases in children, little is known about the gut microbiota that simultaneously affects both diarrhea and constipation or their potential regulatory mechanisms. Here, we conducted a cohort study on 618 individuals (66 with diarrhea and 138 with constipation) via 16S rRNA sequencing of stool. Compared with healthy individuals, the significant reduction (n = 66, Chao1, ACE, p < 0.05) in the microbial diversity was observed in children with diarrhea, while a marked increase was observed in those with constipation (n = 138, Chao1, ACE, Shannon, and Simpson, p < 0.05). Importantly, we firstly determined a reversed effect from Clostridium and Ruminococcus illustrating significant synergistic changes [Clostridium levels decreased in the constipation group (p < 0.001) and increased in the diarrhea group (p = 0.005), while Ruminococcus levels increased in the constipation group (p = 0.033) and decreased in the diarrhea group (p = 0.006)] in the disease phenotypes compared with healthy control. Pathway analysis revealed significant correlation between the membrane transport and endocrine system pathways and the levels of both Clostridium and Ruminococcus, suggesting a potential shared regulatory mechanism in the pathogenesis of both diseases. In summary, this study reveals, for the first time, two core microbiota that might affect the steady intestinal balance in children, which provides important references for the potential diagnosis and treatment of constipation and diarrhea. IMPORTANCE Previous studies have explored the composition and structure of the gut microbiota in different disease states, but there has been little investigation on the potential pathogenic regulatory mechanisms and key microbial biomarkers for clinically similar or dissimilar diseases. This study compared the gut microbiota between children with diarrhea and healthy controls, as well as between children with constipation and healthy controls. We found that the impact of diarrhea and constipation on the gut diversity differed and that Clostridium and Ruminococcus were significantly associated with both diseases, suggesting their potential diagnostic value. Moreover, we identified two metabolic pathways, membrane transport and the endocrine system that were strongly correlated with both diseases indicating possible pathogenic mechanisms. These results provide a theoretical basis for the diagnosis and pathogenic mechanisms of childhood diarrhea and constipation.