Microbiome and metabolome reveal the metabolic and microbial variations induced by depression and constipation

Abstract

Background Depressed patients are often accompanied with constipation symptoms, and vice versa. However, the underlying mechanisms of such a bidirectional correlation have remained elusive. We aim to reveal the possible correlations between depression and constipation from the perspectives of gut microbiome and plasma metabolome. Methods We constructed the depressed model and the constipated model of rats, respectively. First, we measured the locomotor activity status and the gastrointestinal functions of rats. And then, nuclear magnetic resonance plasma metabolomics was applied to reveal the shared and the unique metabolites of depression and constipation. In addition, 16 S ribosomal RNA gene sequencing was used to detect the impacts of constipation and depression on gut microbiota of rats. Finally, a multiscale and multifactorial network, that is, the ‘phenotypes ‐ differential metabolites ‐ microbial biomarkers’ integrated network, was constructed to visualise the mechanisms of connections between depression and constipation. Results We found that spontaneous locomotor activity and gastrointestinal functions of both depressed rats and constipated rats significantly decreased. Further, eight metabolites and 14 metabolites were associated depression and constipation, respectively. Among them, seven metabolites and four metabolic pathways were shared by constipation and depression, mainly perturbing energy metabolism and amino acid metabolism. Additionally, depression and constipation significantly disordered the functions and the compositions of gut microbiota of rats, and decreased the ratio of Firmicutes to Bacteroidetes. Conclusion The current findings provide multiscale and multifactorial perspectives for understanding the correlations between depression and constipation, and demonstrate new mechanisms of comorbidity of depression and constipation.

The prevalence of depressive and anxiety symptoms and functional constipation, and related risk factors among Chinese university students: a cross-sectional study

“…Indeed, gastrointestinal function was signi cantly reduced in rat models of depression and constipation. Furthermore, the authors found that metabolites associated with depression and constipation disrupted energy and amino acid metabolism and dysregulated the function and composition of the intestinal ora [72]. Genome-wide pleiotropic analysis demonstrated that pleiotropic genetic determinants of the association between gastrointestinal disorders and psychiatric disorders were widely distributed across the genome [73].…”

Folate and Its Significance in Depressive Disorders and Suicidality: A Comprehensive Narrative Review

“…These microorganisms possess a gene repertoire that is approximately 150 times larger than the human genome [136]. While there is growing evidence suggesting a link between alterations in the microbiome and depressive disorders [137][138][139][140][141][142][143], it is important to note that currently most findings are correlational, and causative relationships have not been firmly established yet [144]. The exact mechanisms through which the microbiome may influence mental health are unclear, and further research is needed to determine the precise role of the microbiome in depression and other behavioral disorders [145].…”

Professor Song Zongliang's Experience in Treating Diabetic Constipation

“…Constipation is the most common gastrointestinal symptom in patients with diabetes, and its therapeutic effect and psychological factors complement each other. To a certain extent, the different psychological states of patients affect their recovery from the disease [9]. Wang Qishi's "Li Xu Yuan Jian" believes that emotions are closely related to the heart and liver.…”