Role of Tryptophan-Metabolizing Microbiota On Diarrhea Mice Caused by Folium sennae Extracts

Abstract

<jats:title>Abstract</jats:title> <jats:p>(1) Background: Although reports have provided evidence that diarrhea caused by <jats:italic>Folium sennae</jats:italic> can result in intestinal flora diversity disorder, the intestinal bacterial characteristic and specific mechanism are still unknown. The objective of our study was to investigate the mechanism of diarrhea caused by <jats:italic>Folium sennae</jats:italic>, which was associated with intestinal bacterial characteristic reshaping and metabolic abnormality. (2) Methods: The intestinal contents of 2 groups of mice, intervened with Folium sennae extracts and distilled water respectively, were collected and its DNA was extracted for high-throughput sequencing analysis. The active compounds of Folium sennae were filtrated, and their diarrhea-related targets and metabolic pathways were predicted. Virtual Metabolic Human (VMH) was utilized to simulated metabolic function of bacteria associated with Folium sennae -induced diarrhea to verified the metabolic pathways of the drug. (3) Results: For the intervention of <jats:italic>Folium sennae</jats:italic> extracts, Chao1 index and Shannon index were statistical decreased. The Beta diversity clusters of mice interfered by <jats:italic>Folium sennae</jats:italic> extracts were distinctly separate from control group. Combining PPI network analysis, cytochrome P450 (CYP) enzymes metabolism was the main signaling pathway of diarrhea caused by<jats:italic> Folium sennae</jats:italic>. Moreover, the abundance of 10 bacterial flora communities had statistical significance with <jats:italic>Folium sennae</jats:italic> intervention: the abundance of <jats:italic>Paraprevotella</jats:italic>, <jats:italic>streptococcus</jats:italic>, <jats:italic>Epulopiscium,</jats:italic> <jats:italic>Sutterella</jats:italic> and <jats:italic>Mycoplasma</jats:italic> were increased significantly; and the abundance of <jats:italic>Adlercreutzia,</jats:italic> <jats:italic>Lactobacillus</jats:italic>, <jats:italic>Dehalobacterium</jats:italic>, <jats:italic>Dorea </jats:italic>and <jats:italic>Oscillospira</jats:italic> were reduced significantly. 7 of the 10 intestinal flora communities were related to the synthesis of tryptophan derivatives, which affected the transformation of aminotryptophan into L-tryptophan, leading to abnormal tryptophan metabolism in the host. (4) Conclusions: <jats:italic>Folium sennae</jats:italic> targeted cytochrome P450 (CYP) 3A4 to alterd intestinal bacterial characteristic and interven the tryptophan metabolism of intestinal microflora, such as <jats:italic>Streptococcus</jats:italic>, <jats:italic>Sutterella</jats:italic> and <jats:italic>Dorea</jats:italic>, which could be the intestinal microecological mechanism of diarrhea caused by <jats:italic>Folium sennae</jats:italic> extracts.</jats:p>

Correlation Between Kidney Function and Intestinal Biological Characteristics of Adenine and Folium SennaeInduced Diarrhea Model in Mice

“…3 As a bitter-cold laxative commonly used in traditional Chinese medicine (TCM), Folium sennae was administered to mice to form the pathological basis of “excessive consumption of cold products damaged spleen-yang,” in order to get closer to the clinical pathogenesis. 4 Liu et al 5 pointed out that adenine combined with Folium sennae modeling caused mental lethargy, increased urine output, loose feces, weight loss, and reduced food intake in rats with diarrheal irritable bowel syndrome. Although this complex modeling method avoided the limitations of single-factor modeling and improved the success rate of the model by combining different modeling methods, the difference in modeling dose and modeling times also had an obvious impact on the construction of stable disease models during this combined medicine modeling process.…”