Role of tryptophan-metabolizing microbiota in mice diarrhea caused by Folium sennae extracts

Abstract

Background: Although reports have provided evidence that diarrhea caused by Folium sennae can result in intestinal microbiota 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 Folium sennae, which was associated with intestinal bacterial characteristic reshaping and metabolic abnormality. Results: For the intervention of Folium sennae extracts, Chao1 index and Shannon index were statistical decreased. The Beta diversity clusters of mice interfered by Folium sennae extracts were distinctly separated from control group. Combining PPI network analysis, cytochrome P450 enzymes metabolism was the main signaling pathway of diarrhea caused by Folium sennae. Moreover, 10 bacterial flora communities had statistical significant difference with Folium sennae intervention: the abundance of Paraprevotella, Streptococcus, Epulopiscium, Sutterella and Mycoplasma increased significantly; and the abundance of Adlercreutzia, Lactobacillus, Dehalobacterium, Dorea and Oscillospira reduced significantly. Seven of the 10 intestinal microbiota 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. Conclusions: Folium sennae targeted cytochrome P450 3A4 to alter intestinal bacterial characteristic and intervene the tryptophan metabolism of intestinal microbiota, such as Streptococcus, Sutterella and Dorea, which could be the intestinal microecological mechanism of diarrhea caused by Folium sennae extracts.

Gut Microbiota Comparison Between Intestinal Contents and Mucosa in Mice With Repeated Stress-Related Diarrhea Provides Novel Insight

“…Functional diarrhea is more common in people with psychological comorbidity than in the rest of the general population, for its stemming from dysregulation of the gut–brain axis which is mediated by a complex interplay of intestinal microbiota imbalance and central nervous system processing ( Chan et al, 2019 ; Black et al, 2020 ). Consistent with our previous research ( Zhang et al, 2020a ), many studies suggest that the tryptophan metabolic pathway plays an important role in the microbiota–gut–brain axis, synchronizes the gut with the central nervous system, and modifies the psychosocial stress ( Doifode et al, 2020 ; Ma et al, 2020 ). Tryptophan metabolism disorders in intestinal microbiota cause 5-hydroxytryptophan (5-HT), an intermediate product of tryptophan metabolism, to activate the brain–gut nerve response and induce diarrhea ( Spencer and Hu, 2020 ; Ming et al, 2021 ).…”

Elucidation of the Reinforcing Spleen Effect of Jujube Fruits Based on Metabolomics and Intestinal Flora Analysis

“…Spleen deficiency is a common clinical symptom in TCM, which is a comprehensive pathological change of multiorgan and multisystem weakened functions, mainly due to reduced digestion and absorption function. Based on the TCM theory of “bitter cold injures the spleen”, the classical animal model of spleen deficiency caused by Sennae Folium was used in this experiment ( Zhang et al., 2020b ; Zhang et al., 2021 ). The blood routine, organ index, pathological sections and a series of physiological and biochemical indexes closely related to the model of spleen deficiency were selected to evaluate the traditional efficacy of JF in tonifying the spleen.…”

Habitual Sleep Duration and the Colonic Mucosa-Associated Gut Microbiota in Humans—A Pilot Study

“…Sutterella spp., except for S. wadsworthensis, may elicit Th-17 differentiation by adhering to intestinal epithelial cells [34]. Lastly, Sutterella is one of the tryptophan-metabolizing bacteria [35]. The role of tryptophan in the microbiome-brain axis has been increasingly recognized [36].…”