Abstract

BackgroundBuzhongyiqi decoction (BD), Sijunzi decoction (SD), and Shenlingbaizhu decoction (SHD) have been extensively used clinically for the treatment of diseases caused by spleen-Qi deficiency and microbial fermentation has historically been utilized in traditional Chinese medicine (TCM). This study aimed to investigate the mitigative effect of TCM and fermented TCM (FTCM) with Lactobacillus plantarum (LP) on antibiotic-associated diarrhea, and to select an optimal formula and then identify its compounds.MethodsDysbacteriosis in mice was induced by ceftriaxone sodium (CS). The mice were then treated with LP, BD, SD, SHD, fermented BD, fermented SD (FSD), and fermented SHD. Diarrhea indexes, the abundances of gut bacteria, intestinal morphometrics, and mRNA expressions of genes related to intestinal barrier function were assessed. Then, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) were employed to identify and relatively quantify the compounds in the selected decoctions.ResultsCS significantly increased the fecal output weight, the total number of fecal output, and fecal water content, indicating the occurrence of diarrhea. Bacterial culture tests showed that the above symptoms were accompanied by the disruption of specific intestinal flora. TCM, LP, and FTCM alleviated the diarrhea index and recovered the intestinal microbiota. FTCM showed more advantageous than TCM or LP alone. The mRNA expressions of aquaporins (AQPs) and tight junctions (TJs) decreased by CS were enhanced by TCM, LP, and FTCM. In addition, through UHPLC-Q-TOF/MS, (S)-(-)-2-hydroxyisocaproic acid, L-methionine, 4-guanidinobutyric acid (4GBA), and phenyllactate (PLA) in SD and FSD were identified and relatively quantified.ConclusionsTCM, LP, and TCM fermented with LP alleviated CS-induced diarrhea symptoms, and improved the intestinal flora and barrier function. Four compounds including (S)-(-)-2-hydroxyisocaproic acid, L-methionine, 4GBA, and PLA in FSD, which were identified by UHPLC-Q-TOF/MS, might function in modulating intestinal flora and improving villi structure.

Highlights

  • Buzhongyiqi decoction (BD), Sijunzi decoction (SD), and Shenlingbaizhu decoction (SHD) have been extensively used clinically for the treatment of diseases caused by spleen-Qi deficiency and microbial fermentation has historically been utilized in traditional Chinese medicine (TCM)

  • An increasing body of evidence has shown that probiotics inhibit the proliferation of harmful bacteria in the intestine, promote the proliferation of beneficial bacteria, and effectively restore and balance the intestinal flora, which helps in the prevention and treatment of associated diarrhea (AAD) [29]

  • The results revealed that 30 compounds in fermented SD (FSD) were significantly upregulated compared to SD, of which, the four were noteworthy, including (S)-(-)-2-hydroxyisocaproic acid, L-methionine, 4-guanidinobutyric acid (4GBA), and phenyllactate (PLA). (S)-()-2-hydroxyisocaproic acid, known as L-leucine, is a signaling amino acid (AA) in animal metabolism that can elevate villus height in the duodenum and the villus height to crypt depth (VH/CD) of the duodenum and ileum [42]

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Summary

Introduction

Buzhongyiqi decoction (BD), Sijunzi decoction (SD), and Shenlingbaizhu decoction (SHD) have been extensively used clinically for the treatment of diseases caused by spleen-Qi deficiency and microbial fermentation has historically been utilized in traditional Chinese medicine (TCM). Guo et al Chinese Medicine (2022) 17:20 resistance, pathogen overgrowth, alteration in gut microbial composition, increase in bacterial susceptibility, and the risk of repeated infections [1]. Probiotics have been demonstrated to regulate gut microbiota and produce flora metabolites that is of benefit to health via the following mechanisms: direct antimicrobial effects, enhancement of mucosal barrier integrity, and immune modulation [6]. Traditional Chinese medicine (TCM), as one of the oldest medical practices in human history which has been widely applied to clinical diagnoses and treatments [7], can adjust the balance of intestinal flora [8]. It is well known that probiotics are used to ferment Scutellaria Radix [11], Atractylodis Macrocephalae Rhizoma [12], red ginseng [13], and some Chinese prescriptions such as Danggui Buxue Tang [14], Sagunja-tang [15], Ge-Gen-Qin-Lian decoction [16]

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