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Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR+ ILC3

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Abstract

Objective

To investigate the effects of composite Sophora colon-soluble Capsule (CSCC) on gut microbiota-mediated short-chain fatty acids (SCFAs) production and downstream group 3 innate lymphoid cells (ILC3s) of dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice model.

Methods

The main components of CSCC were analyzed by hybrid ultra-high-performance liquid chromatography ion mobility spectromety quadrupole time-of-flight mass spectrometry (UHPLC-IM-QTOF/MS). Twenty-four male BALB/c mice were randomly divided into 4 groups (n=6) by using a computer algorithm-generated random digital, including control, DSS model, mesalazine, and CSCC groups. A DSS-induced colitis mice model was established to determine the effects of CSCC by recording colonic weight, colonic length, index of colonic weight, and histological colonic score. The variations in ILC3s were assessed by immunofluorescence and flow cytometry. The results of gut microbiota and SCFAs were acquired by 16s rDNA and gas chromatography-mass spectrometry (GC-MS) analysis. The expression levels of NCR+ ILC3−, CCR6+ Nkp46− (Lti) ILC3−, and ILCreg-specific markers were detected by enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction and Western blot, respectively.

Results

The main components of CSCC were matrine, ammothamnine, Sophora flavescens neoalcohol J, and Sophora oxytol U. After 7 days of treatment, CSCC significantly alleviated colitis by promoting the reproduction of intestinal probiotics manifested as upregulation of the abundance of Bacteroidetes species and specifically the Bacteroidales_S24-7 genus (P<0.05). Among the SCFAs, the content of butyric acid increased the most after CSCC treatment. Meanwhile, compared with the model group, Lti ILC3s and its biomarkers were significantly downregulated and NCR+ ILC3s were significantly elevated in the CSCC group (P<0.01). Further experiments revealed that ILC3s were differentiated from Lti ILC3s to NCR+ ILC3s, resulting in interleukin-22 production which regulates gut epithelial barrier function.

Conclusion

CSCC may exert a therapeutic effect on UC by improving the gut microbiota, promoting metabolite butyric acid production, and managing the ratio between NCR+ ILC3s and Lti ILC3s.

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Authors and Affiliations

  1. Medical School of Chinese People’s Liberation Army, Bei**g, 100853, China

    Ming-jun Chen

  2. Department of Traditional Chinese Medicine, The Second Medical Center & National Clinical Research Center of Geriatric Diseases, Chinese People’s Liberation Army General Hospital, Bei**g, 100853, China

    Ming-jun Chen, Yang Feng, Lu Gao, Ming-xiong Lin &  Zhan-qi Tong

  3. Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Academy of Military Sciences, Bei**g, 100850, China

    Shi-da Wang

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  1. Ming-jun Chen
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Contributions

Conceptualization was done by Tong ZQ and Feng Y; Chen MJ and Wang SD contributed in experiments conduction, formal analysis, and writing the original draft; Chen MJ, Feng Y and Tong ZQ reviewed and edited the manuscript. All authors confirmed and approved the final manuscript for publication.

Corresponding author

Correspondence to Zhan-qi Tong.

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The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Additional information

Supported by the National Natural Science Foundation of China (No. 81673965) and Bei**g Natural Science Foundation (No. 7224362)

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Chen, Mj., Feng, Y., Gao, L. et al. Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR+ ILC3. Chin. J. Integr. Med. 29, 424–433 (2023). https://doi.org/10.1007/s11655-022-3317-1

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