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

CHEN Ming-jun; FENG Yang; GAO Lu; LIN Ming-xiong; WANG Shi-da; TONG Zhan-qi

doi:10.1007/s11655-022-3317-1

Your Location：

Home >

Browse articles >

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

Original Article | Updated：2023-04-27

- Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR⁺ ILC3
- Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR⁺ ILC3
- 中国结合医学杂志（英文版） 2023年29卷第5期页码：424-433
- Affiliations：
  
  1.Medical School of Chinese People's Liberation Army, Beijing(100853), China
  2.Department of Traditional Chinese Medicine, The Second Medical Center & National Clinical Research Center of Geriatric Diseases, Chinese People's Liberation Army General Hospital, Beijing (100853), China
  3.Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing (100850), China
- Author bio：
  
  Prof. TONG Zhan-qi, E-mail: tong.zhanqi@163.com
- Funds：
  
  the National Natural Science Foundation of China(81673965);Beijing Natural Science Foundation(7224362)
- DOI：10.1007/s11655-022-3317-1
  中图分类号：
- 纸质出版日期：2023-05，
  
  网络出版日期：2022-04-12，
  
  录用日期：2021-05-28
Scan for full text
Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR⁺ ILC3[J]. 中国结合医学杂志（英文版）, 2023,29(5):424-433.

CHEN Ming-jun, FENG Yang, GAO Lu, et al. Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR⁺ ILC3[J]. Chinese Journal of Integrative Medicine, 2023,29(5):424-433.
Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR⁺ ILC3[J]. 中国结合医学杂志（英文版）, 2023,29(5):424-433. DOI： 10.1007/s11655-022-3317-1.

CHEN Ming-jun, FENG Yang, GAO Lu, et al. Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR⁺ ILC3[J]. Chinese Journal of Integrative Medicine, 2023,29(5):424-433. DOI： 10.1007/s11655-022-3317-1.

摘要

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 (

=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 (

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 (

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.

关键词

Keywords

composite Sophora colon-soluble capsuleulcerative colitisgroup 3 innate lymphoid cellsgut microbiotabutyric acid

references

Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, et al. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal Pouch disorders. J Crohns Colitis 2017;11:649-670.

Eisenstein M. Ulcerative colitis: towards remission. Nature 2018;563:S33.

Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353:2462-2476.

Magnusson MK, Strid H, Sapnara M, Lasson A, Bajor A, Ung KA, et al. Anti-TNF therapy response in patients with ulcerative colitis is associated with colonic antimicrobial peptide expression and microbiota composition. J Crohns Colitis 2016;10:943-952.

Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol 2015;12:205-217.

Macia L, Tan J, Vieira AT, Leach K, Stanley D, Luong S, et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat Commun 2015;6:6734.

Imoto Y, Kato A, Takabayashi T, Sakashita M, Norton JE, Suh LA, et al. Short-chain fatty acids induce tissue plasminogen activator in airway epithelial cells via GPR41 and 43. Clin Exp Allergy Clin Immunol 2018;48:544-554.

Takaki-Kuwahara A, Arinobu Y, Miyawaki K, Yamada H, Tsuzuki H, Irino K, et al. CCR6+ group 3 innate lymphoid cells accumulate in inflamed joints in rheumatoid arthritis and produce Th17 cytokines. Arthritis Res Ther 2019;21:198.

Saez de Guinoa J, Jimeno R, Farhadi N, Jervis PJ, Cox LR, Besra GS, et al. CD1d-mediated activation of group 3 innate lymphoid cells drives IL-22 production. EMBO Rep 2017;18:39-47.

Zhou Y, Zhi F. Lower level of bacteroides in the gut microbiota is associated with inflammatory bowel disease: a meta-analysis. Biomed Res Int 2016;2016:5828959.

Yu W, Su X, Chen W, Tian X, Zhang K, Guo G, et al. Three types of gut bacteria collaborating to improve Kui Jie'an enema treat DSS-induced colitis in mice. Biomed Pharmacother 2019;113:108751.

Chun E, Lavoie S, Fonseca-Pereira D, Bae S, Michaud M, Hoveyda HR, et al. Metabolite-sensing receptor Ffar2 regulates colonic group 3 innate lymphoid cells and gut immunity. Immunity 2019;51:871-884.e6.

Ebbo M, Crinier A, Vely F, Vivier E. Innate lymphoid cells:major players in inflammatory diseases. Nat Rev Immunol 2017;17:665-678.

Kobayashi M, Mikami D, Kimura H, Kamiyama K, Morikawa Y, Yokoi S, et al. Short-chain fatty acids, GPR41 and GPR43 ligands, inhibit TNF-alpha-induced MCP-1 expression by modulating p38 and JNK signaling pathways in human renal cortical epithelial cells. Biochem Biophys Res Commun 2017;486:499-505.

Tong ZQ, Yang B, Chen BY, Zhao ML. A multi-center, randomized, single-blind, controlled clinical study on the efficacy of composite Sophora colon-soluble Capsules in treating ulcerative colitis. Chin J Integr Med 2010;16:486-492.

He X, Fang J, Huang L, Wang J, Huang X. Sophora flavescens Ait.:traditional usage, phytochemistry and pharmacology of an important traditional Chinese medicine. J Ethnopharmacol 2015;172:10-29.

Gong Y, Zha Q, Li L, Liu Y, Yang B, Liu L, et al. Efficacy and safety of Fufangkushen colon-coated capsule in the treatment of ulcerative colitis compared with mesalazine: a double-blinded and randomized study. J Ethnopharmacol 2012;141:592-598.

Ding Y, Chen M, Wang Q, Gao L, Feng Y, Wang S, et al. Integrating pharmacology and microbial network analysis with experimental validation to reveal the mechanism of composite Sophora colon-soluble Capsule against ulcerative colitis. Evid Based Complement Alternat Med 2020;2020:1-16.

Sha T, Igaki K, Yamasaki M, Watanabe T, Tsuchimori N. Establishment and validation of a new semi-chronic dextran sulfate sodium-induced model of colitis in mice. Int Immunopharmacol 2013;15:23-29.

Ge W, Wang HY, Zhao HM, Liu XK, Zhong YB, Long J, et al. Effect of Sishen Pill on memory T cells from experimental colitis induced by dextran sulfate sodium. Front Pharmacol 2020;11:908.

Chen F, Yin YT, Zhao HM, Wang HY, Zhong YB, Long J, et al. Sishen Pill treatment of DSS-induced colitis via regulating interaction with inflammatory dendritic cells and gut microbiota. Front Physiol 2020;11:801.

Mahler M, Bristol IJ, Leiter EH, Workman AE, Birkenmeier EH, Elson CO, et al. Differential susceptibility of inbred mouse strains to dextran sulfate sodium-induced colitis. Am J Physiol 1998;274:G544-G551.

Zeng B, Shi S, Ashworth G, Dong C, Liu J, Xing F. ILC3 function as a double-edged sword in inflammatory bowel diseases. Cell Death Dis 2019;10:315.

Cao SY, Ye SJ, Wang WW, Wang B, Zhang T, Pu YQ, et al. Progress in active compounds effective on ulcerative colitis from Chinese medicines. Chin J Nat Med (Chin) 2019;17:81-102.

Ordas I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Ulcerative colitis. Lancet 2012;380:1606-1619.

Lavelle A, Lennon G, Winter DC, O'Connell PR. Colonic biogeography in health and ulcerative colitis. Gut Microbes 2016;7:435-442.

McIlroy J, Ianiro G, Mukhopadhya I, Hansen R, Hold GL. Review article: the gut microbiome in inflammatory bowel disease—avenues for microbial management. Aliment Pharmacol Ther 2018;47:26-42.

Ananthakrishnan AN, Bernstein CN, Iliopoulos D, Macpherson A, Neurath MF, Ali RAR, et al. Environmental triggers in IBD: a review of progress and evidence. Nat Rev Gastroenterol Hepatol 2018;15:39-49.

Sokol H, Leducq V, Aschard H, Pham HP, Jegou S, Landman C, et al. Fungal microbiota dysbiosis in IBD. Gut 2017;66:1039-1048.

Agus A, Planchais J, Sokol H. Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe 2018;23:716-724.

Lu YH, Cong LL. Study on the Chinese medical syndrome distribution of ulcerative colitis. Chin J Integr Tradit West Med(Chin) 2012;32:450-454.

Langhorst J, Wulfert H, Lauche R, Klose P, Cramer H, Dobos GJ, et al. Systematic review of complementary and alternative medicine treatments in inflammatory bowel diseases. J Crohns Colitis 2015;9:86-106.

Shen Z, Zhou Q, Ni Y, He W, Shen H, Zhu L. Traditional Chinese medicine for mild-to-moderate ulcerative colitis:protocol for a network meta-analysis of randomized controlled trials. Medicine (Baltimore) 2019;98:e16881.

Sugimoto S, Naganuma M, Kiyohara H, Arai M, Ono K, Mori K, et al. Clinical efficacy and safety of oral Qing-Dai in patients with ulcerative colitis: a single-center open-label prospective study. Digestion 2016;93:193-201.

Zhang C, Jiang M, Lu A. Considerations of traditional Chinese medicine as adjunct therapy in the management of ulcerative colitis. Clin Rev Allergy Immunol 2013;44:274-283.

Tong ZQ, Yang B, Tong XY. A multi-center randomized double-blinded, placebo-controlled clinical study on efficacy of composite Sophora colon-soluble Capsules in treating ulcerative colitis of internal dampness-heat accumulation syndrome type. Chin J Integr Tradit West Med (Chin) 2011;31:172-176.

Aly SH, Elissawy AM, Eldahshan OA, Elshanawany MA, Efferth T, Singab ANB. The pharmacology of the genus Sophora(Fabaceae): an updated review. Phytomedicine 2019;64:153070.

Chen M, Ding Y, Tong Z. Efficacy and safety of Sophora flavescens (Kushen) based traditional Chinese medicine in the treatment of ulcerative colitis: clinical evidence and potential mechanisms. Front Pharmacol 2020;11:603476.

Fransen F, van Beek AA, Borghuis T, Meijer B, Hugenholtz F, van der Gaast-de Jongh C, et al. The impact of gut microbiota on gender-specific differences in immunity. Front Immunol 2017;8:754.

Liu F, Li Z, Wang X, Xue C, Tang Q, Li RW. Microbial co-occurrence patterns and keystone species in the gut microbial community of mice in response to stress and Chondroitin sulfate Disaccharide. Int J Mol Sci 2019;20:2130.

Machiels K, Sabino J, Vandermosten L, Joossens M, Arijs I, de Bruyn M, et al. Specific members of the predominant gut microbiota predict pouchitis following colectomy and IPAA in UC. Gut 2017;66:79-88.

Maerz JK, Trostel C, Lange A, Parusel R, Michaelis L, Schafer A, et al. Bacterial immunogenicity is critical for the induction of regulatory B cells in suppressing inflammatory immune responses. Front Immunol 2019;10:3093.

Yang W, Yu T, Huang X, Bilotta AJ, Xu L, Lu Y, et al. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity. Nat Commun 2020;11:4457.

Liang YN, Yu JG, Zhang DB, Zhang Z, Ren LL, Li LH, et al. Indigo Naturalis ameliorates dextran sulfate sodium-induced colitis in mice by modulating the intestinal microbiota community. Molecules 2019;24:4086.

Duranti S, Gaiani F, Mancabelli L, Milani C, Grandi A, Bolchi A, et al. Elucidating the gut microbiome of ulcerative colitis: bifidobacteria as novel microbial biomarkers. FEMS Microbiol Ecol 2016;92: fiw191.

Ormerod KL, Wood DL, Lachner N, Gellatly SL, Daly JN, Parsons JD, et al. Genomic characterization of the uncultured Bacteroidales family S24-7 inhabiting the guts of homeothermic animals. Microbiome 2016;4:36.

Tan JK, McKenzie C, Marino E, Macia L, Mackay CR. Metabolite-sensing G protein-coupled receptors-facilitators of diet-related immune regulation. Annu Rev Immunol 2017;35:371-402.

Liu B, Piao X, Niu W, Zhang Q, Ma C, Wu T, et al. Kuijieyuan Decoction improved intestinal barrier injury of ulcerative colitis by affecting TLR4-dependent PI3K/AKT/NF-kappaB oxidative and inflammatory signaling and gut microbiota. Front Pharmacol 2020;11:1036.

Ratsimandresy RA, Indramohan M, Dorfleutner A, Stehlik C. The AIM2 inflammasome is a central regulator of intestinal homeostasis through the IL-18/IL-22/STAT3 pathway. Cell Mol Immunol 2017;14:127-142.

Martinez-Lopez M, Iborra S, Conde-Garrosa R, Mastrangelo A, Danne C, Mann ER, et al. Microbiota sensing by mincle-Syk axis in dendritic cells regulates interleukin-17 and -22 production and promotes intestinal barrier integrity. Immunity 2019;50:446-461.e9.

Warner K, Ohashi PS. ILC regulation of T cell responses in inflammatory diseases and cancer. Semin Immunol 2019;41:101284.

Li J, Shi W, Sun H, Ji Y, Chen Y, Guo X, et al. Activation of DR3 signaling causes loss of ILC3s and exacerbates intestinal inflammation. Nat Commun 2019;10:3371.

Chu C, Moriyama S, Li Z, Zhou L, Flamar AL, Klose CSN, et al. Anti-microbial functions of group 3 innate lymphoid cells in gut-associated lymphoid tissues are regulated by G-protein-coupled receptor 183. Cell Rep 2018;23:3750-3758.

Natsume C, Aoki N, Aoyama T, Senda K, Matsui M, Ikegami A, et al. Fucoxanthin ameliorates atopic dermatitis symptoms by regulating keratinocytes and regulatory innate lymphoid cells. Int J Mol Sci 2020;21:2180.

Wang S, Xia P, Chen Y, Qu Y, Xiong Z, Ye B, et al. Regulatory innate lymphoid cells control innate intestinal inflammation. Cell 2017;171:201-216.e18.

Shao L, Pan S, Zhang QP, Jamal M, Chen LH, Yin Q, et al. An essential role of innate lymphoid cells in the pathophysiology of graft-vs.-host disease. Front Immunol 2019;10:1233.

Derrien M, Belzer C, de Vos WM. Akkermansia muciniphila and its role in regulating host functions. Microb Pathog 2017;106:171-181.

Lopez-Siles M, Enrich-Capo N, Aldeguer X, Sabat-Mir M, Duncan SH, Garcia-Gil LJ, et al. Alterations in the abundance and co-occurrence of Akkermansia muciniphila and Faecalibacterium prausnitzii in the colonic mucosa of inflammatory bowel disease subjects. Front Cell Infect Microbiol 2018;8:281.

Castellanos JG, Longman RS. Innate lymphoid cells link gut microbes with mucosal T cell immunity. Gut Microbes 2019;11:1-6.

More>

浏览量

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

工具集

关联资源

Mechanism of Acupuncture and Moxibustion on Promoting Mucosal Healing in Ulcerative Colitis

Molecular Mechanism of Polysaccharides Extracted from Chinese Medicine Targeting Gut Microbiota for Promoting Health

Progress on Regulation of NLRP3 Inflammasome by Chinese Medicine in Treatment of Ulcerative Colitis

Anti-obesity and Gut Microbiota Modulation Effect of Astragalus Polysaccharides Combined with Berberine on High-Fat Diet-Fed Obese Mice^*

Huangqin Decoction Attenuates DSS-Induced Mucosal Damage and Promotes Epithelial Repair via Inhibiting TNF-α-Induced NF-κB Activation

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

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

DOI：10.1007/s11655-022-3317-1

摘要

Abstract

关键词

Keywords

references

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

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