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      Chinese herbal medicines for treating ulcerative colitis via regulating gut microbiota-intestinal immunity axis

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          Abstract

          Ulcerative colitis (UC) is one of types of inflammatory bowel disease with high recurrence. Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC. Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC. Many Chinese herbal medicines including some of single herb, herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity. Some clinical trials have shown promising results. This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity. The existing clinical trials are also summarized.

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          The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.

          Patrick M. Smith, Michael R. Howitt, Nicolai Panikov … (2013)
          Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota-derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
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            Proteobacteria: microbial signature of dysbiosis in gut microbiota.

            Na-Ri Shin, Tae Woong Whon, Jin-Woo Bae (2015)
            Recent advances in sequencing techniques, applied to the study of microbial communities, have provided compelling evidence that the mammalian intestinal tract harbors a complex microbial community whose composition is a critical determinant of host health in the context of metabolism and inflammation. Given that an imbalanced gut microbiota often arises from a sustained increase in abundance of the phylum Proteobacteria, the natural human gut flora normally contains only a minor proportion of this phylum. Here, we review studies that explored the association between an abnormal expansion of Proteobacteria and a compromised ability to maintain a balanced gut microbial community. We also propose that an increased prevalence of Proteobacteria is a potential diagnostic signature of dysbiosis and risk of disease.
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              Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43.

              Kendle Maslowski, Angelica Vieira, Aylwin Ng … (2009)
              The immune system responds to pathogens by a variety of pattern recognition molecules such as the Toll-like receptors (TLRs), which promote recognition of dangerous foreign pathogens. However, recent evidence indicates that normal intestinal microbiota might also positively influence immune responses, and protect against the development of inflammatory diseases. One of these elements may be short-chain fatty acids (SCFAs), which are produced by fermentation of dietary fibre by intestinal microbiota. A feature of human ulcerative colitis and other colitic diseases is a change in 'healthy' microbiota such as Bifidobacterium and Bacteriodes, and a concurrent reduction in SCFAs. Moreover, increased intake of fermentable dietary fibre, or SCFAs, seems to be clinically beneficial in the treatment of colitis. SCFAs bind the G-protein-coupled receptor 43 (GPR43, also known as FFAR2), and here we show that SCFA-GPR43 interactions profoundly affect inflammatory responses. Stimulation of GPR43 by SCFAs was necessary for the normal resolution of certain inflammatory responses, because GPR43-deficient (Gpr43(-/-)) mice showed exacerbated or unresolving inflammation in models of colitis, arthritis and asthma. This seemed to relate to increased production of inflammatory mediators by Gpr43(-/-) immune cells, and increased immune cell recruitment. Germ-free mice, which are devoid of bacteria and express little or no SCFAs, showed a similar dysregulation of certain inflammatory responses. GPR43 binding of SCFAs potentially provides a molecular link between diet, gastrointestinal bacterial metabolism, and immune and inflammatory responses.
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                Author and article information

                Contributors
                Zhangang Xiao
                Xu Wu
                Journal
                Journal ID (nlm-ta): Chin Herb Med
                Journal ID (iso-abbrev): Chin Herb Med
                Title: Chinese Herbal Medicines
                Publisher: Elsevier
                ISSN (Print): 1674-6384
                ISSN (Electronic): 2589-3610
                Publication date PMC-release: 28 March 2023
                Publication date Collection: April 2023
                Publication date (Electronic): 28 March 2023
                Volume: 15
                Issue: 2
                Pages: 181-200
                Affiliations
                [a ]Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China
                [b ]Luzhou Key Laboratory of Cell Therapy & Cell Drugs, Luzhou 646000, China
                [c ]Sichuan Fifth People’s Hospital, Chengdu 610015, China
                [d ]Department of Spleen and Stomach Diseases, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, China
                [e ]South Sichuan Institute of Translational Medicine, Luzhou 646000, China
                [f ]State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao 999078, China
                Author notes
                [1]

                These authors contributed equally to the work.

                Article
                Publisher Item ID: S1674-6384(23)00030-8
                DOI: 10.1016/j.chmed.2023.03.003
                PMC ID: 10230642
                PubMed ID: 37265772
                SO-VID: 055ae0d6-8b85-417d-9dc7-4e3ed69e4917
                Copyright © © 2022 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 7 October 2022
                Date revision received : 5 January 2023
                Date accepted : 15 March 2023
                Categories
                Subject: Review

                Keywords: chinese herbal medicines,gut microbiota,inflammation,inflammatory bowel disease,intestinal immunity,ulcerative colitis
                Data availability:
                Keywords: chinese herbal medicines, gut microbiota, inflammation, inflammatory bowel disease, intestinal immunity, ulcerative colitis

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