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      Construction of a “Bacteria-Metabolites” Co-Expression Network to Clarify the Anti–Ulcerative Colitis Effect of Flavonoids of Sophora flavescens Aiton by Regulating the “Host–Microbe” Interaction

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          Abstract

          Ulcerative colitis (UC) is considered an immune disease, which is related to the dysbiosis of intestinal microbiota and disorders of the host immune system and metabolism. Sophora flavescens Aiton has been used for the clinical treatment of UC in China and East Asia for thousands of years. It has many traditional prescriptions and modern preparations, and its curative effects are definite. We are the first to report that the flavonoids in Sophora flavescens ( S. flavescens) Aiton EtOAc extract (SFE) could potentially attenuate the dextran sodium sulfate–induced UC in mice, which changed the current understanding of considering alkaloids as the only anti-UC pharmacological substances of S. flavescens Aiton. Based on the 16S rRNA gene sequencing and metabolomic analysis, it was found that the anti-UC effects of SFE were due to the regulation of gut microbiota, reversing the abnormal metabolisms, and regulation of the short-chain fatty acids synthesis. Notably, according to the interaction networks of specific bacteria and “bacteria and metabolites” co-expression network, the SFE could enrich the abundance of the commensal bacterium Lactobacillus, Roseburia, norank_f__Muribaculaceae, Anaerotruncus, Candidatus_Saccharimona, and Parasutterella, which are proposed as potentially beneficial bacteria, thereby playing vital roles in the treatment of UC.

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          Most cited references77

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          Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies.

          Inflammatory bowel disease is a global disease in the 21st century. We aimed to assess the changing incidence and prevalence of inflammatory bowel disease around the world.
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            Ulcerative colitis

            Ulcerative colitis is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. The pathogenesis is multifactorial, involving genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. Patients with ulcerative colitis have mucosal inflammation starting in the rectum that can extend continuously to proximal segments of the colon. Ulcerative colitis usually presents with bloody diarrhoea and is diagnosed by colonoscopy and histological findings. The aim of management is to induce and then maintain remission, defined as resolution of symptoms and endoscopic healing. Treatments for ulcerative colitis include 5-aminosalicylic acid drugs, steroids, and immunosuppressants. Some patients can require colectomy for medically refractory disease or to treat colonic neoplasia. The therapeutic armamentarium for ulcerative colitis is expanding, and the number of drugs with new targets will rapidly increase in coming years.
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              Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis.

              The gastrointestinal (GI) tract contains much of the body's serotonin (5-hydroxytryptamine, 5-HT), but mechanisms controlling the metabolism of gut-derived 5-HT remain unclear. Here, we demonstrate that the microbiota plays a critical role in regulating host 5-HT. Indigenous spore-forming bacteria (Sp) from the mouse and human microbiota promote 5-HT biosynthesis from colonic enterochromaffin cells (ECs), which supply 5-HT to the mucosa, lumen, and circulating platelets. Importantly, microbiota-dependent effects on gut 5-HT significantly impact host physiology, modulating GI motility and platelet function. We identify select fecal metabolites that are increased by Sp and that elevate 5-HT in chromaffin cell cultures, suggesting direct metabolic signaling of gut microbes to ECs. Furthermore, elevating luminal concentrations of particular microbial metabolites increases colonic and blood 5-HT in germ-free mice. Altogether, these findings demonstrate that Sp are important modulators of host 5-HT and further highlight a key role for host-microbiota interactions in regulating fundamental 5-HT-related biological processes.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                14 October 2021
                2021
                : 12
                : 710052
                Affiliations
                [ 1 ]Key Laboratory of Digital Quality Evaluation of Chinese Materia Medical of State Administration of TCM, China, Engineering & Technology Research Center for Chinese Materia Medical Quality of Guangdong Province, School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China
                [ 2 ]The Fifth Affiliated Hospital of Southern Medical University, Guangzhou, China
                [ 3 ]School of Chinese Medicine, Southern Medical University, Guangzhou, China
                Author notes

                Edited by: Jianbo Xiao, University of Vigo, Spain

                Reviewed by: Carlos R. Pungitore, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina

                Priyia Pusparajah, Monash University, Malaysia

                *Correspondence: Yi Liu, liuyi099@ 123456163.com ; Lei Chen, chenlei0080@ 123456163.com

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                710052
                10.3389/fphar.2021.710052
                8553221
                34721011
                46c914af-7a15-4475-9567-2ce78c572d28
                Copyright © 2021 Shao, Li, Gao, Zhao, Lin, Li, Wang, Liu and Chen.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 May 2021
                : 09 September 2021
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                ulcerative colitis, 16s rrna sequencing,gut bacteria,metabolomics,“host–microbe” interaction

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