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Deng F, Yang D, Qing L, Chen Y, Zou J, Jia M, Wang Q, Jiang R, Huang L. Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway: a potential therapeutic approach for neurodegenerative diseases. Neural Regen Res 2025; 20:3095-3112. [PMID: 39589173 PMCID: PMC11881707 DOI: 10.4103/nrr.nrr-d-24-00607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Revised: 08/07/2024] [Accepted: 09/10/2024] [Indexed: 11/27/2024] Open
Abstract
The interaction between the gut microbiota and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut-brain axis. The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites, which activates the vagus nerve and modulates the immune and neuroendocrine systems. Conversely, alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota, creating a dynamic network of microbial-host interactions. This reciprocal regulation affects neurodevelopment, neurotransmitter control, and behavioral traits, thus playing a role in the modulation of neurological diseases. The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation, mitochondrial dysfunction, abnormal energy metabolism, microglial activation, oxidative stress, and neurotransmitter release, which collectively influence the onset and progression of neurological diseases. This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway, along with its implications for potential therapeutic interventions in neurological diseases. Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders. This can be achieved through various methods such as dietary modifications, probiotic supplements, Chinese herbal extracts, combinations of Chinese herbs, and innovative dosage forms. These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.
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Affiliation(s)
- Fengcheng Deng
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Dan Yang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Lingxi Qing
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Yifei Chen
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Jilian Zou
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Meiling Jia
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Qian Wang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Runda Jiang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
| | - Lihua Huang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
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Salem MB, El-Lakkany NM, Hammam OA, Seif el-Din SH. Bacillus clausii spores maintain gut homeostasis in murine ulcerative colitis via modulating microbiota, apoptosis, and the TXNIP/NLRP3 inflammasome cascade. Toxicol Rep 2025; 14:101858. [PMID: 39802600 PMCID: PMC11721221 DOI: 10.1016/j.toxrep.2024.101858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 12/04/2024] [Accepted: 12/08/2024] [Indexed: 01/16/2025] Open
Abstract
Ulcerative colitis (UC), a persistent immune-mediated disorder lacking effective treatment, is distinguished by gut microbiota dysbiosis, abnormal activation of the NLRP3 inflammasome pathway, and apoptosis. Despite growing attention to these factors, understanding their significance in UC pathogenesis remains a challenge. The present study explores the potential therapeutic impact of Bacillus clausii (Bc) spores in a murine UC model induced by drinking 4 % (w/v) dextran sulfate sodium (DSS) in C57BL/6 mice. Subsequently, the DSS-induced mice were orally administered either Bc at varying concentrations (105 and 1010 Colony forming unit, CFU) or sulfasalazine (SSZ) at a dosage of 200 mg/kg for 7 days. The disease-specific activity index (DAI) was calculated daily utilizing parameters such as body weight, diarrhea, and bloody stool. Changes in fecal Firmicutes and Bacteroidetes abundance, colonic TXNIP and NLRP3 contents, as well as colonic caspase-1, IL-1β, Bax, and Bcl-2 expression, were investigated. Additionally, markers related to oxidative stress and inflammation, histopathological changes and caspase-3 immunohistochemistry testing were conducted. DSS-treated mice had significantly higher DAI scores compared to controls, indicating severe colitis. However, SSZ treatment or Bc (105 CFU) dramatically lowered DAI scores, with the highest Bc dosage (1010 CFU) producing the greatest improvement. Furthermore, Bc (1010 CFU) substantially (p < 0.05) boosted fecal Firmicutes while decreased Bacteroidetes, indicating reversal of gut dysbiosis. Bc effectively reduced colonic oxidative stress and inflammation by replenishing GSH and catalase and modulating the NF-κB, Nrf2/HO-1, and TXNIP/NLRP3 pathways. Additionally, Bc (1010 CFU) exhibited histologically almost normal mucosa, with maintained architecture and reduced apoptosis, as seen by normalization of Bcl2 and Bax with decreased caspase-3. Collectively, these findings point to the potential usefulness of Bc spores in preventing and treating DSS-induced colitis, positioning them as a promising candidate for UC management.
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Affiliation(s)
- Maha B. Salem
- Pharmcology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | | | - Olfat A. Hammam
- Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt
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Ahn JS, Kim S, Han EJ, Hong ST, Chung HJ. Increasing spatial working memory in mice with Akkermansia muciniphila. Commun Biol 2025; 8:546. [PMID: 40175647 PMCID: PMC11965532 DOI: 10.1038/s42003-025-07975-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 03/20/2025] [Indexed: 04/04/2025] Open
Abstract
Recent research has shown the gut microbiome's impact on memory, yet limitations hinder the identification of specific microbes linked to cognitive function. We measured spatial working memory in individual mice before and after fecal microbiota transplantation (FMT) to develop a targeted analysis that identifies memory-associated strains while minimizing host genetic effects. Transplantation of human fecal into C57BL/6 mice yielded varied outcomes: some mice showed significant improvements while others had negligible changes, indicating that these changes are due to differences in FMT colonization. Metagenomic analysis, stratified by memory performance, revealed a positive correlation between the abundance of Akkermansia muciniphila and improved memory. Moreover, administering two A. muciniphila strains, GMB 0476 and GMB 2066, to wild-type mice elevated spatial working memory via BDNF activation. Our findings indicate that specific gut microbes, particularly A. muciniphila, may modulate memory and represent potential targets for therapeutic intervention in cognitive enhancement.
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Affiliation(s)
- Ji-Seon Ahn
- Honam Regional Center, Korea Basic Science Institute, Gwangju, 61751, Republic of Korea
| | - Sura Kim
- Department of Biomedical Sciences and Institute for Medical Science, Jeonbuk National University Medical School, Jeonju, Jeonbuk, 54907, Republic of Korea
| | - Eui-Jeong Han
- Honam Regional Center, Korea Basic Science Institute, Gwangju, 61751, Republic of Korea
| | - Seong-Tshool Hong
- Department of Biomedical Sciences and Institute for Medical Science, Jeonbuk National University Medical School, Jeonju, Jeonbuk, 54907, Republic of Korea.
| | - Hea-Jong Chung
- Honam Regional Center, Korea Basic Science Institute, Gwangju, 61751, Republic of Korea.
- College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.
- Department of Bio-Analysis Science, University of Science & Technology, Daejeon, 34113, Republic of Korea.
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Hou S, Yu J, Li Y, Zhao D, Zhang Z. Advances in Fecal Microbiota Transplantation for Gut Dysbiosis-Related Diseases. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2413197. [PMID: 40013938 PMCID: PMC11967859 DOI: 10.1002/advs.202413197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 01/22/2025] [Indexed: 02/28/2025]
Abstract
This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.
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Affiliation(s)
- Shuna Hou
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
- Department of general surgeryThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Jiachen Yu
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Yongshuang Li
- Department of general surgeryThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Duoyi Zhao
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Zhiyu Zhang
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
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Liu CQ, Yang J, Ren HF, Liao GN, Yin Z, Gao SL, Du QJ, Yuan XZ, Ullah H, Li K. Diversity of intestinal microbiota and inflammatory cytokines after severe trauma. Sci Rep 2025; 15:7955. [PMID: 40055423 PMCID: PMC11889259 DOI: 10.1038/s41598-025-92212-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 02/26/2025] [Indexed: 03/17/2025] Open
Abstract
Accumulating evidence has reported that the intestinal microbiota could play important roles in the occurrence and progression of severe trauma. However, the hypothesized potential targeted intestinal microbiota to mediate and regulate the levels of inflammatory cytokines and promote rapid recovery of body after severe trauma remains unclear. This study was aimed to explore the changes and correlation of intestinal microbiota and inflammatory cytokines in rats with severe crush and fracture trauma. The controlled laboratory study design was used, and a crush and fracture severe trauma rat model was established. 16S rRNA high-throughput gene sequencing and ELISA were used to analyze the changes in intestinal microbiota and inflammatory cytokines within one week after trauma. The correlation between intestinal microbiota and inflammatory cytokines was also analyzed. Loss of overall diversity and expansion of intestinal microbiota in the rats due to severe trauma was observed. Specifically, there was a significant increase in the abundance of Muribaculaceae [LDA (Linear Discriminant Analysis)-value = 4.814, P = 0.014] after severe trauma, while Prevotella (LDA-value = 5.235, P = 0.020) and Alloprevotella (LDA-value = 4.443, P = 0.015) were slightly lower in the trauma group than in the control group. The levels of inflammatory cytokines (IL-1α, IL-6, IL-8 and TNF-α) in the trauma group decreased from the first day to the third day and continued to increase until one week after the trauma. Prevotellaceae_UCG_001 was correlated with TNF-a (R = 0.411, P = 0.033); Lactobacillus was negatively correlated with IL-6 (R = - 0.434, P = 0.024) and IL-1α (R = - 0.419, P = 0.030) and positively correlated with IL-8 (R = 0.391, P = 0.045); and Lachnospiraceae_NK4A136_group (R = - 0.559, P = 0.027) and Muribaculaceae (R = - 0.568, P = 0.024) were negatively correlated with IL-8. Severe trauma shows stress-like activities by negatively modulating intestinal microbiota and affecting certain inflammatory cytokines contributing to host health, which implies that the regulation of potentially targeted intestinal microbiota, and further mediating and maintaining the homeostasis of inflammatory cytokines, is expected to promote the accelerating recovery of the body after severe trauma.
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Affiliation(s)
- Chang-Qing Liu
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Jie Yang
- Department of Colorectal Tumour Center, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Hong-Fei Ren
- Department of Gastroenterology of West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Guang-Neng Liao
- Animal Experiment Center of West China Hospital, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Zhe Yin
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Shi-Lin Gao
- Department of Colorectal Tumour Center, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Qiu-Jing Du
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Xing-Zhu Yuan
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China
| | - Hanif Ullah
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
| | - Ka Li
- Department of Operating Room of West China Hospital/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing and Materials, Sichuan University, No. 37, Guoxue Alley, Wuhou District, Chengdu, 610041, Sichuan, China.
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Chen Z, Li L, Guo L, Kang C, Cui X, Pu S, Wang C, Yang Y. A Gastrodia elata polysaccharide for restoring intestinal immunocompromise. Int J Biol Macromol 2025; 307:141781. [PMID: 40054798 DOI: 10.1016/j.ijbiomac.2025.141781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 02/21/2025] [Accepted: 03/04/2025] [Indexed: 03/17/2025]
Abstract
We here extracted a polysaccharide fragment from Gastrodia elata, characterized by a main chain connected via (1 → 4)-α-D-Glcp bonds, with terminal α-D-Glcp-(1→) linked to the main chain through O-6 of (1 → 4,6)-α-D-Glcp and O-3 of (1 → 3,4)-α-D-Glcp (SRGP). Both in vitro and in vivo experiments demonstrated that SRGP activates the TLR4/NF-κB signaling pathway, exerting immunomodulatory effects and alleviating cyclophosphamide (CTX)-induced intestinal mucosal damage in mice. High-throughput 16S rRNA sequencing further revealed that SRGP restores gut microbiota composition and enhances the abundance of specific bacterial populations. Additionally, SRGP improves CTX-induced intestinal mucosal damage by upregulating tight junction proteins, mitigating gut microbiota dysbiosis, and regulating both the overall microbial community and the levels of specific bacteria.
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Affiliation(s)
- Zhuowen Chen
- School of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; Key Laboratory of Sustainable Utilization of Panax Notoginseng Resources of Yunnan Province, Kunming 650500, China
| | - Ling Li
- School of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; Key Laboratory of Sustainable Utilization of Panax Notoginseng Resources of Yunnan Province, Kunming 650500, China
| | - Lanping Guo
- China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Chuanzhi Kang
- China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Xiuming Cui
- School of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; Key Laboratory of Sustainable Utilization of Panax Notoginseng Resources of Yunnan Province, Kunming 650500, China
| | - Shulin Pu
- School of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; Key Laboratory of Sustainable Utilization of Panax Notoginseng Resources of Yunnan Province, Kunming 650500, China
| | - Chengxiao Wang
- School of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; Key Laboratory of Sustainable Utilization of Panax Notoginseng Resources of Yunnan Province, Kunming 650500, China.
| | - Ye Yang
- School of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; Key Laboratory of Sustainable Utilization of Panax Notoginseng Resources of Yunnan Province, Kunming 650500, China.
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Chu MKW, Day AS, Broad L, Costello SP, Edwards S, Bryant RV. Meta-Analysis: Exclusive Enteral Nutrition in Adults With Ulcerative Colitis. Aliment Pharmacol Ther 2025; 61:756-775. [PMID: 39817370 PMCID: PMC11825926 DOI: 10.1111/apt.18495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 10/15/2024] [Accepted: 12/31/2024] [Indexed: 01/18/2025]
Abstract
BACKGROUND Exclusive enteral nutrition (EEN) is an established dietary therapy for Crohn's disease but its role in ulcerative colitis remains unclear. AIMS To investigate the efficacy of EEN in adults with active ulcerative colitis and compare variations in treatment protocols, safety, tolerability and adherence. METHODS We conducted a systematic search of MEDLINE, Embase, Cochrane CENTRAL, Emcare, CINAHL, Web of Science and trial registries for articles published from inception until July 21, 2024. We included all experimental and observational studies that described the use of EEN in adults with active ulcerative colitis. This review was registered on PROSPERO (CRD42022319584). RESULTS Of 3273 articles screened, we included 10 studies (334 adults). Overall, there was no difference between EEN and comparator for ulcerative colitis remission induction (median follow-up 14 days, risk ratio (RR) 1.15, 95% confidence interval (CI) 0.71-1.85; 2 studies). In acute severe ulcerative colitis, there was no difference between EEN and comparator for corticosteroid failure (RR 0.76, 95% CI 0.48-1.20; 2 studies) or risk of colectomy (RR 0.88, 95% CI 0.51-1.51, n = 2 studies) during index admission. The pooled discontinuation rate was 3% (95% CI 0-10; 9 studies). There was heterogeneity in trial design, methodology and assessment of outcomes. CONCLUSION EEN was well tolerated with low therapy discontinuation in adults with active ulcerative colitis. However, there is insufficient evidence to support the use of EEN as an adjunctive therapy to standard of care. Further, well-designed studies with reproducible methodology and endpoints are necessary to evaluate its effectiveness. REGISTRY NUMBER FOR SYSTEMATIC REVIEW PROSPERO 2022 CRD42022319584.
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Affiliation(s)
- Matthew K. W. Chu
- School of Medicine, Faculty of Health and Medical SciencesThe University of AdelaideAdelaideSouth AustraliaAustralia
- Inflammatory Bowel Disease ServiceThe Queen Elizabeth HospitalAdelaideSouth AustraliaAustralia
- Inflammatory Bowel Disease Research GroupThe Basil Hetzel Institute for Translational Health ResearchAdelaideSouth AustraliaAustralia
| | - Alice S. Day
- School of Medicine, Faculty of Health and Medical SciencesThe University of AdelaideAdelaideSouth AustraliaAustralia
- Inflammatory Bowel Disease ServiceThe Queen Elizabeth HospitalAdelaideSouth AustraliaAustralia
- Inflammatory Bowel Disease Research GroupThe Basil Hetzel Institute for Translational Health ResearchAdelaideSouth AustraliaAustralia
- Nutrition & Dietetics DepartmentCentral Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Lani Broad
- Nutrition & Dietetics DepartmentCentral Adelaide Local Health NetworkAdelaideSouth AustraliaAustralia
| | - Samuel P. Costello
- School of Medicine, Faculty of Health and Medical SciencesThe University of AdelaideAdelaideSouth AustraliaAustralia
- Inflammatory Bowel Disease ServiceThe Queen Elizabeth HospitalAdelaideSouth AustraliaAustralia
- Inflammatory Bowel Disease Research GroupThe Basil Hetzel Institute for Translational Health ResearchAdelaideSouth AustraliaAustralia
| | - Suzanne Edwards
- School of Public HealthThe University of AdelaideAdelaideSouth AustraliaAustralia
| | - Robert V. Bryant
- School of Medicine, Faculty of Health and Medical SciencesThe University of AdelaideAdelaideSouth AustraliaAustralia
- Inflammatory Bowel Disease ServiceThe Queen Elizabeth HospitalAdelaideSouth AustraliaAustralia
- Inflammatory Bowel Disease Research GroupThe Basil Hetzel Institute for Translational Health ResearchAdelaideSouth AustraliaAustralia
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Futakuchi T, Furuhashi H, Isshi K, Hara Y, Ono S, Kurokawa R, Takayasu L, Suda W, Sumiyama K. Ex Vivo Analysis of the Effect of Endoscopic Premedications on the Microbiota Profile in Gastric Juice. JGH Open 2025; 9:e70141. [PMID: 40114860 PMCID: PMC11924131 DOI: 10.1002/jgh3.70141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 03/06/2025] [Accepted: 03/09/2025] [Indexed: 03/22/2025]
Abstract
Background and Aim Dimethicone (GAS), lidocaine (XYL), and protease (PRO) are commonly used as premedications during esophagogastroduodenoscopy (EGD). However, the effects of these drugs on the gastric microbiota remain unexplored. Therefore, we aimed to investigate the effects of these premedications on gastric juice collected from patients undergoing EGD. Methods Gastric juice was endoscopically aspirated from six patients and divided into six aliquots for in vitro analysis. The samples were mixed with premedications in corresponding treatment sets: GAS, XYL, PRO, MIX (a mixture of GAS, XYL, and PRO), and control (CTL1 and 2; no medication treatment). After extraction of microbial DNA from the treated samples, the 16S rRNA amplicon sequence was analyzed to determine the microbiota profile in terms of (1) the amount of genomic DNA (gDNA), (2) α-diversity indices, Shannon index, number of observed operational taxonomic units (OTUs), and Chao1 index, (3) weighted and unweighted UniFrac distances, and (4) the relative abundance of phyla and genera. Results The total amount of extracted gDNA did not significantly differ between the six groups. The α-diversity indices did not significantly differ between treatment groups. Although GAS, PRO, and MIX differed significantly from the technical replicates in the weighted UniFrac distance (p = 0.03 all), no significant difference was observed in the unweighted UniFrac distance. However, significant differences were observed in the relative abundance of several bacterial microbiota at the phylum and genus levels. Conclusions Premedications affect the microbiota profile of specific phylum- and genus-level bacterial groups. Trial Registration: University Hospital Medical Information Network Clinical Trials Registry: UMIN-CTR 000040192 and UMIN-CTR 000051289.
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Affiliation(s)
- Toshiki Futakuchi
- Department of Endoscopy The Jikei University School of Medicine Tokyo Japan
| | - Hiroto Furuhashi
- Department of Endoscopy The Jikei University School of Medicine Tokyo Japan
| | - Kimio Isshi
- Department of Endoscopy The Jikei University School of Medicine Tokyo Japan
- Isshi Gastro-Intestinal Clinic Tokyo Japan
| | - Yuko Hara
- Department of Endoscopy The Jikei University School of Medicine Tokyo Japan
| | - Shingo Ono
- Department of Endoscopy The Jikei University School of Medicine Tokyo Japan
| | - Rina Kurokawa
- Laboratory for Symbiotic Microbiome Sciences RIKEN Center for Integrative Medical Sciences Kanagawa Japan
| | - Lena Takayasu
- Laboratory for Symbiotic Microbiome Sciences RIKEN Center for Integrative Medical Sciences Kanagawa Japan
| | - Wataru Suda
- Laboratory for Symbiotic Microbiome Sciences RIKEN Center for Integrative Medical Sciences Kanagawa Japan
| | - Kazuki Sumiyama
- Department of Endoscopy The Jikei University School of Medicine Tokyo Japan
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Yang Q, Kang Y, Tang W, Li M, Zhao C. Interplay of gut microbiota in Kawasaki disease: role of gut microbiota and potential treatment strategies. Future Microbiol 2025; 20:357-369. [PMID: 40013895 PMCID: PMC11938985 DOI: 10.1080/17460913.2025.2469432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 02/17/2025] [Indexed: 02/28/2025] Open
Abstract
Kawasaki disease (KD) is an acute systemic immune vasculitis with predominant involvement of the medium and small arteries. It mostly affects pediatric patients, representing the most common form of pediatric vasculitis in children less than 5 years old. Numerous diseases, especially those related to the immune system, have established links with the intestinal flora. Recent studies have investigated the intestinal flora changes throughout the management of KD. There was gut microbiota dysbiosis in pediatric KD at the acute phase, particularly the downregulation of short-chain fat acids-producing microbiota and the over-proliferation of opportunistic pathogens. The relationship between the response to therapies in individuals with KD and specific microbiota remains uncertain. Targeted microbial supplements and dietary regulation may serve as potential measures to alleviate KD complications and thus improve prognosis. This review provides an overview of the current understanding of the interplay of the gut microbiota and KD. Furthermore, it discusses the possibility of altering the gut microbiota to reinstate a healthy condition.
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Affiliation(s)
- Qing Yang
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
| | - Yaqing Kang
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
| | - Wei Tang
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
| | - Meng Li
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
| | - Cuifen Zhao
- Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
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10
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Sandu R, Singh J. A comprehensive review on calcitonin gene-related peptide in the management of gastrointestinal disorders. Inflammopharmacology 2025; 33:1043-1059. [PMID: 39934537 DOI: 10.1007/s10787-025-01657-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 01/07/2025] [Indexed: 02/13/2025]
Abstract
The prevalence of gastrointestinal disorders caused by alcohol, Helicobacter pylori, non-steroidal anti-inflammatory drugs, chronic stress and sedentary lifestyle is on the rise. Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, has emerged as a protective factor against various gastrointestinal issues. Despite its known benefits, the dual role of CGRP in gastrointestinal damage remains unclear. Discovered 30 years ago through alternative RNA processing of the calcitonin gene, CGRP is known to be a potent vasodilator involved in crucial defensive mechanisms for both physiological and pathological conditions. Promising evidences from preclinical research have attracted the interest of scientists for the exploration of CGRP as a therapeutic neuropeptide. Numerous evidences suggest that this neuropeptide is secreted by the neurons under the influence of endogenous as well as exogenous stimuli. CGRP repairs the gastric mucosal barrier and maintain mucosal integrity by suppressing NF-κB activation, thereby reducing tumour necrosis factor-alpha expression. In addition, recent studies suggest that CGRP modulates immune responses and enhances epithelial cell proliferation, further contributing to its cytoprotective effects. Consequently, CGRP and the CGRP secretagogues represent promising novel targets for clinical applications. This review aims to elucidate the role of CGRP and CGRP secretagogues in the management of gastrointestinal disorders, highlighting its potential as a therapeutic agent in the context of evidence-based modern gastroenterology.
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Affiliation(s)
- Rajesh Sandu
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, SAS Nagar, Mohali, 160062, Punjab, India
| | - Jagtar Singh
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, SAS Nagar, Mohali, 160062, Punjab, India.
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11
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Zheng X, Fan J, Yin J, Chu Y. The role of gut microbiota and plasma metabolites in ulcerative colitis: Insights from Mendelian randomization analysis. Medicine (Baltimore) 2025; 104:e41710. [PMID: 40020117 PMCID: PMC11875619 DOI: 10.1097/md.0000000000041710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Accepted: 02/11/2025] [Indexed: 03/05/2025] Open
Abstract
Emerging research suggests that alterations in gut microbiota composition may play a significant role in the pathogenesis of ulcerative colitis (UC). Plasma metabolites, which are influenced by gut microbiota, have also been implicated, but their role in UC remains unclear. This study aims to determine whether specific plasma metabolites mediate the causal relationship between gut microbiota and UC using Mendelian randomization (MR) analysis. This study employed publicly available summary-level data from genome-wide association studies and metagenomic datasets. Gut microbiota data were derived from the FINRISK cohort (5959 participants), plasma metabolite data from the Canadian Longitudinal Study on Aging (8299 individuals), and UC data from multiple consortia (17,030 cases and 883,787 controls). Forward and reverse MR analyses, supplemented by linkage disequilibrium score regression (LDSC), were conducted to assess causal relationships. Mediation effects of plasma metabolites between gut microbiota and UC were analyzed using the product of coefficients method. Various sensitivity analyses, including MR-Egger and MR-PRESSO, were applied to detect pleiotropy and ensure robust results. The study identified 20 bacterial taxa and 93 plasma metabolites linked to UC. Forward MR analysis showed that Clostridium S felsineum increased UC risk via reduced carnitine levels, with a mediation proportion of 39.77%. Eubacterium callanderi was associated with decreased UC risk through the tryptophan to pyruvate ratio (16.02% mediation). Additionally, species CAG-590 sp000431135 increased UC risk through elevated mannitol/sorbitol levels, mediating 28.38% of the effect. Sensitivity analyses confirmed the robustness of these findings, with minimal heterogeneity and pleiotropy detected. This study highlights the significant role of gut microbiota and their associated plasma metabolites in the pathogenesis of UC. Specific microbial species influence UC through metabolites, suggesting potential therapeutic targets. Modulating carnitine, tryptophan metabolism, or sugar alcohols could offer promising avenues for UC management.
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Affiliation(s)
- XuWen Zheng
- Emergency Department, Wujin Hospital Affiliated with Jiangsu University and Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China
| | - JinNuo Fan
- Emergency Department, Wujin Hospital Affiliated with Jiangsu University and Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China
| | - JinNan Yin
- Emergency Department, Wujin Hospital Affiliated with Jiangsu University and Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, China
| | - Ying Chu
- Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, China
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12
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Chen H, Yuan J, Zhou H, Zhan X, Gao Y, Chen B, Aihemaiti N, Xu X, Dong Y, Liu S, Chen Y, Liu D, Xie T, Xu Y. Characterization of the gut microbiota in urinary calculi patients with preoperative urinary tract infection. Front Cell Infect Microbiol 2025; 15:1417403. [PMID: 40093533 PMCID: PMC11906712 DOI: 10.3389/fcimb.2025.1417403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Accepted: 02/03/2025] [Indexed: 03/19/2025] Open
Abstract
Background Urinary tract infection is one of the most common comorbidities of urinary stones. Disorders of gut microbiota can affect various infectious diseases and the formation of the stones. Therefore, alterations in the gut bacteria profile may be a potential risk factor for the development of infections in patients with urinary tract stones. Methods We conducted a retrospective study to analyze the association of urinary tract infections with gut microbiota and serum metabolism in patients with stones. Results Patients with urolithiasis were predominantly in combination with diabetes mellitus (11.4% vs. 20%) and hypertension (36.4% vs. 50%). There were no statistically significant differences in hematological and urinary parameters. Compared to negative patients, IL-17A was significantly higher in the positive group (25.0 vs 21.1 pg/ml p = 0.038). The majority of pathogens detected in urine cultures were urease-negative bacteria, and urease-positive bacteria accounted for 15% of the total number of patients. We analyzed the community composition of the two groups of patients and found a significant difference in their β-diversity (p = 0.025), suggesting that dysbiosis of the gut bacteria may be associated with the combination of urinary tract infections in urolithiasis. For identification of crucial bacteria, we found changes in the abundance of both Intestinibacter (p = 0.036) and Dialister (p = 0.039), and abundance of Intestinibacter was positively correlated with IFN-α, IL-12P70 (p<0.05), and especially IL-17A (p<0.01), which may result from differences in translational, ribosomal structural and biosynthetic functions in stone patients (p < 0.05). Conclusion Urolithiasis with gut dysbiosis developed a higher incidence of urinary tract infections, which may be associated with the increasing of Intestinibacter and affect the expression of IL-17A by translational, ribosomal structural and biosynthetic function.
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Affiliation(s)
- Hao Chen
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jing Yuan
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Hongmin Zhou
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xiangcheng Zhan
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yuchen Gao
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Bowen Chen
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Nuer Aihemaiti
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xiao Xu
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yunze Dong
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Shuai Liu
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yanhua Chen
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Ding Liu
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Tiancheng Xie
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yunfei Xu
- Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
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Yang CC, Zhang S, Zhang R, Zhao YN, Yang DW, Yang MY, Huang LJ. Application of Saccharomyces boulardii in combination with sulfasalazine in ulcerative colitis patients demonstrates significant effectiveness. World J Gastrointest Surg 2025; 17:102342. [DOI: 10.4240/wjgs.v17.i2.102342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/07/2024] [Accepted: 12/26/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Ulcerative colitis (UC) is a complex inflammatory bowel disease, and its etiology and pathogenesis remain incompletely elucidated.
AIM To analyze the effects of Saccharomyces boulardii in combination with sulfasalazine on intestinal microbiota and intestinal barrier function in patients with UC.
METHODS A retrospective analysis of clinical data from 127 UC patients admitted to our hospital between January 2021 and January 2023 was conducted. All patients met complete inclusion and exclusion criteria. Based on the treatment interventions received, they were divided into a control group (n = 63) and an observation group (n = 64). Both groups of patients received routine treatment upon admission. The control group received sulfasalazine in addition to routine interventions, while the observation group received a combination of Saccharomyces boulardii on the basis of the control group’s treatment. The clinical efficacy, improvement in symptoms, modified Baron endoscopic scores, quality of life “inflammatory bowel disease questionnaire (IBDQ)”, levels of intestinal microbial indicators (such as Lactobacillus, Bifidobacterium, Enterococcus, and Escherichia coli), intestinal mucosal barrier function indicators [diamine oxidase (DAO), lipopolysaccharide (LPS), D-lactic acid (D-LA)], and adverse reaction occurrences were compared between the two groups.
RESULTS (1) Clinical efficacy: The total effective rate in the control group was 79.37%, while in the observation group, it was 93.75%, significantly higher than that of the control group (P < 0.05); (2) Improvement in symptoms: The observation group showed significantly lower relief time for abdominal pain, diarrhea, rectal bleeding, fever symptoms, and mucosal healing time compared to the control group (P < 0.05); (3) Baron endoscopic scores and IBDQ scores: Before treatment, there was no significant difference in Baron endoscopic scores and IBDQ scores between the two groups (P > 0.05). However, after treatment, the observation group showed significantly lower Baron endoscopic scores and higher IBDQ scores compared to the control group (P < 0.05); (4) Levels of intestinal microbial indicators: Before treatment, there was no significant difference in the levels of Lactobacillus, Bifidobacterium, Enterococcus, and Escherichia coli between the two groups (P > 0.05). After treatment, the levels of Lactobacillus and Bifidobacterium in the observation group were significantly higher than those in the control group, while the levels of Enterococcus and Escherichia coli were significantly lower than those in the control group (P < 0.05); (5) Levels of intestinal mucosal barrier function indicators: Before treatment, there was no significant difference in the levels of DAO, LPS, and D-LA between the two groups (P > 0.05). However, after treatment, the levels of DAO, LPS, and D-LA in the observation group were significantly lower than those in the control group (P < 0.05); and (6) Occurrence of adverse reactions: The incidence of adverse reactions in the control group was 9.52%, while in the observation group, it was 10.94%. There was no significant difference in the occurrence of adverse reactions between the two groups (P > 0.05).
CONCLUSION The application of Saccharomyces boulardii in combination with sulfasalazine in UC patients demonstrates significant effectiveness. Compared to sole sulfasalazine intervention, the combined application of Saccharomyces boulardii further promotes the relief of relevant symptoms in patients, alleviates intestinal mucosal inflammation, and improves the quality of life. Its action may be related to rectifying the imbalance in intestinal microbiota and improving intestinal mucosal barrier function. Moreover, the combined use of Saccharomyces boulardii does not increase the risk of adverse reactions in patients, indicating a higher level of medication safety and advocating for its clinical promotion and application.
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Affiliation(s)
- Chun-Chun Yang
- Department of Gastroenterology, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Sui Zhang
- Department of Hepatic, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Rui Zhang
- Department of Gastroenterology Center, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Ya-Nan Zhao
- Department of Gastroenterology Center, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Da-Wei Yang
- Department of Hepatic, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Ming-Yue Yang
- Department of Gastroenterology Center, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
| | - Li-Jing Huang
- Department of Rheumatology and Immunology, The First Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
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Li Y, Li B, Gou Y, Tian X, Chang L, Qu C. Clinical observation of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in treating mild-to-moderate ulcerative colitis. Open Med (Wars) 2025; 20:20241126. [PMID: 40028263 PMCID: PMC11868706 DOI: 10.1515/med-2024-1126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 12/11/2024] [Accepted: 12/12/2024] [Indexed: 03/05/2025] Open
Abstract
Objective The purpose of this article was to unravel the clinical efficacy of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in the treatment of mild-to-moderate ulcerative colitis (UC). Methods Eighty-six mild-to-moderate UC patients were selected as study subjects and randomized into the control group (treated with mesalazine enteric-coated tablets [Salofalk]) and the observation group (treated with mesalazine enteric-coated tablets, Bifidobacterium Tetravaccine Tablets, and Yiyi Baitouweng Decoction retention enema). The clinical efficacy, colonoscopy score, serum levels of inflammatory factors, and the incidence of adverse reactions were compared. Results The clinical efficacy of patients in the observation group was better in contrast to the control group. After 8 weeks of treatment, the colonoscopy score, and levels of TNF-α, IFN-γ, CRP, and ESR were lower, while IL-10 levels were higher in patients of both groups than those before treatment; lower colonoscopy score and levels of TNF-α, IFN-γ, CRP, and ESR and higher IL-10 levels were observed in the observation group versus the control group. Conclusion Probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema have remarkable clinical effects in treating mild-to-moderate UC.
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Affiliation(s)
- Yanlong Li
- Diagnosis and Treatment Center for Spleen and Stomach Diseases, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou730030, Gansu, China
| | - Baoyu Li
- College of Integrated Chinese and Western Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou730000, Gansu, China
| | - Yuqin Gou
- College of Integrated Chinese and Western Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou730000, Gansu, China
| | - Xudong Tian
- Diagnosis and Treatment Center for Spleen and Stomach Diseases, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou730030, Gansu, China
| | - Lijun Chang
- Chronic Non communicable Disease Control Institute, Gansu Provincial Center for Disease Control and Prevention, Lanzhou730000, Gansu, China
| | - Chaoxu Qu
- Endocrinology Department of Spleen and Stomach Diseases, Xigu District Traditional Chinese Medicine Hospital, Lanzhou730060, Gansu, China
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Garfias Noguez C, Ramírez Damián M, Ortiz Moreno A, Márquez Flores YK, Alamilla Beltrán L, Márquez Lemus M, Bermúdez Humarán LG, Sánchez Pardo ME. Microencapsulation and Probiotic Characterization of Lactiplantibacillus plantarum LM-20: Therapeutic Application in a Murine Model of Ulcerative Colitis. Nutrients 2025; 17:749. [PMID: 40077619 PMCID: PMC11901509 DOI: 10.3390/nu17050749] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 02/16/2025] [Accepted: 02/18/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Microencapsulation improves the storage, handling, and administration of probiotics by protecting them from environmental factors and adverse conditions in the gastrointestinal tract. This process facilitates their controlled delivery in the body, which can simplify their use in therapies without compromising their therapeutic efficacy. OBJECTIVES This study investigates the microencapsulation of Lactiplantibacillus plantarum LM-20, its probiotic properties, and its effects in a murine model of ulcerative colitis. METHODS/RESULTS Synbiotic microencapsulation was carried out using spray drying with maltodextrin, gum Arabic, and inulin, achieving an encapsulation efficiency of 90.76%. The resulting microcapsules exhibited remarkable resistance to simulated gastrointestinal conditions in vitro, maintaining a survival rate of 90%. The drying process did not compromise the probiotic characteristics of the bacteria, as they demonstrated enhanced auto-aggregation, hydrophobicity, and phenol tolerance. The therapeutic potential of the microencapsulated synbiotic was evaluated in a murine model of dextran sodium sulfate-induced ulcerative colitis. The results revealed that mice treated with microencapsulated Lactiplantibacillus plantarum LM-20 showed an 83.3% reduction in the disease activity index (DAI) compared to the ulcerative colitis control group. Moreover, a significant decrease was observed in pro-inflammatory cytokine levels (IL-1β and TNF-α) and myeloperoxidase activity, with values comparable to those of the healthy control group. CONCLUSIONS These findings suggest that microencapsulated Lactiplantibacillus plantarum LM-20 could be a promising candidate for therapeutic applications in the prevention and management of ulcerative colitis.
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Affiliation(s)
- Cynthia Garfias Noguez
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Zacatenco, Unidad Profesional Adolfo López Mateos, Zacatenco, Av. Wilfrido Massieu 399, Colonia Nueva Industrial Vallejo, Alcaldía Gustavo A. Madero, Ciudad de México 07738, Mexico; (C.G.N.); (M.R.D.); (A.O.M.); (Y.K.M.F.); (L.A.B.); (M.M.L.)
| | - Morayma Ramírez Damián
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Zacatenco, Unidad Profesional Adolfo López Mateos, Zacatenco, Av. Wilfrido Massieu 399, Colonia Nueva Industrial Vallejo, Alcaldía Gustavo A. Madero, Ciudad de México 07738, Mexico; (C.G.N.); (M.R.D.); (A.O.M.); (Y.K.M.F.); (L.A.B.); (M.M.L.)
| | - Alicia Ortiz Moreno
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Zacatenco, Unidad Profesional Adolfo López Mateos, Zacatenco, Av. Wilfrido Massieu 399, Colonia Nueva Industrial Vallejo, Alcaldía Gustavo A. Madero, Ciudad de México 07738, Mexico; (C.G.N.); (M.R.D.); (A.O.M.); (Y.K.M.F.); (L.A.B.); (M.M.L.)
| | - Yazmín Karina Márquez Flores
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Zacatenco, Unidad Profesional Adolfo López Mateos, Zacatenco, Av. Wilfrido Massieu 399, Colonia Nueva Industrial Vallejo, Alcaldía Gustavo A. Madero, Ciudad de México 07738, Mexico; (C.G.N.); (M.R.D.); (A.O.M.); (Y.K.M.F.); (L.A.B.); (M.M.L.)
| | - Liliana Alamilla Beltrán
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Zacatenco, Unidad Profesional Adolfo López Mateos, Zacatenco, Av. Wilfrido Massieu 399, Colonia Nueva Industrial Vallejo, Alcaldía Gustavo A. Madero, Ciudad de México 07738, Mexico; (C.G.N.); (M.R.D.); (A.O.M.); (Y.K.M.F.); (L.A.B.); (M.M.L.)
| | - Mario Márquez Lemus
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Zacatenco, Unidad Profesional Adolfo López Mateos, Zacatenco, Av. Wilfrido Massieu 399, Colonia Nueva Industrial Vallejo, Alcaldía Gustavo A. Madero, Ciudad de México 07738, Mexico; (C.G.N.); (M.R.D.); (A.O.M.); (Y.K.M.F.); (L.A.B.); (M.M.L.)
| | - Luis G. Bermúdez Humarán
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Domain de Vilvert, 78350 Jouy-en-Josas, France;
| | - María Elena Sánchez Pardo
- Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Campus Zacatenco, Unidad Profesional Adolfo López Mateos, Zacatenco, Av. Wilfrido Massieu 399, Colonia Nueva Industrial Vallejo, Alcaldía Gustavo A. Madero, Ciudad de México 07738, Mexico; (C.G.N.); (M.R.D.); (A.O.M.); (Y.K.M.F.); (L.A.B.); (M.M.L.)
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Chen L, Xie L, Wang L, Zhan X, Zhuo Z, Jiang S, Miao L, Zhang X, Zheng W, Liu TM, He J, Liu Y. Patchoulene epoxide mitigates colitis and hepatic damage induced by dextran sulfate sodium by regulating the colonic microbiota and purine metabolism. Front Immunol 2025; 16:1509114. [PMID: 40028318 PMCID: PMC11868103 DOI: 10.3389/fimmu.2025.1509114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 01/29/2025] [Indexed: 03/05/2025] Open
Abstract
Introduction Ulcerative colitis (UC) is often characterized by dysbiosis of the colonic microbiota and metabolic disturbances, which can lead to liver damage. Patchoulene epoxide (PAO), a tricyclic sesquiterpene derived from the aged essential oil of Pogostemonis Herba, is known for its anti-inflammatory and ulcer-healing properties. However, its dual protective role against UC and liver injury remains largely unexplored. This study aims to elucidate the protective effect and underlying mechanism of PAO against dextran sulfate sodium (DSS)-induced UC and liver injury in mice. Methods Colitis and liver injury in mice were induced by adding 3% DSS to their drinking water continuously for 7 days, and PAO at the doses of 20 and 40 mg/kg was administered orally to mice daily from the first day until the experimental endpoint. Stool consistency scores, blood stool scores, and body weights were recorded weekly. Disease activity index (DAI) was determined before necropsy, where colon and liver tissues were collected for biochemical analyses. Additionally, the fecal microbiome and its metabolites of treated mice were characterized using 16S rRNA amplicon sequencing and metabolomics. Results PAO significantly reduced the disease activity index and mitigated colonic atrophy in UC mice. It also improved colonic and hepatic pathological changes by safeguarding tight and adherens junctions, and suppressing the generation of pro-inflammatory cytokines and lipopolysaccharide. These beneficial effects were attributed to PAO's capability to regulate the colonic microbiota and metabolic processes. PAO was found to enhance the diversity of the colonic microbiota and to shift the microbial balance in UC mice. Specifically, it restored the microbiota from an Akkermansia-dominated state, characteristic of UC, to a healthier Muribaculaceae-dominated composition. Furthermore, PAO corrected the colon metabolic disturbance in UC mice by modulating the purine metabolism, notably increasing the abundance of deoxyadenosine, adenosine and guanine in UC mice. Conclusions The therapeutic effect of PAO on UC and liver injury was mainly attributed to its regulation of colonic microbiota and purine metabolism. These insights emphasize the overall therapeutic benefits of PAO in treating UC and liver injury.
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Affiliation(s)
- Liping Chen
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Lili Xie
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Lifen Wang
- Cancer Center, Faculty of Health Sciences, University of Macau, Macau, Macao SAR, China
| | - Xueli Zhan
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Zhenjian Zhuo
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
- Laboratory Animal Center, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China
| | - Susu Jiang
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Lei Miao
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Xinxin Zhang
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Weiming Zheng
- Institute of Translational Medicine, Faculty of Health Sciences & Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau, China
| | - Tzu-Ming Liu
- Institute of Translational Medicine, Faculty of Health Sciences & Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau, China
| | - Jing He
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Yuhong Liu
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China
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Jin Y, Liu H, Wang Y, Zhang R, Wang Q, Wang Y, Cui H, Wang X, Bian Y. Pathogenesis and treatment of colitis-associated colorectal cancer: Insights from Traditional Chinese Medicine. JOURNAL OF ETHNOPHARMACOLOGY 2025; 338:119096. [PMID: 39532222 DOI: 10.1016/j.jep.2024.119096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 10/11/2024] [Accepted: 11/09/2024] [Indexed: 11/16/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Inflammatory Bowel Disease (IBD) is an inflammatory intestinal disease, and with prolonged illness duration, the annual risk of IBD progressing to colitis-associated colorectal cancer (CAC) gradually increases. In recent years, there has been a noticeable trend towards the application of traditional Chinese medicine (TCM) in the treatment of CAC. AIM OF THIS REVIEW This comprehensive review summarizes the pathogenesis of CAC and details the therapeutic benefits of TCM in treating CAC, including various TCM prescriptions and ingredients, establishing the theoretical foundation for the application of TCM in CAC treatment. METHODS We assessed literature published before March 24, 2024, from several databases, including Web of Science, PubMed, Scopus and Google Scholar. The keywords used include "traditional Chinese medicine", "traditional Chinese medicine prescriptions", "traditional Chinese medicine ingredients", "herbal medicine", "colitis-associated colorectal cancer", "inflammatory bowel disease", "colorectal cancer" and "colitis-cancer transformation". We conducted a comprehensive collection and collation of pertinent scientific articles from various databases, focusing on the efficacy of TCM in the prevention and treatment of "colitis-cancer transformation". RESULTS This paper provides a concise summary and thorough analysis of twenty-eight prescriptions and ingredients of TCM for the prevention and treatment of CAC, based on existing experimental and clinical research. There are positive signs that TCM can effectively prevent and treat the "colitis-cancer transformation" through repairing the intestinal mucosal barrier, correcting intestinal flora imbalance, and regulating intestinal immune responses. CONCLUSION TCM possesses comprehensive regulatory advantages that are multifaceted, multilevel, and multitarget. It has a definite curative effect in the prevention and treatment of CAC. It is essential to enhance the clinical efficacy of TCM in the prevention and treatment of CAC based on syndrome differentiation and treatment, with the assistance of modern medicine.
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Affiliation(s)
- Yutong Jin
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Haizhao Liu
- Department of Integrated Traditional Chinese and Western Medicine, Tianjin First Central Hospital, Nankai University, Tianjin, 300192, China
| | - Yuhui Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Ruixuan Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Qiaochu Wang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300073, China
| | - Yao Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, 150040, China
| | - Huantian Cui
- First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, 650500, China.
| | - Xiangling Wang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
| | - Yuhong Bian
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
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18
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Jiao X, Li Y, Hu Y, Yan R, Fu T, Liu J, Li Z. Antibiotic-Induced dysbiosis of the ocular microbiome affects corneal circadian rhythmic activity in mice. Mucosal Immunol 2025:S1933-0219(25)00010-8. [PMID: 39920996 DOI: 10.1016/j.mucimm.2025.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 01/09/2025] [Accepted: 01/28/2025] [Indexed: 02/10/2025]
Abstract
The ocular surface microbiota plays a critical role in maintaining corneal homeostasis, but its disruption and subsequent effects on corneal functions remain poorly understood. This study investigates how antibiotic-induced microbial depletion affects the corneal circadian transcriptome in C57BL/6J mice. Dysbiosis was induced using a topical antibiotic cocktail, and RNA sequencing was employed to analyze gene expression across eight time points over 24 h. Antibiotic treatment disrupted corneal circadian rhythms, eliminating rhythmicity in 1,812 genes and introducing rhythmicity in 1,928 previously arrhythmic genes. Furthermore, epithelial adhesion was impaired, inflammation was elevated, and neural sensitivity was reduced. More than 50 % of ocular microbial genera exhibited daily oscillations, with six genera showing significant correlations with corneal rhythmic transcripts. Additionally, the administration of TLR agonists restored circadian gene expression patterns, with partial recovery of corneal barrier function and immune homeostasis, further highlighting the potential of microbiota-targeted therapies in treating ocular surface disorders. These findings underscore the critical role of the ocular microbiota in regulating corneal health and suggest that restoring microbial balance via TLR activation may offer new therapeutic avenues for eye diseases.
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Affiliation(s)
- Xinwei Jiao
- Department of Pathology, Medical School, Jinan University, Guangzhou, China; International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China
| | - Yan Li
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yu Hu
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Ruyu Yan
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Ting Fu
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Jun Liu
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Zhijie Li
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
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19
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Kucharski R, Sobocki BK, Stachowska E, Bulman N, Kalinowski L, Kaźmierczak-Siedlecka K. Dental problems and oral microbiome alterations in ulcerative colitis. Front Immunol 2025; 16:1502605. [PMID: 39975550 PMCID: PMC11836005 DOI: 10.3389/fimmu.2025.1502605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 01/13/2025] [Indexed: 02/21/2025] Open
Abstract
Ulcerative colitis is a chronic disease that has not well-established etiology. The role of microbial dysregulation in its pathogenesis has been recently highlighted. Overall, microbiome alterations concern the reduction of bacterial abundance and diversity, resulting in gut microbiome imbalance negatively affecting immunological aspects. There is a link between ulcerative colitis and the oral microbiome. The changes of oral microbiome are found at many levels, from gently dysbiotic composition to the presence of the main periodontal microbes. The analysis of oral microbiome can be a part of personalized medicine due to the fact that it is a potential biomarker. Patients with ulcerative colitis may manifest dental symptoms/problems, such as periodontitis (strongly related to the red-complex pathogens-Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and bacteria belonging to the other complexes, such as Fusobacterium nucleatum and Aggregatibacter actinomycetecomitans), dental caries, oral ulcerations, leukoplakia, halitosis, and others. Notably, the DMFT (Decayed, Missing, Filled Teeth) index is higher in these patients compared to healthy subjects. According to some data, oral lichen planus (which is a disease with an immunological background) can also be observed in ulcerative colitis patients. It seems that deep understanding of ulcerative colitis in association with oral microbiome, immunology, and dental manifestations may be crucial to provide complex treatment from a dental point of view.
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Affiliation(s)
- Robert Kucharski
- Department of Medical Laboratory Diagnostics – Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdańsk, Poland
- Neodentica Dentistry Center, Gdansk, Poland
| | - Bartosz Kamil Sobocki
- Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdańsk, Poland
| | - Ewa Stachowska
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Nikola Bulman
- Department of Medical Laboratory Diagnostics – Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdańsk, Poland
| | - Leszek Kalinowski
- Department of Medical Laboratory Diagnostics – Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdańsk, Poland
- BioTechMed Center, Department of Mechanics of Materials and Structures, Gdansk University of Technology, Gdansk, Poland
| | - Karolina Kaźmierczak-Siedlecka
- Department of Medical Laboratory Diagnostics – Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdańsk, Poland
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20
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Mousavi SN, Momeni N, Chiti H, Mahmoodnasab H, Ahmadi M, Heidarzadeh S. Higher gut Bacteroidetes and Actinobacteria population in early pregnancy is associated with lower risk of gestational diabetes in the second trimester. BMC Pregnancy Childbirth 2025; 25:106. [PMID: 39901086 PMCID: PMC11789361 DOI: 10.1186/s12884-025-07192-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 01/16/2025] [Indexed: 02/05/2025] Open
Abstract
BACKGROUND Despite the association between the gut dysbiosis and metabolic disorders, the main bacterial phylum in the first trimester of pregnancy that predisposes mothers to gestational diabetes mellitus (GDM) in the second trimester is not clear around the world. MATERIALS AND METHODS Three-hundred healthy women aged 18-40 years who were in the first trimester were participated in this cohort study and followed to the screening time for GDM diagnosis (in 24-28 weeks of pregnancy). Stool samples were gathered in the first trimester. GDM was diagnosed based on the International Association of Diabetes and Pregnancy Groups. In total, thirty mothers were diagnosed with GDM. Controls (N = 60) were selected from non-GDM participants matching to the GDM in terms of pre-pregnancy weight, weight gain, dietary intake and familial history of diabetes. The dominant phylum population was determined based on 16SrRNA gene expression. RESULTS Mothers with lower Bacteroidetes and Actinobacteria population in the first trimester were more susceptible to GDM in the screening time (p < 0.001 and p < 0.001). The Firmicutes to Bacteroidetes ratio was significantly higher in mothers with GDM than the controls (p < 0.001). A significant negative correlation was observed between the gut Bacteroidetes (p < 0.001, p < 0.001, p < 0.001) and Actinobacteria (p = 0.004, p < 0.001, p = 0.02) population in the first trimester with the the serum FBS, 1 h-PG and 2 h-PG levels in the screening time. However, the gut Firmicutes to Bacteroidetes ratio (p = 0.003, p = 0.01) showed a significant positive correlation with serum FBS and 1 h-PG levels. CONCLUSIONS A higher Bacteroidetes and Actinobacteria population in the gut of mothers at the first trimester was associated with lower risk of GDM in the screening time. Higher Firmicutes to Bacteroidetes ratio in the gut of mothers was associated with fasting and 1-h glucose intolerance in the screening time.
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Affiliation(s)
- Seyedeh Neda Mousavi
- Zanjan Metabolic Diseases Research Center, Health and Metabolic Diseases Research Institute , Zanjan University of Medical Sciences, Zanjan, Iran.
- Department of Nutrition, School of Public Health, Zanjan University of Medical Sciences, Zanjan, Iran.
| | - Navid Momeni
- Zanjan Metabolic Diseases Research Center, Health and Metabolic Diseases Research Institute , Zanjan University of Medical Sciences, Zanjan, Iran
| | - Hossein Chiti
- Zanjan Metabolic Diseases Research Center, Health and Metabolic Diseases Research Institute , Zanjan University of Medical Sciences, Zanjan, Iran
| | - Howra Mahmoodnasab
- Department of Nutrition, School of Public Health, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mohammad Ahmadi
- Department of Nutrition, School of Public Health, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Siamak Heidarzadeh
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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21
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Ibrahim D, Khater SI, Sherkawy HS, Elgamal A, Hasan AA, Muhammed AA, Farag MFM, Eissa SA, Ismail TA, Eissa HM, Eskandrani AA, Alansari WS, El-Emam MMA. Protective Role of Nano-encapsulated Bifidobacterium breve, Bacilllus coagulans, and Lactobacillus plantarum in Colitis Model: Insights Toward Propagation of Short-Chain Fatty Acids and Reduction of Exaggerated Inflammatory and Oxidative Response. Probiotics Antimicrob Proteins 2025:10.1007/s12602-025-10472-y. [PMID: 39900879 DOI: 10.1007/s12602-025-10472-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/21/2025] [Indexed: 02/05/2025]
Abstract
Irritable bowel disease (IBD), also known as ulcerative colitis and Crohn's disease, is a chronic inflammatory disorder affecting millions of people worldwide. Herein, nano-encapsulated multi-strain probiotics formulation, comprising Bifidobacterium breve DSM24732 and B. coagulans SANK 70258 and L. plantarum DSM24730 (BBLNPs) is used as an effective intervention technique for attenuating IBD through gut microenvironment regulation. The efficacy of the prophylactic role of BBLNPs in alleviating injury induced by dextran sulfate sodium (DSS) was evaluated by assessing oxidative and inflammatory responses, levels of short-chain fatty acids (SCFAs) and their regulation on GPR41/43 pathway, expression of genes related to tight-junctions and autophagy, immunohistochemistry of IL1β and GPR43, and histological examination of inflamed colonic tissue. The severity of clinical signs and paracellular permeability to FITC (fluorescein isothiocyanate)-labeled dextran was significantly decreased after BBLNP treatment. Reduction of oxidative stress-associated biomarkers (MDA, ROS, and H2O2) and acceleration of antioxidant enzyme activities (SOD, CAT, and GSH-Px) were noted in the BBLNP-treated group. Subsiding of inflammatory markers (TNF-α, IL-18, IL-6, TRL-4, CD-8, NLRP3, and caspase 1) and upregulation of tight-junction-related genes (occludin and JAM) was detected in BBLNPs. Administration of BBLNPs remarkably resulted in a higher level of SCFAs which parrel with colonic upregulation of GPR41 and GPR43 expression compared to DSS-treated rats. Notable modulation of autophagy-related genes (p62, mTOR, LC3, and Beclin-1) was identified post BBLNP treatment. The mRNA expressions of p62 and mTOR were significantly downregulated, while LC3 and Beclin-1 were upregulated after prophylactic treatment with BBLNPs. Immune-stained labeled cells showed lower expression of IL-1β and higher expression levels of GPR43 in BBLNPs compared to the DSS-induced group. The intestinal damage caused by DSSwas effectively mitigated by oral BBLNP treatment, as supported by the restoration of healthy colonic tissue architecture. The findings suggest that BBLNPs have a promising avenue in the remission of IBD by modulating inflammation, oxidative stress, microbial metabolites such as SCFAs, and autophagy.
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Affiliation(s)
- Doaa Ibrahim
- Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44511, Egypt.
| | - Safaa I Khater
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, Egypt
| | - Hoda S Sherkawy
- Department of Medical Biochemistry, Faculty of Medicine, Aswan University, Aswan, Egypt
| | - Aya Elgamal
- Department of Animal Histology and Anatomy, Faculty of Veterinary Medicine, Badr University in Cairo (BUC), Cairo, Egypt
| | - Asmaa A Hasan
- Department of Human Anatomy and Embryology, Faculty of Medicine, Aswan University, Aswan, Egypt
| | - Asmaa A Muhammed
- Department of Medical Physiology, Faculty of Medicine, Aswan University, Aswan, 81511, Egypt
| | - Mohamed F M Farag
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
| | - Samar A Eissa
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Kafrelsheikh University, Kafr El-Sheikh, Egypt
| | - Tamer Ahmed Ismail
- Department of Clinical Laboratory Sciences, Turabah University College, Taif University, P.O. Box 11099, 21944, Taif, Saudi Arabia
| | - Hemmat M Eissa
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, Egypt
| | - Areej A Eskandrani
- Chemistry Department, College of Science, Taibah University, Medina, Saudi Arabia
| | - Wafa S Alansari
- Biochemistry Department, Faculty of Science, University of Jeddah, Jeddah, Saudi Arabia
| | - Mahran Mohamed Abd El-Emam
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, Egypt
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22
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Lista S, Munafò A, Caraci F, Imbimbo C, Emanuele E, Minoretti P, Pinto-Fraga J, Merino-País M, Crespo-Escobar P, López-Ortiz S, Monteleone G, Imbimbo BP, Santos-Lozano A. Gut microbiota in Alzheimer's disease: Understanding molecular pathways and potential therapeutic perspectives. Ageing Res Rev 2025; 104:102659. [PMID: 39800223 DOI: 10.1016/j.arr.2025.102659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 11/29/2024] [Accepted: 01/09/2025] [Indexed: 01/15/2025]
Abstract
Accumulating evidence suggests that gut microbiota (GM) plays a crucial role in Alzheimer's disease (AD) pathogenesis and progression. This narrative review explores the complex interplay between GM, the immune system, and the central nervous system in AD. We discuss mechanisms through which GM dysbiosis can compromise intestinal barrier integrity, enabling pro-inflammatory molecules and metabolites to enter systemic circulation and the brain, potentially contributing to AD hallmarks. Additionally, we examine other pathophysiological mechanisms by which GM may influence AD risk, including the production of short-chain fatty acids, secondary bile acids, and tryptophan metabolites. The role of the vagus nerve in gut-brain communication is also addressed. We highlight potential therapeutic implications of targeting GM in AD, focusing on antibiotics, probiotics, prebiotics, postbiotics, phytochemicals, and fecal microbiota transplantation. While preclinical studies showed promise, clinical evidence remains limited and inconsistent. We critically assess clinical trials, emphasizing challenges in translating GM-based therapies to AD patients. The reviewed evidence underscores the need for further research to elucidate precise molecular mechanisms linking GM to AD and determine whether GM dysbiosis is a contributing factor or consequence of AD pathology. Future studies should focus on large-scale clinical trials to validate GM-based interventions' efficacy and safety in AD.
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Affiliation(s)
- Simone Lista
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - Antonio Munafò
- Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence 50139, Italy.
| | - Filippo Caraci
- Department of Drug and Health Sciences, University of Catania, Catania 95125, Italy; Oasi Research Institute-IRCCS, Troina 94018, Italy.
| | - Camillo Imbimbo
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia 27100, Italy.
| | | | | | - José Pinto-Fraga
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - María Merino-País
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - Paula Crespo-Escobar
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - Susana López-Ortiz
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - Giovanni Monteleone
- Department of Systems Medicine, University of Rome Tor Vergata, Rome 00133, Italy; Unit of Gastroenterology, Policlinico Tor Vergata University Hospital, Rome 00133, Italy.
| | - Bruno P Imbimbo
- Department of Research and Development, Chiesi Farmaceutici, Parma 43122, Italy.
| | - Alejandro Santos-Lozano
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain; Physical Activity and Health Research Group (PaHerg), Research Institute of the Hospital 12 de Octubre ('imas12'), Madrid 28041, Spain.
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23
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Zhao H, Fu X, Wang Y, Shang Z, Li B, Zhou L, Liu Y, Liu D, Yi B. Therapeutic Potential of Vanillic Acid in Ulcerative Colitis Through Microbiota and Macrophage Modulation. Mol Nutr Food Res 2025; 69:e202400785. [PMID: 39812000 DOI: 10.1002/mnfr.202400785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 12/17/2024] [Accepted: 12/20/2024] [Indexed: 01/16/2025]
Abstract
This study investigated the protective effects of the dietary polyphenol vanillic acid (VA) on dextran sulfate sodium-induced acute ulcerative colitis (UC) in mice, focusing on its impact on the gut microbiota and inflammatory responses. VA was supplemented following dextran sulfate sodium administration, and key indicators, including body weight, disease activity index, colon length, spleen index, and inflammatory markers, were assessed. VA supplementation significantly alleviated UC symptoms, preserved intestinal barrier integrity, and reduced pro-inflammatory cytokine levels. Additionally, VA positively altered the gut microbiota composition, promoting beneficial bacteria such as Akkermansia muciniphila while suppressing the arachidonic acid metabolism pathway. Fecal microbiota transplantation confirmed that the VA-modified gut microbiota contributed to these protective effects. VA also facilitated macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, further mitigating inflammation. These findings highlight the potential of VA as a natural dietary intervention for UC, emphasizing its role in regulating the gut microbiota and inflammatory pathways, which may have significant nutritional relevance in managing inflammatory bowel diseases.
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Affiliation(s)
- Hu Zhao
- 2nd Abdominal Surgery Department, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, People's Republic of China
- Jiangxi Cancer Institute, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, People's Republic of China
- Department of Burns and Surgery, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, People's Republic of China
| | - Xingxing Fu
- School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, People's Republic of China
| | - Yaru Wang
- School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, People's Republic of China
| | - Zhao Shang
- School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, People's Republic of China
| | - BangHua Li
- Department of Integrated Traditional Chinese and Western Medicine Oncology, and Third Ward of Gastrointestinal Oncology, Nanchang, Jiangxi, People's Republic of China
| | - Li Zhou
- School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, People's Republic of China
| | - Yue Liu
- School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, People's Republic of China
| | - Dan Liu
- School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, People's Republic of China
| | - Bo Yi
- 2nd Abdominal Surgery Department, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, People's Republic of China
- Jiangxi Cancer Institute, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, People's Republic of China
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24
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Levy S, Jiang AK, Grant MR, Arp G, Minabou Ndjite G, Jiang X, Hall B. Convergent evolution of oxidized sugar metabolism in commensal and pathogenic microbes in the inflamed gut. Nat Commun 2025; 16:1121. [PMID: 39875389 PMCID: PMC11775122 DOI: 10.1038/s41467-025-56332-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 01/14/2025] [Indexed: 01/30/2025] Open
Abstract
Inflammation-associated perturbations of the gut microbiome are well characterized, but poorly understood. Here, we demonstrate that disparate taxa recapitulate the metabolism of the oxidized sugars glucarate and galactarate, utilizing enzymatically divergent, yet functionally equivalent, gud/gar pathways. The divergent pathway in commensals includes a putative 5-KDG aldolase (GudL) and an uncharacterized ABC transporter (GarABC) that recapitulate the function of their non-homologous counterparts in pathogens. A systematic bioinformatic search for the gud/gar pathway in gut microbes identified 887 species putatively capable of metabolizing oxidized sugars. Previous studies showed that inflammation-derived nitrate, formed by nitric oxide reacting with superoxide, promotes pathogen growth. Our findings reveal a parallel phenomenon: oxidized sugars, also produced from reactions with nitric oxide, serve as alternative carbon sources for commensal microbes. Previously considered a pathogen virulence factor, oxidized sugar metabolism is also present in specific commensals and may contribute to their increased relative abundance in gastrointestinal inflammation.
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Affiliation(s)
- Sophia Levy
- Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA
| | - Angela K Jiang
- Center for Bioinformatics and Computational Biology, University of Maryland, College Park, College Park, MD, USA
- National Library of Medicine, National Institutes of Health, Bethesda, MD, USA
| | - Maggie R Grant
- Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA
| | - Gabriela Arp
- Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA
| | - Glory Minabou Ndjite
- Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA
| | - Xiaofang Jiang
- National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
| | - Brantley Hall
- Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA.
- Center for Bioinformatics and Computational Biology, University of Maryland, College Park, College Park, MD, USA.
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25
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Zhao Y, Liang S, Fu X, Guo Y, Wang Y, Wang J, Wang X, Wang Z, Tao H, Han B, Wang J. Anti-Inflammatory and Antidiarrheal Effects of Two Strains of Lactic Acid Bacteria Isolated from Healthy Pets on Escherichia coli K88-Induced Diarrhea in Mice. Microorganisms 2025; 13:239. [PMID: 40005605 PMCID: PMC11857690 DOI: 10.3390/microorganisms13020239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/17/2025] [Accepted: 01/19/2025] [Indexed: 02/27/2025] Open
Abstract
Lactic acid bacteria play a crucial role in maintaining the health of the host's gut microbiota. In this study, the anti-inflammatory properties of Limosilactobacillus reuteri LR20-6 and Lacticplantibacillus plantarum L272 were evaluated using a mouse model of diarrhea induced by Escherichia coli. We also investigated their effects on gut microbiota regulation. The results indicated that both Lacticplantibacillus plantarum and Limosilactobacillus reuteri could reduce inflammation by inhibiting the expression of inflammatory factors IL-6 and TNF-α and blocking the MyD88 and NF-kB/p65 signaling pathways. Additionally, after intervention with these strains, the relative abundance of Lactobacillus was significantly increased. This suggested that Lacticplantibacillus plantarum and Limosilactobacillus reuteri could mitigate the severity of E. coli-induced diarrhea and enhance the abundance of beneficial probiotics in the gut of animals.
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Affiliation(s)
- Ya Zhao
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Shukun Liang
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
- College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
| | - Xiaoxin Fu
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Yaping Guo
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Yu Wang
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Jiaxue Wang
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Xiumin Wang
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Zhenlong Wang
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Hui Tao
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Bing Han
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
| | - Jinquan Wang
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (Y.Z.); (S.L.); (X.F.); (Y.G.); (Y.W.); (J.W.); (X.W.); (Z.W.); (H.T.)
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Gong S, Yu Z, Ding Y, Wang Y, Li X, Gu S. Characteristics of functional constipation and analysis of intestinal microbiota in children aged 0-4 in Zunyi region. BMC Pediatr 2025; 25:45. [PMID: 39825285 PMCID: PMC11748605 DOI: 10.1186/s12887-024-05383-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Accepted: 12/30/2024] [Indexed: 01/20/2025] Open
Abstract
BACKGROUND Functional constipation (FC) significantly impacts children's health. This study investigates the prevalence and microbiota characteristics of FC in children aged 0-4 years in Zunyi area. METHODS From October to December 2023, 2039 children aged 0-4 years in Zunyi were selected using stratified sampling and cross-sectional survey methods. A questionnaire based on Rome IV diagnostic criteria was used. Twenty-nine children with FC were randomly selected as the functional constipation group (FCG), and 26 healthy children, matched for age, sex, and area, were selected as the control group (CG). RESULTS A total of 2051 questionnaires were collected, with 2039 valid responses. Among them, 151 children had FC, resulting in a prevalence rate of 7.4%. The prevalence rates in boys and girls were 6.6% and 8.5%, respectively, with no significant gender difference (P > 0.05). Alpha diversity analysis revealed higher richness and diversity of intestinal flora in the FCG compared to the CG. At the phylum level, Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes were dominant in both groups. The FCG showed a higher relative abundance of Firmicutes, Actinobacteria, and Proteobacteria compared to the CG (P < 0.05). CONCLUSIONS The prevalence of FC in children aged 0-4 years in Zunyi is 7.4%. Disease characteristics vary with age and living environment but are unrelated to gender. The gut microbiota of children with FC shows significant alterations, with higher diversity and specific phyla abundance.
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Affiliation(s)
- Shungang Gong
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China
| | - Zhengbo Yu
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China
| | - Yuan Ding
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China
| | - Yue Wang
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China
| | - Xi Li
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China
| | - Shengli Gu
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China.
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Zhang Y, Zhu M, Dai Y, Gao L, Cheng L. Research Progress in Ulcerative Colitis: The Role of Traditional Chinese Medicine on Gut Microbiota and Signaling Pathways. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2024; 52:2277-2336. [PMID: 39756829 DOI: 10.1142/s0192415x24500885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
Abstract
Ulcerative colitis (UC), one among other refractory diseases worldwide, has shown an increasing trend of progression to colorectal cancer in recent years. In the treatment of UC, traditional Chinese medicine has demonstrated good efficacy, with a high cure rate, fewer adverse effects, great improvement in the quality of patient survival, and reduction in the tendency of cancerous transformation. It shows promise as a complementary and alternative therapy. This review aims to evaluate and discuss the current research on UC, signaling pathways, and gut microbiota. We also summarized the mechanisms of action of various Chinese medicines (active ingredients or extracts) and herbal formulas, through signaling pathways and gut microbiota, with the expectation that they can provide references and evidence for treating UC and preventing inflammation-associated colorectal cancer by traditional Chinese medicine. We illustrate that multiple signaling pathways, such as TLR4, STAT3, PI3K/Akt, NF-[Formula: see text]B, and Keap1/Nrf2, can be inhibited by Chinese herbal treatments through the combined regulation of signaling pathways and gut microbiota, which can act individually or synergistically to inhibit intestinal inflammatory cell infiltration, attenuate gut oxidative responses, and repair the intestinal barrier.
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Affiliation(s)
- Yuyi Zhang
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, P. R. China
| | - Mingfang Zhu
- Graduate School, Zunyi Medical University Zunyi, P. R. China
| | - Yueying Dai
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, P. R. China
| | - Longying Gao
- Department of Anorectal, The First Affiliated Hospital of Heilongjiang, University of Chinese Medicine Harbin, P. R. China
| | - Limin Cheng
- Department of Anorectal, The First Affiliated Hospital of Heilongjiang, University of Chinese Medicine Harbin, P. R. China
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Zhong Y, Chang X, Zhao Z, Zheng L, Kuang G, Li P, Liu C, Fan Y, Liang Z, Zhuang K, Xie Q, Liu Y. Bacteroides fragilis capsular polysaccharide A ameliorates ulcerative colitis in rat by recovering intestinal barrier integrity and restoring gut microbiota. Front Pharmacol 2024; 15:1402465. [PMID: 39776580 PMCID: PMC11703662 DOI: 10.3389/fphar.2024.1402465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Accepted: 10/02/2024] [Indexed: 01/11/2025] Open
Abstract
Bacteroides fragilis (B. fragilis) is a Gram-negative, obligate anaerobic, commensal bacterium residing in the human gut and holds therapeutic potential for ulcerative colitis (UC). Previous studies have indicated that capsular polysaccharide A (PSA) of B. fragilis is a crucial component for its effectiveness, possessing various biological activities such as anti-inflammatory, anti-tumor, and immune-modulating effects. We previously isolated and characterized the B. fragilis strain ZY-312 from the feces of a healthy breastfed infant, and extracted its PSA, named TP2. In this study, we explored the impact of TP2 on colonic inflammation and delved into its potential mechanisms. Initially, we used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce colitis in rats and found that TP2 treatment significantly ameliorated TNBS-induced weight loss, increased clinical scores, extensive ulcers, and intestinal epithelial damage in UC rats. Further analysis revealed that TP2 effectively restored the intestinal barrier integrity in UC rats by regulating the expression of Muc-2, tight junction proteins (ZO-1, occludin, claudin-1, and claudin-2), as well as apoptosis-related proteins Bcl-2, BAX, and Cleaved-Caspase-3. Additionally, TP2 suppressed the expression of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL23, while promoting the secretion of anti-inflammatory cytokines IL-10 and IL-22, thereby inhibiting the occurrence of inflammation. TP2 also downregulated the phosphorylation levels of AKT and PI3K, effectively inhibiting the abnormal activation of the PI3K/AKT signaling pathway. More interestingly, 16S rRNA sequencing results showed that TP2 restored the ecological imbalance of the rat intestinal microbiota, with an increase in beneficial bacteria such as Lactobacillus and Limosilactobacillus observed in the treatment group. In conclusion, TP2 through the regulation of intestinal barrier-related cells and proteins, inhibition of apoptosis, modulation of inflammation-related cytokine levels, and control of abnormal activation of the PI3K/AKT signaling pathway, restores intestinal barrier integrity. Additionally, by reshaping the ecological imbalance of the gut microbiota, TP2 ultimately alleviates ulcerative colitis in rats.
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Affiliation(s)
- Yijia Zhong
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Xiujuan Chang
- Guangzhou ZhiYi Biotechnology Co. Ltd., Guangzhou, China
| | - Zihan Zhao
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Lijun Zheng
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Gaobo Kuang
- Guangzhou ZhiYi Biotechnology Co. Ltd., Guangzhou, China
| | - Ping Li
- Guangzhou ZhiYi Biotechnology Co. Ltd., Guangzhou, China
| | | | - Yuqin Fan
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Zhixuan Liang
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Ke Zhuang
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Qiuling Xie
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Yangyang Liu
- Guangzhou ZhiYi Biotechnology Co. Ltd., Guangzhou, China
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Jin Z, Liu Z, Pan J, Wang S, Cui M, He C, Lin M, Liu X, Yu X, Gong F. FGF20 modulates gut microbiota to mitigate dextran sodium sulfate-induced ulcerative colitis in mouse models. Int Immunopharmacol 2024; 142:113044. [PMID: 39217880 DOI: 10.1016/j.intimp.2024.113044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 08/24/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024]
Abstract
Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease (IBD), presents a significant clinical challenge due to the lack of optimal therapeutic strategies. Emerging evidence suggests that fibroblast growth factor 20 (FGF20) may play a crucial role in mitigating UC symptoms, though the mechanistic underpinnings remain elusive. In this study, a mouse model of UC was established using dextran sodium sulfate (DSS) to investigate the potential role of FGF20. Our findings revealed a marked reduction in FGF20 expression in the serum and colonic tissues of DSS-treated mice. Furthermore, FGF20 knockout did not exacerbate colonic damage in these mice. Conversely, overexpression of FGF20 via adeno-associated virus (AAV) significantly alleviated UC-associated symptoms. This alleviation was evidenced by attenuated intestinal shortening, mitigated weight loss, increased colonic goblet cell density and crypt formation, reduced inflammation severity and inflammatory cell infiltration, and enhanced expression of tight junction and mucin proteins. Moreover, FGF20 significantly ameliorated the dysbiosis of gut microbiota in DSS-treated mice by increasing the abundance of beneficial bacteria and decreasing the abundance of harmful bacteria. The beneficial effects of FGF20 were notably attenuated following gut microbiota depletion with an antibiotic regimen. Fecal microbiota transplantation experiments further supported the critical role of gut microbiota in mediating the effects of FGF20 on DSS-treated mice. In conclusion, these findings highlight the potential involvement of gut microbiota in the therapeutic effects of FGF20 in UC.
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Affiliation(s)
- Zhongqian Jin
- The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zhaoyang Liu
- School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China; Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China
| | - Jiaxuan Pan
- School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China; Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China
| | - Shangwen Wang
- School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Mengdie Cui
- Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China
| | - Chenbei He
- School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Mengyi Lin
- School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xuehui Liu
- School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiang Yu
- Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China
| | - Fanghua Gong
- The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China; Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang, China.
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Li C, Deng L, Pu M, Ye X, Lu Q. Coptisine alleviates colitis through modulating gut microbiota and inhibiting TXNIP/NLRP3 inflammasome. JOURNAL OF ETHNOPHARMACOLOGY 2024; 335:118680. [PMID: 39117021 DOI: 10.1016/j.jep.2024.118680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 08/03/2024] [Accepted: 08/06/2024] [Indexed: 08/10/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Ulcerative colitis (UC) is a disease involving the enteric canal which is characterised by chronisch inflammatory reaction. Coptisine (COP), the distinctive component of Coptis chinensis Franch., is famous for its anti-inflammation, antioxidation, anti-bacteria, and anti-cancer. Earlier researches certified that COP is a prospective remedy for colitis, but the mechanism of colitis and the therapeutical target of COP are deficiently elucidated. AIM OF THIS STUDY In this follow-up study, we adopted dextran sulfate sodium (DSS)-elicited UC model to further elucidate the possible mechanism of COP on UC in mice. MATERIALS AND METHODS COP and the positive drug sulfasalazine (SASP) were administered by oral gavage in DSS-induced colitis mouse model. Oxidative stress, inflammatory cytokines, intestinal barrier permeability, protein expression of the TXNIP/NLRP3 inflammasome pathway and intestinal microbiome structure were assessed. RESULTS Among this investigation, our team discovered that COP could mitigate DSS-elicited UC in murines, with prominent amelioration in weight loss, disease activity index, intestinal permeability (serum diamine oxidase and D-lactate), contracted colonal length and histologic alterations. Furthermore, COP greatly lowered the generation of pro-inflammatory factors, malondialdehyde (MDA) activity and reactive oxygen species (ROS) level, while increased superoxide dismutase (SOD) activity in colonal tissues. Additionally, COP downmodulated the proteic expressions of thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1, IL-1β and IL-18. Enteric microbiome sequencing displayed that DSS and COP tremendously influenced the constitution and diversity of enteric microbes in DSS-elicited UC murines. Besides, COP elevated the abundance of probiotic bacteria Bacteroidota, Akkermansia_muciniphila and Bacteroides_acidifaciens, lowered the proportions of potential pathogenic bacteria, such as Lachnospiraceae, Acetatifactor_muris, Clostridium_XlVa, Alistipes and Oscillibacter, and reduced the ratio of Bacillota/Bacteroidota, which vastly helped to reverse the enteric microbiome to a balanceable condition. Alterations in these bacteria were strongly correlated with the colitis relative index. CONCLUSION The mechanism of COP against UC is connected with the suppression of TXNIP/NLRP3 inflammasome signalling pathway and the adjustment of the enteric microbiome profiles. The proofs offer new understandings upon the anti-UC function of COP, which might be a prospective candidate against UC.
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Affiliation(s)
- Cailan Li
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, PR China; Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi 563000, PR China
| | - Li Deng
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China
| | - Min Pu
- Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China
| | - Xuanlin Ye
- Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China
| | - Qiang Lu
- Department of Pharmaceutical Sciences, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, PR China.
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Hu Y, Zhou L, Yang J, Bai R, Marchioni E, Zhao M, Zhou L. Anti-inflammatory mechanism of Houttuynia cordata polysaccharides against ulcerative colitis based on multi-omics conjoint analysis. Int J Biol Macromol 2024; 283:137311. [PMID: 39521219 DOI: 10.1016/j.ijbiomac.2024.137311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 11/03/2024] [Accepted: 11/04/2024] [Indexed: 11/16/2024]
Abstract
The Houttuynia cordata polysaccharide (HCP) was extracted from the traditional Chinese medicine, Houttuynia cordata, known for its anti-inflammatory properties. It has an acidic heteropolysaccharide with a molecular weight of approximately 13.38 kDa, consisting of 7 monosaccharides such as galactose, galacturonic acid, and glucose. Mouse ulcerative colitis (UC) model experiments demonstrated its effective anti-inflammatory activity at concentrations of 100 mg/kg and 300 mg/kg respectively. The objective of this study was to investigate the mechanism of action underlying the therapeutic effects of HCP in UC through omics analysis method. A total of 724 different metabolites and 246 differential lipids were identified. Through metabolomic analysis, six metabolic pathways including the linoleic acid metabolic pathway, caffeine metabolic pathway, mannose and fructose metabolic pathways, methyl histidine metabolic pathway and fatty acid biosynthesis, which were significantly associated with colon-related diseases. Subsequently, lipidomics analysis revealed that the metabolic pathways of α-linolenic and linoleic acid, fatty acid biosynthesis, and glycerolipid metabolism exhibited significant associations with serum lipid metabolism. These findings suggested that HCP had potential therapeutic effects in treating UC.
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Affiliation(s)
- Yueqi Hu
- National Demonstration Center for Experimental Ethnopharmacology Education, School of Pharmaceutical Sciences, South-Central MinZu University, Wuhan 430074, PR China
| | - Li Zhou
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China
| | - Jian Yang
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China
| | - Ruibin Bai
- State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China
| | - Eric Marchioni
- Equipe de Chimie Analytique des Molécules Bioactives et Pharmacognoise, Institut Pluridisciplinaire Hubert Curien (UMR 7178, CNRS/UDS), 74 route du Rhin, 67400 Illkirch, France
| | - Minjie Zhao
- Equipe de Chimie Analytique des Molécules Bioactives et Pharmacognoise, Institut Pluridisciplinaire Hubert Curien (UMR 7178, CNRS/UDS), 74 route du Rhin, 67400 Illkirch, France
| | - Li Zhou
- National Demonstration Center for Experimental Ethnopharmacology Education, School of Pharmaceutical Sciences, South-Central MinZu University, Wuhan 430074, PR China.
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Xiao Q, Luo L, Zhu X, Yan Y, Li S, Chen L, Wang X, Zhang J, Liu D, Liu R, Zhong Y. Formononetin alleviates ulcerative colitis via reshaping the balance of M1/M2 macrophage polarization in a gut microbiota-dependent manner. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 135:156153. [PMID: 39423480 DOI: 10.1016/j.phymed.2024.156153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Revised: 09/18/2024] [Accepted: 10/11/2024] [Indexed: 10/21/2024]
Abstract
BACKGROUND Ulcerative colitis (UC), a type of inflammatory bowel disease, presents substantial challenges in clinical treatment due to the limitations of current medications. Formononetin (FN), a naturally compound with widespread availability, exhibits anti-inflammatory, antioxidant, and immunomodulatory properties. PURPOSE This study aimed to investigate the efficacy of FN against UC and its potential regulatory mechanism. METHODS Here, dextran sulfate sodium (DSS) was employed to replicate experimental colitis in mice with concomitant FN treatment. The distribution and localisation of CD68 and F4/80 macrophages in colonic tissues were visualized by immunofluorescence, their chemokine and inflammatory cytokine concentrations were determined by ELISA, and macrophages and M1/M2 subpopulations were determined by flow cytometry. Additionally, 16 s rRNA and LC-MS techniques were used to detect the colonic intestinal microbiota and metabolite profiles, respectively. Correlation analyses was performed to clarify the interactions between differential bacteria, metabolites and M1/M2 macrophages, and pseudo sterile mice were constructed by depletion of gut flora with quadruple antibiotics, followed by faecal microbial transplantation to evaluate its effects on colitis and M1/M2 macrophage polarisation. RESULTS FN dose-dependently alleviated clinical symptoms and inflammatory injury in colonic tissues of colitis mice, with its high-dose efficacy comparable to that of 5-ASA. Concurrently, FN not only inhibited inflammatory infiltration of macrophages and their M1/M2 polarisation balance in colitis mice, but also improved the composition of colonic microbiota and metabolite profiles. However, FN lost its protective effects against DSS-induced colitis and failed to restore the equilibrium of M1/M2 macrophage differentiation following intestinal flora depletion through quadruple antibiotic treatment. Importantly, fecal microbiota transplantation from FN-treated mice restored FN's protective effects against DSS-induced colitis and reestablished its regulatory role in M1/M2 macrophage polarization. CONCLUSION Collectively, FN ameliorated UC through modulating the balance of M1/M2 macrophage polarization in a gut microbiota-dependent manner.
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Affiliation(s)
- Qiuping Xiao
- College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; Key Laboratory of Effective Material Basis of TCM, Jiangxi Province, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Lin Luo
- College of Acupuncture and Tuina, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Xiyan Zhu
- College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Yuhao Yan
- College of Acupuncture and Tuina, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Shanshan Li
- Laboratory Animal Science and Technology Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Liling Chen
- Laboratory Animal Science and Technology Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Xiaomin Wang
- College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Jie Zhang
- Laboratory Animal Science and Technology Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Duanyong Liu
- Jiangxi Provincial Engineering Research Center of Development and Evaluation of TCM classic prescriptions, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; College of Nursing, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; Key Laboratory of Prevention and Treatment of Immunological and Metabolic Diseases Related to Prescription and Syndrome, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Ronghua Liu
- College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; Key Laboratory of Effective Material Basis of TCM, Jiangxi Province, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Youbao Zhong
- College of Acupuncture and Tuina, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; Laboratory Animal Science and Technology Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; Key Laboratory of Prevention and Treatment of Immunological and Metabolic Diseases Related to Prescription and Syndrome, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China.
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Singhal S, Bhadana R, Jain BP, Gautam A, Pandey S, Rani V. Role of gut microbiota in tumorigenesis and antitumoral therapies: an updated review. Biotechnol Genet Eng Rev 2024; 40:3716-3742. [PMID: 36632709 DOI: 10.1080/02648725.2023.2166268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Indexed: 01/13/2023]
Abstract
Gut microbiota plays a prominent role in regulation of host nutrientmetabolism, drug and xenobiotics metabolism, immunomodulation and defense against pathogens. It synthesizes numerous metabolites thatmaintain the homeostasis of host. Any disbalance in the normalmicrobiota of gut can lead to pathological conditions includinginflammation and tumorigenesis. In the past few decades, theimportance of gut microbiota and its implication in various diseases, including cancer has been a prime focus in the field of research. Itplays a dual role in tumorigenesis, where it can accelerate as wellas inhibit the process. Various evidences validate the effects of gutmicrobiota in development and progression of malignancies, wheremanipulation of gut microbiota by probiotics, prebiotics, dietarymodifications and faecal microbiota transfer play a significant role.In this review, we focus on the current understanding of theinterrelationship between gut microbiota, immune system and cancer,the mechanisms by which they play dual role in promotion andinhibition of tumorigenesis. We have also discussed the role ofcertain bacteria with probiotic characteristics which can be used tomodulate the outcome of the various anti-cancer therapies under theinfluence of the alteration in the composition of gut microbiota.Future research primarily focusing on the microbiota as a communitywhich affect and modulate the treatment for cancer would benoteworthy in the field of oncology. This necessitates acomprehensive knowledge of the roles of individual as well asconsortium of microbiota in relation to physiology and response ofthe host.
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Affiliation(s)
- Shivani Singhal
- Department of Biotechnology, Jaypee Institute of Information Technology, Noida, India
| | - Renu Bhadana
- Department of Biotechnology, Jaypee Institute of Information Technology, Noida, India
| | - Buddhi Prakash Jain
- Department of Zoology, Mahatma Gandhi Central University, Motihari, Bihar, India
| | - Akash Gautam
- Centre for Neural and Cognitive Sciences, School of Medical Sciences, University of Hyderabad, Hyderabad, India
| | - Shweta Pandey
- Department of Biotechnology, Govt Vishwanath Yadav Tamaskar Post-Graduate Autonomous College Durg, Chhattisgarh, India
| | - Vibha Rani
- Department of Biotechnology, Jaypee Institute of Information Technology, Noida, India
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Huang J, Zhong Y, Cheng N, Zhang Z, Huang L, Song L, Cheng S, Zhao H, Liu D. Sishen pills inhibit inflammatory dendritic cell differentiation via miR-505-3p mediated E-cadherin downregulation in ulcerative colitis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 135:156035. [PMID: 39342779 DOI: 10.1016/j.phymed.2024.156035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 08/28/2024] [Accepted: 09/07/2024] [Indexed: 10/01/2024]
Abstract
BACKGROUND Ulcerative colitis (UC) is an autoimmune disease that is highly susceptible to recurrence, which is still a lack of effective drugs with minor side effects in clinic. Intervention of inflammatory differentiation of dendritic cells (DCs) might be an effective strategy to treat UC. Sishen Pills (SSP) is a classic Chinese herbal formula which has been demonstrated the protective effect of UC, but the mechanism remains unclear. PURPOSE To elucidate the protective effects of SSP against UC in mice and reveal its regulatory mechanism of DCs and the key active ingredients for the UC treatment based on transcriptomics, network pharmacology and experiments validation in vivo and vitro. METHOD The key active ingredients of SSP were detected and screened integrating LC-MS/MS and network pharmacology. A mouse UC model was induced with 3% sodium dextran sulfate and treated with SSP for 14 days to evaluate the efficacy. ELISA was used to detect the levels of IL-6, IL-1β and TNF-α in the colon; flow cytometry was used to detect the expression levels of DCs and their subpopulations; whole transcriptomic sequencing of differential RNAs in the colon and RT-PCR to detect key miRNAs to verify the sequencing results. Mouse bone marrow-derived dendritic cells (BMDCs) were isolated, an inflammatory model was constructed using 100 ng/ml LPS, and the effects of SSP on DC proliferation and apoptosis and their surface co-stimulatory molecule expression were examined; IL-6, IL-1β, TNF-α levels were measured by ELISA; RT-PCR and WB were performed to detect miR-505-3p, CDH1, E-cadherin expression. BMDCs with low expression of miR-505-3p were constructed by lentiviral transfection for further validation. The potential key ingredient was re-validated in vivo and vitro experiment. RESULTS Animal experiments showed that SSP alleviated DSS-induced UC symptoms and colonic pathological injury in mice, and inhibited IL-6, IL-1β, TNF-α secretion and inflammatory DC proliferation and activation maturation. Network pharmacology predicted that evodiamine, isobavachalcone, curcumin, and engenol may play a key role in SSP. RNA sequencing revealed that miR-505-3p, as the differential miRNA, shared a large number of transcription factors with E-cadherin, and was involved in inflammatory differentiation regulation. In vivo experiments confirmed that SSP accelerated apoptosis, slowed down proliferation, inhibited inflammatory differentiation and IL-6, IL-1β, and TNF-α secretion in BMDCs, and decreased miR-505-3p, CDH1, and E-cadherin levels. After knocking down miR-505-3p, SSP could not regulate the inflammatory differentiation and IL-6, IL-1β, TNF-α level in BMDCs. Additionally, evodiamine was found and verified to be the key active ingredient of SSP in preventing the inflammatory differatiation of DCs. CONCLUSION SSP prevented the inflammatory differentiation of DCs by downregulating the expression of miR-505-3p, in which Evodiamine may played a key role.
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Affiliation(s)
- Jiaqi Huang
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Youbao Zhong
- Laboratory Animal Research Center for Science and Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Nian Cheng
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Zheyan Zhang
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Li Huang
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Lizhao Song
- Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
| | - Shaomin Cheng
- Formula-Pattern Research Center of Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China.
| | - Haimei Zhao
- College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China.
| | - Duanyong Liu
- Formula-Pattern Research Center of Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China; School of Nursing, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China.
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Lin CY, Lee HL, Wang C, Sung FC, Su TC. Positive Association Between Serum Concentration of 4-Tertiary-octylphenol and Oxidation of DNA and Lipid in Adolescents and Young Adults. EXPOSURE AND HEALTH 2024; 16:1311-1320. [DOI: 10.1007/s12403-024-00628-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 11/14/2023] [Accepted: 01/08/2024] [Indexed: 01/04/2025]
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Aly RM, Abohashem RS, Ahmed HH, Halim ASA. Combinatorial intervention with dental pulp stem cells and sulfasalazine in a rat model of ulcerative colitis. Inflammopharmacology 2024; 32:3863-3879. [PMID: 39078564 PMCID: PMC11550242 DOI: 10.1007/s10787-024-01532-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 07/08/2024] [Indexed: 07/31/2024]
Abstract
BACKGROUND Ulcerative colitis is an inflammatory bowel disease (IBD) that involves inflammation of the colon lining and rectum. Although a definitive cure for IBD has not been identified, various therapeutic approaches have been proposed to mitigate the symptomatic presentation of this disease, primarily focusing on reducing inflammation. The aim of the present study was to evaluate the therapeutic potential of combining dental pulp stem cells (DPSCs) with sulfasalazine in an acetic acid-induced ulcerative colitis rat model and to assess the impact of this combination on the suppression of inflammatory cytokines and the regulation of oxidative stress in vivo. METHODS Ulcerative colitis was induced in rats through transrectal administration of 3% acetic acid. The therapeutic effect of combining DPSCs and sulfasalazine on UC was evaluated by measuring the colonic weight/length ratio and edema markers; performing histopathological investigations of colon tissue; performing immunohistochemical staining for NF-κB-P65 and IL-1β; and evaluating oxidative stress and antioxidant indices via ELISA. Moreover, the proinflammatory markers NF-κB-P65, TNF-α and TLR-4 were assessed in colon tissue via ELISA. Furthermore, qRT‒PCR was used to estimate the expression levels of the TLR-4, NF-κB-P65, and MYD88 genes in colon tissue. RESULTS The investigated macroscopic and microscopic signs of inflammation were markedly improved after the combined administration of sulfasalazine and DPSCs, where a noticeable improvement in histological structure, with an intact mucosal epithelium and mild inflammatory infiltration in the mucosa and submucosa, with slight hemorrhage. The administration of either DPSCs or sulfasalazine, either individually or in combination, significantly reduced ROS levels and significantly increased XOD activity. The immunohistochemical results demonstrated that the combined administration of DPSCs and sulfasalazine attenuated NFκB-p65 and IL-1β expression. Finally, the combined administration of DPSCs and sulfasalazine significantly downregulated MyD88, NF-κB and TLR4 gene expression. CONCLUSIONS Cotreatment with DPSCs and sulfasalazine had synergistic effects on ulcerative colitis, and these effects were relieved.
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Affiliation(s)
- Riham M Aly
- Basic Dental Science Department, Oral & Dental Research Institute, National Research Centre, 33 El Bohouth St, Dokki, Giza, Egypt.
- Stem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, Dokki, Giza, Egypt.
| | - Rehab S Abohashem
- Stem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, Dokki, Giza, Egypt
- Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Giza, Egypt
| | - Hanaa H Ahmed
- Stem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, Dokki, Giza, Egypt
- Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Giza, Egypt
| | - Alyaa S Abdel Halim
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
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Cheng J, Williams JP, Zhou L, Wang PC, Sun LN, Li RH, An JX. Ozone rectal insufflation mitigates chronic rapid eye movement sleep deprivation-induced cognitive impairment through inflammation alleviation and gut microbiota regulation in mice. Med Gas Res 2024; 14:213-224. [PMID: 39073330 DOI: 10.4103/mgr.medgasres-d-23-00036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Accepted: 10/20/2023] [Indexed: 07/30/2024] Open
Abstract
A range of sleep disorders has the potential to adversely affect cognitive function. This study was undertaken with the objective of investigating the effects of ozone rectal insufflation (O3-RI) on cognitive dysfunction induced by chronic REM sleep deprivation, as well as elucidating possible underlying mechanisms. O3-RI ameliorated cognitive dysfunction in chronic REM sleep deprived mice, improved the neuronal damage in the hippocampus region and decreased neuronal loss. Administration of O3-RI may protect against chronic REM sleep deprivation induced cognitive dysfunction by reversing the abnormal expression of Occludin and leucine-rich repeat and pyrin domain-containing protein 3 inflammasome as well as interleukin-1β in the hippocampus and colon tissues. Moreover, the microbiota diversity and composition of sleep deprivation mice were significantly affected by O3-RI intervention, as evidenced by the reversal of the Firmicutes/Bacteroidetes abundance ratio and the relative abundance of the Bacteroides genus. In particular, the relative abundance of the Bacteroides genus demonstrated a pronounced correlation with cognitive impairment and inflammation. Our findings suggested that O3-RI can improve cognitive dysfunction in sleep deprivation mice, and its mechanisms may be related to regulating gut microbiota and alleviating inflammation and damage in the hippocampus and colon.
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Affiliation(s)
- Jie Cheng
- Medical School, University of Chinese Academy of Sciences, Beijing, China
| | - John P Williams
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Li Zhou
- Institute for lnnoration Diagnosis & Treatment in Anesthesiology, School of Anesthesiology, Shandong Second Medical University, Weifang, Shandong Province, China
| | - Peng-Cheng Wang
- Institute for lnnoration Diagnosis & Treatment in Anesthesiology, School of Anesthesiology, Shandong Second Medical University, Weifang, Shandong Province, China
| | - Li-Na Sun
- Institute for lnnoration Diagnosis & Treatment in Anesthesiology, School of Anesthesiology, Shandong Second Medical University, Weifang, Shandong Province, China
| | - Rui-Hua Li
- Institute for lnnoration Diagnosis & Treatment in Anesthesiology, School of Anesthesiology, Shandong Second Medical University, Weifang, Shandong Province, China
| | - Jian-Xiong An
- Medical School, University of Chinese Academy of Sciences, Beijing, China
- Institute for lnnoration Diagnosis & Treatment in Anesthesiology, School of Anesthesiology, Shandong Second Medical University, Weifang, Shandong Province, China
- Center of Anesthesiology, Pain and Sleep Medicine, Rapid Anti-depression, The Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong Province, China
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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Tshikudi DM, Hutchison H, Ghia JE. Pancreastatin Inhibition Alters the Colonic Epithelial Cells Profile in a Sex-Dependent Manner. Int J Mol Sci 2024; 25:12757. [PMID: 39684467 DOI: 10.3390/ijms252312757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 11/17/2024] [Accepted: 11/22/2024] [Indexed: 12/18/2024] Open
Abstract
The impaired mucosal barrier is a hallmark of ulcerative colitis (UC), an inflammatory colonic disorder with epidemiological and pathophysiology sex bias. UC Patients overexpress the colonic epithelial cells (CECs)-derived peptide pancreastatin (PST). Pancreastatin inhibitor 8 (PSTi8), an inhibitor of PST, has shown promising anti-inflammatory effects on UC. However, no data exist in the context of CEC barrier function and integrity. We investigated the impact of PSTi8 treatment on CECs in homeostatic and colitic conditions. PSTi8 (2.5 mg/mL/kg, i.r.) or PBS treatment started one day before colitis induction (5% dextran sodium sulfate for five days) in male and female C57BL/6 mice. The disease activity score was assessed daily. Epithelial-associated cytokines, markers specific to differentiation, proliferation, differentiated CECs, stem cells, CECs regulators, and the PSTi8 G-protein coupled receptor 78 (GPR78) signaling pathway, were evaluated using ELISA, immunofluorescence and qRT-PCR. PSTi8 treatment reduced the epithelial-associated cytokines and differentiated CECs while promoting CEC proliferation and self-renewal in females at a steady state through the GRP78 signaling pathway. PSTi8 treatment exacerbated colitis severity and increased CEC differentiation while reducing proliferation in colitic females. Conversely, PSTi8 treatment reduced males' susceptibility to colitis by preserving stem cells and differentiated CECs. PST regulated colonic mucosal maintenance in a sex- and disease-dependent manner.
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Affiliation(s)
- Diane M Tshikudi
- Department of Immunology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
| | - Hannah Hutchison
- Department of Immunology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
| | - Jean-Eric Ghia
- Department of Immunology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
- Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
- IBD Clinical and Research Centre, University of Manitoba, Winnipeg, MB R3A 1R9, Canada
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Wang H, Deng F, Luo M, Wang X. Case report: Fecal microbiota transplant for Clostridium difficile infection in a pregnant patient with acute severe ulcerative colitis. Front Immunol 2024; 15:1417003. [PMID: 39640265 PMCID: PMC11619044 DOI: 10.3389/fimmu.2024.1417003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 08/20/2024] [Indexed: 12/07/2024] Open
Abstract
Ulcerative colitis (UC) is a chronic colonic mucosal inflammation characterized by reduced gut microbial diversity. Patients with UC at pregnancy are prone to suffer from severe disease progression due to the changes of hormone and immune regulation. Fecal microbiota transplant (FMT) is a promising therapy for UC and recurrent Clostridium difficile infection (CDI). However, acute severe ulcerative colitis (ASUC) treatment especially in patients at pregnancy is clinically challenging. Herein, we report a 34-year-old pregnant woman who manifested with numerous bloody stools and markedly elevated serological inflammatory indicators and was diagnosed with ASUC and concurrent CDI. The use of intravenous injection steroids and anti-TNF-α therapy failed to improve her condition. Frozen encapsulated FMT therapy was finally performed to this patient with clearly improved symptoms and indications of safe delivery without UC flares or complications, and markedly increased diversity of the gut microbiota was also shown in this patient after FMT. This report firstly describes FMT as a safe salvage therapy for a pregnant patient with CDI and ASUC refractory to intravenous steroids and anti-TNF therapy.
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Affiliation(s)
- Hanyu Wang
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Center of Digestive Disease, Central South University, Changsha, Hunan, China
| | - Feihong Deng
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Center of Digestive Disease, Central South University, Changsha, Hunan, China
| | - Min Luo
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Center of Digestive Disease, Central South University, Changsha, Hunan, China
| | - Xuehong Wang
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Research Center of Digestive Disease, Central South University, Changsha, Hunan, China
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Ko Y, Alaedin S, Fernando D, Zhou J, Ho V. A Review of Fecal Microbiota Transplantation in Children-Exploring Its Role in the Treatment of Inflammatory Bowel Diseases. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1899. [PMID: 39597084 PMCID: PMC11596230 DOI: 10.3390/medicina60111899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Revised: 10/23/2024] [Accepted: 11/14/2024] [Indexed: 11/29/2024]
Abstract
Background and Objectives: There is an increasing use of fecal matter transplantation (FMT) worldwide as research into the impact of the gut microbiome in various disease states is growing. FMT is the transfer of stool from a healthy human donor to a patient for the purpose of restoring intestinal dysbiosis. This review will assess the efficacy and safety of FMT in the treatment of pediatric inflammatory bowel diseases (IBDs) and explore the future directions of the use of FMT in children. Materials and Methods: A systematic review was performed where a literature search of publications published prior to 15 September 2023 was performed. Efficacy outcomes and safety data as well as microbiome analysis were reviewed from the studies where applicable. Results: Nine studies on UC and two studies on CD satisfied eligibility criteria and individually analysed. Most of the studies provided microbiome analyses. Conclusions: FMT is a safe treatment for paediatric IBD, and is shown to be effective in inducing clinical response by some studies. However the lack of randomized controlled trials limited the results of our study.
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Affiliation(s)
- Yanna Ko
- School of Medicine, Western Sydney University, Campbelltown Campus, Sydney, NSW 2747, Australia; (Y.K.); (S.A.); (D.F.); (J.Z.)
- Canterbury Hospital, Sydney, NSW 2194, Australia
| | - Sara Alaedin
- School of Medicine, Western Sydney University, Campbelltown Campus, Sydney, NSW 2747, Australia; (Y.K.); (S.A.); (D.F.); (J.Z.)
| | - Dewni Fernando
- School of Medicine, Western Sydney University, Campbelltown Campus, Sydney, NSW 2747, Australia; (Y.K.); (S.A.); (D.F.); (J.Z.)
| | - Jerry Zhou
- School of Medicine, Western Sydney University, Campbelltown Campus, Sydney, NSW 2747, Australia; (Y.K.); (S.A.); (D.F.); (J.Z.)
| | - Vincent Ho
- School of Medicine, Western Sydney University, Campbelltown Campus, Sydney, NSW 2747, Australia; (Y.K.); (S.A.); (D.F.); (J.Z.)
- Camden and Campbelltown Hospitals, Sydney, NSW 2560, Australia
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Zhang J, Duan X, Chen X, Qian S, Ma J, Jiang Z, Hou J. Lactobacillus rhamnosus 1.0320 Postbiotics Ameliorate Dextran Sodium Sulfate-Induced Colonic Inflammation and Oxidative Stress by Regulating the Intestinal Barrier and Gut Microbiota. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:25078-25093. [PMID: 39485947 DOI: 10.1021/acs.jafc.4c06303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2024]
Abstract
Probiotics are increasingly being used as an adjunctive therapy for ulcerative colitis. However, some safety issues have been found in the clinical use of probiotics. Postbiotics have attracted much attention due to their storage stability, safety, and potential functions, but the dose required to exert a significant protective effect is unknown. Therefore, this study evaluated the potential mechanisms of different doses (200, 400, 600 mg/kg) of Lactobacillus rhamnosus 1.0320 postbiotics (1.0320P) in alleviating dextran sodium sulfate (DSS)-induced colitis. The study revealed that 1.0320P could mitigate DSS-induced colitis with signs of reductions in the disease activity index, amelioration of colon tissue damage, decreased secretion of proinflammatory cytokines, reduced oxidative stress levels, and lower bone marrow peroxidase activity. Furthermore, high dose of 1.0320P could upregulated the expression of key proteins in the Nrf2/ARE pathway (NQO1, Nrf2, and HO-1) and downregulated the expression of key proteins in the TLR4/NF-κB signaling pathway (TLR4, MyD88, and NF-κB p65). In addition, high dose of 1.0320P could upregulate the expression of tight junction (TJ) proteins including ZO-1, Occludin, and Claudin-1, contributing to the restoration of the intestinal mucosal barrier function. Additionally, 1.0320P was found to effectively correct imbalances in the intestinal microbiota and enhance the synthesis of short-chain fatty acids (SCFAs), thereby regulating homeostasis in the intestinal internal environment. Overall, our findings suggest that postbiotics could ameliorate colonic inflammation while being somewhat dose-dependent. This study provides new insights into postbiotics as a next-generation biotherapeutic agent for the treatment of ulcerative colitis and even other diseases.
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Affiliation(s)
- Jing Zhang
- Ministry of Education, College of Food Science, Key Laboratory of Dairy Science (Northeast Agricultural University), Harbin 150030, China
| | - Xiaolei Duan
- Ministry of Education, College of Food Science, Key Laboratory of Dairy Science (Northeast Agricultural University), Harbin 150030, China
| | - Xianhui Chen
- Ministry of Education, College of Food Science, Key Laboratory of Dairy Science (Northeast Agricultural University), Harbin 150030, China
| | - Shanshan Qian
- College of Food Science and Engineering, Guiyang University, Guiyang 550005, China
| | - Jiage Ma
- Ministry of Education, College of Food Science, Key Laboratory of Dairy Science (Northeast Agricultural University), Harbin 150030, China
| | - Zhanmei Jiang
- Ministry of Education, College of Food Science, Key Laboratory of Dairy Science (Northeast Agricultural University), Harbin 150030, China
| | - Juncai Hou
- Ministry of Education, College of Food Science, Key Laboratory of Dairy Science (Northeast Agricultural University), Harbin 150030, China
- College of Food Science and Engineering, Guiyang University, Guiyang 550005, China
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Zhang J, Chen Y, Guo X, Li X, Zhang R, Wang M, Zhu W, Yu K. The gut microbial metabolite indole-3-aldehyde alleviates impaired intestinal development by promoting intestinal stem cell expansion in weaned piglets. J Anim Sci Biotechnol 2024; 15:150. [PMID: 39511673 PMCID: PMC11545576 DOI: 10.1186/s40104-024-01111-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 10/07/2024] [Indexed: 11/15/2024] Open
Abstract
BACKGROUND Weaning stress-induced diarrhea is widely recognized as being associated with gut microbiota dysbiosis. However, it has been challenging to clarify which specific intestinal microbiota and their metabolites play a crucial role in the antidiarrhea process of weaned piglets. RESULTS In this study, we first observed that piglets with diarrhea exhibited a lower average daily gain and higher diarrhea score, and elevated levels of lipopolysaccharide (LPS) and D-lactate (D-LA) compared to healthy piglets. Subsequently, we analyzed the differences in intestinal microbial composition and metabolite levels between healthy and diarrheal weaned piglets. Diarrheal piglets demonstrated intestinal microbiota dysbiosis, characterized primarily by a higher Firmicutes to Bacteroidota ratio, a deficiency of Lactobacillus amylovorus and Lactobacillus reuteri, and an increased abundance of Bacteroides sp.HF-5287 and Bacteroides thetaiotaomicron. Functional profiling of the gut microbiota based on Kyoto Encyclopedia of Genes and Genomes (KEGG) data was performed, and the results showed that tryptophan metabolism was the most significantly inhibited pathway in piglets with diarrhea. Most tryptophan metabolites were detected at lower concentrations in diarrheal piglets than in healthy piglets. Furthermore, we explored the effects of dietary indole-3-aldehyde (IAld), a key tryptophan metabolite, on intestinal development and gut barrier function in weaned piglets. Supplementation with 100 mg/kg IAld in the diet increased the small intestine index and improved intestinal barrier function by promoting intestinal stem cell (ISC) expansion in piglets. The promotion of ISC expansion by IAld was also confirmed in porcine intestinal organoids. CONCLUSIONS These findings revealed that intestinal microbial tryptophan metabolite IAld alleviates impaired intestinal development by promoting ISC expansion in weaned piglets.
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Affiliation(s)
- Jiaqi Zhang
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing, 210095, China
| | - Yahui Chen
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing, 210095, China
| | - Xin Guo
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing, 210095, China
| | - Xuan Li
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing, 210095, China
| | - Ruofan Zhang
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing, 210095, China
- Wujiang Animal Health Inspection Institute, Suzhou, 215200, China
| | - Mengting Wang
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing, 210095, China
| | - Weiyun Zhu
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing, 210095, China
| | - Kaifan Yu
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing, 210095, China.
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Wu Q, Yang LS, Huang HL, Li YF, Zhou YJ, Xu HM. Washed microbiota transplantation combined with biological agents promotes histological remission in refractory severe ulcerative colitis with recurrent intestinal infection: A case report. Arab J Gastroenterol 2024; 25:448-454. [PMID: 39079826 DOI: 10.1016/j.ajg.2024.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 06/28/2024] [Accepted: 07/07/2024] [Indexed: 12/02/2024]
Abstract
Ulcerative colitis (UC) is a chronic non-specific colitis disease. In recent years, fecal microbiota transplantation (FMT), including improved washed microbiota transplantation (WMT), and biological agents have helped improve the prognosis of patients with UC. However, a significant number of patients with moderate to severe UC do not get relief from glucocorticoids, immunosuppressants, and TNF-α antagonists. Patients with severe UC are frequently burdened with opportunistic infections and subsequent surgical interventions. Combined treatment modalities are crucial for patients with severe UC and opportunistic infections. Herein, we reported a case of a 25-year-old female with refractory severe UC complicated with recurrent Clostridioides difficile infection and recurrent cytomegalovirus infection for six years. Surgical removal of the affected bowel segment was almost unavoidable. She showed endoscopic and histological recovery after comprehensive WMT and Vedolizumab treatment. The following are our learnings from the case: 1. A combination of WMT and biological agents can potentially obviate the necessity for surgical treatment in patients with refractory severe UC and promote histological remission. 2. Personalized comprehensive treatment and chronic disease management models for patients with UC should be emphasized. 3. WMT can help treat opportunistic infections, which may also strengthen the treatment with gut-targeted biological agents when traditional TNF-α antagonists show poor efficacy.
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Affiliation(s)
- Qiong Wu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
| | - Liu-Si Yang
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
| | - Hong-Li Huang
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
| | - Ying-Fei Li
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
| | - Yong-Jian Zhou
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China.
| | - Hao-Ming Xu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China.
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Sun H, Long SR, Jiang M, Zhang HR, Wang JJ, Liao ZX, Cui J, Wang ZQ. The gut microbiota is essential for Trichinella spiralis-evoked suppression of colitis. PLoS Negl Trop Dis 2024; 18:e0012645. [PMID: 39495798 PMCID: PMC11563474 DOI: 10.1371/journal.pntd.0012645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 11/14/2024] [Accepted: 10/22/2024] [Indexed: 11/06/2024] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) increases the risk of colorectal cancer, and it has the potential to diminish the quality of life. Clinical and experimental evidence demonstrate protective aspects of parasitic helminth infection against IBD. However, studies on the inhibition of inflammation by helminth infection have overlooked a key determinant of health: the gut microbiota. Although infection with helminths induces alterations in the host microbiota composition, the potential influence and mechanism of helminth infections induced changes in the gut microbiota on the development of IBD has not yet been elucidated. In this study, we analyzed the intersection of helminth Trichinella spiralis and gut bacteria in the regulation of colitis and related mechanisms. METHODOLOGY/PRINCIPAL FINDINGS T. spiralis infected mice were treated with antibiotics or cohoused with wild type mice, then challenged with dextran sodium sulfate (DSS)-colitis and disease severity, immune responses and goblet cells assessed. Gut bacteria composition was assessed by 16S rRNA sequencing and short-chain fatty acids (SCFAs) were measured. We found that protection against disease by infection with T. spiralis was abrogated by antibiotic treatment, and cohousing with T. spiralis- infected mice suppressed DSS-colitis in wild type mice. Bacterial community profiling revealed an increase in the abundance of the bacterial genus Muribaculum and unclassified_Muribaculaceae in mice with T. spiralis infection or mice cohoused with T. spiralis- infected mice. Metabolomic analysis demonstrated significantly increased propionic acid in feces from T. spiralis- infected mice. Data also showed that the gut microbiome modulated by T. spiralis exhibited enhanced goblet cell differentiation and elevated IL-10 levels in mice. CONCLUSIONS These findings identify the gut microbiome as a critical component of the anti- colitic effect of T. spiralis and gives beneficial insights into the processes by which helminth alleviates colitis.
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Affiliation(s)
- Hualei Sun
- Department of Nutrition, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Shao Rong Long
- Department of Pathogen Biology, Medical College of Zhengzhou University, Zhengzhou, Henan, China
| | - Miao Jiang
- Department of Pathogen Biology, Medical College of Zhengzhou University, Zhengzhou, Henan, China
| | - Hui Ran Zhang
- Department of Pathogen Biology, Medical College of Zhengzhou University, Zhengzhou, Henan, China
| | - Jing Jing Wang
- Department of Pathogen Biology, Medical College of Zhengzhou University, Zhengzhou, Henan, China
| | - Zi Xuan Liao
- Department of Pathogen Biology, Medical College of Zhengzhou University, Zhengzhou, Henan, China
| | - Jing Cui
- Department of Pathogen Biology, Medical College of Zhengzhou University, Zhengzhou, Henan, China
| | - Zhong Quan Wang
- Department of Pathogen Biology, Medical College of Zhengzhou University, Zhengzhou, Henan, China
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45
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Jeong JS, Baek GH, Kim JW, Kim JH, Chung EH, Ko JW, Kwon MJ, Kim SK, Lee SH, Kim JS, Kim TW. Korean Red Ginseng alleviates dextran sodium sulfate-induced colitis through gut microbiota modulation in mice. J Ginseng Res 2024; 48:581-591. [PMID: 39583173 PMCID: PMC11584195 DOI: 10.1016/j.jgr.2024.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 07/25/2024] [Accepted: 08/08/2024] [Indexed: 11/26/2024] Open
Abstract
Background There is a growing interest in understanding the association between the gut microbiota and inflammatory bowel disease (IBD). Natural compounds, such as Korean Red Ginseng (KRG), show promise for IBD treatment because of their ability to influence gut microbiota. This study explored the effects of KRG on gut microbiota modulation and subsequent intestinal epithelial cell regeneration in an experimental colitis model. Method Using a mouse model of colitis induced by 2 % dextran sodium sulfate, the study administered 200 or 400 mg/kg/day of KRG to evaluate its biological effects. Colitis symptoms were assessed through body weight, disease activity index, colon length, and histological analysis. The microbial composition in the fecal was determined using 16S rRNA sequencing. To evaluate regeneration signals in the colon, western blotting and immunohistochemistry assays were conducted. Result Administration of KRG effectively mitigated colitis symptoms in mice, as indicated by histological examination showing alleviated epithelial damage and inflammation, along with increased mucus production. Microbiota analysis showed that KRG significantly altered microbial diversity, favoring beneficial taxa and suppressing harmful taxa. Moreover, ameliorated β-catenin/transcription factor-4 protein expression, a key signal associated with epithelial cell regeneration, was observed in the KRG treated groups, accompanied by improved intestinal linings. Conclusion These findings suggest that KRG exerts biological effects in colitis by modulating gut microbiota and creating a favorable intestinal environment, thereby reducing regenerative signals. Further research is warranted to elucidate the cellular and molecular mechanisms underlying the interaction of KRG with gut microbiota and pave the way for effective IBD therapies.
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Affiliation(s)
- Ji-Soo Jeong
- College of Veterinary Medicine (BK21 FOUR Program), Chungnam National University, Daejeon, Republic of Korea
| | - Ga-Hyeon Baek
- Department of Nano-Bioengineering, Incheon National University, Incheon, Republic of Korea
| | - Jeong-Won Kim
- College of Veterinary Medicine (BK21 FOUR Program), Chungnam National University, Daejeon, Republic of Korea
| | - Jin-Hwa Kim
- College of Veterinary Medicine (BK21 FOUR Program), Chungnam National University, Daejeon, Republic of Korea
| | - Eun-Hye Chung
- College of Veterinary Medicine (BK21 FOUR Program), Chungnam National University, Daejeon, Republic of Korea
| | - Je-Won Ko
- College of Veterinary Medicine (BK21 FOUR Program), Chungnam National University, Daejeon, Republic of Korea
| | - Mi-Jin Kwon
- R&D Headquarters, Korea Ginseng Corporation, Gwacheon, Republic of Korea
| | - Sang-Kyu Kim
- R&D Headquarters, Korea Ginseng Corporation, Gwacheon, Republic of Korea
| | - Seung-Ho Lee
- R&D Headquarters, Korea Ginseng Corporation, Gwacheon, Republic of Korea
| | - Jun-Seob Kim
- Department of Nano-Bioengineering, Incheon National University, Incheon, Republic of Korea
- Institute for New Drug Development, College of Life Science and Bioengineering, Incheon National University, Incheon, Republic of Korea
| | - Tae-Won Kim
- College of Veterinary Medicine (BK21 FOUR Program), Chungnam National University, Daejeon, Republic of Korea
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Gu X, Yang Z, Kou Y, Yang F, Wang Y, Chen Y, Wang E, Jiang X, Bai Y, Zhang Z, Zhang S. Effects of Retrograde Colonic Enema-Based Fecal Microbiota Transplantation in the Treatment of Childhood Constipation: A Randomized, Double-Blind, Controlled Trial. Am J Gastroenterol 2024; 119:2288-2297. [PMID: 38989869 DOI: 10.14309/ajg.0000000000002958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 06/28/2024] [Indexed: 07/12/2024]
Abstract
INTRODUCTION Management of intractable childhood constipation is still challenging. The efficacy of retrograde colonic enema (RCE) with fecal microbiota transplantation (FMT) in intractable childhood constipation has not been established, although both have demonstrated potential in gastrointestinal diseases. The aim of this study was to determine the safety and efficacy of RCE-based FMT in the treatment of intractable constipation in children. METHODS A randomized, double-blind, controlled trial with 110 children was conducted. The patients were randomly assigned to the FMT with RCE group or the placebo with RCE group. All participants received a daily RCE, followed by a 4-week FMT treatment (twice a week) and a 12-week follow-up period. Spontaneous bowel movements ≥ 3 per week were the main outcomes, and the risk ratio with 95% confidence interval (CI) was calculated. Changes in intestinal bacterial profile were analyzed by BOX-PCR-based DNA fingerprinting and sequencing. The adverse effects were assessed based on symptoms. RESULTS At the end of the follow-up period, 22 patients (40.0%) in the FMT with RCE group and 10 patients (18.2%) in the placebo with RCE group had ≥ 3 spontaneous bowel movements per week (net difference = 21.8%, 95% CI: 13.2%-30.4%; risk ratio: 1.364, 95% CI: 1.063-1.749; P < 0.05). Both RCE and FMT enriched the intestinal bacterial diversity of patients with constipation. The adverse events were all mild self-limiting gastrointestinal symptoms. DISCUSSION FMT enhances the efficacy of RCE, and the use of RCE-based FMT is a safe and effective method in the treatment of intractable constipation in children.
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Affiliation(s)
- Xu Gu
- Departments of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhonghua Yang
- Departments of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Youwei Kou
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Fan Yang
- Departments of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yang Wang
- Departments of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Ying Chen
- Departments of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Enhui Wang
- Departments of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xuzheng Jiang
- Departments of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yuzuo Bai
- Departments of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhibo Zhang
- Departments of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shucheng Zhang
- Departments of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
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Sheng T, Wang L, Yan S, Wei Q, Geng X, Lan W, Chen Y, Liu Y, Li N. Involvement of gut microbiota recovery and autophagy induction in Youhua Kuijie formula's protection against experimental ulcerative colitis. Exp Anim 2024; 73:357-369. [PMID: 38599877 PMCID: PMC11534492 DOI: 10.1538/expanim.23-0166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 04/01/2024] [Indexed: 04/12/2024] Open
Abstract
Ulcerative colitis (UC) is characterized by overactive inflammatory response, impaired intestinal mucosal barrier and disrupted gut microbiota. Youhua Kuijie formula is a classic empirical prescription based on the pathogenesis of UC. The present study was designed to verify the protective effect of Youhua Kuijie formula on DSS-induced UC in mice and uncover the related mechanism. Youhua Kuijie formula were orally administrated to UC mice induced by DSS dissolved in drinking water for ten days. The protective effect of Youhua Kuijie formula was evidenced by reduced pathological symptoms accompanied by palliative inflammatory response and relatively intact intestinal barrier. The data from 16S rRNA gene sequencing and GC-MS untargeted metabolomics indicated that the supplement of Youhua Kuijie formula restructured gut microbiota community structure, and thereby modulated the metabolic profiles in UC mice. The analysis of pathway enrichment analysis suggested the major alterations in metabolic pathway were related to protein digestion and absorption. Besides, the results of the following experiments suggested that Youhua Kuijie formula treatment increased adenosine monophosphate-activated protein kinase (AMPK) activation, decreased mechanistic target of rapamycin (mTOR) phosphorylation, and thereby reversing autophagy deficiency in the intestinal tract of UC mice. Collectively, our results demonstrated that the regulation of AMPK/mTOR was involved in Youhua Kuijie formula administration mediated protective effect on UC.
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Affiliation(s)
- Tianjiao Sheng
- Graduate school, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshandong Road, Shenyang, Liaoning, 110847, P.R. China
- Department of Traditional Chinese Medicine, General Hospital of Northern Theater Command, No.83 Wenhua Road, Shenyang, Liaoning, 110016, P.R. China
| | - Lei Wang
- Department of anorectum, Hulunbuir Zhong Meng Hospital, No. 58 Xidajie Road, Hulunbuir, 021000, P.R. China
| | - Simeng Yan
- Department of 1st Area of Officers' Ward, General Hospital of Northern Theater Command, No.83 Wenhua Road, Shenyang, Liaoning, 110016, P.R. China
| | - Qiuyu Wei
- Graduate school, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshandong Road, Shenyang, Liaoning, 110847, P.R. China
| | - Xiao Geng
- Department of Traditional Chinese Medicine, General Hospital of Northern Theater Command, No.83 Wenhua Road, Shenyang, Liaoning, 110016, P.R. China
| | - Weiru Lan
- The third department of Anorectal hemorrhoids and Fistula, Liaoning University of Traditional Chinese Medicine Affiliated Third Hospital, No. 35, 11th Wei Road, Shenyang, Liaoning, 110003, P.R. China
| | - Yan Chen
- Graduate school, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshandong Road, Shenyang, Liaoning, 110847, P.R. China
| | - Yuedong Liu
- Graduate school, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshandong Road, Shenyang, Liaoning, 110847, P.R. China
| | - Na Li
- Department of Anorectal Surgery, Xianyang Central Hospital, No. 78 Renmin East Road, Xianyang, Shaanxi, 712000, P.R. China
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Al Zahrani AJ, Shori AB, Al-Judaibi E. Fermented Soymilk with Probiotic Lactobacilli and Bifidobacterium Strains Ameliorates Dextran-Sulfate-Sodium-Induced Colitis in Rats. Nutrients 2024; 16:3478. [PMID: 39458472 PMCID: PMC11510403 DOI: 10.3390/nu16203478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 10/07/2024] [Accepted: 10/08/2024] [Indexed: 10/28/2024] Open
Abstract
Background: Current treatments for inflammatory bowel disease (IBD) are relatively futile and the extended use of drugs may reduce effectiveness. Several probiotic strains have shown promise in relieving/treating IBD symptoms. Objectives: The current study investigated the impact of fermented soymilk with a mixture of probiotic starter cultures containing Lactobacillus rhamnosus, L. casei, L. plantarum, L. acidophilus, Bifidobacterium longum, and B. animalis subsp. lactis in rats with dextran sulfate sodium (DSS)-induced colitis compared to control. Methods: Rats were randomly assigned to five groups (5 rats/group; n = 25): G1: negative normal control; G2: positive control (DSS); G3: DSS with sulfasalazine (DSS-Z); G4: DSS with soymilk (DSS-SM), and G5: DSS with fermented soymilk (DSS-FSM). Parameters monitored included the following: the disease activity index (DAI), macroscopic and histological assessments of colitis, and a fecal microbial analysis performed to assess the severity of inflammation and ulceration. Results: The DSS-FSM rats group exhibited lower DAI scores (p < 0.05) than other treated groups during the induction period. A macroscopical examination revealed no ulceration or swelling in the intestinal mucosa of rats in the DSS-FSM-treated group, resembling the findings in the negative control group. In the positive control (DSS group), the colon tissue showed increased inflammation (p < 0.05), whereas those in the DSS-SM- and DSS-FSM-treated rats groups did not show significant macroscopic scores of colitis. The positive DSS control and DSS-Z groups had crypt erosion and ulceration areas, severe crypt damage, and epithelial surface erosion, which were absent in the negative control and DSS-FSM groups. The counts of Lactobacillus spp. and Bifidobacterium spp. remained stable in both G1 and G5 over 4 weeks. The consumption of fermented soymilk with a mixture of probiotics could minimize the severity of DSS-induced colitis in rats. Conclusion, it was found that fermented soymilk containing Lactobacilli and Bifidobacterium might be an effective vehicle for reducing the severity of DSS-induced colitis in rats.
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Affiliation(s)
- Ashwag Jaman Al Zahrani
- Faculty of Science, Department of Biological Sciences, University of Jeddah, Jeddah 21959, Saudi Arabia
| | - Amal Bakr Shori
- Faculty of Science, Department of Biological Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Effat Al-Judaibi
- Faculty of Science, Department of Biological Sciences, University of Jeddah, Jeddah 21959, Saudi Arabia
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49
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Zhao Y, Chen Z, Dong R, Liu Y, Zhang Y, Guo Y, Yu M, Li X, Wang J. Multiomics analysis reveals the potential mechanism of high-fat diet in dextran sulfate sodium-induced colitis mice model. Food Sci Nutr 2024; 12:8309-8323. [PMID: 39479684 PMCID: PMC11521715 DOI: 10.1002/fsn3.4426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 08/05/2024] [Accepted: 08/09/2024] [Indexed: 11/02/2024] Open
Abstract
A high-fat diet (HFD) is recognized as an important contributor to inflammatory bowel disease (IBD). However, the precise underlying mechanism of HFD on IBD remains elusive. This study aimed to investigate the potential mechanism by which HFD affects IBD using 16S rRNA-sequencing and RNA-seq technology. Results indicated that HFD-treated mice exhibited notable alternations in the structure and composition of the gut microbiota, with some of these alternations being associated with the pathogenesis of IBD. Analysis of the colon transcriptome revealed 11 hub genes and 7 hub pathways among control, DSS-induced colitis, and HFD + DSS-treated groups. Further analysis explores the relationship between the hub pathways and genes, as well as the hub genes and gut microbiota. Overall, the findings indicate that the impact of HFD on DSS-induced colitis may be linked to intestinal dysbiosis and specific genes such as Abca8b, Ace2, Apoa1, Apoa4, Apoc3, Aspa, Dpp4, Maob, Slc34a2, Slc7a9, and Trpm6. These results provide valuable insights for determining potential therapeutic targets for addressing HFD-induced IBD.
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Affiliation(s)
- Yuyang Zhao
- Department of GastroenterologyChina‐Japan Union Hospital of Jilin UniversityChangchunJilinChina
| | - Zhimin Chen
- Department of PharmacologyCollege of Basic Medical Sciences, Jilin UniversityChangchunJilinChina
| | - Ruiyi Dong
- College of Physical Education, Hunan Normal UniversityChangshaChina
| | - Yufan Liu
- Department of PharmacologyCollege of Basic Medical Sciences, Jilin UniversityChangchunJilinChina
| | - Yixin Zhang
- Department of PharmacologyCollege of Basic Medical Sciences, Jilin UniversityChangchunJilinChina
| | - Yan Guo
- Department of PharmacologyCollege of Basic Medical Sciences, Jilin UniversityChangchunJilinChina
| | - Meiyi Yu
- Department of PharmacologyCollege of Basic Medical Sciences, Jilin UniversityChangchunJilinChina
| | - Xiang Li
- Department of PharmacologyCollege of Basic Medical Sciences, Jilin UniversityChangchunJilinChina
| | - Jiangbin Wang
- Department of GastroenterologyChina‐Japan Union Hospital of Jilin UniversityChangchunJilinChina
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50
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Freitas ADS, Barroso FAL, Campos GM, Américo MF, Viegas RCDS, Gomes GC, Vital KD, Fernandes SOA, Carvalho RDDO, Jardin J, Miranda APGDS, Ferreira E, Martins FS, Laguna JG, Jan G, Azevedo V, de Jesus LCL. Exploring the anti-inflammatory effects of postbiotic proteins from Lactobacillus delbrueckii CIDCA 133 on inflammatory bowel disease model. Int J Biol Macromol 2024; 277:134216. [PMID: 39069058 DOI: 10.1016/j.ijbiomac.2024.134216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 07/22/2024] [Accepted: 07/25/2024] [Indexed: 07/30/2024]
Abstract
Lactobacillus delbrueckii CIDCA 133 is a promising health-promoting bacterium shown to alleviate intestinal inflammation. However, the specific bacterial components responsible for these effects remain largely unknown. Here, we demonstrated that consuming extractable proteins from the CIDCA 133 strain effectively relieved acute ulcerative colitis in mice. This postbiotic protein fraction reduced the disease activity index and prevented colon shortening in mice. Furthermore, histological analysis revealed colitis prevention with reduced inflammatory cell infiltration into the colon mucosa. Postbiotic consumption also induced an immunomodulatory profile in colitic mice, as evidenced by both mRNA transcript levels (Tlr2, Nfkb1, Nlpr3, Tnf, and Il6) and cytokines concentration (IL1β, TGFβ, and IL10). Additionally, it enhanced the levels of secretory IgA, upregulated the transcript levels of tight junction proteins (Hp and F11r), and improved paracellular intestinal permeability. More interestingly, the consumption of postbiotic proteins modulated the gut microbiota (Bacteroides, Arkkemansia, Dorea, and Oscillospira). Pearson correlation analysis indicated that IL10 and IL1β levels were positively associated with Bacteroides and Arkkemansia_Lactobacillus abundance. Our study reveals that CIDCA 133-derived proteins possess anti-inflammatory properties in colonic inflammation.
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Affiliation(s)
- Andria Dos Santos Freitas
- Federal University of Minas Gerais, Department of Genetics, Ecology, and Evolution, Belo Horizonte, Minas Gerais, Brazil
| | | | - Gabriela Munis Campos
- Federal University of Minas Gerais, Department of Genetics, Ecology, and Evolution, Belo Horizonte, Minas Gerais, Brazil
| | - Monique Ferrary Américo
- Federal University of Minas Gerais, Department of Genetics, Ecology, and Evolution, Belo Horizonte, Minas Gerais, Brazil
| | | | - Gabriel Camargos Gomes
- Federal University of Minas Gerais, Department of Genetics, Ecology, and Evolution, Belo Horizonte, Minas Gerais, Brazil
| | - Kátia Duarte Vital
- Federal University of Minas Gerais, Department of Clinical and Toxicological Analysis, Belo Horizonte, Minas Gerais, Brazil
| | | | | | | | | | - Enio Ferreira
- Federal University of Minas Gerais, Department of General Pathology, Belo Horizonte, Minas Gerais, Brazil
| | - Flaviano Santos Martins
- Federal University of Minas Gerais, Department of Microbiology, Belo Horizonte, Minas Gerais, Brazil
| | - Juliana Guimarães Laguna
- Federal University of Minas Gerais, Department of Genetics, Ecology, and Evolution, Belo Horizonte, Minas Gerais, Brazil
| | | | - Vasco Azevedo
- Federal University of Minas Gerais, Department of Genetics, Ecology, and Evolution, Belo Horizonte, Minas Gerais, Brazil.
| | - Luís Cláudio Lima de Jesus
- Federal University of Minas Gerais, Department of Genetics, Ecology, and Evolution, Belo Horizonte, Minas Gerais, Brazil.
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