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Han Z, Jiang HB, Wang FK, Wang ZY, Pang HF, Wang YY, Wei M. Endoscopic anti-reflux mucosal resection for patients with gastroesophageal reflux disease: Clinical efficacy and impact on gut microbiota. World J Gastrointest Surg 2025; 17:103336. [DOI: 10.4240/wjgs.v17.i6.103336] [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: 02/12/2025] [Revised: 03/17/2025] [Accepted: 04/11/2025] [Indexed: 05/30/2025] Open
Abstract
BACKGROUND In recent years, endoscopic anti-reflux mucosal resection (ARMS) has demonstrated benefits, including good efficacy, ease of operation, low cost, and fewer complications; however, it is still in the exploratory stage.
AIM To evaluate the clinical efficacy of ARMS in patients with gastroesophageal reflux disease (GERD) and its effects on the gut microbiota.
METHODS This single-center, retrospective, self-controlled study included 80 patients with GERD. All patients underwent endoscopic ARMS and were followed for at least 3 months after surgery. The primary outcome measures were changes in the gut microbiota before and after treatment and clinical efficacy.
RESULTS After surgery, the counts of Escherichia coli and Staphylococcus aureus were significantly lower than those before surgery (P < 0.05), whereas the counts of Bifidobacterium and Lactobacillus were significantly higher than those before surgery (P < 0.05). Symptoms, such as reflux and heartburn, were markedly relieved postoperatively. The average Gerd Q score prior to surgery was 11.32 ± 1.26 points, which decreased to 5.89 ± 0.52 points 3 months after surgery. All patients used proton pump inhibitors before surgery, and the proportion of patients using proton pump inhibitors declined significantly postoperatively. Sixteen patients (20.0%) experienced surgery-related adverse reactions within 2 weeks to 1 month post-surgery. The incidence rates of postoperative esophageal stricture and delayed bleeding were 15.0% and 5.0%, respectively.
CONCLUSION Endoscopic ARMS can effectively alleviate reflux symptoms, maintain gut microbiota balance, and improve gastrointestinal function in patients with GERD.
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Affiliation(s)
- Zhe Han
- Second Department of Gastrointestinal Disease Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang 050031, Hebei Province, China
| | - Hai-Bo Jiang
- Second Department of Gastrointestinal Disease Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang 050031, Hebei Province, China
| | - Fan-Ke Wang
- Second Department of Gastrointestinal Disease Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang 050031, Hebei Province, China
| | - Zhong-Yu Wang
- Second Department of Gastrointestinal Disease Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang 050031, Hebei Province, China
| | - Hong-Fei Pang
- Second Department of Gastrointestinal Disease Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang 050031, Hebei Province, China
| | - Yuan-Yuan Wang
- Department of Gastrointestinal Surgery, The First Hospital of Hebei Medical University, Shijiazhuang 050023, Hebei Province, China
| | - Ming Wei
- Second Department of Gastrointestinal Disease Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang 050031, Hebei Province, China
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de Brito CB, do Nascimento Arifa RD, de Oliveira Bezerra R, Dias Igídio CE, de Amorim-Santos BM, de Menezes Santos ACP, Barbosa LM, Barbosa JPP, Cassiano LMG, Kohlhoff M, Fagundes M, Batista RRÁ, Queiroz-Junior CM, Saliba AM, Raposo JDA, Braga FC, Coimbra RS, Teixeira MM, Fagundes CT, Souza DG. Antibiotic-Induced Dysbiosis of the Gut Microbiota Shifts Host Tryptophan Metabolism and Increases the Susceptibility of Mice to Pulmonary Infection With Pseudomonas aeruginosa. Immunology 2025. [PMID: 40387573 DOI: 10.1111/imm.13932] [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: 08/07/2024] [Revised: 04/04/2025] [Accepted: 04/07/2025] [Indexed: 05/20/2025] Open
Abstract
Pseudomonas aeruginosa is an opportunistic bacterium that mainly infects those who have previously been treated with antibiotics. We hypothesised that antibiotic treatment disrupts tryptophan metabolism, leading to increased susceptibility to P. aeruginosa infection. Our results showed that mice receiving antibiotics exhibited intestinal dysbiosis with alterations in host tryptophan metabolism, a higher mortality rate and a higher bacterial load compared to eubiotic mice. In the lungs of the dysbiotic mice, there was an increase in IDO1 (Indoleamine 2,3-dioxygenase 1) activity and an accumulation of kynurenine after infection, and IDO1-/- mice were resistant to infection after induction of dysbiosis. Importantly, dysbiosis led to increased expression and activation of AHR (Aryl Hydrocarbon Receptor) in an IDO1-dependent manner. Blocking AHR activation in dysbiotic mice resulted in a lower bacterial load. Our data showed that increased AHR activation by kynurenine was associated with decreased phagocytosis of P. aeruginosa by macrophages and neutrophils. In conclusion, our results indicate that dysbiosis resulting from prolonged antimicrobial treatment alters tryptophan metabolism, leading to activation of the IDO1-AHR axis and increasing susceptibility to P. aeruginosa infection. Furthermore, these data suggest that IDO1 or AHR are potential host targets for the prevention of opportunistic infections in patients undergoing antimicrobial therapy.
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Affiliation(s)
- Camila Bernardo de Brito
- Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Raquel Duque do Nascimento Arifa
- Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Rafael de Oliveira Bezerra
- Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Carlos Eduardo Dias Igídio
- Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Centro de Pesquisa e Desenvolvimento de Fármacos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Bárbara Maria de Amorim-Santos
- Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Anna Clara Paiva de Menezes Santos
- Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Larissa Mendes Barbosa
- Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - João Paulo Pezzini Barbosa
- Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | | | - Markus Kohlhoff
- Instituto René Rachou (IRR) - FIOCRUZ. FIOCRUZ MG, Belo Horizonte, MG, Brazil
| | - Micheli Fagundes
- Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Centro de Pesquisa e Desenvolvimento de Fármacos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Rafaela Ribeiro Álvares Batista
- Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Centro de Pesquisa e Desenvolvimento de Fármacos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Celso Martins Queiroz-Junior
- Centro de Pesquisa e Desenvolvimento de Fármacos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Alessandra M Saliba
- Departamento de Microbiologia e Imunologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Juliana Divina Almeida Raposo
- Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Fernão Castro Braga
- Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | | | - Mauro Martins Teixeira
- Centro de Pesquisa e Desenvolvimento de Fármacos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Caio Tavares Fagundes
- Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Centro de Pesquisa e Desenvolvimento de Fármacos, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Danielle G Souza
- Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
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Jørgensen SF, Braadland PR, Ueland T, Fraz MSA, Michelsen AE, Holm K, Osnes LT, Trøseid M, Ueland PM, Fevang B, Aukrust P, Hov JR. Tryptophan-kynurenine metabolites associate with inflammation and immunologic phenotypes in common variable immunodeficiency. J Allergy Clin Immunol 2025:S0091-6749(25)00515-9. [PMID: 40378971 DOI: 10.1016/j.jaci.2025.04.031] [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: 12/02/2024] [Revised: 04/23/2025] [Accepted: 04/29/2025] [Indexed: 05/19/2025]
Abstract
BACKGROUND A large proportion of patients with common variable immunodeficiency (CVID) have autoimmune and inflammatory manifestations characterized by chronic T-cell- and monocyte/macrophage activation of unknown etiology. The tryptophan-kynurenine pathway has previously been linked to immune activation involving T cells and monocytes/macrophages, as well as with gut microbial dysbiosis in some inflammatory diseases. OBJECTIVE We aimed to characterize the tryptophan-kynurenine pathway in CVID and its potential association with clinical/immunologic phenotype and gut microbial dysbiosis. METHODS Serum concentrations of a set of tryptophan-kynurenine pathway metabolites and neopterin were measured using liquid chromatography-tandem mass spectrometry in a discovery cohort (n = 40), a validation cohort (n = 53), and healthy controls (n = 60). B-cell phenotype was analyzed in both cohorts, whereas inflammatory markers (enzyme immunoassay), lipopolysaccharide, gut microbial composition, and food frequency questionnaire were measured in the discovery cohort. RESULTS Compared to healthy controls, CVID patients had increased metabolism of the tryptophan-kynurenine pathway as assessed by increased kynurenine/tryptophan ratio, quinolinic acid, and 3-hydroxykynurenine in both the discovery and validation cohorts. The findings were most pronounced in the subgroup with autoimmune/inflammatory complications but was to some degree also observed in CVID patients with infection only. In CVID, the metabolites in the tryptophan-kynurenine pathway associated with soluble (s) markers of monocyte (sCD14, sCD163, neopterin) and T-cell (sCD25) activation as well as B-cell phenotype (eg, naïve B cells). Individual gut microbial taxa may influence tryptophan-kynurenine pathway metabolites, but not lipopolysaccharide or diet. CONCLUSION We found altered levels of several metabolites in the tryptophan-kynurenine pathway in two different CVID cohorts associated with systemic inflammation and B-cell phenotype.
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Affiliation(s)
- Silje F Jørgensen
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
| | - Peder R Braadland
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Thor Ueland
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
| | - Mai S A Fraz
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Annika E Michelsen
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Kristian Holm
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Liv T Osnes
- Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Marius Trøseid
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | | | - Børre Fevang
- Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Pål Aukrust
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Johannes R Hov
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Hu W, Garrison C, Prasad R, Boulton M, Grant M. Indole metabolism and its role in diabetic macrovascular and microvascular complications. AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2025; 53:100532. [PMID: 40230659 PMCID: PMC11995707 DOI: 10.1016/j.ahjo.2025.100532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 03/03/2025] [Accepted: 03/21/2025] [Indexed: 04/16/2025]
Abstract
Tryptophan (Trp), an essential amino acid obtained through dietary sources, plays a crucial role in various physiological processes. The metabolism of Trp branches into three principal pathways: the serotonin pathway, the kynurenine pathway, and the indole pathway. The kynurenine and serotonin pathways are host pathways while the indole pathway is solely the result of bacterial metabolism. Trp metabolites extend their influence beyond protein biosynthesis to affect a spectrum of pathophysiological mechanisms including, but not limited to, neuronal function, immune modulation, inflammatory responses, oxidative stress regulation, and maintenance of intestinal health. This review focuses on indole derivatives and their impact on vascular health. Trp-containing dipeptides are highlighted as a targeted nutraceutical approach to modulate Trp metabolism, enhance beneficial metabolite production, and mitigate risk factors for vascular diseases. The importance of optimizing Trp intake and dietary strategies to harness the benefits of Trp-derived metabolites for vascular health is underscored, bringing to light the need for further research to refine these therapeutic approaches.
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Affiliation(s)
- W. Hu
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
- Department of Food Science and Technology, National University of Singapore, Singapore
| | - C. Garrison
- Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - R. Prasad
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - M.E. Boulton
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - M.B. Grant
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
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5
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Jiang C, Liang J, Hu K, Ye Y, Yang J, Zhang X, Ye G, Zhang J, Zhang D, Zhong B, Yu P, Wang L, Zeng B. Identification of tryptophan metabolism-related biomarkers for nonalcoholic fatty liver disease through network analysis. Endocr Connect 2025; 14:e240470. [PMID: 40183447 PMCID: PMC12023734 DOI: 10.1530/ec-24-0470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 03/20/2025] [Accepted: 04/04/2025] [Indexed: 04/05/2025]
Abstract
Background Increasing evidence demonstrates that tryptophan metabolism is closely related to the development of nonalcoholic fatty liver disease (NAFLD). This study aimed to identify specific biomarkers of NAFLD associated with tryptophan metabolism and research its functional mechanism. Methods We downloaded NAFLD RNA-sequencing data from GSE89632 and GSE24807, and obtained tryptophan metabolism-related genes (TMRGs) from the MsigDB database. The R package limma and WGCNA were used to identify TMRGs-DEGs, and GO, KEGG and Cytoscape were used to analyze and visualize the data. Immune cell infiltration analysis was used to explore the immune mechanism of NAFLD and the biomarkers. We also validated extended levels of biomarkers. Results We identified 375 NAFLD differentially expressed genes (DEGs) and 85 TMRGs-DEGs. GO/KEGG analysis revealed that TMRGs-DEGs were mainly enriched in triglyceride and cholesterol metabolism. ROC curves identified CCL20 (AUC = 0.917), CD160 (AUC = 0.933) and CYP7A1 (AUC = 1) as biomarkers of NAFLD. Immune infiltration analysis showed significant differences in ten immune cells, and the activation of dendritic cells and mast cells were highly positively correlated with NAFLD. CCL20, CD160 and CYP7A1 were highly correlated with M2 macrophage, neutrophil and mast cells activation, respectively. Twenty-seven TMRGs correlated with hub genes, and gene set enrichment analysis demonstrated their function in tryptophan- and lysine-containing metabolic process. We identified 41 therapeutic drug matches which corresponded to two hub genes and four drugs which co-targeted CCL20 and CYP7A1. Finally, three hub genes were validated in our mouse model. Conclusions CCL20, CD160 and CYP7A1 are tryptophan metabolism-related biomarkers of NAFLD, related to glycerol ester and cholesterol metabolism. We screened four compounds which co-target CCL29 and CYP7A1 to provide potential experimental drugs for NAFLD.
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Affiliation(s)
- Cuihua Jiang
- Department of Pain Management, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, China
| | - Jianqi Liang
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Kaibo Hu
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Yanqing Ye
- Department of Gastroenterology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Jiajia Yang
- School of Basic Medicine, Gannan Medical University, Ganzhou, China
| | - Xiaozhi Zhang
- School of Basic Medicine, Gannan Medical University, Ganzhou, China
| | - Guilin Ye
- School of Basic Medicine, Gannan Medical University, Ganzhou, China
| | - Jing Zhang
- Department of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Deju Zhang
- Food and Nutritional Sciences, School of Biological Sciences, The University of Hong Kong, Hong Kong, China
| | - Bin Zhong
- Department of Pharmacy, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Peng Yu
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Liefeng Wang
- School of Basic Medicine, Gannan Medical University, Ganzhou, China
- China Medical University, Shenyang, China
| | - Bin Zeng
- Department of Gastroenterology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- China Medical University, Shenyang, China
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Wang H, Wu J, Wei H, Zhang Y, Wang Y, Wang DW. Increased Tryptophan Catabolism Provides Predictive Value to Chronic Heart Failure Patients with Low-Grade Inflammation. Inflammation 2025; 48:963-973. [PMID: 39012560 DOI: 10.1007/s10753-024-02100-8] [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: 04/10/2024] [Revised: 06/18/2024] [Accepted: 07/02/2024] [Indexed: 07/17/2024]
Abstract
Kynurenine to tryptophan ratio (KTR), which serves as an indicator for evaluating indoleamine-2,3-dioxygenase activity and inflammation, has been reported to be linked with cardiovascular incidences. However, its correlation with cardiovascular outcomes in patients suffering from heart failure (HF) remains to be explored. The objective of this study was to investigate the prognostic value of KTR in HF. The concentration of tryptophan and kynurenine were quantified by liquid chromatography-tandem mass spectrometry, and the KTR value was calculated in a population of 3150 HF patients. The correlation between plasma KTR levels and the occurrence of adverse cardiovascular events was evaluated for its prognostic value. We also assessed the role of KTR in addition to the classic inflammatory biomarker hypersensitive C-reactive protein (hs-CRP) in different subtypes of HF. We found that increased KTR levels were associated with an elevated risk and severity of the primary endpoints in different subtypes of HF. The simultaneous evaluation of KTR and hs-CRP levels enhanced risk categorization among HF patients. Furthermore, the KTR index presented complementary prognostic value for those HF patients with low-grade inflammation (hs-CRP ≤ 6 mg/L). Our results indicated plasma KTR is an independent risk factor for cardiovascular events. Plasma KTR levels in patients with HF can provide both concurrent and complementary prognostic value to hs-CRP.
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Affiliation(s)
- Huiqing Wang
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China
| | - Junfang Wu
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China.
| | - Haoran Wei
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China
| | - Yuxuan Zhang
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China
| | - Yinhui Wang
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China
| | - Dao Wen Wang
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China.
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7
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Floyd JL, Prasad R, Dupont MD, Adu-Rutledge Y, Anshumali S, Paul S, Li Calzi S, Qi X, Malepati A, Johnson E, Jumbo-Lucioni P, Crosson JN, Mason JO, Boulton ME, Welner RS, Grant MB. Intestinal neutrophil extracellular traps promote gut barrier damage exacerbating endotoxaemia, systemic inflammation and progression of diabetic retinopathy in type 2 diabetes. Diabetologia 2025; 68:866-889. [PMID: 39875729 PMCID: PMC11950064 DOI: 10.1007/s00125-024-06349-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 11/01/2024] [Indexed: 01/30/2025]
Abstract
AIMS/HYPOTHESIS Within the small intestine, neutrophils play an integral role in preventing bacterial infection. Upon interaction with bacteria or bacteria-derived antigens, neutrophils initiate a multi-staged response of which the terminal stage is NETosis, formation of protease-decorated nuclear DNA into extracellular traps. NETosis has a great propensity to elicit ocular damage and has been associated with diabetic retinopathy and diabetic macular oedema (DME) progression. Here, we interrogate the relationship between gut barrier dysfunction, endotoxaemia and systemic and intestinal neutrophilia in diabetic retinopathy. METHODS In a cohort of individuals with type 2 diabetes (n=58) with varying severity of diabetic retinopathy and DME, we characterised the abundance of circulating neutrophils by flow cytometry and markers of gut permeability and endotoxaemia by plasma ELISA. In a mouse model of type 2 diabetes, we examined the effects of diabetes on abundance and function of intestinal, blood and bone marrow neutrophils, gut barrier integrity, endotoxaemia and diabetic retinopathy severity. Pharmacological inhibition of NETosis was achieved by i.p. injection of the peptidyl arginine deiminase 4 inhibitor (PAD4i) GSK484 daily for 4 weeks between 6 and 7 months of type 2 diabetes. RESULTS In human participants, neutrophilia was unique to individuals with type 2 diabetes with diabetic retinopathy and DME and was accompanied by heightened circulating markers of gut permeability. At late-stage diabetes, neutrophilia and gut barrier dysfunction were seen in db/db mice. The db/db mice exhibited an increase in stem-like pre-neutrophils in the intestine and bone marrow and a decrease in haematopoietic vascular reparative cells. In the db/db mouse intestine, enhanced loss of gut barrier integrity was associated with elevated intestinal NETosis. Inhibition of NETosis by the PAD4i GSK484 resulted in decreased abundance of premature neutrophils in the intestine and blood and resulted in neutrophil retention in the bone marrow compared with vehicle-treated db/db mice. Additionally, the PAD4i decreased senescence within the gut epithelium and yielded a slowing of diabetic retinopathy progression. CONCLUSIONS/INTERPRETATION Severity of diabetic retinopathy and DME were associated with peripheral neutrophilia, gut barrier dysfunction and endotoxaemia in the human participants. db/db mice exhibited intestinal neutrophilia, specifically stem-like pre-neutrophils, which was associated with elevated NETosis and decreased levels of vascular reparative cells. Chronic inhibition of NETosis in db/db mice reduced intestinal senescence and NETs in the retina. These changes were associated with reduced endotoxaemia and an anti-inflammatory bone marrow milieu with retention of pre-neutrophils in the bone marrow and increased gut infiltration of myeloid angiogenic cells. Collectively, PAD-4i treatment decreased gut barrier dysfunction, restoring physiological haematopoiesis and levels of haematopoietic vascular reparative cells.
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Affiliation(s)
- Jason L Floyd
- Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Ram Prasad
- Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Mariana D Dupont
- Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Yvonne Adu-Rutledge
- Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Shambhavi Anshumali
- Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Sarbodeep Paul
- Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Sergio Li Calzi
- Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Xiaoping Qi
- Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Akanksha Malepati
- Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Emory Johnson
- Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Patricia Jumbo-Lucioni
- Pharmaceutical, Social and Administrative Sciences, Samford University, Birmingham, AL, USA
| | - Jason N Crosson
- Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
- Retina Consultants of Alabama, Birmingham, AL, USA
| | - John O Mason
- Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
- Retina Consultants of Alabama, Birmingham, AL, USA
| | - Michael E Boulton
- Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Robert S Welner
- Department of Medicine, Division Hematology/Oncology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Maria B Grant
- Department of Ophthalmology and Visual Sciences, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
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8
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Pérez Escriva P, Correia Tavares Bernardino C, Letellier E. De-coding the complex role of microbial metabolites in cancer. Cell Rep 2025; 44:115358. [PMID: 40023841 DOI: 10.1016/j.celrep.2025.115358] [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: 08/09/2024] [Revised: 12/11/2024] [Accepted: 02/06/2025] [Indexed: 03/04/2025] Open
Abstract
The human microbiome, an intricate ecosystem of trillions of microbes residing across various body sites, significantly influences cancer, a leading cause of morbidity and mortality worldwide. Recent studies have illuminated the microbiome's pivotal role in cancer development, either through direct cellular interactions or by secreting bioactive compounds such as metabolites. Microbial metabolites contribute to cancer initiation through mechanisms such as DNA damage, epithelial barrier dysfunction, and chronic inflammation. Furthermore, microbial metabolites exert dual roles on cancer progression and response to therapy by modulating cellular metabolism, gene expression, and signaling pathways. Understanding these complex interactions is vital for devising new therapeutic strategies. This review highlights microbial metabolites as promising targets for cancer prevention and treatment, emphasizing their impact on therapy responses and underscoring the need for further research into their roles in metastasis and therapy resistance.
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Affiliation(s)
- Pau Pérez Escriva
- Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Catarina Correia Tavares Bernardino
- Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Elisabeth Letellier
- Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
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9
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Amarasiri RPGSK, Hyun J, Lee SW, Kim JI, Lee HG, Ryu B, Jeon YJ. Therapeutic potential of tryptophan metabolite indoleacrylic acid in inflammatory bowel disease: From cellular mechanisms to zebrafish stress-like behavior. Int Immunopharmacol 2025; 149:114207. [PMID: 39904043 DOI: 10.1016/j.intimp.2025.114207] [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: 12/05/2024] [Revised: 01/22/2025] [Accepted: 01/30/2025] [Indexed: 02/06/2025]
Abstract
Inflammatory bowel disease (IBD) is a chronic condition associated with elevated rates of anxiety and depression and ultimately reduces the quality of life. Thus, preventive care addressing both physical and psychological health is essential. In this study we aimed to explore the protective effects of Indoleacrylic Acid (IA) against lipopolysaccharide (LPS)-induced inflammation using human colorectal adenocarcinoma cells (HT-29) and dextran sulfate sodium (DSS)-induced zebrafish to assess its potential as a novel therapeutic agent for IBD. IA exhibited substantial anti-inflammatory properties in HT-29 cells and zebrafish models. It significantly reduced the production of pro-inflammatory mediators, including PGE2, TNF-α, IL-6, and IL-8, while upregulating MUC2, AhR, and tight junction proteins (ZO-1, occludin, and claudin-1), thereby enhancing mucosal barrier integrity. In zebrafish larvae, IA improved survival rates, boosted mucin production, and reduced macrophage infiltration and heartbeat rate. Behavioral analyses of adult zebrafish revealed that IA alleviated anxiety-like behaviors, as shown by increased locomotion and improved performance in zone preference and light-dark transition tests. By targeting inflammation and anxiety-like symptoms, IA demonstrates a dual benefit by addressing both intestinal inflammation and the psychological burden of IBD. These findings highlight IA's potential as a novel therapeutic agent for managing IBD, offering a comprehensive approach to improving patient outcomes.
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Affiliation(s)
- R P G S K Amarasiri
- Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea
| | - Jimin Hyun
- Department of Food Science and Nutrition, Pukyong National University, Busan 48513, Republic of Korea
| | - Sang-Woon Lee
- Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea
| | - Jae-Il Kim
- Department of Food Science and Nutrition, Pukyong National University, Busan 48513, Republic of Korea
| | - Hyoung-Gon Lee
- Department of Neuroscience, Developmental and Regenerative Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA
| | - Bomi Ryu
- Department of Food Science and Nutrition, Pukyong National University, Busan 48513, Republic of Korea.
| | - You-Jin Jeon
- Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea.
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10
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Yin Z, Sun B, Wang S, Xu X, Cheng L, Gao Y, Jin E. Investigating the role of IDO1 in tumors: correlating IDO1 expression with clinical pathological features and prognosis in lung adenocarcinoma patients. PeerJ 2025; 13:e18776. [PMID: 39989741 PMCID: PMC11846502 DOI: 10.7717/peerj.18776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 12/09/2024] [Indexed: 02/25/2025] Open
Abstract
Purpose This study aimed to investigate the role and expression patterns of IDO1 in various tumors, focusing on its correlation with clinical pathological characteristics and prognosis in patients specifically diagnosed with lung adenocarcinoma. Methods Pan-cancer analysis assessed IDO1 function across different tumor types. Bioinformatics tools, immunohistochemistry techniques, and statistical analyses were employed to evaluate IDO1 expression levels and their association with clinical pathological features and prognosis in patients with lung adenocarcinoma. Results IDO1 was found to be significantly overexpressed in various types of tumors, with higher levels correlating with poorer progression-free survival (PFS) and overall survival (OS). In lung adenocarcinoma patients, IDO1 protein was predominantly localized to the cytoplasm and cell membrane of tumor cells, with higher expression observed in tumor cells closer to normal lung tissue. Statistical analysis revealed no significant differences in IDO1 expression based on the patient's clinical data, including gender, age, tumor location, allergy history, hypertension history, cardiovascular disease history, tumor history, diabetes (both type 1 and type 2), body mass index, smoking history, family history, alcohol history, and tumor maximum diameter (P > 0.05). However, IDO1 expression positively correlated with lymph node metastasis, pleural invasion, tumor recurrence, lower tumor differentiation, solid tumor components, preoperative chemotherapy, and clinical tumor, node, metastasis (TNM) staging (*P < 0.05), while negatively correlating with prior surgical history (*P < 0.05). Patients exhibiting high IDO1 expression levels demonstrated significantly worse PFS and OS (***P < 0.001 and **P = 0.003, respectively). Conclusion High IDO1 expression in lung adenocarcinoma correlates with increased tumor invasiveness, metastatic potential, advanced clinical stage, and poorer prognosis.
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Affiliation(s)
- Zhidong Yin
- Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
- Department of Respiratory Medicine, Affiliated Hangzhou First People’s Hospital, Westlake University, School of Medicine, Hangzhou, Zhejiang Province, China
| | - Bohao Sun
- Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Sisi Wang
- Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Xi Xu
- Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Lu Cheng
- Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Yue Gao
- Department of Geriatric, Affiliated Hangzhou First People’s Hospital, Westlake University, School of Medicine, Hangzhou, Zhejiang Province, China
- Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Major Chronic Disease in the Elderly, Hangzhou, Zhejiang Province, China
| | - Er Jin
- Department of Respiratory Medicine, Affiliated Hangzhou First People’s Hospital, Westlake University, School of Medicine, Hangzhou, Zhejiang Province, China
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11
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Blok L, Hanssen N, Nieuwdorp M, Rampanelli E. From Microbes to Metabolites: Advances in Gut Microbiome Research in Type 1 Diabetes. Metabolites 2025; 15:138. [PMID: 39997763 PMCID: PMC11857261 DOI: 10.3390/metabo15020138] [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: 02/01/2025] [Revised: 02/12/2025] [Accepted: 02/13/2025] [Indexed: 02/26/2025] Open
Abstract
Background: Type 1 diabetes (T1D) is a severe chronic T-cell mediated autoimmune disease that attacks the insulin-producing beta cells of the pancreas. The multifactorial nature of T1D involves both genetic and environmental components, with recent research focusing on the gut microbiome as a crucial environmental factor in T1D pathogenesis. The gut microbiome and its metabolites play an important role in modulating immunity and autoimmunity. In recent years, studies have revealed significant alterations in the taxonomic and functional composition of the gut microbiome associated with the development of islet autoimmunity and T1D. These changes include reduced production of short-chain fatty acids, altered bile acid and tryptophan metabolism, and increased intestinal permeability with consequent perturbations of host (auto)immune responses. Methods/Results: In this review, we summarize and discuss recent observational, mechanistic and etiological studies investigating the gut microbiome in T1D and elucidating the intricate role of gut microbes in T1D pathogenesis. Moreover, we highlight the recent advances in intervention studies targeting the microbiota for the prevention or treatment of human T1D. Conclusions: A deeper understanding of the evolution of the gut microbiome before and after T1D onset and of the microbial signals conditioning host immunity may provide us with essential insights for exploiting the microbiome as a prognostic and therapeutic tool.
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Affiliation(s)
- Lente Blok
- Department of Internal and Vascular Medicine, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands; (N.H.); (M.N.)
| | - Nordin Hanssen
- Department of Internal and Vascular Medicine, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands; (N.H.); (M.N.)
| | - Max Nieuwdorp
- Department of Internal and Vascular Medicine, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands; (N.H.); (M.N.)
| | - Elena Rampanelli
- Department of Internal and Vascular Medicine, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands; (N.H.); (M.N.)
- Amsterdam Institute for Infection and Immunity (AII), Amsterdam, The Netherlands
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12
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Cristina MO, Elizabeth BR, Jose RAM, Berenice PG, Diego Z, Luis CSJ. Mechanisms and Therapeutic Potential of Key Anti-inflammatory Metabiotics: Trans-Vaccenic Acid, Indole-3-Lactic Acid, Thiamine, and Butyric Acid. Probiotics Antimicrob Proteins 2025:10.1007/s12602-025-10475-9. [PMID: 39921846 DOI: 10.1007/s12602-025-10475-9] [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] [Accepted: 01/29/2025] [Indexed: 02/10/2025]
Abstract
Identifying metabolites produced by probiotic bacteria, also known as metabiotics, is becoming increasingly common due to their anti-inflammatory, anti-obesogenic, and immunomodulatory effects. Postbiotics alongside diet, regulate both physical and mental health, as the microbiota members can interact physically with host cells or through secretion of nutrients and metabiotics. These metabiotics also reduce the severity of certain metabolic disorders and support the proper functioning of various organs and systems. In this review, we describe the mechanisms of action of trans-vaccenic acid (TVA), indole-3-lactic acid (ILA), thiamine (vitamin B1), and butyric acid metabolites produced or induced by probiotics such as Lactobacillus and/or Bifidobacterium, among others and previously identified using analytical techniques such as mass spectrometry (LC-MS). Within their mechanisms of action, Trans-vaccenic acid exerts anti-inflammatory effects and helps alleviate complications associated with metabolic diseases. Indole metabolites promote IL-22 production and regulate epithelial cell proliferation and antimicrobial peptide production. Thiamin is essential for energy metabolism regulation, and butyric acid regulates the brain-gut axis and also regulates immune response. This review expands our understanding of the potential therapeutic use of metabiotics.
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Affiliation(s)
- Muñoz-Olivos Cristina
- Laboratory of Medical and Pharmaceutical Biotechnology, Faculty of Biotechnology, Popular and Autonomous, University of the State of Puebla (UPAEP), 72410, Puebla, Mexico
- Department of Sciences and Engineering, Iberoamerican Puebla University, 71820, Puebla, Mexico
| | - Bautista-Rodriguez Elizabeth
- Laboratory of Medical and Pharmaceutical Biotechnology, Faculty of Biotechnology, Popular and Autonomous, University of the State of Puebla (UPAEP), 72410, Puebla, Mexico.
- Clinical Chemistry, Faculty of Health Sciences, Autonomous University of Tlaxcala, 90750, Tlaxcala, Mexico.
| | | | - Palacios-Gonzalez Berenice
- Healthy Aging Laboratory of the National Institute of Genomic Medicine (INMEGEN) at the Aging Research Center (CIE-CINVESTAV), 14330, CDMX, Mexico
| | - Zacapa Diego
- Faculty of Health Sciences, Autonomous University of Tlaxcala. Tlaxcala, 90750, Medicine, Mexico
- Health Research Office, State Coordination of the Mexican Social Security Institute (IMSS-BIENESTAR), Tlaxcala, Mexico
| | - Cortez-Sanchez Jose Luis
- Faculty of Chemical-Biological Sciences, Autonomous University of Campeche, 24039, Campeche, Mexico
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13
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Enache RM, Roşu OA, Profir M, Pavelescu LA, Creţoiu SM, Gaspar BS. Correlations Between Gut Microbiota Composition, Medical Nutrition Therapy, and Insulin Resistance in Pregnancy-A Narrative Review. Int J Mol Sci 2025; 26:1372. [PMID: 39941139 PMCID: PMC11818759 DOI: 10.3390/ijms26031372] [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: 12/09/2024] [Revised: 01/31/2025] [Accepted: 02/04/2025] [Indexed: 02/16/2025] Open
Abstract
Many physiological changes accompany pregnancy, most of them involving metabolic perturbations. Alterations in microbiota composition occur both before and during pregnancy and have recently been correlated with an important role in the development of metabolic complications, such as insulin resistance and gestational diabetes mellitus (GDM). These changes may be influenced by physiological adaptations to pregnancy itself, as well as by dietary modifications during gestation. Medical nutritional therapy (MNT) applied to pregnant women at risk stands out as one of the most important factors in increasing the microbiota's diversity at both the species and genus levels. In this review, we discuss the physiological changes during pregnancy and their impact on the composition of the intestinal microbiota, which may contribute to GDM. We also discuss findings from previous studies regarding the effectiveness of MNT in reducing insulin resistance. In the future, additional studies should aim to identify specific gut microbial profiles that serve as early indicators of insulin resistance during gestation. Early diagnosis, achievable through stool analysis or metabolite profiling, may facilitate the timely implementation of dietary or pharmaceutical modifications, thereby mitigating the development of insulin resistance and its associated sequelae.
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Affiliation(s)
- Robert-Mihai Enache
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania;
| | - Oana Alexandra Roşu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (O.A.R.); (M.P.); (L.A.P.)
- Department of Oncology, Elias University Emergency Hospital, 011461 Bucharest, Romania
| | - Monica Profir
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (O.A.R.); (M.P.); (L.A.P.)
- Department of Oncology, Elias University Emergency Hospital, 011461 Bucharest, Romania
| | - Luciana Alexandra Pavelescu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (O.A.R.); (M.P.); (L.A.P.)
| | - Sanda Maria Creţoiu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (O.A.R.); (M.P.); (L.A.P.)
| | - Bogdan Severus Gaspar
- Department of Surgery, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Surgery Clinic, Bucharest Emergency Clinical Hospital, 014461 Bucharest, Romania
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14
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Sedaka R, Lovelady C, Hallit E, Duyvestyn B, Shinde S, Moran-Reyna A, Lee G, Yamaguchi S, Maynard CL, Saigusa T. Intestinal barrier function declines during polycystic kidney disease progression. Am J Physiol Renal Physiol 2025; 328:F218-F229. [PMID: 39694536 DOI: 10.1152/ajprenal.00058.2024] [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: 02/22/2024] [Revised: 11/25/2024] [Accepted: 12/12/2024] [Indexed: 01/22/2025] Open
Abstract
Most patients with autosomal dominant polycystic kidney disease (ADPKD) develop kidney cysts due to germline PKD1 mutations. In the kidney, Pkd1 loss impairs epithelial cell integrity and increases macrophage infiltration, contributing to cyst growth. Despite its role as the body's largest inflammatory cell reservoir, it has yet to be elucidated whether a similar phenotype presents in the intestines. We hypothesize that loss of Pkd1 leads to a leaky intestinal epithelial barrier and increased inflammation, before rapid cystogenesis. Control and inducible, global Pkd1 knockout (Pkd1KO) mice were euthanized at 3 and 6 mo of age (early and late stage) to evaluate kidney disease progression, small and large intestinal integrity, and inflammation. Early-stage Pkd1KO mice displayed mild cystic kidneys and tubular injury with preserved kidney function. Intestinal epithelial barrier was tighter in KO mice, which was associated with higher expression of cell-cell epithelial integrity markers. However, there was no evidence of local or systemic inflammation in either genotype. Late-stage Pkd1KO mice had severely cystic, impaired kidneys with increased expression of integrity markers, tubular injury, and inflammation. Intestinal epithelial barrier was leakier in late-stage Pkd1KO mice, accompanied by gene reduction of integrity markers, increased inflammation, and elevated water and sodium channel expression. Gut motility and fecal water excretion were increased in Pkd1KO compared with flox mice irrespective of age. Overall, kidney injury appears to precede intestinal injury in ADPKD, whereby the intestinal barrier becomes leaky as cystogenesis progresses.NEW & NOTEWORTHY Though autosomal dominant polycystic kidney disease (ADPKD) is a multisystem disorder, this is the first study to explore a kidney-gut contribution to disease progression. We identified a tightened intestinal epithelial barrier in early PKD, which becomes leaky as kidneys become more cystic, accompanied by a sustained loss of fecal water. Given the only approved ADPKD therapeutic yields adverse aquaretic events, this study emphasizes the need to evaluate extrarenal water loss in patients before prescribing.
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Affiliation(s)
- Randee Sedaka
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Alabama, United States
| | - Caleb Lovelady
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Alabama, United States
| | - Emily Hallit
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Alabama, United States
| | - Branden Duyvestyn
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Alabama, United States
| | - Sejal Shinde
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Alabama, United States
| | - Aida Moran-Reyna
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Alabama, United States
| | - Goo Lee
- Division of Anatomic Pathology, Department of Pathology, University of Alabama at Birmingham, Alabama, United States
| | - Shinobu Yamaguchi
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Alabama, United States
| | - Craig L Maynard
- Division of Molecular & Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Alabama, United States
| | - Takamitsu Saigusa
- Section of Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Alabama, United States
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15
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Uberoi A, Murga-Garrido SM, Bhanap P, Campbell AE, Knight SAB, Wei M, Chan A, Senay T, Tegegne S, White EK, Sutter CH, Mesaros C, Sutter TR, Grice EA. Commensal-derived tryptophan metabolites fortify the skin barrier: Insights from a 50-species gnotobiotic model of human skin microbiome. Cell Chem Biol 2025; 32:111-125.e6. [PMID: 39824155 PMCID: PMC11753614 DOI: 10.1016/j.chembiol.2024.12.007] [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: 05/03/2024] [Revised: 11/01/2024] [Accepted: 12/12/2024] [Indexed: 01/20/2025]
Abstract
The epidermal barrier defends the body against dehydration and harmful substances. The commensal microbiota is essential for proper differentiation and repair of the epidermal barrier, an effect mediated by the aryl hydrocarbon receptor (AHR). However, the microbial mechanisms of AHR activation in skin are less understood. Tryptophan metabolites are AHR ligands that can be products of microbial metabolism. To identify microbially regulated tryptophan metabolites in vivo, we established a gnotobiotic model colonized with fifty human skin commensals and performed targeted mass spectrometry on murine skin. Indole-related metabolites were enriched in colonized skin compared to germ-free skin. In reconstructed human epidermis and in murine models of atopic-like barrier damage, these metabolites improved barrier repair and function individually and as a cocktail. These results provide a framework for the identification of microbial metabolites that mediate specific host functions, which can guide the development of microbe-based therapies for skin disorders.
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Affiliation(s)
- Aayushi Uberoi
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
| | - Sofía M Murga-Garrido
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Preeti Bhanap
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Amy E Campbell
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Simon A B Knight
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Monica Wei
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Anya Chan
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Taylor Senay
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Saba Tegegne
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Ellen K White
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | | | - Clementina Mesaros
- Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Thomas R Sutter
- Department of Biological Sciences, University of Memphis, Memphis, TN, USA
| | - Elizabeth A Grice
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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16
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Sun S, Hu F, Sang Y, Wang S, Liu X, Shi J, Cao H, Tao F, Liu K. Dysregulated tryptophan metabolism contributes to metabolic syndrome in Chinese community-dwelling older adults. BMC Endocr Disord 2025; 25:7. [PMID: 39780122 PMCID: PMC11708088 DOI: 10.1186/s12902-024-01826-8] [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: 09/02/2024] [Accepted: 12/27/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND As the prevalence of metabolic syndrome (MetS) rises among older adults, the associated risks of cardiovascular diseases and diabetes significantly increase, and it is closely linked to various metabolic processes in the body. Dysregulation of tryptophan (TRP) metabolism, particularly alterations in the kynurenine (KYN) and serotonin pathways, has been linked to the onset of chronic inflammation, oxidative stress, and insulin resistance, key contributors to the development of MetS. We aim to investigate the relationship between the TRP metabolites and the risk of MetS in older adults. METHODS Ultra-performance liquid chromatography tandem mass spectrometry was used to detect TRP and its seven metabolites in a study involving 986 participants. Physical examination included the following indicators: blood pressure, body mass index, triglyceride levels, and high-density lipoprotein cholesterol (HDL-C) levels. Multiple linear regression, restricted cubic spline curve, binary logistic analysis, and sex-stratified analysis were used to explore the relationship between the metabolites and the risk of MetS in older adults. RESULTS The results indicated that, after adjusting for covariates, higher levels of TRP, KYN, kynurenic acid (KA), and xanthurenic acid (XA) were risk factors for MetS (P for trend < 0.05). By contrast, higher ratios of 5-hydroxytryptamine to TRP and indole-3-propionic acid to TRP were protective factors against MetS (P for trend < 0.05). CONCLUSIONS TRP and its metabolites may serve as potential indicators for assessing and managing MetS in older adults, complementing existing biomarkers. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Shujing Sun
- School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China
| | - Fangting Hu
- School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China
| | - Yanru Sang
- School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China
| | - Sheng Wang
- Center for Scientific Research, Anhui Medical University, Hefei, Anhui, 230032, China
| | - Xuechun Liu
- Hefei Hospital affiliated to Anhui Medical University (Hefei Second People's Hospital), Hefei, Anhui, 230011, China
| | - Jiafeng Shi
- School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China
| | - Hongjuan Cao
- Lu'an Center of Disease Control and Prevention, Lu'an, Anhui, 237000, China
| | - Fangbiao Tao
- School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China
- Center for Big Data and Population Health, Institute of Health and Medicine, Hefei, Anhui, 230032, China
| | - Kaiyong Liu
- School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China.
- Center for Big Data and Population Health, Institute of Health and Medicine, Hefei, Anhui, 230032, China.
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17
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Wang X, Zhou XJ, Qiao X, Falchi M, Liu J, Zhang H. The evolving understanding of systemic mechanisms in organ-specific IgA nephropathy: a focus on gut-kidney crosstalk. Theranostics 2025; 15:656-681. [PMID: 39744688 PMCID: PMC11671385 DOI: 10.7150/thno.104631] [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: 10/04/2024] [Accepted: 11/18/2024] [Indexed: 01/11/2025] Open
Abstract
The interplay between multiple organs, known as inter-organ crosstalk, represents a complex and essential research domain in understanding the mechanisms and therapies for kidney diseases. The kidneys not only interact pathologically with many other organs but also communicate with other systems through various signaling pathways. It is of paramount importance to comprehend these mechanisms for the development of more efficient therapeutic strategies. Despite extensive research in IgA nephropathy (IgAN), the most common kidney disease, the elaboration mechanism of IgAN remains challenging. Numerous studies suggest that alterations in the intestinal microbiome and its metabolites are pivotal in the progression of IgAN, opening new avenues for understanding its mechanisms. Interestingly, certain presumed probiotics, such as Akkermansia muciniphila, have been implicated in the onset of IgAN, making the exploration of gut microbiota in the context of IgAN pathogenesis even more intriguing. In this review, we summarize the status of gut microbiology studies of IgAN and explore the possible mechanisms and intervention prospects. Future research and treatment directions may increasingly emphasize systemic, multi-organ combined interventions to decelerate the advancement of kidney disease and enhance the overall prognosis of patients.
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Affiliation(s)
- Xin Wang
- Renal Division, Peking University First Hospital, Beijing, China
- Peking University Institute of Nephrology, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Xu-Jie Zhou
- Renal Division, Peking University First Hospital, Beijing, China
- Peking University Institute of Nephrology, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
| | - Xue Qiao
- State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Mario Falchi
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
| | - Jing Liu
- CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, University of Chinese Academy of Science, Beijing, 100190, China
| | - Hong Zhang
- Renal Division, Peking University First Hospital, Beijing, China
- Peking University Institute of Nephrology, Beijing, China
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China
- State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China
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18
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Xu K, Motiwala Z, Corona-Avila I, Makhanasa D, Alkahalifeh L, Khan MW. The Gut Microbiome and Its Multifaceted Role in Cancer Metabolism, Initiation, and Progression: Insights and Therapeutic Implications. Technol Cancer Res Treat 2025; 24:15330338251331960. [PMID: 40208053 PMCID: PMC12032467 DOI: 10.1177/15330338251331960] [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: 10/30/2024] [Revised: 02/27/2025] [Accepted: 02/28/2025] [Indexed: 04/11/2025] Open
Abstract
This review summarizes the intricate relationship between the microbiome and cancer initiation and development. Microbiome alterations impact metabolic pathways, immune responses, and gene expression, which can accelerate or mitigate cancer progression. We examine how dysbiosis affects tumor growth, metastasis, and treatment resistance. Additionally, we discuss the potential of microbiome-targeted therapies, such as probiotics and fecal microbiota transplants, to modulate cancer metabolism. These interventions offer the possibility of reversing or controlling cancer progression, enhancing the efficacy of traditional treatments like chemotherapy and immunotherapy. Despite promising developments, challenges remain in identifying key microbial species and pathways and validating microbiome-targeted therapies through large-scale clinical trials. Nonetheless, the intersection of microbiome research and cancer initiation and development presents an exciting frontier for innovative therapies. This review offers a fresh perspective on cancer initiation and development by integrating microbiome insights, highlighting the potential for interdisciplinary research to enhance our understanding of cancer progression and treatment strategies.
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Affiliation(s)
- Kai Xu
- Division of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, Chicago, IL, USA
| | - Zainab Motiwala
- Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India
| | - Irene Corona-Avila
- Division of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, Chicago, IL, USA
| | - Dhruvi Makhanasa
- Division of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, Chicago, IL, USA
| | | | - Md. Wasim Khan
- Division of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, Chicago, IL, USA
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19
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Yarahmadi A, Afkhami H, Javadi A, Kashfi M. Understanding the complex function of gut microbiota: its impact on the pathogenesis of obesity and beyond: a comprehensive review. Diabetol Metab Syndr 2024; 16:308. [PMID: 39710683 PMCID: PMC11664868 DOI: 10.1186/s13098-024-01561-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 12/15/2024] [Indexed: 12/24/2024] Open
Abstract
Obesity is a multifactorial condition influenced by genetic, environmental, and microbiome-related factors. The gut microbiome plays a vital role in maintaining intestinal health, increasing mucus creation, helping the intestinal epithelium mend, and regulating short-chain fatty acid (SCFA) production. These tasks are vital for managing metabolism and maintaining energy balance. Dysbiosis-an imbalance in the microbiome-leads to increased appetite and the rise of metabolic disorders, both fuel obesity and its issues. Furthermore, childhood obesity connects with unique shifts in gut microbiota makeup. For instance, there is a surge in pro-inflammatory bacteria compared to children who are not obese. Considering the intricate nature and variety of the gut microbiota, additional investigations are necessary to clarify its exact involvement in the beginnings and advancement of obesity and related metabolic dilemmas. Currently, therapeutic methods like probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), dietary interventions like Mediterranean and ketogenic diets, and physical activity show potential in adjusting the gut microbiome to fight obesity and aid weight loss. Furthermore, the review underscores the integration of microbial metabolites with pharmacological agents such as orlistat and semaglutide in restoring microbial homeostasis. However, more clinical tests are essential to refine the doses, frequency, and lasting effectiveness of these treatments. This narrative overview compiles the existing knowledge on the multifaceted role of gut microbiota in obesity and much more, showcasing possible treatment strategies for addressing these health challenges.
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Affiliation(s)
- Aref Yarahmadi
- Department of Biology, Khorramabad Branch, Islamic Azad University, Khorramabad, Iran
| | - Hamed Afkhami
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran.
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran.
- Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran.
| | - Ali Javadi
- Department of Medical Sciences, Faculty of Medicine, Qom Medical Sciences, Islamic Azad University, Qom, Iran.
| | - Mojtaba Kashfi
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran.
- Fellowship in Clinical Laboratory Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.
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20
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Hong JS, Jeong YD, Park HJ, Choi YH, Min YJ, Kim C, Back SH, Kim DW, Kim YM, Kim JE. Effects of Italian ryegrass with multi-enzymes supplementation on growth performance, gut microbial, and manure odor emission in finisher pig. JOURNAL OF ANIMAL SCIENCE AND TECHNOLOGY 2024; 66:1182-1192. [PMID: 39691618 PMCID: PMC11647401 DOI: 10.5187/jast.2024.e23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 02/15/2024] [Accepted: 02/17/2024] [Indexed: 12/19/2024]
Abstract
This study investigated the effects of addition of Italian ryegrass with multi-enzyme on growth performance, fecal odor, and microbiome. The experiment had a two-factor factorial design, using three levels of Italian ryegrass (0%, 2.5%, and 5%) and two levels of multi-enzymes (no enzyme and commercially recommended level) to formulate experimental diets. In total, 60 crossbred Landrace × Yorkshire × Duroc (LYD) pigs (88.35 ± 2.57 kg) were allocated into six dietary treatments with five replicates. After four weeks, fecal samples were collected via rectal massage for microbiome and odorous compound analysis. Results showed no significant difference (p > 0.05) in growth performance, except for feed intake (p < 0.05), which was higher in enzyme-added diets. Fecal microbiome exhibited no differences (p > 0.05) between treatments, with Firmicutes and Bacteroidetes being the major phyla, similar to the general pig population. Alpha and beta diversity analyses showed no significant differences (p > 0.05). Odorous compounds displayed no significant differences (p > 0.05), except for indoles (p < 0.05) influenced by the enzyme. In conclusion, 5% Italian ryegrass with multi-enzymes can be used as an alternative feed ingredient, having no negative effects on the growth performance, microbiome, and odorous compounds of growing pigs.
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Affiliation(s)
- Jun-Seon Hong
- Swine Science Division, National Institute of Animal Science, Rural Development Administration, Cheonan 31000, Korea
| | - Yong-Dae Jeong
- Swine Science Division, National Institute of Animal Science, Rural Development Administration, Cheonan 31000, Korea
| | - Hyun-Ju Park
- Swine Science Division, National Institute of Animal Science, Rural Development Administration, Cheonan 31000, Korea
| | - Yo-Han Choi
- Swine Science Division, National Institute of Animal Science, Rural Development Administration, Cheonan 31000, Korea
| | - Ye-Jin Min
- Swine Science Division, National Institute of Animal Science, Rural Development Administration, Cheonan 31000, Korea
| | - Chaehyun Kim
- Swine Science Division, National Institute of Animal Science, Rural Development Administration, Cheonan 31000, Korea
| | - Soo-Hyun Back
- Swine Science Division, National Institute of Animal Science, Rural Development Administration, Cheonan 31000, Korea
| | - Doo-Wan Kim
- Swine Science Division, National Institute of Animal Science, Rural Development Administration, Cheonan 31000, Korea
| | - Yong-Min Kim
- Swine Science Division, National Institute of Animal Science, Rural Development Administration, Cheonan 31000, Korea
| | - Jo-Eun Kim
- Swine Science Division, National Institute of Animal Science, Rural Development Administration, Cheonan 31000, Korea
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21
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Nakashima M, Suga N, Fukumoto A, Yoshikawa S, Matsuda S. Caveolae with serotonin and NMDA receptors as promising targets for the treatment of Alzheimer's disease. INTERNATIONAL JOURNAL OF PHYSIOLOGY, PATHOPHYSIOLOGY AND PHARMACOLOGY 2024; 16:96-110. [PMID: 39583750 PMCID: PMC11579522 DOI: 10.62347/mtwv3745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 10/13/2024] [Indexed: 11/26/2024]
Abstract
Alzheimer's disease is the most general type of cognitive impairments. Until recently, strategies that prevent its clinical progression have remained more elusive. Consequently, research direction should be for finding effective neuroprotective agents. It has been suggested oxidative stress, mitochondrial injury, and inflammation level might lead to brain cell death in many neurological disorders. Therefore, several autophagy-targeted bioactive compounds may be promising candidate therapeutics for the prevention of brain cell damage. Interestingly, some risk genes to Alzheimer's disease are expressed within brain cells, which may be linked to cholesterol metabolism, lipid transport, endocytosis, exocytosis and/or caveolae formation, suggesting that caveolae may be a fruitful therapeutic target to improve cognitive impairments. This review would highlight the latest advances in therapeutic technologies to improve the treatment of Alzheimer's disease. In particular, a paradigm that serotonin and N-methyl-d-aspartate (NMDA) receptors agonist/antagonist within caveolae structure might possibly improve the cognitive impairment. Consequently, cellular membrane biophysics should improve our understanding of the pathology of the cognitive dysfunction associated with Alzheimer's disease. Here, this research direction for the purpose of therapy may open the potential to move a clinical care toward disease-modifying treatment strategies with certain benefits for patients.
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Affiliation(s)
- Moeka Nakashima
- Department of Food Science and Nutrition, Nara Women's University Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Naoko Suga
- Department of Food Science and Nutrition, Nara Women's University Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Akari Fukumoto
- Department of Food Science and Nutrition, Nara Women's University Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Sayuri Yoshikawa
- Department of Food Science and Nutrition, Nara Women's University Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Satoru Matsuda
- Department of Food Science and Nutrition, Nara Women's University Kita-Uoya Nishimachi, Nara 630-8506, Japan
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22
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González A, Fullaondo A, Odriozola I, Odriozola A. Microbiota and beneficial metabolites in colorectal cancer. ADVANCES IN GENETICS 2024; 112:367-409. [PMID: 39396841 DOI: 10.1016/bs.adgen.2024.08.002] [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: 10/15/2024]
Abstract
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide. In recent years, the impact of the gut microbiota on the development of CRC has become clear. The gut microbiota is the community of microorganisms living in the gut symbiotic relationship with the host. These microorganisms contribute to the development of CRC through various mechanisms that are not yet fully understood. Increasing scientific evidence suggests that metabolites produced by the gut microbiota may influence CRC development by exerting protective and deleterious effects. This article reviews the metabolites produced by the gut microbiota, which are derived from the intake of complex carbohydrates, proteins, dairy products, and phytochemicals from plant foods and are associated with a reduced risk of CRC. These metabolites include short-chain fatty acids (SCFAs), indole and its derivatives, conjugated linoleic acid (CLA) and polyphenols. Each metabolite, its association with CRC risk, the possible mechanisms by which they exert anti-tumour functions and their relationship with the gut microbiota are described. In addition, other gut microbiota-derived metabolites that are gaining importance for their role as CRC suppressors are included.
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Affiliation(s)
- Adriana González
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain
| | - Asier Fullaondo
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain
| | - Iñaki Odriozola
- Health Department of Basque Government, Donostia-San Sebastián, Spain
| | - Adrian Odriozola
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain.
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23
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Wang C, Xu Q, Wei C, Hu Q, Xiao Y, Jin Y. Kynurenine Attenuates Ulcerative Colitis Mediated by the Aryl Hydrocarbon Receptor. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:21000-21012. [PMID: 39271472 DOI: 10.1021/acs.jafc.4c04933] [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: 09/15/2024]
Abstract
The higher prevalence of ulcerative colitis (UC) and the side effects of its therapeutic agents contribute to finding novel treatments. This study aimed to investigate whether kynurenine (KYN), a tryptophan metabolite, has the possibility of alleviating UC and further clarifying the underlying mechanism. The effect of KYN on treating UC was evaluated by intestinal pathology, inflammatory cytokines, and tight-junction proteins in colitis mice and LPS-stimulated Caco-2 cells. Our results revealed that KYN relieved pathological symptoms of UC, improved intestinal barrier function, enhanced AhR expression, and inhibited NF-κB signaling pathway activation in the colon of colitis mice. Moreover, the improved intestinal barrier function, the decreased inflammasome production, and the inhibited activation of the NF-κB signaling pathway by KYN were dependent on AhR in Caco-2 cells. KYN could trigger AhR activation, inactivate the NF-κB signaling pathway, and inhibit NLRP3 inflammasome production, thus alleviating intestinal epithelial barrier dysfunction and reducing intestinal inflammation. In conclusion, the present study reveals that KYN ameliorates UC by improving the intestinal epithelial barrier and activating the AhR-NF-κB-NLRP3 signaling pathway, and it can be a promising therapeutic agent and dietary supplement for alleviating UC.
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Affiliation(s)
- Caihong Wang
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Qihao Xu
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | | | - Qinglian Hu
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Yingping Xiao
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Yuanxiang Jin
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
- Xianghu Laboratory, Hangzhou 311231, China
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24
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Ranhotra HS. Discrete interplay of gut microbiota L-tryptophan metabolites in host biology and disease. Mol Cell Biochem 2024; 479:2273-2290. [PMID: 37861881 DOI: 10.1007/s11010-023-04867-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 09/24/2023] [Indexed: 10/21/2023]
Abstract
The gut microbiota and the host maintain a conjoint relationship and together achieve optimal physiology via a multitude of interactive signalling cues. Dietary-derived L-tryptophan (L-trp) is enzymatically metabolized by the resident symbiotic gut microbiota to indole and various indole derivatives. Indole and indole metabolites secreted by the gut bacteria act locally in the intestinal cells as well as distally and modulate tissue-specific functions which are beneficial to the host. Functions attributed to these microbial indole metabolites in the host include regulation of intestinal permeability, immunity and mucosal roles, inflammation, and insulin sensitivity. On the other hand, dysregulation of gut microbiota L-trp metabolism compromises the optimal availability of indole and indole metabolites and can induce the onset of metabolic disorders, inflammation, liver steatosis, and decrease gut barrier integrity. Gut dysbiosis is regarded as one of the prime reasons for this deregulated microbial-derived indole metabolites. A number of indole metabolites from the gut bacteria have been identified recently displaying variable affinity towards xenobiotic nuclear receptors. Microbial metabolite mimicry concept can be used to design and develop novel indole-moiety-containing compounds with higher affinity towards the receptors and efficacy in preclinical studies. Such compounds may serve as therapeutic drugs in clinical trials in the future. In this article, I review L-trp metabolism in the host and gut microbiota and the various physiological functions, patho-physiologies associated with the microbial-released indole metabolites in the host, including the metabolite mimicry-based concept to develop tailored indole-containing novel experimental drugs.
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Affiliation(s)
- Harmit S Ranhotra
- Department of Biochemistry, St. Edmund's College, Shillong, 793 003, India.
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25
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Vashishth S, Ambasta RK, Kumar P. Deciphering the microbial map and its implications in the therapeutics of neurodegenerative disorder. Ageing Res Rev 2024; 100:102466. [PMID: 39197710 DOI: 10.1016/j.arr.2024.102466] [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: 07/31/2024] [Revised: 08/19/2024] [Accepted: 08/19/2024] [Indexed: 09/01/2024]
Abstract
Every facet of biological anthropology, including development, ageing, diseases, and even health maintenance, is influenced by gut microbiota's significant genetic and metabolic capabilities. With current advancements in sequencing technology and with new culture-independent approaches, researchers can surpass older correlative studies and develop mechanism-based studies on microbiome-host interactions. The microbiota-gut-brain axis (MGBA) regulates glial functioning, making it a possible target for the improvement of development and advancement of treatments for neurodegenerative diseases (NDDs). The gut-brain axis (GBA) is accountable for the reciprocal communication between the gastrointestinal and central nervous system, which plays an essential role in the regulation of physiological processes like controlling hunger, metabolism, and various gastrointestinal functions. Lately, studies have discovered the function of the gut microbiome for brain health-different microbiota through different pathways such as immunological, neurological and metabolic pathways. Additionally, we review the involvement of the neurotransmitters and the gut hormones related to gut microbiota. We also explore the MGBA in neurodegenerative disorders by focusing on metabolites. Further, targeting the blood-brain barrier (BBB), intestinal barrier, meninges, and peripheral immune system is investigated. Lastly, we discuss the therapeutics approach and evaluate the pre-clinical and clinical trial data regarding using prebiotics, probiotics, paraprobiotics, fecal microbiota transplantation, personalised medicine, and natural food bioactive in NDDs. A comprehensive study of the GBA will felicitate the creation of efficient therapeutic approaches for treating different NDDs.
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Affiliation(s)
- Shrutikirti Vashishth
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University (Formerly DCE), Delhi 110042, India
| | - Rashmi K Ambasta
- Department of Medicine, School of Medicine, VUMC, Vanderbilt University, TN, USA
| | - Pravir Kumar
- Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, Delhi Technological University (Formerly DCE), Delhi 110042, India.
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26
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Ji G, Zhao J, Si X, Song W. Targeting bacterial metabolites in tumor for cancer therapy: An alternative approach for targeting tumor-associated bacteria. Adv Drug Deliv Rev 2024; 211:115345. [PMID: 38834140 DOI: 10.1016/j.addr.2024.115345] [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: 02/03/2024] [Revised: 05/11/2024] [Accepted: 05/29/2024] [Indexed: 06/06/2024]
Abstract
Emerging evidence reveal that tumor-associated bacteria (TAB) can facilitate the initiation and progression of multiple types of cancer. Recent work has emphasized the significant role of intestinal microbiota, particularly bacteria, plays in affecting responses to chemo- and immuno-therapies. Hence, it seems feasible to improve cancer treatment outcomes by targeting intestinal bacteria. While considering variable richness of the intestinal microbiota and diverse components among individuals, direct manipulating the gut microbiota is complicated in clinic. Tumor initiation and progression requires the gut microbiota-derived metabolites to contact and reprogram neoplastic cells. Hence, directly targeting tumor-associated bacteria metabolites may have the potential to provide alternative and innovative strategies to bypass the gut microbiota for cancer therapy. As such, there are great opportunities to explore holistic approaches that incorporates TAB-derived metabolites and related metabolic signals modulation for cancer therapy. In this review, we will focus on key opportunistic areas by targeting TAB-derived metabolites and related metabolic signals, but not bacteria itself, for cancer treatment, and elucidate future challenges that need to be addressed in this emerging field.
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Affiliation(s)
- Guofeng Ji
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
| | - Jingjing Zhao
- Department of Clinical Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, China
| | - Xinghui Si
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China
| | - Wantong Song
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China.
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27
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Ren C, Zhang S, Chen Y, Deng K, Kuang M, Gong Z, Zhang K, Wang P, Huang P, Zhou Z, Gong A. Exploring nicotinamide adenine dinucleotide precursors across biosynthesis pathways: Unraveling their role in the ovary. FASEB J 2024; 38:e23804. [PMID: 39037422 DOI: 10.1096/fj.202400453r] [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: 03/02/2024] [Revised: 05/31/2024] [Accepted: 06/26/2024] [Indexed: 07/23/2024]
Abstract
Natural Nicotinamide Adenine Dinucleotide (NAD+) precursors have attracted much attention due to their positive effects in promoting ovarian health. However, their target tissue, synthesis efficiency, advantages, and disadvantages are still unclear. This review summarizes the distribution of NAD+ at the tissue, cellular and subcellular levels, discusses its biosynthetic pathways and the latest findings in ovary, include: (1) NAD+ plays distinct roles both intracellularly and extracellularly, adapting its distribution in response to requirements. (2) Different precursors differs in target tissues, synthetic efficiency, biological utilization, and adverse effects. Importantly: tryptophan is primarily utilized in the liver and kidneys, posing metabolic risks in excess; nicotinamide (NAM) is indispensable for maintaining NAD+ levels; nicotinic acid (NA) constructs a crucial bridge between intestinal microbiota and the host with diverse functions; nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) increase NAD+ systemically and can be influenced by delivery route, tissue specificity, and transport efficiency. (3) The biosynthetic pathways of NAD+ are intricately intertwined. They provide multiple sources and techniques for NAD+ synthesis, thereby reducing the dependence on a single molecule to maintain cellular NAD+ levels. However, an excess of a specific precursor potentially influencing other pathways. In addition, Protein expression analysis suggest that ovarian tissues may preferentially utilize NAM and NMN. These findings summarize the specific roles and potential of NAD+ precursors in enhancing ovarian health. Future research should delve into the molecular mechanisms and intervention strategies of different precursors, aiming to achieve personalized prevention or treatment of ovarian diseases, and reveal their clinical application value.
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Affiliation(s)
- Caifang Ren
- School of Medicine, Jiangsu University, Zhenjiang, China
- Hematological Disease Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China
| | - Shuang Zhang
- School of Medicine, Jiangsu University, Zhenjiang, China
| | - Yanyan Chen
- School of Medicine, Jiangsu University, Zhenjiang, China
| | - Kaiping Deng
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Meiqian Kuang
- School of Medicine, Jiangsu University, Zhenjiang, China
| | - Zihao Gong
- School of Medicine, Jiangsu University, Zhenjiang, China
| | - Ke Zhang
- School of Medicine, Jiangsu University, Zhenjiang, China
| | - Panqi Wang
- School of Medicine, Jiangsu University, Zhenjiang, China
| | - Pan Huang
- School of Medicine, Jiangsu University, Zhenjiang, China
| | - Zhengrong Zhou
- School of Medicine, Jiangsu University, Zhenjiang, China
| | - Aihua Gong
- School of Medicine, Jiangsu University, Zhenjiang, China
- Hematological Disease Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China
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28
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Chajadine M, Laurans L, Radecke T, Mouttoulingam N, Al-Rifai R, Bacquer E, Delaroque C, Rytter H, Bredon M, Knosp C, Vilar J, Fontaine C, Suffee N, Vandestienne M, Esposito B, Dairou J, Launay JM, Callebert J, Tedgui A, Ait-Oufella H, Sokol H, Chassaing B, Taleb S. Harnessing intestinal tryptophan catabolism to relieve atherosclerosis in mice. Nat Commun 2024; 15:6390. [PMID: 39080345 PMCID: PMC11289133 DOI: 10.1038/s41467-024-50807-x] [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: 08/04/2023] [Accepted: 07/22/2024] [Indexed: 08/02/2024] Open
Abstract
Tryptophan (Trp) is an essential amino acid, whose metabolism is a key gatekeeper of intestinal homeostasis. Yet, its systemic effects, particularly on atherosclerosis, remain unknown. Here we show that high-fat diet (HFD) increases the activity of intestinal indoleamine 2, 3-dioxygenase 1 (IDO), which shifts Trp metabolism from the production of microbiota-derived indole metabolites towards kynurenine production. Under HFD, the specific deletion of IDO in intestinal epithelial cells leads to intestinal inflammation, impaired intestinal barrier, augmented lesional T lymphocytes and atherosclerosis. This is associated with an increase in serotonin production and a decrease in indole metabolites, thus hijacking Trp for the serotonin pathway. Inhibition of intestinal serotonin production or supplementation with indole derivatives alleviates plaque inflammation and atherosclerosis. In summary, we uncover a pivotal role of intestinal IDO in the fine-tuning of Trp metabolism with systemic effects on atherosclerosis, paving the way for new therapeutic strategies to relieve gut-associated inflammatory diseases.
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Affiliation(s)
- Mouna Chajadine
- Université Paris Cité, Inserm, PARCC, F-75015, Paris, France
| | | | - Tobias Radecke
- Université Paris Cité, Inserm, PARCC, F-75015, Paris, France
| | | | - Rida Al-Rifai
- Université Paris Cité, Inserm, PARCC, F-75015, Paris, France
| | - Emilie Bacquer
- Université Paris Cité, Inserm, PARCC, F-75015, Paris, France
| | - Clara Delaroque
- Microbiome-Host interactions, Institut Pasteur, Université Paris Cité, INSERM U1306, Paris, France
- INSERM U1016, Team "Mucosal microbiota in chronic inflammatory diseases", CNRS UMR10 8104, Université Paris Cité, Paris, France
| | - Héloïse Rytter
- Microbiome-Host interactions, Institut Pasteur, Université Paris Cité, INSERM U1306, Paris, France
- INSERM U1016, Team "Mucosal microbiota in chronic inflammatory diseases", CNRS UMR10 8104, Université Paris Cité, Paris, France
| | - Marius Bredon
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, F-75012, Paris, France
- Paris Centre for Microbiome Medicine (PaCeMM) FHU, Paris, France
| | - Camille Knosp
- Université Paris Cité, Inserm, PARCC, F-75015, Paris, France
| | - José Vilar
- Université Paris Cité, Inserm, PARCC, F-75015, Paris, France
| | - Coralie Fontaine
- Inserm U1297, Institut des Maladies Métaboliques et Cardiovasculaires, Université de Toulouse, BP 84225, 31 432 Toulouse cedex 04, cedex, France
| | - Nadine Suffee
- Université Paris Cité, Inserm, PARCC, F-75015, Paris, France
| | | | - Bruno Esposito
- Université Paris Cité, Inserm, PARCC, F-75015, Paris, France
| | - Julien Dairou
- Université Paris cité, CNRS, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, F-75006 Paris, France. 45 rue des Saints Pères, 75006, Paris, France
| | - Jean Marie Launay
- Assistance Publique Hôpitaux de Paris, Service de Biochimie and INSERM U942, Hôpital Lariboisière, Paris, France
| | - Jacques Callebert
- Assistance Publique Hôpitaux de Paris, Service de Biochimie and INSERM U942, Hôpital Lariboisière, Paris, France
| | - Alain Tedgui
- Université Paris Cité, Inserm, PARCC, F-75015, Paris, France
| | | | - Harry Sokol
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, F-75012, Paris, France
- Paris Centre for Microbiome Medicine (PaCeMM) FHU, Paris, France
- Université Paris-Saclay, INRAe, AgroParisTech, Micalis institute, Jouy-en-Josas, France Université Paris-Saclay, INRAe, AgroParisTech, Micalis institute, Jouy-en-Josas, France
| | - Benoit Chassaing
- Microbiome-Host interactions, Institut Pasteur, Université Paris Cité, INSERM U1306, Paris, France
- INSERM U1016, Team "Mucosal microbiota in chronic inflammatory diseases", CNRS UMR10 8104, Université Paris Cité, Paris, France
| | - Soraya Taleb
- Université Paris Cité, Inserm, PARCC, F-75015, Paris, France.
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Hu Y, Zhang R, Li J, Wang H, Wang M, Ren Q, Fang Y, Tian L. Association Between Gut and Nasal Microbiota and Allergic Rhinitis: A Systematic Review. J Asthma Allergy 2024; 17:633-651. [PMID: 39006241 PMCID: PMC11246088 DOI: 10.2147/jaa.s472632] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 07/01/2024] [Indexed: 07/16/2024] Open
Abstract
Allergic rhinitis is a chronic non-infectious inflammation of the nasal mucosa mediated by specific IgE. Recently, the human microbiome has drawn broad interest as a potential new target for treating this condition. This paper succinctly summarizes the main findings of 17 eligible studies published by February 2024, involving 1044 allergic rhinitis patients and 954 healthy controls from 5 countries. These studies examine differences in the human microbiome across important mucosal interfaces, including the nasal and intestinal areas, between patients and controls. Overall, findings suggest variations in the gut microbiota between allergic rhinitis patients and healthy individuals, although the specific bacterial taxa that significantly changed were not always consistent across studies. Due to the limited scope of existing research and patient coverage, the relationship between the nasal microbiome and allergic rhinitis remains inconclusive. The article discusses the potential immune-regulating role of the gut microbiome in allergic rhinitis. Further well-designed clinical trials with large-scale recruitment of allergic rhinitis patients are encouraged.
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Affiliation(s)
- Yucheng Hu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China
| | - Rong Zhang
- Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China
| | - Junjie Li
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China
| | - Huan Wang
- Chengdu university of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China
| | - Meiya Wang
- Chengdu university of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China
| | - Qiuyi Ren
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China
| | - Yueqi Fang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China
| | - Li Tian
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China
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Zhang J, Lin B, Zhang Y, Hu X, Liu T, Liu EH, Liu S. Baitouweng decoction alleviates ulcerative colitis by regulating tryptophan metabolism through DOPA decarboxylase promotion. Front Pharmacol 2024; 15:1423307. [PMID: 38974042 PMCID: PMC11224817 DOI: 10.3389/fphar.2024.1423307] [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: 04/26/2024] [Accepted: 05/31/2024] [Indexed: 07/09/2024] Open
Abstract
Background Baitouweng decoction (BTW) is a classic botanical drugs formula that has been widely used clinically for the treatment of gut-related disorders in China. However, its role in ameliorating ulcerative colitis (UC) remains to be explored. Purpose The study aimed to determine the therapeutic efficacy and potential mechanism of action of BTW on dextran sodium sulfate (DSS)-induced colitis mice. Methods In vivo: 3.5% DSS-induced experimental colitis mice were treated with BTW (Pulsatilla chinensis (Bunge) Regel, Phellodendron chinense C. K. Schneid, Coptis chinensis Franch and Fraxinus chinensis Roxb), kynurenine or DOPA decarboxylase (DDC) inhibitor (carbidopa). In vitro: Caco-2 cells were stimulated with TNF-α to activate inflammation and later treated with various concentrations of BTW and carbidopa. Model evaluation included body weight, disease activity index (DAI) score, colon length and histopathology. Cytokine levels were measured by flow cytometry. Protein levels were analyzed by proteomics and functionally annotated. The levels of tryptophan metabolites in mouse serum and colon were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Alcian Blue/Phosphate Acid Schiff (AB/PAS) staining, immunohistochemistry and western blot were used to assess the intestinal barrier function and detect the protein expression levels. Results BTW significantly reduced the DAI, ameliorated colonic injury and regulated inflammatory cytokines in DSS-induced colitis mice. The botanical drugs formula also promoted intestinal epithelial barrier repair by enhancing the expression of the tight junction (TJ) proteins. Tryptophan metabolic signaling pathway was significantly enriched in DSS-induced UC mice, and BTW decreased the level of kynurenine, increased indole metabolites. The therapeutic effect of BTW was evidently reduced when kynurenine was given to mice. Also, BTW promoted DDC protein expression and activated the aryl hydrocarbon receptor (AHR)/IL-22 signaling pathway. Conclusion BTW improves ulcerative colitis by promoting DDC expression, regulating the conversion of tryptophan metabolism from the kynurenine pathway to the indole metabolism pathway, thereby modulating tryptophan metabolism to increase indole metabolites, and activating AHR receptors to restore intestinal barrier function.
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Affiliation(s)
- Junzhi Zhang
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Binyan Lin
- College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Ying Zhang
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Xiaochao Hu
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Tongtong Liu
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - E-Hu Liu
- College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shijia Liu
- The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
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Santonocito R, Paladino L, Vitale AM, D’Amico G, Zummo FP, Pirrotta P, Raccosta S, Manno M, Accomando S, D’Arpa F, Carini F, Barone R, Rappa F, Marino Gammazza A, Bucchieri F, Cappello F, Caruso Bavisotto C. Nanovesicular Mediation of the Gut-Brain Axis by Probiotics: Insights into Irritable Bowel Syndrome. BIOLOGY 2024; 13:296. [PMID: 38785778 PMCID: PMC11117693 DOI: 10.3390/biology13050296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 04/15/2024] [Accepted: 04/23/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND Dysbiosis, influenced by poor diet or stress, is associated with various systemic diseases. Probiotic supplements are recognized for stabilizing gut microbiota and alleviating gastrointestinal issues, like irritable bowel syndrome (IBS). This study focused on the tryptophan pathways, which are important for the regulation of serotonin levels, and on host physiology and behavior regulation. METHODS Nanovesicles were isolated from the plasma of subjects with chronic diarrhea, both before and after 60 days of consuming a probiotic mix (Acronelle®, Bromatech S.r.l., Milan, Italy). These nanovesicles were assessed for the presence of Tryptophan 2,3-dioxygenase 2 (TDO 2). Furthermore, the probiotics mix, in combination with H2O2, was used to treat HT29 cells to explore its cytoprotective and anti-stress effect. RESULTS In vivo, levels of TDO 2 in nanovesicles were enhanced in the blood after probiotic treatment, suggesting a role in the gut-brain axis. In the in vitro model, a typical H2O2-induced stress effect occurred, which the probiotics mix was able to recover, showing a cytoprotective effect. The probiotics mix treatment significantly reduced the heat shock protein 60 kDa levels and was able to preserve intestinal integrity and barrier function by restoring the expression and redistribution of tight junction proteins. Moreover, the probiotics mix increased the expression of TDO 2 and serotonin receptors. CONCLUSIONS This study provides evidence for the gut-brain axis mediation by nanovesicles, influencing central nervous system function.
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Affiliation(s)
- Radha Santonocito
- Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy; (R.S.); (L.P.); (A.M.V.); (G.D.); (F.P.Z.); (F.C.); (R.B.); (F.R.); (A.M.G.); (F.B.); or (F.C.)
| | - Letizia Paladino
- Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy; (R.S.); (L.P.); (A.M.V.); (G.D.); (F.P.Z.); (F.C.); (R.B.); (F.R.); (A.M.G.); (F.B.); or (F.C.)
| | - Alessandra Maria Vitale
- Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy; (R.S.); (L.P.); (A.M.V.); (G.D.); (F.P.Z.); (F.C.); (R.B.); (F.R.); (A.M.G.); (F.B.); or (F.C.)
| | - Giuseppa D’Amico
- Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy; (R.S.); (L.P.); (A.M.V.); (G.D.); (F.P.Z.); (F.C.); (R.B.); (F.R.); (A.M.G.); (F.B.); or (F.C.)
| | - Francesco Paolo Zummo
- Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy; (R.S.); (L.P.); (A.M.V.); (G.D.); (F.P.Z.); (F.C.); (R.B.); (F.R.); (A.M.G.); (F.B.); or (F.C.)
| | - Paolo Pirrotta
- Euro-Mediterranean Institute of Science and Technology (IEMEST), 90139 Palermo, Italy;
| | - Samuele Raccosta
- Cell-Tech Hub, Institute of Biophysics, National Research Council of Italy, 90146 Palermo, Italy; (S.R.); (M.M.)
| | - Mauro Manno
- Cell-Tech Hub, Institute of Biophysics, National Research Council of Italy, 90146 Palermo, Italy; (S.R.); (M.M.)
| | - Salvatore Accomando
- Department of Health Promotion, Mother and Childcare, Internal Medicine and Medical Specialities “G D‘Alessandro”, PROMISE, University of Palermo, 90127 Palermo, Italy;
| | - Francesco D’Arpa
- Department of Surgical, Oncological and Stomatological Disciplines, DICHIRONS, University of Palermo, 90127 Palermo, Italy;
| | - Francesco Carini
- Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy; (R.S.); (L.P.); (A.M.V.); (G.D.); (F.P.Z.); (F.C.); (R.B.); (F.R.); (A.M.G.); (F.B.); or (F.C.)
| | - Rosario Barone
- Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy; (R.S.); (L.P.); (A.M.V.); (G.D.); (F.P.Z.); (F.C.); (R.B.); (F.R.); (A.M.G.); (F.B.); or (F.C.)
| | - Francesca Rappa
- Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy; (R.S.); (L.P.); (A.M.V.); (G.D.); (F.P.Z.); (F.C.); (R.B.); (F.R.); (A.M.G.); (F.B.); or (F.C.)
| | - Antonella Marino Gammazza
- Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy; (R.S.); (L.P.); (A.M.V.); (G.D.); (F.P.Z.); (F.C.); (R.B.); (F.R.); (A.M.G.); (F.B.); or (F.C.)
| | - Fabio Bucchieri
- Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy; (R.S.); (L.P.); (A.M.V.); (G.D.); (F.P.Z.); (F.C.); (R.B.); (F.R.); (A.M.G.); (F.B.); or (F.C.)
| | - Francesco Cappello
- Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy; (R.S.); (L.P.); (A.M.V.); (G.D.); (F.P.Z.); (F.C.); (R.B.); (F.R.); (A.M.G.); (F.B.); or (F.C.)
- Euro-Mediterranean Institute of Science and Technology (IEMEST), 90139 Palermo, Italy;
| | - Celeste Caruso Bavisotto
- Section of Human Anatomy, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, 90127 Palermo, Italy; (R.S.); (L.P.); (A.M.V.); (G.D.); (F.P.Z.); (F.C.); (R.B.); (F.R.); (A.M.G.); (F.B.); or (F.C.)
- Euro-Mediterranean Institute of Science and Technology (IEMEST), 90139 Palermo, Italy;
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Shao J, Qu L, Liu Y, Zhang J, Liu Y, Deng J, Ma X, Fan D. Ginsenoside Rk3 Regulates Tryptophan Metabolism along the Brain-Gut Axis by Targeting Tryptophan Hydroxylase and Remodeling the Intestinal Microenvironment to Alleviate Depressive-Like Behavior in Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:7100-7120. [PMID: 38488514 DOI: 10.1021/acs.jafc.3c07599] [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: 04/04/2024]
Abstract
Depression is a neuropsychiatric disease that significantly impacts the physical and mental health of >300 million people worldwide and places a major burden on society. Ginsenosides are the main active ingredient in ginseng and have been proven to have various pharmacological effects on the nervous system. Herein, we investigated the antidepressant effect of ginsenoside Rk3 and its underlying mechanism in a murine model of depression. Rk3 significantly improved depression-like behavior in mice, ameliorated the disturbance of the hypothalamus-pituitary-adrenal axis, and alleviated neuronal damage in the hippocampus and prefrontal cortex of mice. Additionally, Rk3 improved the abnormal metabolism of tryptophan in brain tissue by targeting tryptophan hydroxylase, thereby reducing neuronal apoptosis and synaptic structural damage in the mouse hippocampus and prefrontal cortex. Furthermore, Rk3 reshaped the composition of the gut microbiota of mice and regulated intestinal tryptophan metabolism, which alleviated intestinal barrier damage. Thus, this study provides valuable insights into the role of Rk3 in the tryptophan metabolic cycle along the brain-gut axis, suggesting that Rk3 may have the potential for treating depression.
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Affiliation(s)
- Jingjing Shao
- Shaanxi Institute of Microbiology, Xiying Road 76, Xi'an, Shaanxi 710043, China
- Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China
| | - Linlin Qu
- Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China
| | - Yao Liu
- Shaanxi Institute of Microbiology, Xiying Road 76, Xi'an, Shaanxi 710043, China
- Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China
| | - Jingjing Zhang
- Shaanxi Institute of Microbiology, Xiying Road 76, Xi'an, Shaanxi 710043, China
- Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China
| | - Yannan Liu
- Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China
| | - Jianjun Deng
- Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China
| | - Xiaoxuan Ma
- Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China
| | - Daidi Fan
- Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China
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Longtine AG, Greenberg NT, Bernaldo de Quirós Y, Brunt VE. The gut microbiome as a modulator of arterial function and age-related arterial dysfunction. Am J Physiol Heart Circ Physiol 2024; 326:H986-H1005. [PMID: 38363212 PMCID: PMC11279790 DOI: 10.1152/ajpheart.00764.2023] [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: 12/08/2023] [Revised: 01/26/2024] [Accepted: 02/13/2024] [Indexed: 02/17/2024]
Abstract
The arterial system is integral to the proper function of all other organs and tissues. Arterial function is impaired with aging, and arterial dysfunction contributes to the development of numerous age-related diseases, including cardiovascular diseases. The gut microbiome has emerged as an important regulator of both normal host physiological function and impairments in function with aging. The purpose of this review is to summarize more recently published literature demonstrating the role of the gut microbiome in supporting normal arterial development and function and in modulating arterial dysfunction with aging in the absence of overt disease. The gut microbiome can be altered due to a variety of exposures, including physiological aging processes. We explore mechanisms by which the gut microbiome may contribute to age-related arterial dysfunction, with a focus on changes in various gut microbiome-related compounds in circulation. In addition, we discuss how modulating circulating levels of these compounds may be a viable therapeutic approach for improving artery function with aging. Finally, we identify and discuss various experimental considerations and research gaps/areas of future research.
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Affiliation(s)
- Abigail G Longtine
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, United States
| | - Nathan T Greenberg
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, United States
| | - Yara Bernaldo de Quirós
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, United States
- Instituto Universitario de Sanidad Animal y Seguridad Alimentaria, Universidad de las Palmas de Gran Canaria, Las Palmas, Spain
| | - Vienna E Brunt
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, United States
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
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Kaur H, Kaur G, Ali SA. Postbiotics Implication in the Microbiota-Host Intestinal Epithelial Cells Mutualism. Probiotics Antimicrob Proteins 2024; 16:443-458. [PMID: 36933160 DOI: 10.1007/s12602-023-10062-w] [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] [Accepted: 03/08/2023] [Indexed: 03/19/2023]
Abstract
To sustain host health and provide the microbial community with a nutrient-rich environment, the host and gut microbiota must interact with one another. These interactions between commensal bacterial and intestinal epithelial cells (IECs) serve as the first line of defense against gut microbiota in preserving intestinal homeostasis. In this microenvironment, the post-biotics and similar molecules such as p40 exert several beneficial effects through regulation of IECs. Importantly, post-biotics were discovered to be transactivators of the EGF receptor (EGFR) in IECs, inducing protective cellular responses and alleviating colitis. The transient exposure to post-biotics such as p40 during the neonatal period reprograms IECs by upregulation of a methyltransferase, Setd1β, leading to a sustained increase in TGF- β release for the expansion of regulatory T cells (Tregs) in the intestinal lamina propria and durable protection against colitis in adulthood. This crosstalk between the IECs and post-biotic secreted factors was not reviewed previously. Therefore, this review describes the role of probiotic-derived factors in the sustainability of intestinal health and improving gut homeostasis via certain signaling pathways. In the era of precision medicine and targeted therapies, more basic, preclinical, and clinical evidence is needed to clarify the efficacy of probiotics released as functional factors in maintaining intestinal health and preventing and treating disease.
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Affiliation(s)
- Harpreet Kaur
- Animal Biochemistry Division, ICAR-NDRI, Karnal, 132001, India
| | - Gurjeet Kaur
- Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, 2052, Australia
- Mark Wainwright Analytical Centre, Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, NSW, 2052, Australia
| | - Syed Azmal Ali
- Cell Biology and Proteomics Lab, Animal Biotechnology Center, ICAR-NDRI, Karnal, 132001, India.
- Division Proteomics of Stem Cells and Cancer, German Cancer Research Center, Heidelberg, 69120, Germany.
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Ma Y, Gou S, Zhu Z, Sun J, Shahbazi MA, Si T, Xu C, Ru J, Shi X, Reis RL, Kundu SC, Ke B, Nie G, Xiao B. Transient Mild Photothermia Improves Therapeutic Performance of Oral Nanomedicines with Enhanced Accumulation in the Colitis Mucosa. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2309516. [PMID: 38085512 DOI: 10.1002/adma.202309516] [Citation(s) in RCA: 19] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 11/29/2023] [Indexed: 01/12/2024]
Abstract
The treatment outcomes of oral medications against ulcerative colitis (UC) have long been restricted by low drug accumulation in the colitis mucosa and subsequent unsatisfactory therapeutic efficacy. Here, high-performance pluronic F127 (P127)-modified gold shell (AuS)-polymeric core nanotherapeutics loading with curcumin (CUR) is constructed. Under near-infrared irradiation, the resultant P127-AuS@CURs generate transient mild photothermia (TMP; ≈42 °C, 10 min), which facilitates their penetration through colonic mucus and favors multiple cellular processes, including cell internalization, lysosomal escape, and controlled CUR release. This strategy relieves intracellular oxidative stress, improves wound healing, and reduces immune responses by polarizing the proinflammatory M1-type macrophages to the anti-inflammatory M2-type. Upon oral administration of hydrogel-encapsulating P127-AuS@CURs plus intestinal intralumen TMP, their therapeutic effects against acute and chronic UC are demonstrated to be superior to those of a widely used clinical drug, dexamethasone. The treatment of P127-AuS@CURs (+ TMP) elevates the proportions of beneficial bacteria (e.g., Lactobacillus and Lachnospiraceae), whose metabolites can also mitigate colitis symptoms by regulating genes associated with antioxidation, anti-inflammation, and wound healing. Overall, the intestinal intralumen TMP offers a promising approach to enhance the therapeutic outcomes of noninvasive medicines against UC.
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Affiliation(s)
- Ya Ma
- State Key Laboratory of Resource Insects, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Chongqing, 400715, China
| | - Shuangquan Gou
- State Key Laboratory of Resource Insects, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Chongqing, 400715, China
| | - Zhenhua Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China
| | - Jianfeng Sun
- Botnar Research Centre, Nuffield Department of Orthopedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Headington, Oxford, OX3 7LD, UK
| | - Mohammad-Ali Shahbazi
- Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, Netherlands
| | - Tieyan Si
- School of Physics, Harbin Institute of Technology, Harbin, 150001, China
| | - Cheng Xu
- State Key Laboratory of Resource Insects, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Chongqing, 400715, China
| | - Jinlong Ru
- Chair of Prevention of Microbial Diseases, School of Life Sciences Weihenstephan, Technical University of Munich, 85354, Freising, Germany
| | - Xiaoxiao Shi
- State Key Laboratory of Resource Insects, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Chongqing, 400715, China
| | - Rui L Reis
- 3Bs Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Barco, Guimaraes, 4805-017, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga, Guimaraes, 4800-058, Portugal
| | - Subhas C Kundu
- 3Bs Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Barco, Guimaraes, 4805-017, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga, Guimaraes, 4800-058, Portugal
| | - Bowen Ke
- Department of Anesthesiology, Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Guangjun Nie
- CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China
| | - Bo Xiao
- State Key Laboratory of Resource Insects, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Chongqing, 400715, China
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Abujrais S, Ubhayasekera SJKA, Bergquist J. Analysis of tryptophan metabolites and related compounds in human and murine tissue: development and validation of a quantitative and semi-quantitative method using high resolution mass spectrometry. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2024; 16:1074-1082. [PMID: 38282545 DOI: 10.1039/d3ay01959d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2024]
Abstract
This study explores the metabolic differences between human and murine plasma in addition to differences between murine subcutaneous and visceral white adipose tissue. A quantitative and semi-quantitative targeted method was developed and validated for this purpose. The quantitative method includes tryptophan and its metabolites in addition to tyrosine, phenylalanine, taurine, B vitamins, neopterin, cystathionine and hypoxanthine. While the semi-quantitative method includes; 3-indoleacetic acid, 5-hydroxyindoleacetic acid, acetylcholine, asymmetric dimethylarginine, citrulline and methionine. Sample preparation was based on protein precipitation, while quantification was conducted using ultrahigh-performance liquid chromatography coupled to a quadrupole Orbitrap tandem mass spectrometer with electrospray ionization in the parallel reaction monitoring (PRM) mode. The low limit of quantification for all metabolites ranged from 1 to 200 ng mL-1. Matrix effects and recoveries for stable isotope labelled internal standards were evaluated, with most having a coefficient of variation (CV) of less than 15%. Results showed that a majority of the analytes passed both the intra- and interday precision and accuracy criteria. The comparative analysis of human and murine plasma metabolites reveals species-specific variations within the tryptophan metabolic pathway. Notably, murine plasma generally exhibits elevated concentrations of most compounds in this pathway, with the exceptions of kynurenine and quinolinic acid. Moreover, the investigation uncovers noteworthy metabolic disparities between murine visceral and subcutaneous white adipose tissues, with the subcutaneous tissue demonstrating significantly higher concentrations of tryptophan, phenylalanine, tyrosine, and serotonin. The findings also show that even a semi-quantitative method can provide comparable results to quantitative methods from other studies and be effective for assessing metabolites in a complex sample. Overall, this study provides a robust platform to compare human and murine metabolism, providing a valuable insight to future investigations.
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Affiliation(s)
- Sandy Abujrais
- Analytical Chemistry and Neurochemistry, Department of Chemistry - BMC, Uppsala University, Box 599, 75124, Uppsala, Sweden.
- The ME/CFS Collaborative Research Centre at Uppsala University, Sweden
| | - S J Kumari A Ubhayasekera
- Analytical Chemistry and Neurochemistry, Department of Chemistry - BMC, Uppsala University, Box 599, 75124, Uppsala, Sweden.
- The ME/CFS Collaborative Research Centre at Uppsala University, Sweden
| | - Jonas Bergquist
- Analytical Chemistry and Neurochemistry, Department of Chemistry - BMC, Uppsala University, Box 599, 75124, Uppsala, Sweden.
- The ME/CFS Collaborative Research Centre at Uppsala University, Sweden
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Ross FC, Mayer DE, Gupta A, Gill CIR, Del Rio D, Cryan JF, Lavelle A, Ross RP, Stanton C, Mayer EA. Existing and Future Strategies to Manipulate the Gut Microbiota With Diet as a Potential Adjuvant Treatment for Psychiatric Disorders. Biol Psychiatry 2024; 95:348-360. [PMID: 37918459 DOI: 10.1016/j.biopsych.2023.10.018] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 09/20/2023] [Accepted: 10/23/2023] [Indexed: 11/04/2023]
Abstract
Nutrition and diet quality play key roles in preventing and slowing cognitive decline and have been linked to multiple brain disorders. This review compiles available evidence from preclinical studies and clinical trials on the impact of nutrition and interventions regarding major psychiatric conditions and some neurological disorders. We emphasize the potential role of diet-related microbiome alterations in these effects and highlight commonalities between various brain disorders related to the microbiome. Despite numerous studies shedding light on these findings, there are still gaps in our understanding due to the limited availability of definitive human trial data firmly establishing a causal link between a specific diet and microbially mediated brain functions and symptoms. The positive impact of certain diets on the microbiome and cognitive function is frequently ascribed with the anti-inflammatory effects of certain microbial metabolites or a reduction of proinflammatory microbial products. We also critically review recent research on pro- and prebiotics and nondietary interventions, particularly fecal microbiota transplantation. The recent focus on diet in relation to brain disorders could lead to improved treatment outcomes with combined dietary, pharmacological, and behavioral interventions.
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Affiliation(s)
- Fiona C Ross
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Dylan E Mayer
- Institute of Human Nutrition, Columbia University, New York, New York
| | - Arpana Gupta
- Goodman-Luskin Microbiome Center, G. Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California
| | - Chris I R Gill
- Nutrition Innovation Centre for Food and Health, Ulster University, Coleraine, United Kingdom
| | - Daniele Del Rio
- Department of Food and Drugs, University of Parma, Parma, Italy
| | - John F Cryan
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Aonghus Lavelle
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - R Paul Ross
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Catherine Stanton
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Teagasc Moorepark Food Research Centre, Fermoy, Cork, Ireland.
| | - Emeran A Mayer
- Goodman-Luskin Microbiome Center, G. Oppenheimer Center for Neurobiology of Stress and Resilience, UCLA Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
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38
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Liu C, Xu Q, Dong S, Ding H, Li B, Zhang D, Liang Y, Li L, Liu Q, Cheng Y, Wu J, Zhu J, Zhong M, Cao Y, Zhang G. New mechanistic insights of anti-obesity by sleeve gastrectomy-altered gut microbiota and lipid metabolism. Front Endocrinol (Lausanne) 2024; 15:1338147. [PMID: 38375198 PMCID: PMC10875461 DOI: 10.3389/fendo.2024.1338147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 01/09/2024] [Indexed: 02/21/2024] Open
Abstract
Background The obesity epidemic has been on the rise due to changes in living standards and lifestyles. To combat this issue, sleeve gastrectomy (SG) has emerged as a prominent bariatric surgery technique, offering substantial weight reduction. Nevertheless, the mechanisms that underlie SG-related bodyweight loss are not fully understood. Methods In this study, we conducted a collection of preoperative and 3-month postoperative serum and fecal samples from patients who underwent laparoscopic SG at the First Affiliated Hospital of Shandong First Medical University (Jinan, China). Here, we took an unbiased approach of multi-omics to investigate the role of SG-altered gut microbiota in anti-obesity of these patients. Non-target metabolome sequencing was performed using the fecal and serum samples. Results Our data show that SG markedly increased microbiota diversity and Rikenellaceae, Alistipes, Parabacteroides, Bactreoidales, and Enterobacteraies robustly increased. These compositional changes were positively correlated with lipid metabolites, including sphingolipids, glycerophospholipids, and unsaturated fatty acids. Increases of Rikenellaceae, Alistipes, and Parabacteroide were reversely correlated with body mass index (BMI). Conclusion In conclusion, our findings provide evidence that SG induces significant alterations in the abundances of Rikenellaceae, Alistipes, Parabacteroides, and Bacteroidales, as well as changes in lipid metabolism-related metabolites. Importantly, these changes were found to be closely linked to the alleviation of obesity. On the basis of these findings, we have identified a number of microbiotas that could be potential targets for treatment of obesity.
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Affiliation(s)
- Chuxuan Liu
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Qian Xu
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Shuohui Dong
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Huanxin Ding
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Bingjun Li
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Dexu Zhang
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Yongjuan Liang
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Linchuan Li
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Qiaoran Liu
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Yugang Cheng
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Jing Wu
- Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Jiankang Zhu
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Mingwei Zhong
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Yihai Cao
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden
| | - Guangyong Zhang
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
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Liikonen V, Gomez-Gallego C, Kolehmainen M. The effects of whole grain cereals on tryptophan metabolism and intestinal barrier function: underlying factors of health impact. Proc Nutr Soc 2024; 83:42-54. [PMID: 37843435 DOI: 10.1017/s0029665123003671] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2023]
Abstract
This review aims to investigate the relationship between the health impact of whole grains mediated via the interaction with intestinal microbiota and intestinal barrier function with special interest on tryptophan metabolism, focusing on the role of the intestinal microbiota and their impact on barrier function. Consuming various types of whole grains can lead to the growth of different microbiota species, which in turn leads to the production of diverse metabolites, including those derived from tryptophan metabolism, although the impact of whole grains on intestinal microbiota composition results remains inconclusive and vary among different studies. Whole grains can exert an influence on tryptophan metabolism through interactions with the intestinal microbiota, and the presence of fibre in whole grains plays a notable role in establishing this connection. The impact of whole grains on intestinal barrier function is closely related to their effects on the composition and activity of intestinal microbiota, and SCFA and tryptophan metabolites serve as potential links connecting whole grains, intestinal microbiota and the intestinal barrier function. Tryptophan metabolites affect various aspects of the intestinal barrier, such as immune balance, mucus and microbial barrier, tight junction complexes and the differentiation and proliferation of epithelial cells. Despite the encouraging discoveries in this area of research, the evidence regarding the effects of whole grain consumption on intestine-related activity remains limited. Hence, we can conclude that we are just starting to understand the actual complexity of the intestinal factors mediating in part the health impacts of whole grain cereals.
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Affiliation(s)
- Vilma Liikonen
- Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O.Box 1627, 70211 Kuopio, Finland
| | - Carlos Gomez-Gallego
- Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O.Box 1627, 70211 Kuopio, Finland
| | - Marjukka Kolehmainen
- Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O.Box 1627, 70211 Kuopio, Finland
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Niu C, Lv W, Zhu X, Dong Z, Yuan K, Jin Q, Zhang P, Li P, Mao M, Dong T, Chen Z, Luo J, Hou L, Zhang C, Hao K, Chen S, Huang Z. Intestinal Translocation of Live Porphyromonas gingivalis Drives Insulin Resistance. J Dent Res 2024; 103:197-207. [PMID: 38185909 DOI: 10.1177/00220345231214195] [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] [Indexed: 01/09/2024] Open
Abstract
Periodontitis has been emphasized as a risk factor of insulin resistance-related systemic diseases. Accumulating evidence has suggested a possible "oral-gut axis" linking oral infection and extraoral diseases, but it remains unclear whether periodontal pathogens can survive the barriers of the digestive tract and how they play their pathogenic roles. The present study established a periodontitis mouse model through oral ligature plus Porphyromonas gingivalis inoculation and demonstrated that periodontitis aggravated diet-induced obesity and insulin resistance, while also causing P. gingivalis enrichment in the intestine. Metabolic labeling strategy validated that P. gingivalis could translocate to the gastrointestinal tract in a viable state. Oral administration of living P. gingivalis elicited insulin resistance, while administration of pasteurized P. gingivalis had no such effect. Combination analysis of metagenome sequencing and nontargeted metabolomics suggested that the tryptophan metabolism pathway, specifically indole and its derivatives, was involved in the pathogenesis of insulin resistance caused by oral administration of living P. gingivalis. Moreover, liquid chromatography-high-resolution mass spectrometry analysis confirmed that the aryl hydrocarbon receptor (AhR) ligands, mainly indole acetic acid, tryptamine, and indole-3-aldehyde, were reduced in diet-induced obese mice with periodontitis, leading to inactivation of AhR signaling. Supplementation with Ficz (6-formylindolo (3,2-b) carbazole), an AhR agonist, alleviated periodontitis-associated insulin resistance, in which the restoration of gut barrier function might play an important role. Collectively, these findings reveal that the oral-gut translocation of viable P. gingivalis works as a fuel linking periodontitis and insulin resistance, in which reduction of AhR ligands and inactivation of AhR signaling are involved. This study provides novel insight into the role of the oral-gut axis in the pathogenesis of periodontitis-associated comorbidities.
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Affiliation(s)
- C Niu
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, P. R. China
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, P. R. China
- Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China
| | - W Lv
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, P. R. China
| | - X Zhu
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, P. R. China
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, P. R. China
- Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China
| | - Z Dong
- Department of Oral Implantology, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, P. R. China
| | - K Yuan
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, P. R. China
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, P. R. China
- Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China
| | - Q Jin
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, P. R. China
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, P. R. China
- Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China
| | - P Zhang
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, P. R. China
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, P. R. China
- Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China
| | - P Li
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, P. R. China
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, P. R. China
- Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China
| | - M Mao
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, P. R. China
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, P. R. China
- Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China
| | - T Dong
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, P. R. China
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, P. R. China
- Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China
| | - Z Chen
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, P. R. China
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, P. R. China
- Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China
| | - J Luo
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, P. R. China
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, P. R. China
- Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China
| | - L Hou
- Department of Nursing, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - C Zhang
- Department of Oral Implantology, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, P. R. China
| | - K Hao
- Department of Oral Implantology, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, P. R. China
| | - S Chen
- Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, P. R. China
- Department of Oral Implantology, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, P. R. China
| | - Z Huang
- Department of Endodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
- College of Stomatology, Shanghai Jiao Tong University, Shanghai, P. R. China
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, P. R. China
- Shanghai Key Laboratory of Stomatology, Shanghai, P. R. China
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Huang Y, Chen L, Liu F, Xiong X, Ouyang Y, Deng Y. Tryptophan, an important link in regulating the complex network of skin immunology response in atopic dermatitis. Front Immunol 2024; 14:1300378. [PMID: 38318507 PMCID: PMC10839033 DOI: 10.3389/fimmu.2023.1300378] [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: 10/05/2023] [Accepted: 12/31/2023] [Indexed: 02/07/2024] Open
Abstract
Atopic dermatitis (AD) is a common chronic relapsing inflammatory skin disease, of which the pathogenesis is a complex interplay between genetics and environment. Although the exact mechanisms of the disease pathogenesis remain unclear, the immune dysregulation primarily involving the Th2 inflammatory pathway and accompanied with an imbalance of multiple immune cells is considered as one of the critical etiologies of AD. Tryptophan metabolism has long been firmly established as a key regulator of immune cells and then affect the occurrence and development of many immune and inflammatory diseases. But the relationship between tryptophan metabolism and the pathogenesis of AD has not been profoundly discussed throughout the literatures. Therefore, this review is conducted to discuss the relationship between tryptophan metabolism and the complex network of skin inflammatory response in AD, which is important to elucidate its complex pathophysiological mechanisms, and then lead to the development of new therapeutic strategies and drugs for the treatment of this frequently relapsing disease.
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Affiliation(s)
- Yaxin Huang
- Department of Dermatology & Sexually Transmitted Disease (STD), the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Lingna Chen
- Department of Dermatology & Sexually Transmitted Disease (STD), the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Fuming Liu
- Department of Dermatology & Sexually Transmitted Disease (STD), the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Xia Xiong
- Department of Dermatology & Sexually Transmitted Disease (STD), the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Yongliang Ouyang
- Department of Dermatology & Sexually Transmitted Disease (STD), Chengdu First People’s Hospital, Chengdu, Sichuan, China
- Health Management Center, Luzhou People’s Hospital, Luzhou, China
| | - Yongqiong Deng
- Department of Dermatology & Sexually Transmitted Disease (STD), the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
- Department of Dermatology & Sexually Transmitted Disease (STD), Chengdu First People’s Hospital, Chengdu, Sichuan, China
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Saberi-Karimian M, Safarian-Bana H, Fazeli M, Tabatabaeizadeh SA, Ferns GA, Ghayour-Mobarhan M. Gut microbiota and metabolic syndrome: What's new? METABOLIC SYNDROME 2024:527-541. [DOI: 10.1016/b978-0-323-85732-1.00050-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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43
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Taleb S. Are tryptophan metabolites new predictive biomarkers for CVD? Atherosclerosis 2023; 387:117385. [PMID: 38016872 DOI: 10.1016/j.atherosclerosis.2023.117385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 11/08/2023] [Indexed: 11/30/2023]
Affiliation(s)
- Soraya Taleb
- Université Paris Cité, Inserm, PARCC, F-75015, Paris, France.
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44
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Hu Y, Li J, Wang B, Zhu L, Li Y, Ivey KL, Lee KH, Eliassen AH, Chan A, Huttenhower C, Hu FB, Qi Q, Rimm EB, Sun Q. Interplay between diet, circulating indolepropionate concentrations and cardiometabolic health in US populations. Gut 2023; 72:2260-2271. [PMID: 37739776 PMCID: PMC10841831 DOI: 10.1136/gutjnl-2023-330410] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 08/23/2023] [Indexed: 09/24/2023]
Abstract
OBJECTIVES To identify indolepropionate (IPA)-predicting gut microbiota species, investigate potential diet-microbiota interactions, and examine the prospective associations of circulating IPA concentrations with type 2 diabetes (T2D) and coronary heart disease (CHD) risk in free-living individuals. DESIGN We included 287 men from the Men's Lifestyle Validation Study, a substudy of the Health Professionals Follow-Up Study (HPFS), who provided up to two pairs of faecal samples and two blood samples. Diet was assessed using 7-day diet records. Associations between plasma concentrations of tryptophan metabolites and T2D CHD risk were examined in 13 032 participants from Nurses' Health Study (NHS), NHSII and HPFS. RESULTS We identified 17 microbial species whose abundance was significantly associated with plasma IPA concentrations. A significant association between higher tryptophan intake and higher IPA concentrations was only observed among men who had higher fibre intake and a higher microbial species score consisting of the 17 species (p-interaction<0.01). Dietary and plasma concentrations of tryptophan and most kynurenine pathway metabolites were positively associated with T2D risk (HRQ5 vs Q1 ranged from 1.17 to 1.46) while a significant inverse association was found for IPA (HRQ5 vs Q1 (95% CI) 0.70 (0.56 to 0.88)). No associations were found in CHD for any plasma tryptophan metabolites. CONCLUSIONS Specific microbial species and dietary fibre jointly predicted significantly higher circulating IPA concentrations at higher tryptophan intake. Dietary and plasma tryptophan, as well as its kynurenine pathway metabolites, demonstrated divergent associations from those for IPA, which was significantly predictive of lower risk of T2D.
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Affiliation(s)
- Yang Hu
- Department of Nutrition, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
| | - Jun Li
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Biqi Wang
- Department of Medicine, UMASS Medical School, Worcester, Massachusetts, USA
| | - Lu Zhu
- Department of Nutrition, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
| | - Yanping Li
- Department of Nutrition, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
| | - Kerry L Ivey
- Department of Nutrition, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
| | - Kyu Ha Lee
- Department of Nutrition, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
- Department of Epidemiology, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
- Department of Biostatistics, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
| | - A Heather Eliassen
- Department of Epidemiology, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Andrew Chan
- Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
- Immunology and Infectious Diseases, Harvard University T. H. Chan School of Public Health, Boston, Boston, Massachusetts, USA
| | - Curtis Huttenhower
- Department of Biostatistics, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
- Immunology and Infectious Diseases, Harvard University T. H. Chan School of Public Health, Boston, Boston, Massachusetts, USA
- Eli and Edythe L. Broad Institute of Harvard and MIT, Flinders University College of Nursing and Health Sciences, Cambridge, MA, USA
| | - Frank B Hu
- Department of Nutrition, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
- Department of Epidemiology, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Qibin Qi
- Department of Epidemiology and Population Health, Yeshiva University Albert Einstein College of Medicine, Bronx, New York, USA
| | - Eric B Rimm
- Department of Nutrition, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
- Department of Epidemiology, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Qi Sun
- Department of Nutrition, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
- Department of Epidemiology, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
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45
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Turpin T, Thouvenot K, Gonthier MP. Adipokines and Bacterial Metabolites: A Pivotal Molecular Bridge Linking Obesity and Gut Microbiota Dysbiosis to Target. Biomolecules 2023; 13:1692. [PMID: 38136564 PMCID: PMC10742113 DOI: 10.3390/biom13121692] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 11/13/2023] [Accepted: 11/19/2023] [Indexed: 12/24/2023] Open
Abstract
Adipokines are essential mediators produced by adipose tissue and exert multiple biological functions. In particular, adiponectin, leptin, resistin, IL-6, MCP-1 and PAI-1 play specific roles in the crosstalk between adipose tissue and other organs involved in metabolic, immune and vascular health. During obesity, adipokine imbalance occurs and leads to a low-grade pro-inflammatory status, promoting insulin resistance-related diabetes and its vascular complications. A causal link between obesity and gut microbiota dysbiosis has been demonstrated. The deregulation of gut bacteria communities characterizing this dysbiosis influences the synthesis of bacterial substances including lipopolysaccharides and specific metabolites, generated via the degradation of dietary components, such as short-chain fatty acids, trimethylamine metabolized into trimethylamine-oxide in the liver and indole derivatives. Emerging evidence suggests that these bacterial metabolites modulate signaling pathways involved in adipokine production and action. This review summarizes the current knowledge about the molecular links between gut bacteria-derived metabolites and adipokine imbalance in obesity, and emphasizes their roles in key pathological mechanisms related to oxidative stress, inflammation, insulin resistance and vascular disorder. Given this interaction between adipokines and bacterial metabolites, the review highlights their relevance (i) as complementary clinical biomarkers to better explore the metabolic, inflammatory and vascular complications during obesity and gut microbiota dysbiosis, and (ii) as targets for new antioxidant, anti-inflammatory and prebiotic triple action strategies.
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Affiliation(s)
| | | | - Marie-Paule Gonthier
- Université de La Réunion, INSERM, UMR 1188 Diabète Athérothrombose Thérapies Réunion Océan Indien (DéTROI), 97410 Saint-Pierre, La Réunion, France; (T.T.); (K.T.)
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46
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Hou Y, Li J, Ying S. Tryptophan Metabolism and Gut Microbiota: A Novel Regulatory Axis Integrating the Microbiome, Immunity, and Cancer. Metabolites 2023; 13:1166. [PMID: 37999261 PMCID: PMC10673612 DOI: 10.3390/metabo13111166] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 11/16/2023] [Accepted: 11/18/2023] [Indexed: 11/25/2023] Open
Abstract
Tryptophan metabolism and gut microbiota form an integrated regulatory axis that impacts immunity, metabolism, and cancer. This review consolidated current knowledge on the bidirectional interactions between microbial tryptophan processing and the host. We focused on how the gut microbiome controls tryptophan breakdown via the indole, kynurenine, and serotonin pathways. Dysbiosis of the gut microbiota induces disruptions in tryptophan catabolism which contribute to disorders like inflammatory conditions, neuropsychiatric diseases, metabolic syndromes, and cancer. These disruptions affect immune homeostasis, neurotransmission, and gut-brain communication. Elucidating the mechanisms of microbial tryptophan modulation could enable novel therapeutic approaches like psychobiotics and microbiome-targeted dietary interventions. Overall, further research on the microbiota-tryptophan axis has the potential to revolutionize personalized diagnostics and treatments for improving human health.
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Affiliation(s)
- Yingjian Hou
- Target Discovery Center, China Pharmaceutical University, Nanjing 211198, China;
| | - Jing Li
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha 410000, China
| | - Shuhuan Ying
- School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
- Shanghai Bocimed Pharmaceutical Research Co., Ltd., Shanghai 201203, China
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47
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Hui Y, Zhao J, Yu Z, Wang Y, Qin Y, Zhang Y, Xing Y, Han M, Wang A, Guo S, Yuan J, Zhao Y, Ning X, Sun S. The Role of Tryptophan Metabolism in the Occurrence and Progression of Acute and Chronic Kidney Diseases. Mol Nutr Food Res 2023; 67:e2300218. [PMID: 37691068 DOI: 10.1002/mnfr.202300218] [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: 04/10/2023] [Revised: 07/10/2023] [Indexed: 09/12/2023]
Abstract
Acute kidney injury (AKI) and chronic kidney disease (CKD) are common kidney diseases in clinics with high morbidity and mortality, but their pathogenesis is intricate. Tryptophan (Trp) is a fundamental amino acid for humans, and its metabolism produces various bioactive substances involved in the pathophysiology of AKI and CKD. Metabolomic studies manifest that Trp metabolites like kynurenine (KYN), 5-hydroxyindoleacetic acid (5-HIAA), and indoxyl sulfate (IS) increase in AKI or CKD and act as biomarkers that facilitate the early identification of diseases. Meanwhile, KYN and IS act as ligands to exacerbate kidney damage by activating aryl hydrocarbon receptor (AhR) signal transduction. The reduction of renal function can cause the accumulation of Trp metabolites which in turn accelerate the progression of AKI or CKD. Besides, gut dysbiosis induces the expansion of Enterobacteriaceae family to produce excessive IS, which cannot be excreted due to the deterioration of renal function. The application of Trp metabolism as a target in AKI and CKD will also be elaborated. Thus, this study aims to elucidate Trp metabolism in the development of AKI and CKD, and explores the relative treatment strategies by targeting Trp from the perspective of metabolomics to provide a reference for their diagnosis and prevention.
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Affiliation(s)
- Yueqing Hui
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
| | - Jin Zhao
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
| | - Zixian Yu
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
| | - Yuwei Wang
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
- Department of Postgraduate Student, Xi'an Medical University, Xi'an, Shaanxi, 710021, China
| | - Yunlong Qin
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
- Department of Nephrology, 980th Hospital of PLA Joint Logistical Support Force (Bethune International Peace Hospital), Shijiazhuang, Hebei, 050082, China
| | - Yumeng Zhang
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
- Department of Postgraduate Student, Xi'an Medical University, Xi'an, Shaanxi, 710021, China
| | - Yan Xing
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
| | - Mei Han
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
- Department of Postgraduate Student, Xi'an Medical University, Xi'an, Shaanxi, 710021, China
| | - Anjing Wang
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
- Department of Postgraduate Student, Xi'an Medical University, Xi'an, Shaanxi, 710021, China
| | - Shuxian Guo
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
| | - Jinguo Yuan
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
| | - Yueru Zhao
- School of Clinical Medicine, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China
| | - Xiaoxuan Ning
- Department of Geriatric, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
| | - Shiren Sun
- Department of Nephrology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
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48
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Fang M, Lei Z, Ruilin M, Jing W, Leqiang D. High temperature stress induced oxidative stress, gut inflammation and disordered metabolome and microbiome in tsinling lenok trout. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2023; 266:115607. [PMID: 37862746 DOI: 10.1016/j.ecoenv.2023.115607] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 10/09/2023] [Accepted: 10/14/2023] [Indexed: 10/22/2023]
Abstract
Tsinling lenok trout (Brachymystax lenok tsinlingensis Li) is a species of cold-water salmon that faces serious challenges due to global warming. High temperature stress has been found to damage the gut integrity of cold-water fish, impacting their growth and immunity. However, limited research exists on the causal relationship between gut microbial disturbance and metabolic dysfunction in cold-water fish induced by high temperature stress. To address this gap, we conducted a study to investigate the effects of high temperature stress (24 °C) on the gut tissue structure, antioxidant capacity, gut microorganisms, and metabolome reactions of tsinling lenok trout. Our analysis using 16 S rDNA gene sequencing revealed significant changes in the gut microbial composition and metabolic profile. Specifically, the abundance of Firmicutes and Gemmatimonadetes decreased significantly with increasing temperature, while the abundance of Bacteroidetes increased significantly. Metabolic analysis revealed a significant decrease in the abundance of glutathione, which is synthesized from glutamate and glycine, under high temperature stress. Additionally, there was a notable reduction in the levels of adenosine, inosine, xanthine, guanosine, and deoxyguanosine, which are essential for DNA/RNA synthesis. Conversely, there was a significant increase in the abundance of D-glucose 6 P. Furthermore, high temperature stress adversely affects intestinal structure and barrier function. Our findings provide valuable insights into the mechanism of high temperature stress in cold-water fish and serve as a foundation for future research aimed at mitigating the decline in production performance caused by such stress.
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Affiliation(s)
- M Fang
- Key Laboratory of Resource Utilization of Agricultural Solid Waste in Gansu Province, Tianshui Normal University, South Xihe Road, Qinzhou, Tianshui 741000, Gansu, PR China.
| | - Z Lei
- Key Laboratory of Resource Utilization of Agricultural Solid Waste in Gansu Province, Tianshui Normal University, South Xihe Road, Qinzhou, Tianshui 741000, Gansu, PR China
| | - M Ruilin
- Key Laboratory of Resource Utilization of Agricultural Solid Waste in Gansu Province, Tianshui Normal University, South Xihe Road, Qinzhou, Tianshui 741000, Gansu, PR China
| | - W Jing
- Key Laboratory of Resource Utilization of Agricultural Solid Waste in Gansu Province, Tianshui Normal University, South Xihe Road, Qinzhou, Tianshui 741000, Gansu, PR China
| | - D Leqiang
- Key Laboratory of Resource Utilization of Agricultural Solid Waste in Gansu Province, Tianshui Normal University, South Xihe Road, Qinzhou, Tianshui 741000, Gansu, PR China
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Nong Y, Zhang C, Guo Y, Qin Y, Zhong X, Feng L, Pan Z, Deng L, Guo H, Su Z. Quality control for a traditional Chinese medicine, Millettia speciosa Champ, using ultra-high-performance liquid chromatography fingerprint, serum pharmacochemistry and network pharmacology. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2023; 15:5166-5180. [PMID: 37753596 DOI: 10.1039/d3ay01051a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/28/2023]
Abstract
Millettia speciosa (M. speciosa) Champ (MSC) is a healthy food type with medicinal and edible homology, which is now considered a clinically significant anti-rheumatoid arthritis medicine. However, there is currently no standardized or generally accepted research strategy by which we can assess M. speciosa. Thus, it is essential to develop novel theories, strategies and evaluation methods for the scientific quality control of M. speciosa. Herein, our use ultra-high-performance liquid chromatography (UPLC)-MS/MS analysis identified 12 common bioactive components absorbed into MSC serum. Next, network pharmacology analysis exhibited that 5 MSC components may be those active components in treating rheumatoid arthritis and may be considered potential quality markers. These 5 components were then quantified using a fast UPLC approach, based on the quality marker of measurability, showing that lenticin can be regarded as the MSC quality marker. The cumulative study findings, based on systematic assessment of chemical composition both in vivo and in vitro, and the potential efficacy of M. speciosa, provide a novel approach for M. speciosa quality control.
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Affiliation(s)
- Yunyuan Nong
- Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, 530021, China.
| | - Chi Zhang
- Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, 530021, China.
| | - Yue Guo
- Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, 530021, China.
- Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning, Guangxi, 530022, China
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China
| | - Yuelian Qin
- Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, 530021, China.
| | - Xinyu Zhong
- Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, 530021, China.
| | - Linlin Feng
- Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, 530021, China.
| | - Ziping Pan
- Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, 530021, China.
| | - Lijun Deng
- Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, 530021, China.
| | - Hongwei Guo
- Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, 530021, China.
- Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Zhiheng Su
- Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, 530021, China.
- Guangxi Beibu Gulf Marine Biomedicine Precision Development and High-value Utilization Engineering Research Center, Guangxi Medical University, Nanning, Guangxi, 530021, China
- Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Guangxi Medical University, Nanning, Guangxi, 530021, China
- Guangxi Health Commission Key Laboratory of Basic Research on Antigeriatric Drugs, Guangxi Medical University, Nanning, Guangxi, 530021, China
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50
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Poto R, Laniro G, de Paulis A, Spadaro G, Marone G, Gasbarrini A, Varricchi G. Is there a role for microbiome-based approach in common variable immunodeficiency? Clin Exp Med 2023; 23:1981-1998. [PMID: 36737487 PMCID: PMC9897624 DOI: 10.1007/s10238-023-01006-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Accepted: 01/18/2023] [Indexed: 02/05/2023]
Abstract
Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low levels of serum immunoglobulins and increased susceptibility to infections, autoimmune disorders and cancer. CVID embraces a plethora of heterogeneous manifestations linked to complex immune dysregulation. While CVID is thought to be due to genetic defects, the exact cause of this immune disorder is unknown in the large majority of cases. Compelling evidences support a linkage between the gut microbiome and the CVID pathogenesis, therefore a potential for microbiome-based treatments to be a therapeutic pathway for this disorder. Here we discuss the potential of treating CVID patients by developing a gut microbiome-based personalized approach, including diet, prebiotics, probiotics, postbiotics and fecal microbiota transplantation. We also highlight the need for a better understanding of microbiota-host interactions in CVID patients to prime the development of improved preventive strategies and specific therapeutic targets.
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Affiliation(s)
- Remo Poto
- Department of Translational Medical Sciences, University of Naples Federico II, 80131, Naples, Italy
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131, Naples, Italy
- World Allergy Organization (WAO), Center of Excellence, 80131, Naples, Italy
- Department of Oncology and Molecular Medicine, Istituto Superiore Di Sanità (ISS), Rome, Italy
| | - Gianluca Laniro
- Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
- Department of Translational Medicine and Surgery, Catholic University of Rome, Rome, Italy
| | - Amato de Paulis
- Department of Translational Medical Sciences, University of Naples Federico II, 80131, Naples, Italy
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131, Naples, Italy
- World Allergy Organization (WAO), Center of Excellence, 80131, Naples, Italy
| | - Giuseppe Spadaro
- Department of Translational Medical Sciences, University of Naples Federico II, 80131, Naples, Italy
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131, Naples, Italy
- World Allergy Organization (WAO), Center of Excellence, 80131, Naples, Italy
| | - Gianni Marone
- Department of Translational Medical Sciences, University of Naples Federico II, 80131, Naples, Italy
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131, Naples, Italy
- World Allergy Organization (WAO), Center of Excellence, 80131, Naples, Italy
- Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131, Naples, Italy
| | - Antonio Gasbarrini
- Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
- Department of Translational Medicine and Surgery, Catholic University of Rome, Rome, Italy
| | - Gilda Varricchi
- Department of Translational Medical Sciences, University of Naples Federico II, 80131, Naples, Italy.
- Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131, Naples, Italy.
- World Allergy Organization (WAO), Center of Excellence, 80131, Naples, Italy.
- Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, 80131, Naples, Italy.
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