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Fiala O, Hanzlova M, Borska L, Fiala Z, Holmannova D. Beyond physical exhaustion: Understanding overtraining syndrome through the lens of molecular mechanisms and clinical manifestation. SPORTS MEDICINE AND HEALTH SCIENCE 2025; 7:237-248. [PMID: 40264836 PMCID: PMC12010411 DOI: 10.1016/j.smhs.2025.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 01/22/2025] [Accepted: 01/28/2025] [Indexed: 04/24/2025] Open
Abstract
Background Overtraining Syndrome (OTS) is a condition resulting from excessive physical activity without adequate recovery, predominantly affecting elite athletes and military personnel. While overreaching can be a temporary state, non-functional overreaching may progress to chronic OTS. This review explores various hypotheses regarding the pathogenesis of OTS, including glycogen depletion, dysregulated cytokine response, oxidative stress, and alterations in the autonomic nervous system function. It also highlights the systemic impact of OTS on multiple organ systems, immune function, and overall health, linking the condition to chronic inflammation and an increased disease susceptibility. Additionally, it addresses the role of the gut microbiome in health modulation through physical activity. Methods This narrative review was conducted through a structured search of peer-reviewed journal articles in databases such as PubMed, Web of Science, and Google Scholar, focusing on studies involving human participants and published in English. Results OTS has systemic effects on multiple organ systems, immune function, and overall health, leading to chronic inflammation and increased disease susceptibility. Athletes with OTS exhibit higher morbidity rates, influenced by factors such as sleep deprivation and stress. The review also emphasizes the role of the gut microbiome as a significant modulator of health through physical activity. Conclusion Balanced training and recovery are crucial for preventing OTS and maintaining optimal health and quality of life in physically active individuals. Understanding the complex pathophysiology of OTS is essential for developing effective prevention and treatment strategies.
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Affiliation(s)
- Ondrej Fiala
- Department of Preventive Medicine, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, 500 03, Hradec Kralove, Czech Republic
| | - Michaela Hanzlova
- Department of Preventive Medicine, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, 500 03, Hradec Kralove, Czech Republic
| | - Lenka Borska
- Department of Preventive Medicine, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, 500 03, Hradec Kralove, Czech Republic
| | - Zdenek Fiala
- Department of Preventive Medicine, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, 500 03, Hradec Kralove, Czech Republic
| | - Drahomira Holmannova
- Department of Preventive Medicine, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, 500 03, Hradec Kralove, Czech Republic
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Budin M, Sandiford NA, Gehrke T, Citak M. Body mass index matters: morbid obese patients have different microorganism profiles in the setting of periprosthetic hip joint infections. INTERNATIONAL ORTHOPAEDICS 2025; 49:1309-1317. [PMID: 40183945 DOI: 10.1007/s00264-025-06513-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Accepted: 03/20/2025] [Indexed: 04/05/2025]
Abstract
PURPOSE This study investigated the relationship between BMI and microorganism profiles, with a particular focus on gut microorganisms in patients with PJI following total hip arthroplasty (THA). It also explored comorbidities, that may contribute to these variations. METHODS This study included all patients treated at our institution for a PJI of a THA between 1996 and 2021. Patients were categorized into four distinct BMI groups: <30; 30-34.9; 35-39.9; ≥ 40. Bivariate and logistic regression analysis were conducted, with presentation of odds ratio (OR) and 95% confidence interval (CI). RESULTS A total of 3645 hip PJI cases were recruited for the final analysis. Patients with a BMI ≥ 40 had approximately a ten fold higher risk for Streptococcus dysgalactiae (p < 0.001; OR = 9.92; 95% CI 3.87-25.44) and a seven fold higher risk for Proteus mirabilis (p < 0.001; OR = 7.43; 95% CI 3.13-17.67) and Klebsiella pneumoniae (p < 0.001; OR = 6.9; 95% CI 2.47-19.31). Furthermore, polymicrobial infections (p < 0.001; OR = 2.17; 95% CI 1.50-3.15) were found to be significantly more prevalent in patients with a BMI ≥ 40. CONCLUSION Obese patients (BMI ≥ 30) displayed a distinct microorganism profile in hip PJIs, mainly dominated by Firmicutes and Proteobacteria. Comorbidities such as diabetes, hypertension, and hyperlipidaemia may contribute to a leaky gut syndrome, increasing PJI risk caused by gut microorganisms. Optimizing comorbidities may help reduce the risk of hip PJI. Further research is needed to clarify the relationship between obesity, gut microbiome alterations and hip PJI development.
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Mekadim C, Mrazek J, Fliegerová KO, Sechovcová H, Mahayri TM, Jarošíková R, Husáková J, Wosková V, Tůma P, Polák J, Sojáková D, Němcová A, Dubský M, Fejfarová V. The effect of the administration form of antibiotic therapy on the gut microbiome in patients with infected diabetic foot ulcers - DFIATIM trial. BMC Microbiol 2025; 25:339. [PMID: 40437354 PMCID: PMC12117690 DOI: 10.1186/s12866-025-04041-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Accepted: 05/12/2025] [Indexed: 06/01/2025] Open
Abstract
BACKGROUND Diabetic foot infections (DFIs) contribute to the global disability burden. Beta-lactams are the most commonly used antibiotics for treating DFIs. However, the use of antibiotics may lead to disruption of the healthy balance of the gut microbiota, causing dysbiosis. METHODS Patients with infected diabetic foot ulcers (iDFUs) were treated with two kinds of beta-lactams (amoxicillin/clavulanic acid or ceftazidime) according to microbial sensitivity of causative agents via bolus or continuous administration modes. Changes in the gut microbiome of patients were analyzed. Diabetic patients without iDFUs were used as a control group. 16 S ribosomal RNA gene amplicon sequencing was performed on stool samples collected from participants. RESULTS Alpha diversity and beta diversity of gut microbiota of treated patients did not show significant differences between bolus and continuous modes. However, significant differences were observed between gut microbiota diversity of treated patients and control group. PCoA plots showed individualized responses of the patient's gut microbiota to antibiotics at different times using both administration forms associated with the pre-treatment state of microbiota composition. Enterococcus, Sellimonas, and Lachnoclostridium were the common bacterial markers differentially abundant in the gut microbiota of antibiotic-treated patients with iDFUs while Roseburia, Dorea, and Monoglobus were mainly abundant in the gut microbiota of patients without iDFUs. Predicted pathways like "Transporters", "ABC transporters" and "Phosphotranspherase system (PTS)" were upregulated in the gut microbiome of patients treated with bolus regime which may lead to increased intestinal barrier permeability. CONCLUSION The present study reported alterations in gut microbiota composition and functionality and provided the bacterial markers as well as potential metabolic signatures associated with each administration mode in patients with iDFUs, which may be used as a reference set for future studies of the effect of antibiotics administration on the gut microbiome of patients with iDFUs. This study shed light on the importance of understanding the effect of antibiotic administration form on gut microbiome in patients with iDFUs. TRIAL REGISTRATION The DFIATIM Clinical Trial (Full title: "Rationalisation of ATB therapy in diabetic foot infection and its impact on the intestinal microbiota") is submitted to the European Union Clinical Trials Database under the EudraCT Number: 2019-001997-27. The date of registration is July 17th, 2020.
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Affiliation(s)
- Chahrazed Mekadim
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, v.v.i, Videnska 1083, Prague, 142 00, Czech Republic.
| | - Jakub Mrazek
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, v.v.i, Videnska 1083, Prague, 142 00, Czech Republic
| | - Kateřina Olša Fliegerová
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, v.v.i, Videnska 1083, Prague, 142 00, Czech Republic
| | - Hana Sechovcová
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, v.v.i, Videnska 1083, Prague, 142 00, Czech Republic
| | - Tiziana Maria Mahayri
- Laboratory of Anaerobic Microbiology, Institute of Animal Physiology and Genetics, Czech Academy of Sciences, v.v.i, Videnska 1083, Prague, 142 00, Czech Republic
| | - Radka Jarošíková
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Department of Internal Medicine, Second Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Jitka Husáková
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Veronika Wosková
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Petr Tůma
- Department of Hygiene, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Jan Polák
- Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Dominika Sojáková
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Andrea Němcová
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Michal Dubský
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Vladimíra Fejfarová
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Department of Internal Medicine, Second Faculty of Medicine, Charles University, Prague, Czech Republic
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Zhou S, Hua S, Chen X, Ni M, Liu J, Wang Y, Wu W, Ding A, Qin Z, Yang X, Chen X, Zhu B, Wu H. ZeXieYin formula alleviates atherosclerosis by regulating SBAs levels through the FXR/FGF15 pathway and restoring intestinal barrier integrity. Chin Med 2025; 20:68. [PMID: 40414923 PMCID: PMC12103746 DOI: 10.1186/s13020-025-01116-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 04/22/2025] [Indexed: 05/27/2025] Open
Abstract
BACKGROUND Atherosclerosis (AS) is the most common cardiovascular disease (CVD), despite an overall declining incidence, AS remains a leading cause of death worldwide. The ZeXieYin formula (ZXYF), one of the thirteen formulas recorded in HuangDiNeiJin, a classical book of Traditional Chinese Medicine (TCM), has previously demonstrated efficacy in reducing blood lipids and combating AS. However, the precise mechanism by which it regulates blood lipids remains unclear. Given the close correlation between bile acid metabolism and cholesterol metabolism, it is imperative to elucidate the intrinsic mechanisms through which ZXYF treats AS. PURPOSE OF THE RESEARCH This study aims to investigate the pivotal role of enterohepatic bile acid circulation in enhancing intestinal barrier function and mitigating AS by ZXYF. MATERIALS AND METHODS The AS model was established by subjecting male ApoE-/- mice to a high-fat diet (HFD). Moreover, to determine the impact of ZXYF on the integrity of the intestinal barrier, we quantified proinflammatory cytokines using RT-qPCR and ELISA. Additionally, we identified tight-junction proteins in the ileal tissues through IF. Finally, the intestinal flora metabolite and fecal bile acid composition were analyzed using 16S rRNA analysis, untargeted metabolomics analysis, and targeted metabolomics analysis. RESULTS The ZXYF significantly improved dyslipidemia and alleviated the formation of arterial plaques in AS mice. Furthermore, the administration of ZXYF resulted in a concurrent reduction in circulating lipopolysaccharide (LPS) levels and downregulation of pro-inflammatory cytokine mRNA expression in the ileum. Additionally, there was an enhancement observed in the expression of tight junction proteins within the intestinal tissue of AS mice. Further studies found that ZXYF significantly elevated the total bile acids (TBA) and total cholesterol (TC) levels in the fecal of AS mice. The untargeted and targeted metabolomic analyses further revealed that ZXYF exerts regulatory effects on bile acid phenotype by decreasing secondary bile acids (SBAs) levels through modulation of gut microbiota composition, such as enrichment of Akkermansia (AKK) abundance, and inhibition of enterohepatic circulation of bile acids. ZXYF specifically increased the expression of hepatic bile acid synthesis enzymes CYP7A1 by modulating the FXR/FGF15 signaling pathway, thereby promoting enhanced de novo bile acid synthesis and facilitating cholesterol catabolic excretion. CONCLUSION The findings of our research indicate that ZXYF exerts a defensive role in the advancement of AS. The mechanism underlying the role of ZXYF in combating AS is closely associated with gut microbiota reshaping and regulation of enterohepatic bile acid circulation.
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Affiliation(s)
- Shihan Zhou
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
- Union Laboratory of Traditional Chinese Medicine for Brain Science and Gerontology, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, People's Republic of China
| | - Shangbo Hua
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
- Department of Hepatobiliary Surgery, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan, China
| | - Xinyi Chen
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
- Union Laboratory of Traditional Chinese Medicine for Brain Science and Gerontology, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, People's Republic of China
| | - Meiling Ni
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
- Union Laboratory of Traditional Chinese Medicine for Brain Science and Gerontology, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, People's Republic of China
| | - Jing Liu
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
| | - Yanqing Wang
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
- Union Laboratory of Traditional Chinese Medicine for Brain Science and Gerontology, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, People's Republic of China
| | - Wanning Wu
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
| | - Anni Ding
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
| | - Zizhen Qin
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
| | - Xinyu Yang
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China
| | - Xiaowei Chen
- Union Laboratory of Traditional Chinese Medicine for Brain Science and Gerontology, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, People's Republic of China
- School of Elderly Care Services and Management, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China
| | - Boran Zhu
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China.
- Union Laboratory of Traditional Chinese Medicine for Brain Science and Gerontology, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, People's Republic of China.
| | - Haoxin Wu
- Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, China.
- Union Laboratory of Traditional Chinese Medicine for Brain Science and Gerontology, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, People's Republic of China.
- Key Laboratory of Integrative Biomedicine for Brain Diseases at the School of Chinese Medicine, Nanjing University of Chinese Medicine, No. 138 Xianlin Road, Nanjing, 210023, China.
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Han J, Meng X, Kong H, Li X, Chen P, Zhang XA. Links between short-chain fatty acids and osteoarthritis from pathology to clinic via gut-joint axis. Stem Cell Res Ther 2025; 16:251. [PMID: 40390010 PMCID: PMC12090658 DOI: 10.1186/s13287-025-04386-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Accepted: 05/09/2025] [Indexed: 05/21/2025] Open
Abstract
Short-chain fatty acids (SCFAs), the primary metabolites produced by the microbial fermentation of dietary fibers in the gut, have a key role in protecting gut health. Increasing evidence indicates SCFAs can exert effects on distant tissues and organs beyond the gut via blood circulation. Osteoarthritis (OA) is a chronic inflammatory joint disease that severely diminishes the physical function and quality of life. However, effective clinical treatments for OA remain elusive. Recent studies have shown that SCFAs can exert beneficial effects on damaged joints in OA. SCFAs can mitigate OA progression by preserving intestinal barrier function and maintaining the integrity of cartilage and subchondral bone, suggesting that they have substantial potential to be the adjunctive treatment strategy for OA. This review described the SCFAs in the human body and their cellular signaling mechanism, and summarized the multiple effects of SCFAs (especially butyrate, propionate, and acetate) on the prevention and treatment of OA by regulating the gut-joint axis, providing novel insights into their promising clinical applications.
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Affiliation(s)
- Juanjuan Han
- College of Exercise and Health, Shenyang Sport University, Shenyang, 110100, China
| | - Xin Meng
- College of Exercise and Health, Shenyang Sport University, Shenyang, 110100, China
| | - Hui Kong
- College of Exercise and Health, Shenyang Sport University, Shenyang, 110100, China
| | - Xinran Li
- College of Exercise and Health, Shenyang Sport University, Shenyang, 110100, China
| | - Peijie Chen
- School of Exercise and Health, Shanghai University of Sport, Shanghai, 200438, China
| | - Xin-An Zhang
- College of Exercise and Health, Shenyang Sport University, Shenyang, 110100, China.
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Dubé-Zinatelli E, Mayotte E, Cappelletti L, Ismail N. Impact of the maternal microbiome on neonatal immune development. J Reprod Immunol 2025; 170:104542. [PMID: 40403512 DOI: 10.1016/j.jri.2025.104542] [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: 09/30/2024] [Revised: 03/22/2025] [Accepted: 05/15/2025] [Indexed: 05/24/2025]
Abstract
Historically, multigenerational health and disease transmission have primarily focused on genetic inheritance. However, the discovery that beneficial microorganisms known as commensal microbiota outnumber human genes tenfold has reshaped this perspective, highlighting their critical role in maintaining homeostasis and protecting against pathogens. Unlike the human genome, commensal microbiota is not genetically inherited but is acquired anew with each generation. with initial gut colonization playing a pivotal role in shaping an infant's immune system, neurodevelopment, and long-term health, all heavily influenced by maternal factors. In this review, we examine emerging research on maternal microbial influences on the fetus beginning in utero. We provide an updated overview of the current insights into the impact of the vaginal microbiome during parturition on offspring immunity and discuss the potential long-term health implications for infants born via cesarean section. We explore the advantages and limitations of techniques designed to mitigate these effects, such as vaginal seeding and emphasize that the development of the neonatal immune system is a dynamic process influenced by maternal factors beyond birth, including the transfer of microbiota through breast milk and skin contact. Finally, we present gaps in current research and propose future research directions to deepen our understanding of the impacts of the maternal microbiome on her child. Together, these insights demonstrate how maternal influence on offspring health and immunity extends beyond genetic factors, encompassing the transmission of microbiota, which, in turn, has profound long-term implications for health and disease resilience, offering a novel perspective on intergenerational health dynamics.
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Affiliation(s)
- Eleni Dubé-Zinatelli
- NISE Laboratory, School of Psychology, Faculty of Social Science, University of Ottawa, 136 Jean-Jacques Lussier, Vanier Hall, Room 2076B, Ottawa, Ontario K1N 6N5, Canada.
| | - Edwige Mayotte
- NISE Laboratory, School of Psychology, Faculty of Social Science, University of Ottawa, 136 Jean-Jacques Lussier, Vanier Hall, Room 2076B, Ottawa, Ontario K1N 6N5, Canada.
| | - Luna Cappelletti
- NISE Laboratory, School of Psychology, Faculty of Social Science, University of Ottawa, 136 Jean-Jacques Lussier, Vanier Hall, Room 2076B, Ottawa, Ontario K1N 6N5, Canada.
| | - Nafissa Ismail
- NISE Laboratory, School of Psychology, Faculty of Social Science, University of Ottawa, 136 Jean-Jacques Lussier, Vanier Hall, Room 2076B, Ottawa, Ontario K1N 6N5, Canada; LIFE Research Institute, University of Ottawa, Thompson Hall, 25 University Private, room 227, Ottawa, Ontario K1N 6N5, Canada; University of Ottawa Brain and Mind Research Institute, Faculty of Medicine, University of Ottawa, Roger Guindon Hall, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.
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Andreou E, Papaneophytou C. Boosting Immunity Through Nutrition and Gut Health: A Narrative Review on Managing Allergies and Multimorbidity. Nutrients 2025; 17:1685. [PMID: 40431425 PMCID: PMC12114198 DOI: 10.3390/nu17101685] [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: 04/26/2025] [Revised: 05/12/2025] [Accepted: 05/13/2025] [Indexed: 05/29/2025] Open
Abstract
The increasing global burden of allergic diseases and multimorbidity underscores the urgent need for innovative strategies to strengthen immune health. This review explores the complex relationships among nutrition, gut microbiota, immune regulation, allergic diseases, and multimorbidity. It highlights how targeted nutritional and microbial interventions may influence disease outcomes. Dietary components and microbial metabolites dynamically modulated immune function, highlighting the critical role of the gut-immune-metabolism axis in disease pathogenesis and management. Personalized nutrition, guided by advances in diagnostics such as component-resolved diagnostics, basophil activation tests, and epigenetic biomarkers, allows for precise dietary interventions tailored to individual allergy phenotypes and multimorbidity profiles. The Mediterranean diet, breastfeeding, and microbiota-targeted therapies have emerged as effective strategies to enhance immune resilience, reduce inflammation, and manage allergic reactions. Technological advancements, including artificial intelligence-driven dietary assessments, wearable devices, and mobile applications, have further revolutionized personalized dietary management, enabling real-time, precise nutritional monitoring and intervention. Despite these advances, challenges in implementing personalized nutrition persist, including variability in dietary patterns, cultural and socioeconomic factors, and accessibility concerns. Future research should focus on long-term interventional and longitudinal studies to validate precision nutrition strategies and enhance clinical applicability. This integrative approach, combining nutrition, microbiome science, technology, and personalized healthcare, holds substantial promises for sustainable disease prevention and enhanced immune resilience across diverse populations.
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Affiliation(s)
| | - Christos Papaneophytou
- Department of Life Sciences, School of Life and Health Sciences, University of Nicosia, 2417 Nicosia, Cyprus;
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Cebi M, Yilmaz Y. Epithelial barrier hypothesis in the context of nutrition, microbial dysbiosis, and immune dysregulation in metabolic dysfunction-associated steatotic liver. Front Immunol 2025; 16:1575770. [PMID: 40438102 PMCID: PMC12116361 DOI: 10.3389/fimmu.2025.1575770] [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: 02/12/2025] [Accepted: 04/25/2025] [Indexed: 06/01/2025] Open
Abstract
In recent years, the prevalence of chronic liver diseases, particularly Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), has increased significantly. This upward trend is largely associated with lifestyle-related factors such as unhealthy dietary habits, physical inactivity, and various environmental influences. Among the key elements contributing to the pathogenesis of MASLD, the integrity of the intestinal epithelial barrier emerges as a critical determinant, given its central role in maintaining immune homeostasis along the gut-liver axis. Disruption of this barrier, often driven by excessive consumption of saturated fats and refined carbohydrates in combination with low dietary fiber intake, can lead to microbial dysbiosis. This imbalance in the gut microbiota triggers immune dysregulation and promotes systemic inflammation, thereby exacerbating hepatic injury. This review discusses the contribution of epithelial barrier dysfunction to the development and progression of MASLD, with a particular focus on how increased intestinal permeability may initiate and sustain chronic liver inflammation. Additionally, the influence of dietary and environmental factors on epithelial integrity, immune responses, and the inflammatory cascade is addressed. A better understanding of the complex interplay between gut barrier impairment, immune modulation, and liver pathology may offer valuable insights into MASLD pathophysiology and contribute to the development of more targeted therapeutic strategies.
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Affiliation(s)
- Merve Cebi
- Department of Medical Biology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Türkiye
| | - Yusuf Yilmaz
- Department of Gastroenterology, School of Medicine, Recep Tayyip Erdoğan University, Rize, Türkiye
- The Global NASH Council, Washington, DC, United States
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Rettura F, Lambiase C, Tedeschi R, Grosso A, Cancelli L, Ricchiuti A, Bottari A, Giacomelli L, de Bortoli N, Bellini M. Mucoprotectants and gut barrier: mechanisms of action and clinical applications in IBS. Is there a possible role? Front Pharmacol 2025; 16:1538791. [PMID: 40421206 PMCID: PMC12104585 DOI: 10.3389/fphar.2025.1538791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 04/14/2025] [Indexed: 05/28/2025] Open
Abstract
Impaired gut barrier function plays a pivotal role in the pathophysiology of irritable bowel syndrome (IBS), particularly in IBS with diarrhea. Mucoprotectants, such as xyloglucan, gelatin tannate and pea protein tannins, offer a novel therapeutic approach by restoring intestinal permeability and reducing inflammation. This review assesses preclinical and clinical evidence supporting mucoprotectants in IBS with diarrhea management. Preclinical studies indicate their efficacy in reducing intestinal permeability and inflammation, while clinical trials demonstrate improvements in stool consistency, abdominal pain and bloating. Despite these promising results, comparative studies are needed to establish the superiority of specific mucoprotectants and their optimal use in clinical practice.
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Affiliation(s)
- Francesco Rettura
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
- Regional Center for Functional and Motility Digestive Disorders, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
- Gastroenterology Unit, Annunziata Hospital, Cosenza, Italy
| | - Christian Lambiase
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
- Regional Center for Functional and Motility Digestive Disorders, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Riccardo Tedeschi
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
- Regional Center for Functional and Motility Digestive Disorders, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Antonio Grosso
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
- Regional Center for Functional and Motility Digestive Disorders, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Lorenzo Cancelli
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
- Regional Center for Functional and Motility Digestive Disorders, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Angelo Ricchiuti
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
- Regional Center for Functional and Motility Digestive Disorders, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Andrea Bottari
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
- Regional Center for Functional and Motility Digestive Disorders, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | | | - Nicola de Bortoli
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
- Regional Center for Functional and Motility Digestive Disorders, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Massimo Bellini
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
- Regional Center for Functional and Motility Digestive Disorders, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
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Escorcia Mora P, Valbuena D, Diez-Juan A. The Role of the Gut Microbiota in Female Reproductive and Gynecological Health: Insights into Endometrial Signaling Pathways. Life (Basel) 2025; 15:762. [PMID: 40430189 PMCID: PMC12113314 DOI: 10.3390/life15050762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Revised: 05/05/2025] [Accepted: 05/06/2025] [Indexed: 05/29/2025] Open
Abstract
Fertility is a dynamic, multifactorial process governed by hormonal, immune, metabolic, and environmental factors. Recent evidence highlights the gut microbiota as a key systemic regulator of reproductive health, with notable impacts on endometrial function, implantation, pregnancy maintenance, and the timing of birth. This review examines the gut-endometrial axis, focusing on how gut microbial communities influence reproductive biology through molecular signaling pathways. We discuss the modulatory roles of microbial-derived metabolites-including short-chain fatty acids, bile acids, and tryptophan catabolites-in shaping immune tolerance, estrogen metabolism, and epithelial integrity at the uterine interface. Emphasis is placed on shared mechanisms such as β-glucuronidase-mediated estrogen recycling, Toll-like receptor (TLR)-driven inflammation, Th17/Treg cell imbalance, and microbial translocation, which collectively implicate dysbiosis in the etiology of gynecological disorders including endometriosis, polycystic ovary syndrome (PCOS), recurrent implantation failure (RIF), preeclampsia (PE), and preterm birth (PTB). Although most current evidence remains correlational, emerging insights from metagenomic and metabolomic profiling, along with microbiota-depletion models and Mendelian randomization studies, underscore the biological significance of gut-reproductive crosstalk. By integrating concepts from microbiology, immunology, and reproductive molecular biology, this review offers a systems-level perspective on host-microbiota interactions in female fertility.
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Affiliation(s)
| | | | - Antonio Diez-Juan
- R&D Department, Igenomix (Part of Vitrolife Group), Ronda de Narcís Monturiol, nº11, B, Edificios Europark, Parque Tecnológico, 46980 Paterna, Valencia, Spain; (P.E.M.); (D.V.)
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11
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D’Urso F, Paladini F, Miraglia A, D’Amuri A, Chieppa M, Pollini M, Broccolo F. Translating Patent Innovation into Clinical Practice: Two Decades of Therapeutic Advancements in Dysbiosis Management. Microorganisms 2025; 13:1064. [PMID: 40431238 PMCID: PMC12114573 DOI: 10.3390/microorganisms13051064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 04/26/2025] [Accepted: 04/30/2025] [Indexed: 05/29/2025] Open
Abstract
Dysbiosis, characterized by a microbial imbalance, particularly within the gut microbiota, has emerged as a significant health concern linked to various diseases. This study analyzed 8097 patent documents from The Lens database (2005-2024) to examine global innovation trends in dysbiosis management. The patent filings showed exponential growth, peaking at 1222 documents in 2022, with the United States leading in publications (4361 documents). The analysis revealed three primary innovation clusters: bacterial-based therapeutics (44.8% of patents), specific therapeutic applications (27.6%), and diagnostic methods (15.9%). The disease associations predominantly included inflammatory conditions, infections, and cancer. The patent classifications highlighted a significant focus on probiotic development and microbiota modulation. The surge in patent activity since 2014 correlates with advances in DNA sequencing technology and the growing recognition of dysbiosis's role in human health. This analysis provides valuable insights into the evolving landscape of microbiome therapeutics and future directions for dysbiosis management.
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Affiliation(s)
- Fabiana D’Urso
- Department of Experimental Medicine (DiMeS), University of Salento, 73100 Lecce, Italy; (F.P.); (A.M.); (A.D.); (M.C.); (M.P.)
| | | | | | | | | | | | - Francesco Broccolo
- Department of Experimental Medicine (DiMeS), University of Salento, 73100 Lecce, Italy; (F.P.); (A.M.); (A.D.); (M.C.); (M.P.)
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12
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He L, Zhang L, Meng F, Wei J, Chen F, Qin S, Jin G, Cao H. Dietary emulsifier Polysorbate 80-induced lipotoxicity promotes intestinal senescence. Food Res Int 2025; 209:116165. [PMID: 40253120 DOI: 10.1016/j.foodres.2025.116165] [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: 09/29/2024] [Revised: 02/11/2025] [Accepted: 03/09/2025] [Indexed: 04/21/2025]
Abstract
Intestinal senescence, often characterized by increased oxidative stress, is linked to gastrointestinal disorders such as inflammatory bowel disease and colorectal cancer. While previous studies have suggested that diets rich in food additives, such as the emulsifier Polysorbate 80 (P80), may influence gut health, the impact of P80 exposure on intestinal senescence remains unclear. This study aimed to explore the effects of P80 on intestinal senescence in a senescence-accelerated mouse prone model. The results revealed that P80 exposure could damage the intestinal barrier, induce oxidative stress, and accelerate intestinal senescence. Mechanistically, P80 activated the peroxisome proliferator-activated receptor-α (PPARα) and fatty acid-binding protein 1 (FABP1) axis, increasing intestinal fatty acid absorption and triggering lipotoxicity, which promoted senescence. Additionally, P80 exacerbated D-galactose-induced epithelial cell senescence and lipid accumulation via the PPARα signalling pathway. Importantly, the PPARα antagonist GW6471 mitigated fatty acid uptake and reduced senescence in the intestine. In conclusion, the emulsifier P80 accelerated intestinal senescence by regulating the PPARα-FABP1 axis to induce intestinal fatty acid uptake and lipotoxicity, suggesting new insights into the adverse effects of food additives on gut health.
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Affiliation(s)
- Linlin He
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052, China
| | - Lan Zhang
- Department of Infective disease, Tianjin First Central Hospital, Tianjin, China
| | - Fanyi Meng
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052, China
| | - Jingge Wei
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052, China
| | - Fei Chen
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052, China
| | - Siqi Qin
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052, China
| | - Ge Jin
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052, China..
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052, China..
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13
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Mingels S. Paediatric pain and malnutrition in low-income countries: A narrative review. Nutr Health 2025:2601060251336823. [PMID: 40304640 DOI: 10.1177/02601060251336823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/02/2025]
Abstract
Background: Despite its omnipresence, paediatric pain remains poorly understood and documented, especially in low-income countries. Such pain can be a symptom of long-term subclinical conditions such as systemic chronic inflammation (SCI). The latter can be related to malnutrition. Aim: To explore a potential association between paediatric pain and malnutrition in low-income countries. Methods: Narrative review, including a literature search in the PubMed, EMBASE, Web of Science and Scopus databases (update 24 March 2025). The search query comprised controlled terminology and free text words relating to 'Malnutrition', 'Pain', 'SCI' and 'Paediatric'. Results: To comprehend the complex relation between malnutrition and paediatric pain, associations between (1a) malnutrition, and nociceptive brain development, (1b) malnutrition, the gut microbiome and SCI, and (2) SCI and pain were explored. (1a) Early noxious exposure (e.g. malnutrition-related SCI) can cause long-term alterations in pain perception, brain function and structures. The consequences of malnutrition on the nociceptive brain depend on the life-cycle. (1b) Moderate acute malnutrition causes chronic inflammation and exaggerated inflammatory responses. Such responses could indicate hyper-inflammatory phenotypes. (2) Systemic-induced inflammation causes a widespread increase in musculoskeletal pain sensitivity. Conclusion: Malnutrition could contribute to the development of a nociceptive brain and SCI. Malnutrition-related SCI could induce changes in pain perception/thresholds, and predispose to developing chronic pain. If a relation between malnutrition and SCI predisposes children to develop pain, the prevailing biophysical approach needs revision. A multidimensional interdisciplinary approach seems more relevant. Such approach includes social, cognitive, socioeconomic, lifestyle, nutritional (e.g. integrating nutritional and microbiome-targeted interventions) and environmental dimensions.
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Affiliation(s)
- Sarah Mingels
- Musculoskeletal Research Unit, Department of Rehabilitation Sciences, Faculty of Movement and Rehabilitation Sciences, Leuven University, Leuven, Belgium
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Filipe Rosa L, Gonda S, Roese N, Bischoff SC. Tannic Acid and Ethacridine Lactate Attenuate Markers of Stress-Induced Intestinal Barrier Dysfunctions in Murine Small Intestinal Organoids. Biomolecules 2025; 15:650. [PMID: 40427543 PMCID: PMC12109227 DOI: 10.3390/biom15050650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2025] [Revised: 04/02/2025] [Accepted: 04/29/2025] [Indexed: 05/29/2025] Open
Abstract
(1) Background: Tannacomp® is a drug consisting of tannin albuminate, a complex of tannic acid (TA) and ethacridine lactate (Eta) used for treating acute and traveler's diarrhea. TA is thought to modulate gastrointestinal barrier function, but the underlying mechanisms and whether Eta has similar effects remains unclear. (2) Methods: to investigate the effects of TA and Eta on the intestinal barrier, stress responses were induced in murine intestinal organoids by lipopolysaccharide (LPS) exposure or withdrawal of growth factors from cell culture medium (GFRed). Further, organoids were exposed to either TA (0.01 mg/mL) or Eta (0.002 mg/mL) and markers of inflammatory response and gut barrier function were assessed. (3) Results: TA and Eta reduced several inflammatory markers such as interleukin 6, interleukin 1β, tumor necrosis factor α, and myeloid differentiation primary response 88 in stressed organoids. In addition, TA and Eta attenuated LPS- and GFRed-mediated gut barrier dysfunctions, with normalization of tight junction, adherent junction and mucin gene expression and reduction of Nod2- and matrix metalloproteinase 7-dependent activation of antimicrobial peptides. (4) Conclusions: our data show that TA and Eta modulate markers of inflammation and the intestinal barrier and suggest novel mechanisms of action of this drug that could broaden its treatment indications.
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Affiliation(s)
- Louisa Filipe Rosa
- Institute of Nutritional Medicine, University of Hohenheim, Fruwirthstr. 12, 70599 Stuttgart, Germany;
| | - Steffen Gonda
- MEDICE Arzneimittel Pütter GmbH & Co. KG, Kuhloweg 37, 58638 Iserlohn, Germany
| | - Nadine Roese
- MEDICE Arzneimittel Pütter GmbH & Co. KG, Kuhloweg 37, 58638 Iserlohn, Germany
| | - Stephan C. Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Fruwirthstr. 12, 70599 Stuttgart, Germany;
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15
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Lee SY, Han K, Kwon HS, Koh ES, Chung S. Fecal Calprotectin as a Prognostic Biomarker for Mortality and Renal Outcomes in Chronic Kidney Disease. Biomolecules 2025; 15:557. [PMID: 40305332 PMCID: PMC12025133 DOI: 10.3390/biom15040557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Revised: 04/03/2025] [Accepted: 04/07/2025] [Indexed: 05/02/2025] Open
Abstract
BACKGROUND/OBJECTIVES Fecal calprotectin (FC) is a biomarker of intestinal inflammation widely used in the assessment of gastrointestinal disorders. However, its role in chronic kidney disease (CKD) remains unclear. Given the growing recognition of the gut-kidney axis in CKD pathophysiology, this study aimed to investigate the association between FC levels, systemic inflammation, renal outcomes, and mortality in CKD patients. METHODS We enrolled a total of 515 CKD patients who underwent fecal calprotectin measurement between 2016 and 2023. After applying the exclusion criteria (inflammatory bowel disease, ongoing renal replacement therapy, or incomplete laboratory data), 260 patients were included in the final analysis and stratified into low-FC (<102 μg/g, n = 130) and high-FC (≥102 μg/g, n = 130) groups based on the median FC value. Factors associated with kidney disease progression and patient survival were analyzed. RESULTS Patients in the high-FC group (≥102 μg/g) were significantly older (72.8 ± 14.63 vs. 64.02 ± 18.15 years, p < 0.0001) and had a higher prevalence of diabetes mellitus (55.38% vs. 42.31%, p = 0.0349), heart failure (21.54% vs. 7.69%, p = 0.0016), and history of acute kidney injury (33.85% vs. 18.46%, p = 0.0048). Elevated FC was independently associated with increased mortality risk (hazards ratio [HR] 1.658, 95% confidence interval [CI] 1.034-2.658, p = 0.0357) with higher mortality rates (48.36 vs. 18.46 per 100,000 person-years). Subgroup analyses revealed stronger associations between FC and mortality in males (HR 2.160, 95% CI 1.046-4.463, p = 0.0375), elderly patients (≥75 years) (HR 2.122, 95% CI 1.209-3.725, p = 0.0088), and non-diabetic patients (HR 2.487, 95% CI 1.141-5.421, p = 0.0219). While FC was not significantly associated with end-stage kidney disease (ESKD) progression (odds ratio [OR] 1.289, 95% CI 0.455-3.650, p = 0.6323), higher FC levels paradoxically predicted slower estimated glomerular filtration rate (eGFR) decline (OR 2.763, 95% CI 1.139-6.699, p = 0.0245). Combined analysis revealed patients with both elevated FC and high-sensitivity C-reactive protein (hs-CRP) had the highest mortality risk (HR 3.504, 95% CI 1.163-10.554, p < 0.0001) compared to those with low levels of both markers. CONCLUSIONS FC is a potential prognostic biomarker for mortality in CKD patients, independently of traditional inflammatory markers. Further research is warranted to elucidate the mechanisms underlying its paradoxical relationship with renal outcomes and its potential role in risk stratification and therapeutic targeting in CKD.
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Affiliation(s)
- So Young Lee
- Division of Nephrology, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Republic of Korea;
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul 06978, Republic of Korea;
| | - Hyuk-Sang Kwon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Republic of Korea;
| | - Eun Sil Koh
- Division of Nephrology, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Republic of Korea;
| | - Sungjin Chung
- Division of Nephrology, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Republic of Korea;
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16
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Fountoulakis PN, Theofilis P, Vlachakis PK, Karakasis P, Pamporis K, Sagris M, Dimitroglou Y, Tsioufis P, Oikonomou E, Tsioufis K, Tousoulis D. Gut Microbiota in Heart Failure-The Role of Inflammation. Biomedicines 2025; 13:911. [PMID: 40299538 PMCID: PMC12024997 DOI: 10.3390/biomedicines13040911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 03/30/2025] [Accepted: 03/31/2025] [Indexed: 04/30/2025] Open
Abstract
Heart failure (HF) has become an immense health concern affecting almost 1-2% of the population globally. It is a complex syndrome characterized by activation of the sympathetic nervous system and the Renin-Angiotensin-Aldosterone (RAAS) axis as well as endothelial dysfunction, oxidative stress, and inflammation. The recent literature points towards the interaction between the intestinal flora and the heart, also called the gut-heart axis. The human gastrointestinal tract is naturally inhabited by various microbes, which are distinct for each patient, regulating the functions of many organs. Alterations of the gut microbiome, a process called dysbiosis, may result in systemic diseases and have been associated with heart failure through inflammatory and autoimmune mechanisms. The disorder of intestinal permeability favors the translocation of microbes and many metabolites capable of inducing inflammation, thus further contributing to the deterioration of normal cardiac function. Besides diet modifications and exercise training, many studies have revealed possible gut microbiota targeted treatments for managing heart failure. The aim of this review is to demonstrate the impact of the inflammatory environment induced by the gut microbiome and its metabolites on heart failure and the elucidation of these novel therapeutic approaches.
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Affiliation(s)
- Petros N. Fountoulakis
- 1st Department of Cardiology, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (P.N.F.); (P.T.); (P.K.V.); (K.P.); (M.S.); (Y.D.); (P.T.); (K.T.)
| | - Panagiotis Theofilis
- 1st Department of Cardiology, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (P.N.F.); (P.T.); (P.K.V.); (K.P.); (M.S.); (Y.D.); (P.T.); (K.T.)
| | - Panayotis K. Vlachakis
- 1st Department of Cardiology, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (P.N.F.); (P.T.); (P.K.V.); (K.P.); (M.S.); (Y.D.); (P.T.); (K.T.)
| | - Paschalis Karakasis
- 2nd Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece;
| | - Konstantinos Pamporis
- 1st Department of Cardiology, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (P.N.F.); (P.T.); (P.K.V.); (K.P.); (M.S.); (Y.D.); (P.T.); (K.T.)
| | - Marios Sagris
- 1st Department of Cardiology, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (P.N.F.); (P.T.); (P.K.V.); (K.P.); (M.S.); (Y.D.); (P.T.); (K.T.)
| | - Yannis Dimitroglou
- 1st Department of Cardiology, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (P.N.F.); (P.T.); (P.K.V.); (K.P.); (M.S.); (Y.D.); (P.T.); (K.T.)
| | - Panagiotis Tsioufis
- 1st Department of Cardiology, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (P.N.F.); (P.T.); (P.K.V.); (K.P.); (M.S.); (Y.D.); (P.T.); (K.T.)
| | - Evangelos Oikonomou
- 3rd Department of Cardiology, Thoracic Diseases General Hospital “Sotiria”, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Konstantinos Tsioufis
- 1st Department of Cardiology, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (P.N.F.); (P.T.); (P.K.V.); (K.P.); (M.S.); (Y.D.); (P.T.); (K.T.)
| | - Dimitris Tousoulis
- 1st Department of Cardiology, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (P.N.F.); (P.T.); (P.K.V.); (K.P.); (M.S.); (Y.D.); (P.T.); (K.T.)
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Li ZY, Luo HY, Xu F, Xu Y, Ma CH, Zhang SL, Xu S, Ma YY, Li N, Miao CY. Metrnl protects intestinal barrier function by regulating tight junctions via the IKKβ/IκBα/NFκB/MLCK/MLC signaling pathway. Cell Death Discov 2025; 11:155. [PMID: 40199887 PMCID: PMC11979045 DOI: 10.1038/s41420-025-02457-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 03/12/2025] [Accepted: 03/27/2025] [Indexed: 04/10/2025] Open
Abstract
Meteorin-like (Metrnl), also known as Subfatin, IL-41, or Cometin, is a secreted protein predominantly expressed in the intestinal epithelium. The intestinal barrier, primarily consisting of epithelial cells connected by tight junctions, is essential for maintaining gut homeostasis by preventing harmful substances from entering the body. Despite Metrnl's high expression in the intestine, its role in barrier function remains unclear. In this study, we investigated Metrnl's role in intestinal barrier function using both loss-of-function (using global and intestinal epithelium-specific knockout mice) and gain-of-function (using intestinal epithelium-specific overexpression mice) approaches. Our findings showed that Metrnl deficiency disrupted tight junctions between enterocytes and exacerbated endotoxin-induced barrier dysfunction. Mechanistically, Metrnl deficiency triggered activation of the IKKβ/IκBα/NFκB signaling pathway, leading to increased MLCK expression and MLC phosphorylation. The NFκB inhibitor PDTC reversed this effect both in vivo and in vitro. Macrophages played an essential role in Metrnl's intestinal barrier protective effects during endotoxemia, but were not necessary in burn-induced barrier injury, suggesting potential differences in mechanism between these conditions. Notably, recombinant Metrnl protein administration protected against barrier dysfunction, and genetic overexpression of Metrnl in enterocytes preserved barrier function and alleviated DSS-induced colitis. These findings establish Metrnl as a key regulator of intestinal barrier integrity through the IKKβ/IκBα/NFκB/MLCK/MLC pathway, highlighting its potential therapeutic value in treating barrier dysfunction disorders. Intestinal barrier dysfunction triggers, such as endotoxin and severe burns, may induce the release of Metrnl from vascular endothelium. This leads to an increase in circulating Metrnl. Both circulating Metrnl and local Metrnl inhibit inflammation and the IKKβ/IκBα/NFκB/MLCK/MLC signaling pathway in enterocytes, thereby protecting tight junctions from disruption caused by endotoxin or burns.
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Affiliation(s)
- Zhi-Yong Li
- Department of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai, 200433, China.
- Department of Pathology, Faculty of Medical Imaging, Second Military Medical University/Naval Medical University, Shanghai, 200433, China.
| | - Heng-Yu Luo
- Department of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai, 200433, China
| | - Fei Xu
- Department of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai, 200433, China
| | - Yao Xu
- Department of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai, 200433, China
| | - Chun-Hui Ma
- Department of Pathology, Faculty of Medical Imaging, Second Military Medical University/Naval Medical University, Shanghai, 200433, China
| | - Sai-Long Zhang
- Department of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai, 200433, China
| | - Sheng Xu
- Department of Immunology, Second Military Medical University/Naval Medical University, Shanghai, 200433, China
| | - Yuan-Yuan Ma
- Senior Department of Hematology, The Fifth Medical Center of People's Liberation Army(PLA), General Hospital, Beijing, 100010, China
| | - Nan Li
- Department of Immunology, Second Military Medical University/Naval Medical University, Shanghai, 200433, China
| | - Chao-Yu Miao
- Department of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai, 200433, China.
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Matar A, Abdelnaem N, Camilleri M. Bone Broth Benefits: How Its Nutrients Fortify Gut Barrier in Health and Disease. Dig Dis Sci 2025:10.1007/s10620-025-08997-x. [PMID: 40180691 DOI: 10.1007/s10620-025-08997-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Accepted: 03/14/2025] [Indexed: 04/05/2025]
Abstract
Bone broth is a traditional nutrient revered by different people from ancient times to the modern era as a remedy for various illnesses. This review investigates the nutritional components of bone broth, focusing primarily on the most abundant amino acids and minerals saturated in bone broth and their impact on health, particularly in the context of intestinal barrier integrity, intestinal permeability, inflammation, and their application in inflammatory bowel disease. Through comprehensive reviews of animal and human studies, this research highlights that bone broth includes amino acids (glutamine, glycine, proline, histidine, arginine), minerals (Ca, P, K, Mg, Zn) that are beneficial and not just a traditional remedy, resolving questions that have been posed for generations. The benefits documented for components in bone broth support the enhancement of gut health, alleviate inflammation in the intestinal barrier, improve intestinal barrier function in health and disease states, particularly in inflammatory bowel disease, as well as enhancing nutrient absorption. Bone broth offers a nutrient-dense option for enhancing overall health and may offer an alternative to dietary supplements with claims for enhanced gut health. We aim to foster interest in and provide evidence to substantiate claims for bone broth as a potential remedy, particularly for maintaining remission in conditions like IBD and possibly functional diarrhea and to encourage further research.
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Affiliation(s)
- Ayah Matar
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St. S.W., Charlton Building, Rm. 8-110, Rochester, MN, 55905, USA
| | - Nada Abdelnaem
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St. S.W., Charlton Building, Rm. 8-110, Rochester, MN, 55905, USA
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St. S.W., Charlton Building, Rm. 8-110, Rochester, MN, 55905, USA.
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Bona MD, Mota ACCC, Nascimento DSM, Magalhães LMVC, Lima SCVC, Lyra CO, Morais AHA, Marchioni DM, Lima AAM, Maciel BLL. Intestinal absorption area is correlated with cardiovascular risk factors associated with obesity and metabolic syndrome. Nutr Metab Cardiovasc Dis 2025; 35:103803. [PMID: 39939256 DOI: 10.1016/j.numecd.2024.103803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 11/06/2024] [Accepted: 11/19/2024] [Indexed: 02/14/2025]
Abstract
BACKGROUND AND AIM This study aimed to evaluate if the intestinal permeability is associated with overweight/obesity with or without metabolic syndrome (MetS) and correlate intestinal permeability parameters with cardiovascular risk factors. METHODS AND RESULTS This was a cross-sectional study that individuals were divided in three groups: 1) controls (n = 34), 2) overweight/obesity (n = 29), and 3) overweight/obesity + MetS (n = 29). Anthropometric and blood biochemical parameters were used to estimate cardiovascular risk factors. Intestinal permeability was evaluated using the lactulose/mannitol test in urine samples analyzed by High Performance Liquid Chromatography with Pulsed Amperometry Detection. Correlations between intestinal permeability and anthropometric and biochemical parameters were evaluated using Spearman's correlations (r2). Logistic regression models were performed to elucidate variables associated with intestinal permeability parameters. The percentage of urinary excretion of lactulose, mannitol, and the lactulose/mannitol ratio was similar between the studied groups. The percentage of urinary mannitol excretion was positively associated with diastolic blood pressure (r2 = 0.24, p = 0.23), fasting glucose (r2 = 0.26, p = 0.013), fasting insulin (r2 = 0.25, p = 0.015) and HOMA-IR (r2 = 0.26, p = 0.012). The logistic regression showed fasting insulin was associated with a higher mannitol urinary excretion (AOR = 1.08, 95 % CI = 1.02-1.14). CONCLUSION Intestinal permeability was not disrupted in overweight/obesity and MetS, however the results suggest that the increased cardiovascular risk factors were associated with a higher intestinal absorption area. Further studies should investigate other intestinal parameters related to overweight/obesity and MetS in humans.
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Affiliation(s)
- Mariana D Bona
- Institute of Biomedicine, Department of Medicine, Federal University of Ceará, Fortaleza, 60430-270, Brazil; Graduate Medical Science Program, Department of Medicine, Federal University of Ceará, Fortaleza, 60430-270, Brazil
| | - Ana C C C Mota
- Graduate Health Science Program, Center for Health Science, Federal University of Rio Grande do Norte, Natal, 59078-970, Brazil
| | - Daniele S M Nascimento
- Graduate Health Science Program, Center for Health Science, Federal University of Rio Grande do Norte, Natal, 59078-970, Brazil
| | - Lyvia M V C Magalhães
- Institute of Biomedicine, Department of Medicine, Federal University of Ceará, Fortaleza, 60430-270, Brazil
| | - Severina C V C Lima
- Department of Nutrition, Center for Health Science, Federal University of Rio Grande do Norte, Natal, 59078-970, Brazil; Graduate Nutrition Program, Center for Health Science, Federal University of Rio Grande do Norte, Natal, 59078-970, Brazil; Graduate Health Science Program, Center for Health Science, Federal University of Rio Grande do Norte, Natal, 59078-970, Brazil
| | - Clélia O Lyra
- Department of Nutrition, Center for Health Science, Federal University of Rio Grande do Norte, Natal, 59078-970, Brazil; Graduate Nutrition Program, Center for Health Science, Federal University of Rio Grande do Norte, Natal, 59078-970, Brazil; Graduate Health Science Program, Center for Health Science, Federal University of Rio Grande do Norte, Natal, 59078-970, Brazil
| | - Ana H A Morais
- Department of Nutrition, Center for Health Science, Federal University of Rio Grande do Norte, Natal, 59078-970, Brazil; Graduate Nutrition Program, Center for Health Science, Federal University of Rio Grande do Norte, Natal, 59078-970, Brazil
| | - Dirce M Marchioni
- University of São Paulo, School of Public Health, Department of Nutrition, SP, Brazil
| | - Aldo A M Lima
- Institute of Biomedicine, Department of Medicine, Federal University of Ceará, Fortaleza, 60430-270, Brazil; Graduate Medical Science Program, Department of Medicine, Federal University of Ceará, Fortaleza, 60430-270, Brazil
| | - Bruna L L Maciel
- Department of Nutrition, Center for Health Science, Federal University of Rio Grande do Norte, Natal, 59078-970, Brazil; Graduate Nutrition Program, Center for Health Science, Federal University of Rio Grande do Norte, Natal, 59078-970, Brazil; Graduate Health Science Program, Center for Health Science, Federal University of Rio Grande do Norte, Natal, 59078-970, Brazil.
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20
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Wu S, Gao J, Han Y, Zhang W, Li X, Kong D, Wang H, Zuo L. Balancing act: The dual role of claudin-2 in disease. Ann N Y Acad Sci 2025; 1546:75-89. [PMID: 40101185 DOI: 10.1111/nyas.15311] [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] [Indexed: 03/20/2025]
Abstract
Claudin-2 (CLDN2), a tight junction protein, is predominantly found in leaky epithelial cell layers where it plays a pivotal role in forming paracellular pores necessary for the efficient transport of cations and water. Its abundance is intricately regulated by upstream signals, modulating its synthesis, transport, and localization to adapt to diverse environmental changes. Aberrant expression levels of CLDN2 are observed in numerous pathological conditions including cancer, inflammation, immune disorders, fibrosis, and kidney and biliary stones. Recent advances have uncovered the mechanisms by which the loss or restoration of CLDN2 affects functions such as epithelial barrier, cell proliferation, renewal, migration, invasion, and tissue regeneration. This exerts a dual-directional influence on the pathogenesis, perpetuation, and progression of diseases, indicating the potential to both accelerate and decelerate the course of disease evolution. Here, we discuss these nuanced bidirectional regulatory effects mediated by CLDN2, and how it may contribute to the progression or regression of disease when it becomes unbalanced.
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Affiliation(s)
- Shanshan Wu
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, China
- Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, China
| | - Jia Gao
- Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, China
- Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, China
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yiran Han
- Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, China
- The First College of Clinical Medicine, Anhui Medical University, Hefei, China
| | - Wenzhe Zhang
- Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, China
- The First College of Clinical Medicine, Anhui Medical University, Hefei, China
| | - Xue Li
- Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, China
- The First College of Clinical Medicine, Anhui Medical University, Hefei, China
| | - Derun Kong
- Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Hua Wang
- Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, China
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Li Zuo
- Innovation and Entrepreneurship Laboratory for College Students, Anhui Medical University, Hefei, China
- Laboratory of Molecular Biology, Department of Biochemistry, School of Basic Medical Science, Anhui Medical University, Hefei, China
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21
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You M, Zhou L, Wu F, Zhang L, Zhu SX, Zhang HX. Probiotics for the treatment of hyperlipidemia: Focus on gut-liver axis and lipid metabolism. Pharmacol Res 2025; 214:107694. [PMID: 40068270 DOI: 10.1016/j.phrs.2025.107694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 02/19/2025] [Accepted: 03/07/2025] [Indexed: 03/23/2025]
Abstract
Hyperlipidemia, a metabolic disorder marked by dysregulated lipid metabolism, is a key contributor to the onset and progression of various chronic diseases. Maintaining normal lipid metabolism is critical for health, as disruptions lead to dyslipidemia. The gut and liver play central roles in lipid homeostasis, with their bidirectional communication, known as the gut-liver axis, modulated by bile acids (BAs), gut microbiota, and their metabolites. BAs are essential for regulating their own synthesis, lipid metabolism, and anti-inflammatory responses, primarily through the farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Available evidence suggests that high-fat diet-induced the gut microbiota dysbiosis can induce "leaky gut," allowing toxic microbial metabolites to enter the liver via portal circulation, triggering liver inflammation and lipid metabolism disturbances, ultimately leading to hyperlipidemia. Extensive studies have highlighted the roles of probiotics and Traditional Chinese Medicine (TCM) in restoring gut-liver axis balance and modulating lipid metabolism through regulating the levels of lipopolysaccharides, short-chain fatty acids, and BAs. However, the therapeutic potential of probiotics and TCM for hyperlipidemia remains unclear. Here, firstly, we explore the intricate interplay among gut microbiota and metabolites, lipid metabolism, gut-liver axis, and hyperlipidemia. Secondly, we summarize the mechanisms by which probiotics and TCM can alleviate hyperlipidemia by altering the composition of gut microbiota and regulating lipid metabolism via the gut-liver axis. Finally, we emphasize that more clinical trials of probiotics and TCM are necessary to examine their effects on lipid metabolism and hyperlipidemia.
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Affiliation(s)
- Min You
- School of Medicine, Jianghan University, Wuhan, Hubei, China; Institute of Acupuncture and Moxibustion, Jianghan University, Wuhan, Hubei, China
| | - Li Zhou
- School of Medicine, Jianghan University, Wuhan, Hubei, China; Institute of Acupuncture and Moxibustion, Jianghan University, Wuhan, Hubei, China
| | - Fan Wu
- School of Medicine, Jianghan University, Wuhan, Hubei, China; Institute of Acupuncture and Moxibustion, Jianghan University, Wuhan, Hubei, China
| | - Lei Zhang
- School of Medicine, Jianghan University, Wuhan, Hubei, China; Institute of Acupuncture and Moxibustion, Jianghan University, Wuhan, Hubei, China
| | - Shu-Xiu Zhu
- School of Medicine, Jianghan University, Wuhan, Hubei, China; Institute of Acupuncture and Moxibustion, Jianghan University, Wuhan, Hubei, China.
| | - Hong-Xing Zhang
- School of Medicine, Jianghan University, Wuhan, Hubei, China; Institute of Acupuncture and Moxibustion, Jianghan University, Wuhan, Hubei, China.
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22
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Funayama T, Nozu T, Ishioh M, Sumi C, Saito T, Hatayama M, Yamamoto M, Shindo M, Takahashi S, Okumura T. Brain AMPK signaling improves intestinal barrier function through brain orexin and the vagal pathway in rats. Neurosci Lett 2025; 854:138208. [PMID: 40158792 DOI: 10.1016/j.neulet.2025.138208] [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: 10/29/2024] [Revised: 02/25/2025] [Accepted: 03/19/2025] [Indexed: 04/02/2025]
Abstract
Leaky gut, an increased intestinal permeability, has been described in many diseases. We have recently demonstrated that neuropeptides such as orexin in the brain improved leaky gut, suggesting that the brain is involved in maintaining intestinal barrier function. It has been suggested that AMPK in the hypothalamus play a role in food intake. Because the hypothalamus is involved in the regulation of not only feeding behavior but also gut function, the present study was performed to clarify a hypothesis that AMPK in the brain regulate gut barrier function. Colonic permeability was determined by quantifying the absorbed Evans blue within the colonic tissue in rats. Intracisternal AICAR, an AMPK activator, could reduce LPS-induced colonic hyperpermeability while peripherally administered AICAR failed to change it. The improvement of colonic hyperpermeability by intracisternal AICAR was blocked by intracisternal but not subcutaneous compound C, AMPK inhibitor, atropine or vagotomy. The improvement of colonic hyperpermeability by intracisternal AICAR was blocked by intracisternal orexin receptor antagonist but not oxytocin or GLP-1 receptor antagonist. Intracisternal compound C prevented brain oxytocin or GLP-1 but not orexin-induced improvement of colonic hyperpermeability. These results suggest that activation of brain AMPK is capable of reducing colonic hyperpermeability through brain orexin signaling and the vagus nerve. In addition, endogenous AMPK in the brain may mediate the oxytocin or GLP-induced improvement of colonic hyperpermeability. We would suggest that improvement of leaky gut by activation of brain AMPK may play a role in leaky gut-related diseases.
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Affiliation(s)
- Takuya Funayama
- Division of Hematology, Department of Medicine, Asahikawa Medical University, Japan
| | - Tsukasa Nozu
- Department of Regional Medicine and Education, Asahikawa Medical University, Japan; Department of General Medicine, Asahikawa Medical University, Japan
| | - Masatomo Ishioh
- Department of General Medicine, Asahikawa Medical University, Japan
| | - Chihiro Sumi
- Division of Hematology, Department of Medicine, Asahikawa Medical University, Japan
| | - Takeshi Saito
- Division of Hematology, Department of Medicine, Asahikawa Medical University, Japan
| | - Mayumi Hatayama
- Division of Hematology, Department of Medicine, Asahikawa Medical University, Japan
| | - Masayo Yamamoto
- Division of Hematology, Department of Medicine, Asahikawa Medical University, Japan
| | - Motohiro Shindo
- Division of Hematology, Department of Medicine, Asahikawa Medical University, Japan
| | - Shuichiro Takahashi
- Division of Hematology, Department of Medicine, Asahikawa Medical University, Japan
| | - Toshikatsu Okumura
- Division of Hematology, Department of Medicine, Asahikawa Medical University, Japan; Division of Gastroenterology, Department of Medicine, Asahikawa Medical University, Japan.
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23
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Stamation R. Endogenous Ethanol Production in the Human Alimentary Tract: A Literature Review. J Gastroenterol Hepatol 2025; 40:783-790. [PMID: 39853762 PMCID: PMC11968154 DOI: 10.1111/jgh.16869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 11/28/2024] [Accepted: 12/22/2024] [Indexed: 01/26/2025]
Abstract
Endogenous ethanol production, or auto-brewery syndrome (ABS), is a rare condition of the human alimentary canal that results in intoxication without alcohol consumption. Despite its clinical significance, ABS remains largely undiagnosed because of a lack of awareness among clinicians. Published cases have reported extensive biopsychosocial comorbidities accompanying delayed diagnosis and incomplete management; these include social rejection and family separation, court-ordered alcohol rehabilitation and psychiatric admission, legal and employment ramifications, and deteriorating mental health and suicidality. In this mini review, we aim to educate and enlighten clinicians by discussing literature findings pertaining to the pathophysiological mechanisms of gut dysbiosis due to overgrowth of Saccharomyces cerevisiae, E. coli and Klebsiella, impaired intestinal barrier function, and dysregulation of the hypothalamic-pituitary-adrenal axis. Furthermore, we discuss recently discovered associations with sleep quality and mood disorders and explore the medical sequelae of metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis. Drawing on these data, we propose protocols for initial care in the emergency room, subsequent critical care, diagnostic testing with glucose challenge testing, and definitive microbiological testing during the acute phase of illness. We also present an empirical treatment outline while awaiting confirmation of causative organisms and sensitivities.
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Affiliation(s)
- Renee Stamation
- Department of Rural HealthUniversity of Melbourne, Echuca Clinical SchoolEchucaVictoriaAustralia
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24
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Schnabl B, Damman CJ, Carr RM. Metabolic dysfunction-associated steatotic liver disease and the gut microbiome: pathogenic insights and therapeutic innovations. J Clin Invest 2025; 135:e186423. [PMID: 40166938 PMCID: PMC11957707 DOI: 10.1172/jci186423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/02/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of liver disease worldwide, and our understanding of its pathogenesis continues to evolve. MASLD progresses from steatosis to steatohepatitis, fibrosis, and cirrhosis, and this Review explores how the gut microbiome and their metabolites contribute to MASLD pathogenesis. We explore the complexity and importance of the intestinal barrier function and how disruptions of the intestinal barrier and dysbiosis work in concert to promote the onset and progression of MASLD. The Review focuses on specific bacterial, viral, and fungal communities that impact the trajectory of MASLD and how specific metabolites (including ethanol, bile acids, short chain fatty acids, and other metabolites) contribute to disease pathogenesis. Finally, we underscore how knowledge of the interaction between gut microbes and the intestinal barrier may be leveraged for MASLD microbial-based therapeutics. Here, we include a discussion of the therapeutic potential of prebiotics, probiotics, postbiotics, and microbial-derived metabolites.
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Affiliation(s)
- Bernd Schnabl
- Department of Medicine, Division of Gastroenterology, UCSD, San Diego, California, USA
- Department of Medicine, VA San Diego Healthcare System, San Diego, California, USA
| | - Christopher J. Damman
- Department of Medicine, Division of Gastroenterology, University of Washington, Seattle, Washington, USA
| | - Rotonya M. Carr
- Department of Medicine, Division of Gastroenterology, University of Washington, Seattle, Washington, USA
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25
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Xu R, Yu Y, Chen T. Exploring the dark side of probiotics to pursue light: Intrinsic and extrinsic risks to be opportunistic pathogens. Curr Res Food Sci 2025; 10:101044. [PMID: 40235735 PMCID: PMC11999689 DOI: 10.1016/j.crfs.2025.101044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 03/24/2025] [Accepted: 03/26/2025] [Indexed: 04/17/2025] Open
Abstract
Probiotics, live microorganisms with multiple health benefits, have gained popularity for their roles in maintaining daily health and treating a variety of diseases. However, they have the potential to be opportunistic pathogens in some conditions. This review delves into the intrinsic and extrinsic risks associated with probiotics. Intrinsic risks involve the production of harmful substances, such as toxins and invasive factors, biofilm formation, bacteria emboli, antibiotic resistance with relevant genetic materials, genetic plasticity, and metabolic issues, while extrinsic risks include problems in regulatory oversight and public awareness, host health status and appropriately administration. It emphasizes the need for a balanced view of their therapeutic benefits and potential hazards, advocating for further research to understand the complex interactions between probiotics and the human microbiome, to optimize the safety and efficacy of probiotics.
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Affiliation(s)
- Ruiyan Xu
- Ophthalmologic Centre, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China
| | - Yifeng Yu
- Ophthalmologic Centre, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Tingtao Chen
- Ophthalmologic Centre, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
- Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China
- National Engineering Research Centre for Bioengineering Drugs and the Technologies, Institution of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang, 330031, China
- Jiangxi Province Key Laboratory of Bioengineering Drugs, School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
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26
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Wei ZX, Jiang SH, Qi XY, Cheng YM, Liu Q, Hou XY, He J. scRNA-seq of the intestine reveals the key role of mast cells in early gut dysfunction associated with acute pancreatitis. World J Gastroenterol 2025; 31:103094. [PMID: 40182603 PMCID: PMC11962851 DOI: 10.3748/wjg.v31.i12.103094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 01/09/2025] [Accepted: 02/21/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Intestinal barrier dysfunction is a prevalent and varied manifestation of acute pancreatitis (AP). Molecular mechanisms underlying the early intestinal barrier in AP remain poorly understood. AIM To explore the biological processes and mechanisms of intestinal injury associated with AP, and to find potential targets for early prevention or treatment of intestinal barrier injury. METHODS This study utilized single-cell RNA sequencing of the small intestine, alongside in vitro and in vivo experiments, to examine intestinal barrier function homeostasis during the early stages of AP and explore involved biological processes and potential mechanisms. RESULTS Seventeen major cell types and 33232 cells were identified across all samples, including normal, AP1 (4x caerulein injections, animals sacrificed 2 h after the last injection), and AP2 (8x caerulein injections, animals sacrificed 4 h after the last injection). An average of 980 genes per cell was found in the normal intestine, compared to 927 in the AP1 intestine and 1382 in the AP2 intestine. B cells, dendritic cells, mast cells (MCs), and monocytes in AP1 and AP2 showed reduced numbers compared to the normal intestine. Enterocytes, brush cells, enteroendocrine cells, and goblet cells maintained numbers similar to the normal intestine, while cytotoxic T cells and natural killer (NK) cells increased. Enterocytes in early AP exhibited elevated programmed cell death and intestinal barrier dysfunction but retained absorption capabilities. Cytotoxic T cells and NK cells showed enhanced pathogen-fighting abilities. Activated MCs, secreted chemokine (C-C motif) ligand 5 (CCL5), promoted neutrophil and macrophage infiltration and contributed to barrier dysfunction. CONCLUSION These findings enrich our understanding of biological processes and mechanisms in AP-associated intestinal injury, suggesting that CCL5 from MCs is a potential target for addressing dysfunction.
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Affiliation(s)
- Zu-Xing Wei
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Shi-He Jiang
- Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Xiao-Yan Qi
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Yi-Miao Cheng
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Qiong Liu
- Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Xu-Yang Hou
- Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Jun He
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
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Chen YP, Shi LL, Li YY, Zhang YM, Zhang SZ, Hou HD, Chen Y, Zhuo QH, Liu YQ, Wei BJ, Zhang LY. Isoliquiritigenin alleviates radiation-induced intestinal injury in lung cancer by inhibiting TNF-α/caspase3 signaling pathway. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04007-z. [PMID: 40137968 DOI: 10.1007/s00210-025-04007-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 03/02/2025] [Indexed: 03/29/2025]
Abstract
To construct a model of intestinal injury induced by radiotherapy for lung cancer and to study the protective effect and mechanism of isoliquiritigenin. The lungs of mice were irradiated with 0, 2, 4, 6, 8 Gy X-rays to screen the optimal radiation dose. A mouse model of lung cancer was established, and the tumor was irradiated once. At 3, 7, and 10 days after irradiation, H&E was used to detect the pathological manifestations of colon tissue in mice, and WB was used to detect the expression level of tight junction protein in colon tissue, so as to screen the best time point and study its possible mechanism. Molecular docking was used to study the tightness of isoliquiritigenin binding to TNF-α. Isoliquiritigenin (40 mg/kg) was given on the next day after 4 Gy X-ray irradiation. The levels of TNF-α and apoptosis, intestinal mucosal barrier function, MUC2 protein expression, and colon stem cell proliferation were detected. 4Gy X-ray local irradiation induced obvious colon injury in mice, and the injury was obvious on the 7th day. Isoliquiritigenin significantly improved the general condition, colonic histopathological changes, intestinal stem cell proliferation, and colonic tight junction function of lung cancer-bearing mice after radiotherapy. Further studies have found that isoliquiritigenin can downregulate the activation of TNF-α/Caspase-3 signaling pathway by inhibiting the expression of pro-inflammatory factor TNF-α, alleviate the apoptosis of colonic epithelial cells, improve the upregulation of colonic tight junction function, regulate the expression of MUC2, and promote the proliferation of intestinal stem cells, which may be related to the stable binding of isoliquiritigenin to TNF-α. Radiotherapy-induced bystander effect of lung cancer may be related to the abnormal expression of TNF-α. Isoliquiritigenin may downregulate the expression of TNF-α by binding to TNF-α, inhibit the apoptosis of colon cells, promote the proliferation of intestinal stem cells, and maintain the intestinal mucosal barrier to alleviate the colon injury induced by radiation bystander effect.
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Affiliation(s)
- Ya-Ping Chen
- Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities Gansu University of Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Liang-Liang Shi
- Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities Gansu University of Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Yang-Yang Li
- Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities Gansu University of Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Yi-Ming Zhang
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Shang-Zu Zhang
- Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities Gansu University of Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Hong-Dou Hou
- Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities Gansu University of Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Yan Chen
- Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities Gansu University of Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Qi-Hong Zhuo
- Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities Gansu University of Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Yong-Qi Liu
- Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities Gansu University of Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China
- Key Laboratory of Dunhuang Medicine and Transformation at Provincial and Ministerial Level, Gansu university of Traditional Chinese Medicine, Lanzhou, China
| | - Ben-Jun Wei
- Key Laboratory of Dunhuang Medicine and Transformation at Provincial and Ministerial Level, Gansu university of Traditional Chinese Medicine, Lanzhou, China.
| | - Li-Ying Zhang
- Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities Gansu University of Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China.
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Zhou Z, Li X, Xiong M, He Y, Cheng X, Deng J, Li Y, Zhang X, Zhang Z, Zhou C, Yang X. Association between the dietary inflammatory index, bowel habits, and systemic serum inflammatory markers: insights from NHANES (2005-2010). Front Nutr 2025; 12:1543715. [PMID: 40206947 PMCID: PMC11978653 DOI: 10.3389/fnut.2025.1543715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 03/06/2025] [Indexed: 04/11/2025] Open
Abstract
Objective To examine the relationship between the Dietary Inflammatory Index (DII), abnormal bowel habits, and systemic serum inflammatory markers. Methods Data from 9,880 participants in the National Health and Nutrition Examination Survey (NHANES) 2005-2010 were analyzed. The DII was calculated from two 24-h dietary recalls. Bowel habits were assessed using the Bristol Stool Form Scale, and systemic inflammatory markers included AAPR, IBI, NLR, LMR, PNLR, LCR, LA, and PLR. Statistical analyses were performed using R, Zstats, and EmpowerStats to evaluate associations. Results Higher DII scores were positively associated with abnormal bowel habits, including constipation [β (95% CI): 0.11 (0.01-0.22)] and diarrhea [β (95% CI): 0.42 (0.32-0.53)], and with PNLR [β (95% CI): 0.01 (0.01-0.01)], PNLRQ4 [β (95% CI): 0.13 (0.05-0.20)], IBI [β (95% CI): 0.02 (0.01-0.02)], and IBIQ4 [β (95% CI): 0.33 (0.25-0.42)] (p < 0.05). Negative associations were found with AAPR [β (95% CI): -0.33 (-0.60 - -0.06)] and AAPRQ4 [β (95% CI): -0.18 (-0.34 - -0.01)], while no significant associations were observed with LA, LCR, or LMR. Subgroup analyses confirmed stable associations between DII and both chronic diarrhea and constipation across seven subgroups. Smoothed curve fitting revealed nonlinear relationships. A J-shaped association between DII and chronic constipation was identified in BMI and IBI subgroups. For BMI >30, the breakpoint (K) was 1.89, with ORs of 1.228 (95% CI: 1.097-1.375) below and 3.318 (95% CI: 1.531-7.191) above this point. In the IBI Q4 subgroup, the breakpoint was 1.96, with ORs of 1.145 (95% CI: 1.013-1.294) below and 5.794 (95% CI: 2.359-14.228) above. In the diarrhea group, a U-shaped association was observed in the AAPR Q4 population, with a breakpoint of -1.312 and ORs of 0.657 (95% CI: 0.478-0.901) below and 1.266 (95% CI: 1.057-1.518) above. Conclusion Higher DII scores are linked to an increased risk of chronic constipation and diarrhea and are associated with systemic inflammatory markers and factors such as BMI.
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Affiliation(s)
- Zeyang Zhou
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Soochow, China
| | - Xiangyong Li
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Soochow, China
| | - Mengya Xiong
- Department of Operating Room, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yuee He
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Soochow, China
| | - Xinmeng Cheng
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Soochow, China
| | - Jianbo Deng
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Soochow, China
| | - Yanan Li
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Soochow, China
| | - Xiaoyang Zhang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Soochow, China
| | - Zhengcao Zhang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Soochow, China
| | - Chenxi Zhou
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Soochow, China
| | - Xiaodong Yang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Soochow, China
- National Center of Technology Innovation for Biopharmaceuticals, Suzhou, China
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Romeo M, Dallio M, Di Nardo F, Napolitano C, Vaia P, Martinelli G, Federico P, Olivieri S, Iodice P, Federico A. The Role of the Gut-Biliary-Liver Axis in Primary Hepatobiliary Liver Cancers: From Molecular Insights to Clinical Applications. J Pers Med 2025; 15:124. [PMID: 40278303 PMCID: PMC12028696 DOI: 10.3390/jpm15040124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2025] [Revised: 03/14/2025] [Accepted: 03/20/2025] [Indexed: 04/26/2025] Open
Abstract
Background: Hepatobiliary liver cancers (HBLCs) represent the sixth most common neoplasm in the world. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) constitute the main HBLC types, with alarming epidemiological projections. Methods: In recent decades, alterations in gut microbiota, with mutual implications on the gut-liver axis and gut-biliary axis permeability status, have been massively investigated and proposed as HBLC pathogenetic deus ex machina. Results: In the HCC setting, elevated intestinal levels of Escherichia coli and other Gram-negative bacteria have been demonstrated, resulting in a close association with increased lipopolysaccharide (LPS) serum levels and, consequently, chronic systemic inflammation. In contrast, the intestinal microbiota of HCC individuals feature reduced levels of Lactobacillus spp., Bifidobacterium spp., and Enterococcus spp. In the CC setting, evidence has revealed an increased expression of Lactobacillus spp., with enhanced levels of Actynomices spp. and Alloscardovia spp. Besides impaired strains/species representation, gut-derived metabolites, including bile acids (BAs), short-chain fatty acids (SCFAs), and oxidative-stress-derived products, configure a network severely impacting the progression of HBLC. Conclusions: In the era of Precision Medicine, the clarification of microbiota composition and functioning in HCC and CC settings can contribute to the identification of individual signatures, potentially providing novel diagnostic markers, therapeutic approaches, and prognostic/predictive tools.
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Affiliation(s)
- Mario Romeo
- Department of Precision Medicine, Hepatogastroenterology Division, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (M.R.); (F.D.N.); (C.N.); (P.V.); (G.M.); (S.O.); (A.F.)
| | - Marcello Dallio
- Department of Precision Medicine, Hepatogastroenterology Division, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (M.R.); (F.D.N.); (C.N.); (P.V.); (G.M.); (S.O.); (A.F.)
| | - Fiammetta Di Nardo
- Department of Precision Medicine, Hepatogastroenterology Division, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (M.R.); (F.D.N.); (C.N.); (P.V.); (G.M.); (S.O.); (A.F.)
| | - Carmine Napolitano
- Department of Precision Medicine, Hepatogastroenterology Division, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (M.R.); (F.D.N.); (C.N.); (P.V.); (G.M.); (S.O.); (A.F.)
| | - Paolo Vaia
- Department of Precision Medicine, Hepatogastroenterology Division, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (M.R.); (F.D.N.); (C.N.); (P.V.); (G.M.); (S.O.); (A.F.)
| | - Giuseppina Martinelli
- Department of Precision Medicine, Hepatogastroenterology Division, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (M.R.); (F.D.N.); (C.N.); (P.V.); (G.M.); (S.O.); (A.F.)
| | - Pierluigi Federico
- Pharmaceutical Department, ASL NA3 Sud, Torre del Greco, 80059 Naples, Italy;
| | - Simone Olivieri
- Department of Precision Medicine, Hepatogastroenterology Division, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (M.R.); (F.D.N.); (C.N.); (P.V.); (G.M.); (S.O.); (A.F.)
| | | | - Alessandro Federico
- Department of Precision Medicine, Hepatogastroenterology Division, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (M.R.); (F.D.N.); (C.N.); (P.V.); (G.M.); (S.O.); (A.F.)
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Zhu L, Luo Y, Liu Y, Sun S, Yuan J, Zhang L, Zhong W, Ma S, Yu Z, Zhou J, Chen X, Zhao J. Clostridium butyricum ameliorates indomethacin-induced enteropathy by promoting MUC2 secretion via suppressing the Notch pathway. Front Microbiol 2025; 16:1509876. [PMID: 40177488 PMCID: PMC11961966 DOI: 10.3389/fmicb.2025.1509876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 03/04/2025] [Indexed: 04/05/2025] Open
Abstract
Nonsteroidal anti-inflammatory drug (NSAID) enteropathy is a serious clinical complication with no effective treatments available. Modulating the intestinal microbiota through dietary and nutritional targets is a promising strategy for preventing NSAID enteropathy. This study aimed to investigate the protective effect and underlying mechanisms of the probiotic Clostridium butyricum (CB) on indomethacin (IND)-induced enteropathy. C57BL/6J mice received CB treatment for 14 days along with concurrent IND gavage for the final 7 days. Caco2 cells were stimulated with IND to evaluate the effect of CB supernatant (CBS) on the intestinal barrier function, and LS174T cells were used to validate the modulatory action of CBS on the Notch signaling pathway. Our findings revealed that CB treatment prevented anorexia and weight loss, reduced the severity of enteropathy, and decreased the inflammatory response of the small intestine. CB also increased the expression of tight junction proteins and reduced permeability in mice and Caco2 cells. Additionally, CB suppressed apoptosis and promoted proliferation in the small intestine. Further research found that CB increased the number of goblet cells and MUC2 secretion. Mechanistically, CB may promote MUC2 secretion by suppressing the Notch signaling pathway, consistent with the results of intervention in LS174T cells with CBS. In conclusion, CB might prevent NSAID enteropathy by increasing MUC2 secretion through the inhibition of the Notch pathway. Our study identified the potential efficacy of CB as a preventive strategy against NSAID enteropathy and showed promising prospects for CB as a food supplement.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Xin Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Jingwen Zhao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
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Mallardi D, Maqoud F, Guido D, Aloisio M, Linsalata M, Russo F. Mapping Research Trends on Intestinal Permeability in Irritable Bowel Syndrome with a Focus on Nutrition: A Bibliometric Analysis. Nutrients 2025; 17:1064. [PMID: 40292517 PMCID: PMC11945834 DOI: 10.3390/nu17061064] [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: 02/28/2025] [Revised: 03/14/2025] [Accepted: 03/16/2025] [Indexed: 04/30/2025] Open
Abstract
Irritable Bowel Syndrome (IBS) is a complex gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits, often linked to disruptions in intestinal barrier function. Increased intestinal permeability plays a key role in IBS pathogenesis, affecting immune responses, gut microbiota, and inflammation. This study conducts a bibliometric analysis to explore global research trends on intestinal permeability in IBS, focusing on key contributors, collaboration networks, and thematic shifts, particularly the interplay between the intestinal barrier, gut microbiota, and dietary components. A total of 411 articles were retrieved from Scopus, with 232 studies analyzed using Bibliometrix in R. To optimize screening, ASReview, a machine learning tool, was employed, utilizing the Naïve Bayes algorithm combined with Term Frequency-Inverse Document Frequency (TF-IDF) for adaptive ranking of articles by relevance. This approach significantly improved screening step efficacy. The analysis highlights growing research interest, with China and the USA as leading contributors. Key themes include the role of gut microbiota in modulating permeability, the impact of dietary components (fiber, probiotics, bioactive compounds) on tight junction integrity, and the exploration of therapeutic agents. Emerging studies suggest integrating gut barrier modulation with nutritional and microbiome-targeted strategies for IBS management. This study provides a comprehensive overview of research on intestinal permeability in IBS, mapping its evolution and identifying major trends. By highlighting key contributors and thematic areas, it offers insights to guide future investigations into the interplay between gut permeability, diet, and microbiota, advancing understanding of IBS pathophysiology and management.
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Affiliation(s)
- Domenica Mallardi
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology-IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy; (D.M.); (F.M.); (M.A.); (M.L.)
| | - Fatima Maqoud
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology-IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy; (D.M.); (F.M.); (M.A.); (M.L.)
| | - Davide Guido
- Data Science Unit, National Institute of Gastroenterology-IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy;
| | - Michelangelo Aloisio
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology-IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy; (D.M.); (F.M.); (M.A.); (M.L.)
| | - Michele Linsalata
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology-IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy; (D.M.); (F.M.); (M.A.); (M.L.)
| | - Francesco Russo
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology-IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy; (D.M.); (F.M.); (M.A.); (M.L.)
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Muscia Saez V, Perdicaro DJ, Cremonini E, Costantino VV, Fontana AR, Oteiza PI, Vazquez Prieto MA. Grape pomace extract attenuates high fat diet-induced endotoxemia and liver steatosis in mice. Food Funct 2025; 16:2515-2529. [PMID: 40029158 DOI: 10.1039/d4fo06332e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2025]
Abstract
Obesity is a prominent global health concern associated with chronic inflammation and metabolic disorders, such as insulin resistance, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). Excessive consumption of saturated fats exacerbates these conditions by increasing intestinal barrier permeability and circulating endotoxins. This study aims to investigate, in a murine model of high-fat diet (HFD)-induced obesity, the potential beneficial effects of a grape pomace extract (GPE), rich in phenolic compounds, at mitigating endotoxemia, and liver steatosis. Underlying mechanisms were characterized in an in vitro model of intestinal inflammation and permeabilization, as induced by tumor necrosis factor alpha (TNFα) in Caco-2 cell monolayers. Consumption of a HFD (60% calories from fat) for 13 weeks induced obesity, insulin resistance, and liver damage, evidenced by higher levels of plasma alanine aminotransferase (ALT), hepatic triglycerides content, and steatosis. In addition, HFD caused metabolic endotoxemia, hepatic toll-like receptor 4 (TLR4) upregulation and inflammation. GPE supplementation significantly reduced body weight and subcutaneous and visceral adipose tissue weight, and attenuated metabolic dysregulation. Furthermore, GPE decreased circulating LPS levels and mitigated HFD-mediated hepatic TLR4 upregulation, nuclear factor kappa B (NF-κB) activation, and downstream expression of proteins involved in oxidative stress and inflammation (NOX4, TNFα, and F4/80). In Caco-2 cells, GPE mitigated TNFα-induced monolayer permeabilization, decreased tight junction (TJ) protein levels, enhanced cellular oxidant production, activated redox-sensitive signaling, i.e., NF-κB and ERK1/2, and increased NOX1 and MLCK mRNA levels, the latter being a key regulator of monolayer permeability. The above findings suggest that GPE may protect against HFD-induced obesity and associated metabolic dysfunction (insulin resistance and NAFLD) by modulating intestinal barrier integrity and related endotoxemia.
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Affiliation(s)
- V Muscia Saez
- Laboratorio de Nutrición y Fisiopatología de la Obesidad, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo e Instituto de Medicina y Biología Experimental de Cuyo (IMBECU)-CONICET, M5502JMA, Mendoza, Argentina.
| | - D J Perdicaro
- Laboratorio de Nutrición y Fisiopatología de la Obesidad, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo e Instituto de Medicina y Biología Experimental de Cuyo (IMBECU)-CONICET, M5502JMA, Mendoza, Argentina.
| | - E Cremonini
- Departments of Nutrition and Environmental Toxicology, University of California, Davis, USA
| | - V V Costantino
- Laboratorio de Fisiopatología Renal, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo e Instituto de Medicina y Biología Experimental de Cuyo (IMBECU)-CONICET, Argentina
| | - A R Fontana
- Laboratorio de Bioquímica Vegetal, Instituto de Biología Agrícola de Mendoza (IBAM), Facultad de Ciencias Agrarias, CONICET-Universidad Nacional de Cuyo, M5528AHB, Chacras de Coria, Argentina
| | - P I Oteiza
- Departments of Nutrition and Environmental Toxicology, University of California, Davis, USA
| | - M A Vazquez Prieto
- Laboratorio de Nutrición y Fisiopatología de la Obesidad, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo e Instituto de Medicina y Biología Experimental de Cuyo (IMBECU)-CONICET, M5502JMA, Mendoza, Argentina.
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Wang L, Lian YJ, Dong JS, Liu MK, Liu HL, Cao ZM, Wang QN, Lyu WL, Bai YN. Traditional Chinese medicine for chronic atrophic gastritis: Efficacy, mechanisms and targets. World J Gastroenterol 2025; 31:102053. [PMID: 40061592 PMCID: PMC11886037 DOI: 10.3748/wjg.v31.i9.102053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 12/06/2024] [Accepted: 01/21/2025] [Indexed: 02/18/2025] Open
Abstract
Chronic atrophic gastritis (CAG) is an important stage of precancerous lesions of gastric cancer. Effective treatment and regulation of CAG are essential to prevent its progression to malignancy. Traditional Chinese medicine (TCM) has shown multi-targeted efficacy in CAG treatment, with advantages in enhancing gastric mucosal barrier defense, improving microcirculation, modulating inflammatory and immune responses, and promoting lesion healing, etc. Clinical studies and meta-analyses indicate that TCM provides significant benefits, with specific Chinese herbal compounds and monomers demonstrating protective effects on the gastric mucosa through mechanisms including anti-inflammation, anti-oxidation, and regulation of cellular proliferation and apoptosis, etc. Finally, it is pointed out that the efficacy of TCM in the treatment of CAG requires standardized research and unified standards, and constantly clarifies and improves the evaluation criteria of each dimension of gastric mucosal barrier function.
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Affiliation(s)
- Li Wang
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Yan-Jie Lian
- Division of Cardiovascular, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China
| | - Jin-Sheng Dong
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Ming-Kun Liu
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Hong-Liang Liu
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Zheng-Min Cao
- Department of Infectious Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Qing-Nan Wang
- Department of Dermatology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Wen-Liang Lyu
- Department of Infectious Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Yu-Ning Bai
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
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Zhao Y, Zeng Z, Zheng W, Zhang Z, Zhang H, Luo Y, Zhao K, Ding Y, Lu W, Hao F, Huang Y, Shen L. Cow Placenta Peptides Ameliorate D-Galactose-Induced Intestinal Barrier Damage by Regulating TLR/NF-κB Pathway. Vet Sci 2025; 12:229. [PMID: 40266951 PMCID: PMC11945863 DOI: 10.3390/vetsci12030229] [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: 01/18/2025] [Revised: 02/19/2025] [Accepted: 02/26/2025] [Indexed: 04/25/2025] Open
Abstract
This study investigated the protective effects and mechanisms of cow placenta peptides (CPP) on intestinal barrier damage in aging model mice. Forty-eight male ICR mice were assigned to four groups: a control group (N), an aging model group (M), a CPP treatment group (T), and a vitamin C treatment group (P). Groups T and P received oral administration of CPP (2000 mg/kg/day) and vitamin C (100 mg/kg/day), respectively, while groups M, T, and P were subjected to intraperitoneal injections of D-galactose (D-gal) (300 mg/kg/day). Group N received an equivalent volume of normal saline via intraperitoneal injection. Treatments were administered once daily for 8 weeks. The results demonstrated that CPP significantly alleviated D-galactose-induced intestinal structural damage, increasing the villus height-to-crypt depth ratio and reducing serum diamine oxidase (DAO) and lipopolysaccharide (LPS) levels. CPP notably alleviated intestinal oxidative stress and inflammation, restored tight junction expression, and enhanced intestinal barrier integrity. Transcriptome sequencing identified 1396 DEGs associated with CPP's effects, highlighting TLR4, IL-1β, and Mmp9 as core regulatory genes through protein-protein interaction network analysis. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses implicated the TLR4/NF-κB signaling pathway, which was further validated. Western blotting confirmed that CPP significantly down-regulated TLR4, IKKβ, and p-NF-κB p65 protein expression in the intestines of aging mice. In conclusion, CPP effectively alleviates D-gal-induced intestinal barrier damage in aging mice by enhancing antioxidant defense and inhibiting the TLR4/NF-κB signaling pathway, thereby diminishing inflammation and protecting intestinal barrier integrity.
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Affiliation(s)
- Yuquan Zhao
- The Key Laboratory of Animal Disease and Human Health of Sichuan Province, The Medical Research Center for Cow Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (Z.Z.); (W.Z.); (Z.Z.); (H.Z.); (Y.L.); (K.Z.); (Y.D.)
| | - Zhi Zeng
- The Key Laboratory of Animal Disease and Human Health of Sichuan Province, The Medical Research Center for Cow Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (Z.Z.); (W.Z.); (Z.Z.); (H.Z.); (Y.L.); (K.Z.); (Y.D.)
| | - Weijian Zheng
- The Key Laboratory of Animal Disease and Human Health of Sichuan Province, The Medical Research Center for Cow Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (Z.Z.); (W.Z.); (Z.Z.); (H.Z.); (Y.L.); (K.Z.); (Y.D.)
| | - Zeru Zhang
- The Key Laboratory of Animal Disease and Human Health of Sichuan Province, The Medical Research Center for Cow Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (Z.Z.); (W.Z.); (Z.Z.); (H.Z.); (Y.L.); (K.Z.); (Y.D.)
| | - Hanwen Zhang
- The Key Laboratory of Animal Disease and Human Health of Sichuan Province, The Medical Research Center for Cow Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (Z.Z.); (W.Z.); (Z.Z.); (H.Z.); (Y.L.); (K.Z.); (Y.D.)
| | - Yuxin Luo
- The Key Laboratory of Animal Disease and Human Health of Sichuan Province, The Medical Research Center for Cow Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (Z.Z.); (W.Z.); (Z.Z.); (H.Z.); (Y.L.); (K.Z.); (Y.D.)
| | - Kunshan Zhao
- The Key Laboratory of Animal Disease and Human Health of Sichuan Province, The Medical Research Center for Cow Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (Z.Z.); (W.Z.); (Z.Z.); (H.Z.); (Y.L.); (K.Z.); (Y.D.)
| | - Yuyan Ding
- The Key Laboratory of Animal Disease and Human Health of Sichuan Province, The Medical Research Center for Cow Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (Z.Z.); (W.Z.); (Z.Z.); (H.Z.); (Y.L.); (K.Z.); (Y.D.)
| | - Wei Lu
- Jiangsu Agri-Animal Husbandry Vocational College, Taizhou 225300, China; (W.L.); (F.H.)
| | - Fuxing Hao
- Jiangsu Agri-Animal Husbandry Vocational College, Taizhou 225300, China; (W.L.); (F.H.)
| | - Yixin Huang
- The Key Laboratory of Animal Disease and Human Health of Sichuan Province, The Medical Research Center for Cow Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (Z.Z.); (W.Z.); (Z.Z.); (H.Z.); (Y.L.); (K.Z.); (Y.D.)
| | - Liuhong Shen
- The Key Laboratory of Animal Disease and Human Health of Sichuan Province, The Medical Research Center for Cow Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; (Y.Z.); (Z.Z.); (W.Z.); (Z.Z.); (H.Z.); (Y.L.); (K.Z.); (Y.D.)
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Jin Z, Zhang Y, Hu H, Li Q, Zhang L, Zhao K, Liu W, Li L, Gao C. Closed-loop theranostic microgels for immune microenvironment modulation and microbiota remodeling in ulcerative colitis. Biomaterials 2025; 314:122834. [PMID: 39288617 DOI: 10.1016/j.biomaterials.2024.122834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 08/26/2024] [Accepted: 09/10/2024] [Indexed: 09/19/2024]
Abstract
Inflammatory bowel disease (IBD) is characterized by the upregulation of reactive oxygen species (ROS) and dysfunction of gut immune system, and microbiota. The conventional treatments mainly focus on symptom control with medication by overuse of drugs. There is an urgent need to develop a closed-loop strategy that combines in situ monitoring and precise treatment. Herein, we innovatively designed the 'cluster munition structure' theranostic microgels to realize the monitoring and therapy for ulcerative colitis (a subtype of IBD). The superoxide anion specific probe (tetraphenylethylene-coelenterazine, TPC) and ROS-responsive nanogels consisting of postbiotics urolithin A (UA) were loaded into alginate and ion-crosslinked to obtain the theranostic microgels. The theranostic microgels could be delivered to the inflammatory site, where the environment-triggered breakup of the microgels and release of the nanogels were achieved in sequence. The TPC-UA group had optimal results in reducing inflammation, repairing colonic epithelial tissue, and remodeling microbiota, leading to inflammation amelioration and recovery of tight junction between the colonic epithelium, and maintenance of gut microbiota. During the recovery process, the local chemiluminescence intensity, which is proportional to the degree of inflammation, was gradually inhibited. The cluster munition of theranostic microgels displayed promising outcomes in monitoring inflammation and precise therapy, and demonstrated the potential for inflammatory disease management.
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Affiliation(s)
- Zeyuan Jin
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, China.
| | - Yaqi Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
| | - Haijun Hu
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, China
| | - Qian Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Liwen Zhang
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, China
| | - Kefei Zhao
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, China
| | - Wenxing Liu
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, China; Center for Healthcare Materials, Shaoxing Institute, Zhejiang University, Shaoxing, 312099, China.
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
| | - Changyou Gao
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310058, China; Center for Healthcare Materials, Shaoxing Institute, Zhejiang University, Shaoxing, 312099, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou, 310058, China.
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Grover M, Vanuytsel T, Chang L. Intestinal Permeability in Disorders of Gut-Brain Interaction: From Bench to Bedside. Gastroenterology 2025; 168:480-495. [PMID: 39236897 DOI: 10.1053/j.gastro.2024.08.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 06/27/2024] [Accepted: 08/20/2024] [Indexed: 09/07/2024]
Abstract
Intestinal barrier function lies at a critical interface of a range of peripheral and central processes that influence disorders of gut-brain interactions (DGBI). Although rigorously tested, the role of barrier dysfunction in driving clinical phenotype of DGBI remains to be fully elucidated. In vitro, in vivo, and ex vivo strategies can test various aspects of the broader permeability and barrier mechanisms in the gut. Luminal mediators of host, bacterial, and dietary origin can influence the barrier function and a disrupted barrier can also influence the luminal milieu. Critical to our understanding is how barrier dysfunction is influenced by stress and other comorbidities that associate with DGBI and the crosstalk between barrier and neural, hormonal, and immune responses. Additionally, the microbiome's significant role in the communication between the brain and gut has led to the integrative model of a microbiome gut-brain axis with reciprocal interactions between brain networks and networks composed of multiple cells in the gut, including immune cells, enterochromaffin cells, gut microbiota and the derived luminal mediators. This review highlights the techniques for assessment of barrier function, appraises evidence for barrier dysfunction in DGBI including mechanistic studies in humans, as well as provides an overview of therapeutic strategies that can be used to directly or indirectly restore barrier function in DGBI patients.
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Affiliation(s)
- Madhusudan Grover
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Tim Vanuytsel
- Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (ChroMeta), KULeuven, Leuven, Belgium
| | - Lin Chang
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, University of California, Los Angeles, California.
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Gawey BJ, Mars RA, Kashyap PC. The role of the gut microbiome in disorders of gut-brain interaction. FEBS J 2025; 292:1357-1377. [PMID: 38922780 PMCID: PMC11664017 DOI: 10.1111/febs.17200] [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: 01/14/2024] [Revised: 04/03/2024] [Accepted: 06/05/2024] [Indexed: 06/28/2024]
Abstract
Disorders of Gut-Brain Interaction (DGBI) are widely prevalent and commonly encountered in gastroenterology practice. While several peripheral and central mechanisms have been implicated in the pathogenesis of DGBI, a recent body of work suggests an important role for the gut microbiome. In this review, we highlight how gut microbiota and their metabolites affect physiologic changes underlying symptoms in DGBI, with a particular focus on their mechanistic influence on GI transit, visceral sensitivity, intestinal barrier function and secretion, and CNS processing. This review emphasizes the complexity of local and distant effects of microbial metabolites on physiological function, influenced by factors such as metabolite concentration, duration of metabolite exposure, receptor location, host genetics, and underlying disease state. Large-scale in vitro work has elucidated interactions between host receptors and the microbial metabolome but there is a need for future research to integrate such preclinical findings with clinical studies. The development of novel, targeted therapeutic strategies for DGBI hinges on a deeper understanding of these metabolite-host interactions, offering exciting possibilities for the future of treatment of DGBI.
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Affiliation(s)
- Brent J Gawey
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Ruben A Mars
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Purna C Kashyap
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
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38
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Cheng Y, Li Y, Fan Z, Wang N, Wang M, Li Y, Liu C, Li H, Yan F. The effects of restraint stress and orthodontic tooth movements on the intestinal epithelial structure and metabolic function in rats. PLoS One 2025; 20:e0319779. [PMID: 40014578 PMCID: PMC11867309 DOI: 10.1371/journal.pone.0319779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 02/07/2025] [Indexed: 03/01/2025] Open
Abstract
Chronic stress and orthodontic treatment have been revealed to trigger systemic stress responses in rats. This study aimed to investigate the effects of restraint stress and orthodontic treatment on the intestinal epithelial structure, barrier function, flora, and metabolism in rats. Twenty 8-week-old male Wistar rats were randomly divided into four groups: sham-stressed non-orthodontic (CC), sham-stressed orthodontic (CO), stressed non-orthodontic (SC), and stressed orthodontic (SO). The stress intervention involved subjecting the rats to restraint stress for 21 days, while the orthodontic intervention consisted of maxillary first molar traction from days 8 to 21. Histological and immunohistochemical staining were used to observe the epithelial structure and barrier function of the colon. The intestinal flora and metabolite alterations were investigated by 16S rRNA high-throughput sequencing and untargeted metabolomics sequencing. Colonic epithelial tissue disruption, mucus cells reduction, and a decreased expression of intestinal tight junction proteins were observed in the CO, SC, and SO groups. Lactobacillus spp. abundance was significantly lower in the CO group than in the CC group. Prevotella spp. abundance was significantly lower in the SC and SO groups than in the CC and CO groups. The differential metabolite enrichment pathways between each inter-group comparison might all be related to amino acid biosynthesis, protein digestion and absorption, and cofactor biosynthesis. Both restraint stress and orthodontic treatment may adversely affect the colonic epithelial structure and barrier function of rats. The intestinal flora structure and types of metabolites were also affected cumulatively.
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Affiliation(s)
- Ye Cheng
- Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China
| | - Yue Li
- Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China
| | - Ziqing Fan
- Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China
| | - Nannan Wang
- Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China
| | - Min Wang
- Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China
| | - Yanfen Li
- Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China
| | - Chao Liu
- Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China
| | - Huang Li
- Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China
| | - Fuhua Yan
- Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China
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Ullah H, Arbab S, Chang C, Bibi S, Muhammad N, Rehman SU, Suleman, Ullah I, Hassan IU, Tian Y, Li K. Gut microbiota therapy in gastrointestinal diseases. Front Cell Dev Biol 2025; 13:1514636. [PMID: 40078367 PMCID: PMC11897527 DOI: 10.3389/fcell.2025.1514636] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 02/03/2025] [Indexed: 03/14/2025] Open
Abstract
The human gut microbiota, consisting of trillions of microorganisms, plays a crucial role in gastrointestinal (GI) health and disease. Dysbiosis, an imbalance in microbial composition, has been linked to a range of GI disorders, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, and colorectal cancer. These conditions are influenced by the interactions between the gut microbiota, the host immune system, and the gut-brain axis. Recent research has highlighted the potential for microbiome-based therapeutic strategies, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary modifications, to restore microbial balance and alleviate disease symptoms. This review examines the role of gut microbiota in the pathogenesis of common gastrointestinal diseases and explores emerging therapeutic approaches aimed at modulating the microbiome. We discuss the scientific foundations of these interventions, their clinical effectiveness, and the challenges in their implementation. The review underscores the therapeutic potential of microbiome-targeted treatments as a novel approach to managing GI disorders, offering personalized and alternative options to conventional therapies. As research in this field continues to evolve, microbiome-based interventions hold promise for improving the treatment and prevention of gastrointestinal diseases.
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Affiliation(s)
- Hanif Ullah
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, Nursing Key Laboratory of Sichuan Province, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Safia Arbab
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, China
| | - Chengting Chang
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, Nursing Key Laboratory of Sichuan Province, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Saira Bibi
- Department of Zoology Hazara University Manshera, Dhodial, Pakistan
| | - Nehaz Muhammad
- Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology, Hebei Collaborative Innovation Center for Eco-Environment, College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei, China
| | - Sajid Ur Rehman
- School of Public Health and Emergency Management, School of Medicine, Southern University of Science and Technology, Shenzhen, China
| | - Suleman
- Department of Zoology, Government Post Graduate Collage, Swabi, Pakistan
- Higher Education Department, Civil Secretariat Peshawar, Peshawar, Pakistan
| | - Irfan Ullah
- Department of Biotechnology and Genetics Engineering, Hazara University, Manshera, Pakistan
| | - Inam Ul Hassan
- Department of Microbiology, Hazara University Manshera, Manshera, Pakistan
| | - Yali Tian
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, Nursing Key Laboratory of Sichuan Province, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Ka Li
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, Nursing Key Laboratory of Sichuan Province, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
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Zhou X, Yang Y, Su Z, Luo Z. Dexmedetomidine Protects the Brain: Exploring the α2AR/FAK Pathway in Post-Stroke Intestinal Barrier Repair. FRONT BIOSCI-LANDMRK 2025; 30:27159. [PMID: 40018945 DOI: 10.31083/fbl27159] [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: 10/27/2024] [Revised: 12/19/2024] [Accepted: 01/09/2025] [Indexed: 03/01/2025]
Abstract
INTRODUCTION Globally, ischemic stroke is a major cause of mortality and disability, posing a significant challenge in clinical practice and public health. Recent studies have reported that stroke leads to the impairment of the intestinal barrier and the migration of intestinal bacteria to multiple organs. This process exacerbates neurological damage by further impairing intestinal barrier function and leading to bacterial translocation. Dexmedetomidine (Dex), an α2-adrenoceptor (α2AR) agonist, has proven anti-cerebral ischemic effects, yet its effects in post-stroke intestinal dysfunction remain unclear. This study aimed to determine whether Dex mitigates intestinal dysfunction and brain injury following cerebral ischemia-reperfusion. METHODS A C57BL/6J mouse model of middle cerebral artery occlusion (MCAO) was used for in vivo experiments, while lipopolysaccharide (LPS)-induced Caco-2 monolayers served as an in vitro model of intestinal barrier dysfunction. Neuronal apoptosis was evaluated using neuronal nuclei (NeuN) and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) double labeling. Reverse transcription-quantitative PCR (RT-qPCR) was performed to measure pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. Intestinal permeability was assessed using histological score, serum fluorescein isothiocyanate (FITC)-dextran fluorescence, and endotoxin levels. The expression levels of epithelial cadherin (E-cadherin), zonula occludens-1 (ZO-1), and occludin were analyzed by western blot and immunofluorescence. Statistical analyses included analysis of variance with Tukey's post-hoc test. RESULTS Dex treatment significantly reduced cerebral infarct volume (p < 0.001) and improved neurological scores compared to MCAO controls. Neuronal apoptosis was significantly inhibited (p < 0.01), as evidenced by reduced TUNEL-positive cells in Dex-treatment MCAO mice. TNF-α, IL-1β and IL-6 were markedly downregulated (p < 0.05). While MCAO increased intestinal permeability (elevated serum FITC-dextran and endotoxin levels, p < 0.01), Dex treatment restored barrier integrity. Dex upregulated E-cadherin expression significantly (p < 0.05) but did not restore the decreased levels of ZO-1 and occludin following MCAO. Dex promoted intestinal permeability repair and alleviated brain injury via the α2AR/focal adhesion kinase (FAK) pathway in MCAO mice. Similarly, Dex mitigated LPS-induced barrier dysfunction in Caco-2 monolayers by restoring FAK expression and improving intestinal barrier integrity. CONCLUSIONS Dex alleviates post-stroke intestinal barrier dysfunction and mitigates brain injury, possibly through activating the α2AR/FAK pathway. These findings underscore a potential therapeutic strategy for addressing secondary complications of ischemic stroke and improving patient outcomes.
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Affiliation(s)
- Xinting Zhou
- Department of Anaesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China
| | - Yan Yang
- Department of Anaesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China
| | - Zixuan Su
- Department of Anaesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China
| | - Zhonghui Luo
- Department of Anaesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, 421001 Hengyang, Hunan, China
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Parodi E, Novi M, Bottino P, La Porta E, Merlotti G, Castello LM, Gotta F, Rocchetti A, Quaglia M. The Complex Role of Gut Microbiota in Systemic Lupus Erythematosus and Lupus Nephritis: From Pathogenetic Factor to Therapeutic Target. Microorganisms 2025; 13:445. [PMID: 40005809 PMCID: PMC11858628 DOI: 10.3390/microorganisms13020445] [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: 12/30/2024] [Revised: 02/07/2025] [Accepted: 02/13/2025] [Indexed: 02/27/2025] Open
Abstract
The role of gut microbiota (GM) and intestinal dysbiosis in triggering the onset and/or modulating the severity and progression of lupus nephritis (LN) has been the object of intense research over the last few years. Some alterations at the phyla level, such as the abundance of Proteobacteria and reduction in Firmicutes/Bacteroidetes (F/B) ratio and in α-diversity have been consistently reported in systemic lupus erythematosus (SLE), whereas a more specific role has been ascribed to some species (Bacteroides thetaiotaomicron and Ruminococcus gnavus) in LN. Underlying mechanisms include microbial translocation through a "leaky gut" and subsequent molecular mimicry, immune dysregulation (alteration of IFNγ levels and of balance between Treg and Th17 subsets), and epigenetic interactions. Levels of bacterial metabolites, such as butyrate and other short-chain fatty acids (SCFAs), appear to play a key role in modulating LN. Beyond bacterial components of GM, virome and mycobiome are also increasingly recognized as important players in the modulation of an immune response. On the other hand, microbiota-based therapy appears promising and includes diet, prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT). The modulation of microbiota could correct critical alterations, such as F/B ratio and Treg/Th17 imbalance, and blunt production of autoantibodies and renal damage. Despite current limits, GM is emerging as a powerful environmental factor that could be harnessed to interfere with key mechanisms leading to SLE, preventing flares and organ damage, including LN. The aim of this review is to provide a state-of-the-art analysis of the role of GM in triggering and modulating SLE and LN on the one hand, while exploring possible therapeutic manipulation of GM to control the disease on the other hand.
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Affiliation(s)
- Emanuele Parodi
- Nephrology and Dialysis Unit, SS. Antonio e Biagio e Cesare Arrigo University Hospital, 15121 Alessandria, Italy;
| | - Marialuisa Novi
- Gastroenterology Unit, SS. Antonio e Biagio e Cesare Arrigo University Hospital, 15121 Alessandria, Italy;
| | - Paolo Bottino
- Microbiology Unit, SS. Antonio e Biagio e Cesare Arrigo University Hospital, 15121 Alessandria, Italy; (F.G.); (A.R.)
| | - Edoardo La Porta
- Nephrology and Dialysis Unit, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy;
| | - Guido Merlotti
- Department of Primary Care, Azienda Socio Sanitaria Territoriale (ASST) of Pavia, 27100 Pavia, Italy;
| | - Luigi Mario Castello
- Internal Medicine Unit, SS. Antonio e Biagio e Cesare Arrigo University Hospital, 15121 Alessandria, Italy;
- Department of Translational Medicine, Università del Piemonte Orientale (UPO), 28100 Novara, Italy
| | - Franca Gotta
- Microbiology Unit, SS. Antonio e Biagio e Cesare Arrigo University Hospital, 15121 Alessandria, Italy; (F.G.); (A.R.)
| | - Andrea Rocchetti
- Microbiology Unit, SS. Antonio e Biagio e Cesare Arrigo University Hospital, 15121 Alessandria, Italy; (F.G.); (A.R.)
| | - Marco Quaglia
- Nephrology and Dialysis Unit, SS. Antonio e Biagio e Cesare Arrigo University Hospital, 15121 Alessandria, Italy;
- Department of Translational Medicine, Università del Piemonte Orientale (UPO), 28100 Novara, Italy
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Jarrett H, Medlin S, Morehen JC. The Role of the Gut Microbiome and Probiotics in Sports Performance: A Narrative Review Update. Nutrients 2025; 17:690. [PMID: 40005018 PMCID: PMC11858190 DOI: 10.3390/nu17040690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 02/12/2025] [Accepted: 02/13/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives: Gut microbiome modulation through probiotics is a growing area of research, with several investigations reporting beneficial health outcomes for the host. Physical exercise has been shown to impact gut microbiome diversity. Emerging evidence suggests that probiotic supplementation can affect exercise performance. However, the mechanisms and domain-specific effects of gut microbiome modulation on performance remain to be elucidated. This narrative review aims to investigate the potential mechanisms underpinning the ergogenic benefits of probiotics and further define the current evidence base for specific performance domains. Discussion: The literature suggests that improved recovery after intense training regimes, enhanced nutrient absorption, alleviation of gastrointestinal symptoms, and improved immune function may underpin the beneficial effects of probiotics on sporting performance. A small number of trials also suggest that probiotic supplementation may improve symptoms of performance anxiety. However, further research is warranted on this topic. The evidence is most substantial for improvements in endurance performance, whilst only a few trials have investigated the impact upon power performance, albeit with promising results. Conclusions/Future Perspectives: In summary, probiotic supplementation has been shown to improve sporting performance; future research may wish to further explore the impact on power performance and investigate specific mechanisms of action.
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Affiliation(s)
- Harry Jarrett
- Department for Research and Development, Heights, London W1D 2LG, UK;
| | - Sophie Medlin
- Department for Research and Development, Heights, London W1D 2LG, UK;
- City Dietitians, London WC2E 7PP, UK
| | - James C. Morehen
- Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool L3 2EX, UK;
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Kerezoudi EN, Zervakis GI, Pletsa V, Kyriacou A, Brummer RJ, Rangel I. Pleurotus eryngii Mushrooms Fermented with Human Fecal Microbiota Protect Intestinal Barrier Integrity: Immune Modulation and Signalling Pathways Counter Deoxycholic Acid-Induced Disruption in Healthy Colonic Tissue. Nutrients 2025; 17:694. [PMID: 40005021 PMCID: PMC11858169 DOI: 10.3390/nu17040694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 02/12/2025] [Accepted: 02/13/2025] [Indexed: 02/27/2025] Open
Abstract
Background: This study explores the potential of the Pleurotus eryngii mushroom fermentation supernatant (FS-PEWS) as an intervention for mitigating sodium deoxycholate (SDC)-induced intestinal barrier dysfunction and inflammation. Methods: FS-PEWS was assessed for its protective effects against SDC-induced barrier dysfunction and inflammation using an in vitro Caco-2 cell model and ex vivo colonic biopsies from healthy adult donors, where barrier integrity, permeability, immunomodulation and receptor-mediated pathways were evaluated. Results: In Caco-2 cells, SDC exposure downregulated ZO-1, occludin, and claudin-1 expression, with FS-PEWS restoring ZO-1 and claudin-1 levels while maintaining cell viability. In colonic biopsies from healthy adults, FS-PEWS maintained tissue integrity and selectively mitigated transcellular permeability without affecting paracellular permeability when combined with the stressor. Additionally, FS-PEWS exhibited potent anti-inflammatory effects, reducing pro-inflammatory cytokines, e.g., TNF-α, IL-6, and IL-1β and modulating receptor-mediated pathways, i.e., TLR-4, dectin-1. Conclusions: These results demonstrate the potential of FS-PEWS to sustain intestinal barrier function and modulate immune responses under stress, highlighting its therapeutic potential for managing gut barrier dysfunction and inflammation associated with microbial metabolite-induced disruptions.
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Affiliation(s)
- Evangelia N. Kerezoudi
- Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Örebro University, 70182 Örebro, Sweden; (R.J.B.); (I.R.)
- Department of Nutrition and Dietetics, Harokopio University, 17676 Athens, Greece;
| | - Georgios I. Zervakis
- Laboratory of General and Agricultural Microbiology, Department of Crop Science, Agricultural University of Athens, 11855 Athens, Greece;
| | - Vasiliki Pletsa
- Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece;
| | - Adamantini Kyriacou
- Department of Nutrition and Dietetics, Harokopio University, 17676 Athens, Greece;
| | - Robert J. Brummer
- Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Örebro University, 70182 Örebro, Sweden; (R.J.B.); (I.R.)
| | - Ignacio Rangel
- Nutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Örebro University, 70182 Örebro, Sweden; (R.J.B.); (I.R.)
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He R, Qi P, Shu L, Ding Y, Zeng P, Wen G, Xiong Y, Deng H. Dysbiosis and extraintestinal cancers. J Exp Clin Cancer Res 2025; 44:44. [PMID: 39915884 PMCID: PMC11804008 DOI: 10.1186/s13046-025-03313-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: 08/26/2024] [Accepted: 01/31/2025] [Indexed: 02/09/2025] Open
Abstract
The gut microbiota plays a crucial role in safeguarding host health and driving the progression of intestinal diseases. Despite recent advances in the remarkable correlation between dysbiosis and extraintestinal cancers, the underlying mechanisms are yet to be fully elucidated. Pathogenic microbiota, along with their metabolites, can undermine the integrity of the gut barrier through inflammatory or metabolic pathways, leading to increased permeability and the translocation of pathogens. The dissemination of pathogens through the circulation may contribute to the establishment of an immune-suppressive environment that promotes carcinogenesis in extraintestinal organs either directly or indirectly. The oncogenic cascade always engages in the disruption of hormonal regulation and inflammatory responses, the induction of genomic instability and mutations, and the dysregulation of adult stem cell proliferation. This review aims to comprehensively summarize the existing evidence that points to the potential role of dysbiosis in the malignant transformation of extraintestinal organs such as the liver, breast, lung, and pancreas. Additionally, we delve into the limitations inherent in current methodologies, particularly the challenges associated with differentiating low loads gut-derived microbiome within tumors from potential sample contamination or symbiotic microorganisms. Although still controversial, an understanding of the contribution of translocated intestinal microbiota and their metabolites to the pathological continuum from chronic inflammation to tumors could offer a novel foundation for the development of targeted therapeutics.
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Affiliation(s)
- Ruishan He
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, No. 133 South Guangchang Road, Nanchang, Jiangxi Province, 330003, China
| | - Pingqian Qi
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, No. 133 South Guangchang Road, Nanchang, Jiangxi Province, 330003, China
| | - Linzhen Shu
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, No. 133 South Guangchang Road, Nanchang, Jiangxi Province, 330003, China
| | - Yidan Ding
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, No. 133 South Guangchang Road, Nanchang, Jiangxi Province, 330003, China
| | - Peng Zeng
- Department of Breast Surgery, Jiangxi Armed Police Corps Hospital, Nanchang, China
| | - Guosheng Wen
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, No. 133 South Guangchang Road, Nanchang, Jiangxi Province, 330003, China
| | - Ying Xiong
- Department of General Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330031, Jiangxi, China
| | - Huan Deng
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Affiliated Rehabilitation Hospital, Jiangxi Medical College, Nanchang University, No. 133 South Guangchang Road, Nanchang, Jiangxi Province, 330003, China.
- Tumor Immunology Institute, Nanchang University, Nanchang, 330006, Jiangxi, China.
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Zhu L, Yang X. Gut Microecological Prescription: A Novel Approach to Regulating Intestinal Micro-Ecological Balance. Int J Gen Med 2025; 18:603-626. [PMID: 39931312 PMCID: PMC11807788 DOI: 10.2147/ijgm.s504616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 01/21/2025] [Indexed: 02/13/2025] Open
Abstract
The intestinal microecology is comprises intestinal microorganisms and other components constituting the entire ecosystem, presenting characteristics of stability and dynamic balance. Current research reveals intestinal microecological imbalances are related to various diseases. However, fundamental research and clinical applications have not been effectively integrated. Considering the importance and complexity of regulating the intestinal microecological balance, this study provides an overview of the high-risk factors affecting intestinal microecology and detection methods. Moreover, it proposes the definition of intestinal microecological imbalance and the definition, formulation, and outcomes of gut microecological prescription to facilitate its application in clinical practice, thus promoting clinical research on intestinal microecology and improving the quality of life of the population.
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Affiliation(s)
- Lingping Zhu
- The Affiliated Nanhua Hospital, Department of General Practice, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China
- School of Public Health, Fudan University, Shanghai, 200433, People’s Republic of China
| | - Xuefeng Yang
- The Affiliated Nanhua Hospital, Department of General Practice, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China
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Rauert C, Charlton N, Bagley A, Dunlop SA, Symeonides C, Thomas KV. Assessing the Efficacy of Pyrolysis-Gas Chromatography-Mass Spectrometry for Nanoplastic and Microplastic Analysis in Human Blood. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2025; 59:1984-1994. [PMID: 39851066 PMCID: PMC11800385 DOI: 10.1021/acs.est.4c12599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 01/14/2025] [Accepted: 01/15/2025] [Indexed: 01/25/2025]
Abstract
Humans are constantly exposed to micro- and nanosized plastics (MNPs); however, there is still limited understanding of their fate within the body, partially due to limitations with current analytical techniques. The current study assessed the appropriateness of pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) analysis for the quantification of a range of polymers in human blood. An extraction protocol that reduced matrix interferences (false positives) of polyethylene (PE) and polyvinyl chloride (PVC) was developed and validated. Extraction recoveries ranged 7-109%, although surface-modified polystyrene (carboxylated) increased nanoparticle recoveries from 17 to 52%. Realistic detection limits were calculated for each polymer, accounting for matrix suppression and extraction recovery. These were up to 20 times higher than nominal detection limits calculated with Milli-Q water. Finally, the method was tested with a pilot study of the Australian population. PE interferences were reduced but still present, and no other polymers were above detection limits. It was concluded that Py-GC-MS is currently not a suitable analysis method for PE and PVC in biological matrices due to the presence of interferences and nonspecific pyrolysis products. Furthermore, while it is plausible to detect some polymers in blood, the estimated exposure concentrations needed are approaching the detection limits of the technique.
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Affiliation(s)
- Cassandra Rauert
- Queensland
Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, 20 Cornwall Street, Woolloongabba, Queensland 4102, Australia
- Minderoo
Centre − Plastics and Human Health, 20 Cornwall Street, Woolloongabba, Queensland 4102, Australia
| | - Nathan Charlton
- Queensland
Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, 20 Cornwall Street, Woolloongabba, Queensland 4102, Australia
- Minderoo
Centre − Plastics and Human Health, 20 Cornwall Street, Woolloongabba, Queensland 4102, Australia
| | - Angus Bagley
- Queensland
Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, 20 Cornwall Street, Woolloongabba, Queensland 4102, Australia
- Minderoo
Centre − Plastics and Human Health, 20 Cornwall Street, Woolloongabba, Queensland 4102, Australia
| | - Sarah A. Dunlop
- Minderoo
Foundation, Perth, Western Australia 6009, Australia
- School
of Biological Sciences, The University of Western Australia, Perth, Western Australia 6009, Australia
| | - Christos Symeonides
- Minderoo
Foundation, Perth, Western Australia 6009, Australia
- Centre
for Community Child Health, Royal Children’s
Hospital, Parkville, Victoria 3056, Australia
| | - Kevin V. Thomas
- Queensland
Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, 20 Cornwall Street, Woolloongabba, Queensland 4102, Australia
- Minderoo
Centre − Plastics and Human Health, 20 Cornwall Street, Woolloongabba, Queensland 4102, Australia
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Sharma A, Lee HJ. Antimicrobial Activity of Probiotic Bacteria Isolated from Plants: A Review. Foods 2025; 14:495. [PMID: 39942088 PMCID: PMC11817414 DOI: 10.3390/foods14030495] [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: 01/03/2025] [Revised: 01/27/2025] [Accepted: 01/31/2025] [Indexed: 02/16/2025] Open
Abstract
Lactic acid bacteria (LAB) constitute a heterogeneous group of bacteria isolated from fermented foods, animals, plants, and mammalian guts, with many health-promoting properties. Probiotics with antagonistic properties against human pathogens and foodborne bacteria have garnered significant attention from the scientific fraternity. A dedicated review focusing on plant-derived probiotic bacteria and their antagonistic properties has not been comprehensively reviewed. Thus, this review aimed at providing an overview of LAB isolates derived from several unconventional sources such as fruits, seeds, fruit pulp, leaves, roots, vegetables, grasses, and flowers and with their antibacterial, antifungal, and antiviral properties. This paper reviewed the antimicrobial properties of different genera, Lactobacillus, Leuconostoc, Weissella, Enterococcus, Pediococcus, Bacillus, and Fructobacillus, their postbiotics, and paraprobiotics. Several important mechanisms, including the secretion of bacteriocins, bacteriocin-like substances, reuterin, organic acids (lactic and acetic), peptides, exopolysaccharides, and hydrogen peroxide, have been attributed to their antimicrobial actions against pathogens. However, their precise mode of action is poorly understood; hence, further research should be conducted to reveal detailed mechanisms. Finally, the review discusses the summary and future implications. Given the significance, LAB and derived antimicrobial compounds can potentially be exploited in food preservation and safety or for medicinal applications after evaluating their safety.
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Affiliation(s)
- Anshul Sharma
- Department of Food and Nutrition, College of BioNano Technology, Gachon University, Seongnam-si 13120, Republic of Korea;
- Institute for Ageing and Clinical Nutrition Research, Gachon University, Seongnam-si 13120, Republic of Korea
| | - Hae-Jeung Lee
- Department of Food and Nutrition, College of BioNano Technology, Gachon University, Seongnam-si 13120, Republic of Korea;
- Institute for Ageing and Clinical Nutrition Research, Gachon University, Seongnam-si 13120, Republic of Korea
- Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences and Technology, Gachon University, Incheon 21999, Republic of Korea
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Funayama T, Nozu T, Ishioh M, Igarashi S, Tanaka H, Sumi C, Saito T, Toki Y, Hatayama M, Yamamoto M, Shindo M, Takahashi S, Okumura T. Splenectomy prevents brain orexin, ghrelin, or oxytocin but not GLP-1-induced improvement of intestinal barrier function in rats. Neurogastroenterol Motil 2025; 37:e14949. [PMID: 39450642 DOI: 10.1111/nmo.14949] [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: 05/21/2024] [Revised: 09/30/2024] [Accepted: 10/15/2024] [Indexed: 10/26/2024]
Abstract
BACKGROUND Accumulating evidence has suggested that neuropeptides such as orexin, ghrelin, or oxytocin act centrally in the brain to regulate intestinal barrier function through the vagus nerve. It has been reported that the vagal cholinergic anti-inflammatory pathway was blocked by splenectomy. In the present study, we therefore examined the effect of splenectomy on neuropeptides-induced improvement of increased intestinal permeability. METHODS Colonic permeability was determined in vivo by quantifying the absorbed Evans blue in colonic tissue for 15 min spectrophotometrically in rats. RESULTS Splenectomy increased colonic permeability. The increased permeability by splenectomy was significantly blocked by vagal activation induced by carbachol or 2-deoxy-d-glucose which was prevented by atropine, suggesting vagal activation could prevent colonic hyperpermeability in splenectomized rats. In the splenectomized rats, intracisternal injection of orexin, ghrelin, oxytocin, or butyrate failed to inhibit increased colonic permeability while intracisternal glucagon-like peptide-1 (GLP-1) analogue, liraglutide, potently blocked the increased colonic permeability in a dose-dependent manner. The liraglutide-induced improvement of increased colonic permeability was blocked by atropine in splenectomized rats. Intracisternal injection of GLP-1 receptor antagonist attenuated 2-deoxy-d-glucose-induced improvement of colonic hyperpermeability in splenectomized rats. CONCLUSION The present results suggested that the spleen is important in the improvement of intestinal barrier function by brain orexin, ghrelin or oxytocin, and butyrate. On the other hand, GLP-1 acts centrally in the brain to improve colonic hyperpermeability in a spleen-independent manner. All these results suggest that dual mechanisms (spleen dependent or independent) may exist for the brain-gut regulation in intestinal barrier function.
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Affiliation(s)
- Takuya Funayama
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Tsukasa Nozu
- Department of General Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Masatomo Ishioh
- Department of General Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Sho Igarashi
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Hiroki Tanaka
- Department of Pathology, Asahikawa Medical University, Asahikawa, Japan
| | - Chihiro Sumi
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Takeshi Saito
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Yasumichi Toki
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Mayumi Hatayama
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Masayo Yamamoto
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
| | - Motohiro Shindo
- Department of Medicine, Asahikawa Medical University, Asahikawa, Japan
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Yang J, Shang N, Li Z, Xu J, Zhou X, Zhou H, Luo W, Xu P, Zhou Y, Sheng X, Zhu Z, Zhang M, Ma X, Tan M, Wu H. Oral Lactoferrin-Responsive Formulation Anchoring around Inflammatory Bowel Region for IBD Therapy. Adv Healthc Mater 2025; 14:e2402731. [PMID: 39722174 DOI: 10.1002/adhm.202402731] [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: 07/24/2024] [Revised: 10/11/2024] [Indexed: 12/28/2024]
Abstract
Oral formulation is the ideal treatment method for inflammatory bowel disease (IBD) therapy, but the mucosal damage and diarrhea symptoms impede the drug retention around the inflammatory region, severely limiting IBD therapeutic efficacy. To address this, an oral astaxanthin (Ast) precise delivery formulation is developed with the selective Ast anchoring around the inflammatory region by the novel lactoferrin (LF)-responsive flocculation. This formulation also heightens the apparent solubility of Ast with the minimized edible safety risks for the edible raw materials. For in vivo IBD therapy, the precise delivery formulation exhibits remarkable outcomes, including a significant increase in colon length and a 100% survival rate. Furthermore, it is verified that the mechanism of treatment is primarily attributed to the improved immunoregulation, epithelial repair, and gut microbiota remodeling after the LF-responsive flocculation. This effective inflammatory-responsive delivery design is instructive and valuable to develop more precise delivery systems for IBD therapy.
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Affiliation(s)
- Jinfan Yang
- College of Bioresources Chemical and Materials Engineering, Shaanxi University of Science & Technology, Xi'an, Shaanxi, 710021, China
- Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Ning Shang
- College of Bioresources Chemical and Materials Engineering, Shaanxi University of Science & Technology, Xi'an, Shaanxi, 710021, China
- Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Zhengqing Li
- College of Bioresources Chemical and Materials Engineering, Shaanxi University of Science & Technology, Xi'an, Shaanxi, 710021, China
- Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Ji Xu
- Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
- School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Xin Zhou
- Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
- School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Hui Zhou
- Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Wen Luo
- Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
- School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Peng Xu
- Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
- School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Yucheng Zhou
- General Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China
| | - Xueru Sheng
- Liaoning Key Lab of Lignocellulose Chemistry and BioMaterials, College of Light Industry and Chemical Engineering, Dalian Polytechnic University, Dalian, 116034, China
| | - Zheng Zhu
- Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China
| | - Mingzhen Zhang
- School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Xiaobin Ma
- Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
| | - Mingqian Tan
- Academy of Food Interdisciplinary Science, School of Food Science and Technology, Dalian Polytechnic University, Qinggongyuan1, Ganjingzi District, Dalian, Liaoning, 116034, China
| | - Hao Wu
- Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
- School of Basic Medical Sciences, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China
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Damianos J, Abdelnaem N, Camilleri M. Gut Goo: Physiology, Diet, and Therapy of Intestinal Mucus and Biofilms in Gastrointestinal Health and Disease. Clin Gastroenterol Hepatol 2025; 23:205-215. [PMID: 39426645 PMCID: PMC11761393 DOI: 10.1016/j.cgh.2024.09.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 09/05/2024] [Accepted: 09/16/2024] [Indexed: 10/21/2024]
Abstract
The gastrointestinal tract has remarkable capacity to withstand considerable insults from exposure to abrasive food particles, chemicals, allergens, and pathogenic microbes. Maintaining a robust epithelial barrier sequesters these potentially harmful substances in the lumen, preventing absorption into the systemic circulation. Normal functioning of this barrier is central in diverse physiological processes including digestion, immunity, inflammation, and gut-brain signaling. One crucial component of the barrier is the mucus layer covering the epithelium. There is increased appreciation of the importance of mucus in maintenance of the gut barrier, and how dysregulation of the mucus layer contributes to several common gastrointestinal pathologies. This manuscript reviews the physical and chemical properties of mucus, its maintenance and turnover, and its role in maintaining gut barrier integrity. The dynamic interactions of the mucus layer within the gut ecosystem are illustrated by highlighting how a weakened mucus layer or defective mucus production facilitate pathogenic microbial colonization and mucosal biofilm formation. These may potentially contribute to the pathogenesis of gastrointestinal diseases such as inflammatory bowel diseases or result in secretion and mucosal damage and inflammation in bile acid diarrhea. A final goal is to review how certain dietary factors, especially low-fiber diets and emulsifiers common in Western diets, can harm the mucus layer. This report summarizes evidence from preclinical and human studies that document damage to the mucus layer, and reviews approaches, including diets and probiotics, that promote a healthy mucus layer and break down pathogenic biofilms, thereby potentially preventing and/or treating gastrointestinal diseases that impact mucosal integrity.
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Affiliation(s)
- John Damianos
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Nada Abdelnaem
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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