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Lista S, Munafò A, Caraci F, Imbimbo C, Emanuele E, Minoretti P, Pinto-Fraga J, Merino-País M, Crespo-Escobar P, López-Ortiz S, Monteleone G, Imbimbo BP, Santos-Lozano A. Gut microbiota in Alzheimer's disease: Understanding molecular pathways and potential therapeutic perspectives. Ageing Res Rev 2025; 104:102659. [PMID: 39800223 DOI: 10.1016/j.arr.2025.102659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 11/29/2024] [Accepted: 01/09/2025] [Indexed: 01/15/2025]
Abstract
Accumulating evidence suggests that gut microbiota (GM) plays a crucial role in Alzheimer's disease (AD) pathogenesis and progression. This narrative review explores the complex interplay between GM, the immune system, and the central nervous system in AD. We discuss mechanisms through which GM dysbiosis can compromise intestinal barrier integrity, enabling pro-inflammatory molecules and metabolites to enter systemic circulation and the brain, potentially contributing to AD hallmarks. Additionally, we examine other pathophysiological mechanisms by which GM may influence AD risk, including the production of short-chain fatty acids, secondary bile acids, and tryptophan metabolites. The role of the vagus nerve in gut-brain communication is also addressed. We highlight potential therapeutic implications of targeting GM in AD, focusing on antibiotics, probiotics, prebiotics, postbiotics, phytochemicals, and fecal microbiota transplantation. While preclinical studies showed promise, clinical evidence remains limited and inconsistent. We critically assess clinical trials, emphasizing challenges in translating GM-based therapies to AD patients. The reviewed evidence underscores the need for further research to elucidate precise molecular mechanisms linking GM to AD and determine whether GM dysbiosis is a contributing factor or consequence of AD pathology. Future studies should focus on large-scale clinical trials to validate GM-based interventions' efficacy and safety in AD.
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Affiliation(s)
- Simone Lista
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - Antonio Munafò
- Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence 50139, Italy.
| | - Filippo Caraci
- Department of Drug and Health Sciences, University of Catania, Catania 95125, Italy; Oasi Research Institute-IRCCS, Troina 94018, Italy.
| | - Camillo Imbimbo
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia 27100, Italy.
| | | | | | - José Pinto-Fraga
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - María Merino-País
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - Paula Crespo-Escobar
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - Susana López-Ortiz
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain.
| | - Giovanni Monteleone
- Department of Systems Medicine, University of Rome Tor Vergata, Rome 00133, Italy; Unit of Gastroenterology, Policlinico Tor Vergata University Hospital, Rome 00133, Italy.
| | - Bruno P Imbimbo
- Department of Research and Development, Chiesi Farmaceutici, Parma 43122, Italy.
| | - Alejandro Santos-Lozano
- i+HeALTH Strategic Research Group, Department of Health Sciences, Miguel de Cervantes European University (UEMC), Valladolid 47012, Spain; Physical Activity and Health Research Group (PaHerg), Research Institute of the Hospital 12 de Octubre ('imas12'), Madrid 28041, Spain.
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Alcedo González J, Estremera-Arévalo F, Cobián Malaver J, Santos Vicente J, Alcalá-González LG, Naves J, Barba Orozco E, Barber Caselles C, Serrano-Falcón B, Accarino Garaventa A, Alonso-Cotoner C, Serra Pueyo J. Common questions and rationale answers about the intestinal bacterial overgrowth syndrome (SIBO). GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502216. [PMID: 38852778 DOI: 10.1016/j.gastrohep.2024.502216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 05/15/2024] [Accepted: 05/24/2024] [Indexed: 06/11/2024]
Abstract
The recognition and treatment of intestinal bacterial overgrowth syndrome are matters of controversy. The symptoms that have guided the search for the disorder suffer from lack of specificity, especially in the absence of well-defined predisposing factors. The accuracy of diagnostic procedures has been questioned and the proposed therapies achieve generally low effectiveness figures, with large differences between available studies. It is also unknown whether the normalization of tests is really a guarantee of cure. Within this framework of uncertainty, and in order to contribute to the guidance and homogenization of medical practice, a group of experts from the AEG and ASENEM have formulated the key questions on the management of this pathology and have provided answers to them, in accordance with the available scientific evidence. In addition, they have drawn up statements based on the conclusions of the review and have voted on them individually to reflect the degree of consensus for each statement.
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Affiliation(s)
- Javier Alcedo González
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria (IIS) Aragón, Zaragoza, España.
| | - Fermín Estremera-Arévalo
- Servicio de Aparato Digestivo, Hospital Universitario de Navarra, Navarrabiomed, Universidad Pública de Navarra - IdiSNA, Navarra, España
| | | | - Javier Santos Vicente
- Laboratorio de Neuro-Inmuno-Gastroenterología, Unidad de Investigación de Aparato Digestivo, Institut de Recerca (VHIR), Servicio de Aparato Digestivo, Hospital Universitario Vall d'Hebron, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Instituto de Salud Carlos III, Madrid, España
| | | | - Juan Naves
- Servicio de Aparato Digestivo, Hospital del Mar, Barcelona, España
| | - Elizabeth Barba Orozco
- Unidad de Neurogastroenterología y Motilidad, Hospital Clínic de Barcelona, Barcelona, España; Departamento de Gastroenterología, Universidad de Barcelona, Barcelona, España
| | | | - Blanca Serrano-Falcón
- Servicio de Aparato Digestivo, Hospital Universitario Virgen de las Nieves, Granada, España
| | | | - Carmen Alonso-Cotoner
- Laboratorio de Neuro-Inmuno-Gastroenterología, Unidad de Investigación de Aparato Digestivo, Institut de Recerca (VHIR), Servicio de Aparato Digestivo, Hospital Universitario Vall d'Hebron, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Instituto de Salud Carlos III, Madrid, España; Facultad de Medicina, Universidad Autónoma de Barcelona, Barcelona, España
| | - Jordi Serra Pueyo
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Instituto de Salud Carlos III, Madrid, España; Área de Aparato Digestivo, Hospital Universitario Vall d'Hebron, Barcelona, España
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Remes-Troche JM, Coss-Adame E, Schmulson M, García-Zermeño KR, Amieva-Balmori M, Carmona-Sánchez R, Gómez-Escudero O, Gómez-Castaños PC, Icaza-Chávez ME, López-Colombo A, Morel-Cerda EC, Valdovinos-Díaz MÁ, Valdovinos-García LR, Villar-Chávez AS. Pharmacologic treatment of irritable bowel syndrome. Position statement of the Asociación Mexicana de Gastroenterología, 2024. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2025; 90:77-110. [PMID: 40307155 DOI: 10.1016/j.rgmxen.2024.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 10/30/2024] [Indexed: 05/02/2025]
Abstract
INTRODUCTION The aim of this position statement is to provide health professionals with an updated and evidence-based guideline for the pharmacologic management of irritable bowel syndrome (IBS) in Mexico. MATERIAL AND METHODS A literature review was conducted that included relevant guidelines and studies, up to the date of its publication. The mechanism of action, specific indications in IBS, safety profile, and availability of each therapeutic class were evaluated. The recommendations were developed by 14 experts, considering the clinical reality of IBS patients in Mexico. RESULTS Specific recommendations were issued for each class. Antispasmodics (alone or combined) are used as first-line therapy for pain management, whereas antidiarrheals, such as loperamide, are used for reducing diarrhea in diarrhea-predominant IBS (IBS-D) and laxatives are used for constipation in constipation-predominant IBS (IBS-C). 5-HT4 agonists (prucalopride and mosapride) are recommended in IBS-C and 5-HT3 antagonists (ondansetron) are recommended in IBS-D. Linaclotide is the only secretagogue available in Mexico and is used in IBS-C. Rifaximin-alpha stands out for its efficacy in a subgroup of patients with IBS-D or mixed IBS. Probiotics are conditionally recommended as adjuvant therapy due to heterogeneous evidence. Neuromodulators (tricyclic antidepressants, selective serotonin reuptake inhibitors, etc.) are recommended as second-line treatment for pain management. Mesalazine can be used in IBS-D, but the corresponding evidence is weak. CONCLUSION Overall, these recommendations provide a solid framework for personalizing treatment, based on the clinical characteristics of the Mexican patient with IBS.
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Affiliation(s)
- J M Remes-Troche
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico.
| | - E Coss-Adame
- Departamento de Gastroenterología, Laboratorio de Motilidad Gastrointestinal, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - M Schmulson
- Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Medicina Experimental Dr. Ruy Pérez Tamayo, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), CDMX, Mexico
| | - K R García-Zermeño
- Centro Integral de Gastroenterología y Motilidad Avanzada (CIGMA), Boca del Río, Veracruz, Mexico
| | - M Amieva-Balmori
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, Mexico
| | - R Carmona-Sánchez
- Servicio de Gastroenterología, Práctica privada, San Luis Potosí, Mexico
| | - O Gómez-Escudero
- Clínica de Gastroenterología, Endoscopia y Motilidad Gastrointestinal, Endoneurogastro, Hospital Ángeles Puebla, Puebla, Mexico
| | - P C Gómez-Castaños
- Servicio de Gastroenterología y Endoscopia Gastrointestinal, Centro de Investigación y Docencia en Ciencias de la Salud, Universidad Autónoma de Sinaloa, Culiacán, Sinaloa, Mexico
| | - M E Icaza-Chávez
- Hospital Christus Muguerza Faro del Mayab, Mérida, Yucatán, Mexico
| | | | - E C Morel-Cerda
- Laboratorio de Motilidad Gastrointestinal, Hospital Civil Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico
| | | | - L R Valdovinos-García
- Servicio de Cirugía Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Instituto Politécnico Nacional, Escuela Superior de Medicina, Mexico City, Mexico
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Airola C, Severino A, Spinelli I, Gasbarrini A, Cammarota G, Ianiro G, Ponziani FR. "Pleiotropic" Effects of Antibiotics: New Modulators in Human Diseases. Antibiotics (Basel) 2024; 13:1176. [PMID: 39766566 PMCID: PMC11727521 DOI: 10.3390/antibiotics13121176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 11/22/2024] [Accepted: 11/29/2024] [Indexed: 01/15/2025] Open
Abstract
Antibiotics, widely used medications that have significantly increased life expectancy, possess a broad range of effects beyond their primary antibacterial activity. While some are recognized as adverse events, others have demonstrated unexpected benefits. These adjunctive effects, which have been defined as "pleiotropic" in the case of other pharmacological classes, include immunomodulatory properties and the modulation of the microbiota. Specifically, macrolides, tetracyclines, and fluoroquinolones have been shown to modulate the immune system in both acute and chronic conditions, including autoimmune disorders (e.g., rheumatoid arthritis, spondyloarthritis) and chronic inflammatory pulmonary diseases (e.g., asthma, chronic obstructive pulmonary disease). Azithromycin, in particular, is recommended for the long-term treatment of chronic inflammatory pulmonary diseases due to its well-established immunomodulatory effects. Furthermore, antibiotics influence the human microbiota. Rifaximin, for example, exerts a eubiotic effect that enhances the balance between the gut microbiota and the host immune cells and epithelial cells. These pleiotropic effects offer new therapeutic opportunities by interacting with human cells, signaling molecules, and bacteria involved in non-infectious diseases like spondyloarthritis and inflammatory bowel diseases. The aim of this review is to explore the pleiotropic potential of antibiotics, from molecular and cellular evidence to their clinical application, in order to optimize their use. Understanding these effects is essential to ensure careful use, particularly in consideration of the threat of antimicrobial resistance.
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Affiliation(s)
- Carlo Airola
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (A.S.); (I.S.); (A.G.); (G.C.); (G.I.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy
| | - Andrea Severino
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (A.S.); (I.S.); (A.G.); (G.C.); (G.I.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy
| | - Irene Spinelli
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (A.S.); (I.S.); (A.G.); (G.C.); (G.I.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (A.S.); (I.S.); (A.G.); (G.C.); (G.I.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy
| | - Giovanni Cammarota
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (A.S.); (I.S.); (A.G.); (G.C.); (G.I.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy
| | - Gianluca Ianiro
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (A.S.); (I.S.); (A.G.); (G.C.); (G.I.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.A.); (A.S.); (I.S.); (A.G.); (G.C.); (G.I.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy
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Crucillà S, Caldart F, Michelon M, Marasco G, Costantino A. Functional Abdominal Bloating and Gut Microbiota: An Update. Microorganisms 2024; 12:1669. [PMID: 39203511 PMCID: PMC11357468 DOI: 10.3390/microorganisms12081669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 08/02/2024] [Accepted: 08/07/2024] [Indexed: 09/03/2024] Open
Abstract
(1) Background: Functional abdominal bloating and distension (FAB/FAD) are common disorders of the gut-brain interaction. Their physiopathology is complex and not completely clarified, although gut microbiota imbalances play a central role. The treatment of FAB/FAD still represents a clinical challenge for both patients and healthcare providers. Gut microbiota modulation strategies might play a crucial role in their management. The aim of this narrative review was to update the current evidence on FAB/FAD, with a focus on gut microbiota. (2) Methods: In October 2023, a review was conducted through the Medline, PubMed, and Embase databases. Selected literature included all available English-edited studies (randomized controlled trials and cross-sectional, cohort, and case-control studies). (3) Results: Twelve studies were selected, most of which investigated the relationship between IBS and microbiota, with bloating being one of its symptoms. The studies suggest that restoring a balanced microbiome appears to be the most promising solution for better management of FAB/FAD. Targeted approaches, such as the use of probiotics, prebiotics, antibiotics such as rifaximin or dietary modifications, may hold the key to alleviating symptoms. Other therapeutic options, such as diet, neuromodulators, and brain-gut behavioral therapies (i.e., cognitive-behavioral therapy) have shown promising outcomes, but strong data are still lacking. (4) Conclusions: Targeted approaches that focus on the gut microbiota, such as the use of probiotics, prebiotics, and antibiotics, are essential in managing FAB/FAD. Understanding the complex relationship between gut microbiota and FAB/FAD is crucial for developing effective treatments. Further studies are needed to explore the specific roles of different microbial populations in patients with FAB/FAD to enhance therapeutic strategies.
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Affiliation(s)
- Salvatore Crucillà
- Gastroenterology B Unit, Pancreas Center, University of Verona, 37134 Verona, Italy;
| | - Federico Caldart
- Gastroenterology B Unit, Pancreas Center, University of Verona, 37134 Verona, Italy;
| | - Marco Michelon
- Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy;
| | - Giovanni Marasco
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy;
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Andrea Costantino
- Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy;
- Unit of Gastroenterology and Endoscopy, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
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Compare D, Sgamato C, Rocco A, Coccoli P, Ambrosio C, Nardone G. The Leaky Gut and Human Diseases: "Can't Fill the Cup if You Don't Plug the Holes First". Dig Dis 2024; 42:548-566. [PMID: 39047703 DOI: 10.1159/000540379] [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: 03/25/2024] [Accepted: 07/03/2024] [Indexed: 07/27/2024]
Abstract
BACKGROUND The gut barrier is a sophisticated and dynamic system that forms the frontline defense between the external environment and the body's internal milieu and includes various structural and functional components engaged not only in digestion and nutrient absorption but also in immune regulation and overall health maintenance. SUMMARY When one or more components of the intestinal barrier lose their structure and escape their function, this may result in a leaky gut. Mounting evidence emphasizes the crucial role of the gut microbiome in preserving the integrity of the gut barrier and provides insights into the pathophysiological implications of conditions related to leaky gut in humans. Assessment of intestinal permeability has evolved from invasive techniques to noninvasive biomarkers, but challenges remain in achieving consensus about the best testing methods and their accuracy. Research on the modulation of gut permeability is just starting, and although no medical guidelines for the treatment of leaky gut syndrome are available, several treatment strategies are under investigation with promising results. KEY MESSAGES This review discusses the composition of the intestinal barrier, the pathophysiology of the leaky gut and its implications on human health, the measurement of intestinal permeability, and the therapeutic strategies to restore gut barrier integrity.
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Affiliation(s)
- Debora Compare
- Department of Clinical Medicine and Surgery, Gastroenterology, University Federico II of Naples, Naples, Italy
| | - Costantino Sgamato
- Department of Clinical Medicine and Surgery, Gastroenterology, University Federico II of Naples, Naples, Italy
| | - Alba Rocco
- Department of Clinical Medicine and Surgery, Gastroenterology, University Federico II of Naples, Naples, Italy
| | - Pietro Coccoli
- Department of Clinical Medicine and Surgery, Gastroenterology, University Federico II of Naples, Naples, Italy
| | - Carmen Ambrosio
- Department of Clinical Medicine and Surgery, Gastroenterology, University Federico II of Naples, Naples, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Gastroenterology, University Federico II of Naples, Naples, Italy
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Eeda V, Patil NY, Joshi AD, Awasthi V. Advancements in metabolic-associated steatotic liver disease research: Diagnostics, small molecule developments, and future directions. Hepatol Res 2024; 54:222-234. [PMID: 38149861 PMCID: PMC10923026 DOI: 10.1111/hepr.14008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 12/19/2023] [Accepted: 12/21/2023] [Indexed: 12/28/2023]
Abstract
Metabolic (dysfunction)-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, is a growing global health concern with no approved pharmacological treatments. At the same time, there are no standard methods to definitively screen for the presence of MASLD because of its progressive nature and symptomatic commonality with other disorders. Recent advances in molecular understanding of MASLD pathophysiology have intensified research on development of new drug molecules, repurposing of existing drugs approved for other indications, and an educated use of dietary supplements for its treatment and prophylaxis. This review focused on depicting the latest advancements in MASLD research related to small molecule development for prophylaxis or treatment and diagnosis, with emphasis on mechanistic basis at the molecular level.
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Affiliation(s)
- Venkateswararao Eeda
- Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
| | - Nikhil Yuvaraj Patil
- Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
| | - Aditya Dilip Joshi
- Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
| | - Vibhudutta Awasthi
- Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
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Nohesara S, Abdolmaleky HM, Zhou JR, Thiagalingam S. Microbiota-Induced Epigenetic Alterations in Depressive Disorders Are Targets for Nutritional and Probiotic Therapies. Genes (Basel) 2023; 14:2217. [PMID: 38137038 PMCID: PMC10742434 DOI: 10.3390/genes14122217] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 12/08/2023] [Accepted: 12/11/2023] [Indexed: 12/24/2023] Open
Abstract
Major depressive disorder (MDD) is a complex disorder and a leading cause of disability in 280 million people worldwide. Many environmental factors, such as microbes, drugs, and diet, are involved in the pathogenesis of depressive disorders. However, the underlying mechanisms of depression are complex and include the interaction of genetics with epigenetics and the host immune system. Modifications of the gut microbiome and its metabolites influence stress-related responses and social behavior in patients with depressive disorders by modulating the maturation of immune cells and neurogenesis in the brain mediated by epigenetic modifications. Here, we discuss the potential roles of a leaky gut in the development of depressive disorders via changes in gut microbiota-derived metabolites with epigenetic effects. Next, we will deliberate how altering the gut microbiome composition contributes to the development of depressive disorders via epigenetic alterations. In particular, we focus on how microbiota-derived metabolites such as butyrate as an epigenetic modifier, probiotics, maternal diet, polyphenols, drugs (e.g., antipsychotics, antidepressants, and antibiotics), and fecal microbiota transplantation could positively alleviate depressive-like behaviors by modulating the epigenetic landscape. Finally, we will discuss challenges associated with recent therapeutic approaches for depressive disorders via microbiome-related epigenetic shifts, as well as opportunities to tackle such problems.
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Affiliation(s)
- Shabnam Nohesara
- Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA;
| | - Hamid Mostafavi Abdolmaleky
- Nutrition/Metabolism Laboratory, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boson, MA 02215, USA;
| | - Jin-Rong Zhou
- Nutrition/Metabolism Laboratory, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boson, MA 02215, USA;
| | - Sam Thiagalingam
- Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA;
- Department of Pathology & Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA
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Raghib MF, Bernitsas E. From Animal Models to Clinical Trials: The Potential of Antimicrobials in Multiple Sclerosis Treatment. Biomedicines 2023; 11:3069. [PMID: 38002068 PMCID: PMC10668955 DOI: 10.3390/biomedicines11113069] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 11/05/2023] [Accepted: 11/14/2023] [Indexed: 11/26/2023] Open
Abstract
Multiple sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system (CNS). Microbes, including bacteria and certain viruses, particularly Epstein-Barr virus (EBV), have been linked to the pathogenesis of MS. While there is currently no cure for MS, antibiotics and antivirals have been studied as potential treatment options due to their immunomodulatory ability that results in the regulation of the immune process. The current issue addressed in this systematic review is the effect of antimicrobials, including antibiotics, antivirals, and antiparasitic agents in animals and humans. We performed a comprehensive search of PubMed, Google Scholar, and Scopus for articles on antimicrobials in experimental autoimmune encephalomyelitis animal models of MS, as well as in people with MS (pwMS). In animal models, antibiotics tested included beta-lactams, minocycline, rapamycin, macrolides, and doxycycline. Antivirals included acyclovir, valacyclovir, and ganciclovir. Hydroxychloroquine was the only antiparasitic that was tested. In pwMS, we identified a total of 24 studies, 17 of them relevant to antibiotics, 6 to antivirals, and 1 relevant to antiparasitic hydroxychloroquine. While the effect of antimicrobials in animal models was promising, only minocycline and hydroxychloroquine improved outcome measures in pwMS. No favorable effect of the antivirals in humans has been observed yet. The number and size of clinical trials testing antimicrobials have been limited. Large, multicenter, well-designed studies are needed to further evaluate the effect of antimicrobials in MS.
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Affiliation(s)
- Muhammad Faraz Raghib
- Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201, USA;
| | - Evanthia Bernitsas
- Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201, USA;
- Sastry Neuroimaging Laboratory, Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201, USA
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10
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Thavamani A, Sankararaman S, Al-Shakhshir H, Retuerto M, Velayuthan S, Sferra TJ, Ghannoum M. Impact of Erythromycin as a Prokinetic on the Gut Microbiome in Children with Feeding Intolerance-A Pilot Study. Antibiotics (Basel) 2023; 12:1606. [PMID: 37998808 PMCID: PMC10668753 DOI: 10.3390/antibiotics12111606] [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: 09/24/2023] [Revised: 10/27/2023] [Accepted: 11/01/2023] [Indexed: 11/25/2023] Open
Abstract
BACKGROUND Studies have demonstrated that the gut microbiome changes upon exposure to systemic antibiotics. There is a paucity of literature regarding impact on the gut microbiome by long-term usage of erythromycin ethyl succinate (EES) when utilized as a prokinetic. METHODS Stool samples from pediatric patients with feeding intolerance who received EES (N = 8) as a prokinetic were analyzed for both bacteriome and mycobiome. Age-matched children with similar clinical characteristics but without EES therapy were included as controls (N = 20). RESULTS In both groups, Proteobacteria, Firmicutes, and Bacteroidetes were the most abundant bacterial phyla. Ascomycota was the most abundant fungal phyla, followed by Basidiomycota. There were no significant differences in richness between the groups for both bacterial and fungal microbiome. Alpha diversity (at genus and species levels) and beta diversity (at the genus level) were not significantly different between the groups for both bacterial and fungal microbiome. At the species level, there was a significant difference between the groups for fungal microbiota, with a p-value of 0.029. We also noted that many fungal microorganisms had significantly higher p-values in the EES group than controls at both genera and species levels. CONCLUSIONS In this observational case-control study, the prokinetic use of EES was associated with changes in beta diversity between the groups for mycobiome at the species level. Many fungal microorganisms were significantly higher in the EES group when compared to the controls. Confirmation of these results in larger trials will provide further evidence regarding the impact of EES on gut microbiota when utilized as a prokinetic agent.
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Affiliation(s)
- Aravind Thavamani
- Division of Pediatric Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, UH Rainbow Babies and Children’s Hospital, Cleveland, OH 44106, USA; (A.T.); (S.V.); (T.J.S.)
- Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
| | - Senthilkumar Sankararaman
- Division of Pediatric Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, UH Rainbow Babies and Children’s Hospital, Cleveland, OH 44106, USA; (A.T.); (S.V.); (T.J.S.)
- Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
| | - Hilmi Al-Shakhshir
- Department of Radiology and Imaging Sciences, Emory School of Medicine, Atlanta, GA 30307, USA;
- Department of Radiology and Imaging Sciences Atlanta VA Medical Center, Decatur, GA 30033, USA
| | - Mauricio Retuerto
- Center for Medical Mycology, Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; (M.R.); (M.G.)
| | - Sujithra Velayuthan
- Division of Pediatric Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, UH Rainbow Babies and Children’s Hospital, Cleveland, OH 44106, USA; (A.T.); (S.V.); (T.J.S.)
- Division of Pediatric Neurogastroenterology and Motility, Department of Pediatrics, Nationwide Children’s Hospital, Columbus, OH 43205, USA
| | - Thomas J. Sferra
- Division of Pediatric Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, UH Rainbow Babies and Children’s Hospital, Cleveland, OH 44106, USA; (A.T.); (S.V.); (T.J.S.)
- Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
| | - Mahmoud Ghannoum
- Center for Medical Mycology, Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; (M.R.); (M.G.)
- Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
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11
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Boicean A, Birlutiu V, Ichim C, Brusnic O, Onișor DM. Fecal Microbiota Transplantation in Liver Cirrhosis. Biomedicines 2023; 11:2930. [PMID: 38001930 PMCID: PMC10668969 DOI: 10.3390/biomedicines11112930] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 10/25/2023] [Accepted: 10/26/2023] [Indexed: 11/26/2023] Open
Abstract
The human gastrointestinal tract houses a diverse array of probiotic and pathogenic bacteria and any alterations in this microbial composition can exert a significant influence on an individual's well-being. It is well-established that imbalances in the gut microbiota play a pivotal role in the development of liver diseases. In light of this, a new adjuvant therapy for liver diseases could be regulating the intestinal microbiota. Through fecal microbiota transplantation, patients whose microbiomes are compromised are treated with stool from healthy donors in an attempt to restore a normal microbiome and alleviate their symptoms. A review of cross-sectional studies and case reports suggests that fecal microbiota transplants may offer effective treatment for chronic liver diseases. Adding to the potential of this emerging therapy, recent research has indicated that fecal microbiota transplantation holds promise as a therapeutic approach specifically for liver cirrhosis. By introducing a diverse range of beneficial microorganisms into the gut, this innovative treatment aims to address the microbial imbalances often observed in cirrhotic patients. While further validation is still required, these preliminary findings highlight the potential impact of fecal microbiota transplantation as a novel and targeted method for managing liver cirrhosis. We aimed to summarize the current state of understanding regarding this procedure, as a new therapeutic method for liver cirrhosis, as well as to explain its clinical application and future potential.
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Affiliation(s)
- Adrian Boicean
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (V.B.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Victoria Birlutiu
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (V.B.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Cristian Ichim
- County Clinical Emergency Hospital of Sibiu, 550245 Sibiu, Romania; (A.B.); (V.B.)
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| | - Olga Brusnic
- Department of Gastroenterology, University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Târgu Mures, Romania
| | - Danusia Maria Onișor
- Department of Gastroenterology, University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Târgu Mures, Romania
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12
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Luo M, Xie P, Deng X, Fan J, Xiong L. Rifaximin Ameliorates Loperamide-Induced Constipation in Rats through the Regulation of Gut Microbiota and Serum Metabolites. Nutrients 2023; 15:4502. [PMID: 37960154 PMCID: PMC10648458 DOI: 10.3390/nu15214502] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 10/10/2023] [Accepted: 10/20/2023] [Indexed: 11/15/2023] Open
Abstract
Structural changes in the gut microbiota are closely related to the development of functional constipation, and regulating the gut microbiota can improve constipation. Rifaximin is a poorly absorbed antibiotic beneficial for regulating gut microbiota, but few studies have reported its effects on constipation. The purpose of this study was to investigate the effect of rifaximin on loperamide-induced constipation in SD rats. The results showed that rifaximin improved constipation by increasing serum 5-HT, SP, and the mRNA expression of AQP3, AQP8, and reducing the mRNA expression of TLR2 and TLR4. In addition, rifaximin could regulate the gut microbiota of constipated rats, such as increasing the potentially beneficial bacteria Akkermansia muciniphila and Lactobacillus murinus, reducing the Bifidobacterium pseudolongum. According to metabolomics analysis, many serum metabolites, including bile acids and steroids, were changed in constipated rats and were recovered via rifaximin intervention. In conclusion, rifaximin might improve loperamide-induced constipation in rats by increasing serum excitatory neurotransmitters and neuropeptides, modulating water metabolism, and facilitating intestinal inflammation. Muti-Omics analysis results showed that rifaximin has beneficial regulatory effects on the gut microbiota and serum metabolites in constipated rats, which might play critical roles in alleviating constipation. This study suggests that rifaximin might be a potential strategy for treating constipation.
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Affiliation(s)
| | | | | | | | - Lishou Xiong
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; (M.L.); (P.X.); (X.D.); (J.F.)
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13
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Torre A, Córdova-Gallardo J, Frati Munari AC. Rifaximin Alfa and Liver Diseases: More Than a Treatment for Encephalopathy, a Disease Modifier. Ther Clin Risk Manag 2023; 19:839-851. [PMID: 37899985 PMCID: PMC10612522 DOI: 10.2147/tcrm.s425292] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 09/17/2023] [Indexed: 10/31/2023] Open
Abstract
RFX, a rifamycin-based antibacterial agent obtained by the culture of the actinomycete Streptomyces mediterranei, has a broad antibacterial spectrum covering gram- positive, gram-negative, aerobic, and anaerobic bacteria. RFX is an antibiotic that elicits its effect by inhibiting bacterial RNA synthesis. When administered orally, its intestinal absorption is extremely low (<0.4%), restricting antibacterial activity mainly in the intestinal tract, with few systemic side effects. RFX has been recommended by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver guidelines for the treatment of HE. RFX may contribute to restore hepatic function and to decrease the development of liver fibrosis. Its efficacy has been shown in patients with previous hepatic encephalopathy and several complications, such as infections, including spontaneous bacterial peritonitis, ascites and oesophageal variceal bleeding. Thus, RFX has an outstanding role in the therapeutic arsenal in hepatic cirrhosis, under the concept of disease modifier.
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Affiliation(s)
- Aldo Torre
- Guest Research, Metabolic Unit Department, Instituto Nacional de Ciencias Médicas Y Nutrición “Salvador Zubirán”, México City, Mexico
- Guest Research, Liver Unit Department, Hospital General de México, México City, Mexico
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14
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Airola C, Severino A, Porcari S, Fusco W, Mullish BH, Gasbarrini A, Cammarota G, Ponziani FR, Ianiro G. Future Modulation of Gut Microbiota: From Eubiotics to FMT, Engineered Bacteria, and Phage Therapy. Antibiotics (Basel) 2023; 12:antibiotics12050868. [PMID: 37237771 DOI: 10.3390/antibiotics12050868] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 05/03/2023] [Accepted: 05/05/2023] [Indexed: 05/28/2023] Open
Abstract
The human gut is inhabited by a multitude of bacteria, yeasts, and viruses. A dynamic balance among these microorganisms is associated with the well-being of the human being, and a large body of evidence supports a role of dysbiosis in the pathogenesis of several diseases. Given the importance of the gut microbiota in the preservation of human health, probiotics, prebiotics, synbiotics, and postbiotics have been classically used as strategies to modulate the gut microbiota and achieve beneficial effects for the host. Nonetheless, several molecules not typically included in these categories have demonstrated a role in restoring the equilibrium among the components of the gut microbiota. Among these, rifaximin, as well as other antimicrobial drugs, such as triclosan, or natural compounds (including evodiamine and polyphenols) have common pleiotropic characteristics. On one hand, they suppress the growth of dangerous bacteria while promoting beneficial bacteria in the gut microbiota. On the other hand, they contribute to the regulation of the immune response in the case of dysbiosis by directly influencing the immune system and epithelial cells or by inducing the gut bacteria to produce immune-modulatory compounds, such as short-chain fatty acids. Fecal microbiota transplantation (FMT) has also been investigated as a procedure to restore the equilibrium of the gut microbiota and has shown benefits in many diseases, including inflammatory bowel disease, chronic liver disorders, and extraintestinal autoimmune conditions. One of the most significant limits of the current techniques used to modulate the gut microbiota is the lack of tools that can precisely modulate specific members of complex microbial communities. Novel approaches, including the use of engineered probiotic bacteria or bacteriophage-based therapy, have recently appeared as promising strategies to provide targeted and tailored therapeutic modulation of the gut microbiota, but their role in clinical practice has yet to be clarified. The aim of this review is to discuss the most recently introduced innovations in the field of therapeutic microbiome modulation.
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Affiliation(s)
- Carlo Airola
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Andrea Severino
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Serena Porcari
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - William Fusco
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Benjamin H Mullish
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, St Mary's Hospital Campus, Imperial College London, London W2 1NY, UK
- Departments of Gastroenterology and Hepatology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London W2 1NY, UK
| | - Antonio Gasbarrini
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Giovanni Cammarota
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Gianluca Ianiro
- Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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15
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Ivashkin V, Shifrin O, Maslennikov R, Poluektova E, Korolev A, Kudryavtseva A, Krasnov G, Benuni N, Barbara G. Eubiotic effect of rifaximin is associated with decreasing abdominal pain in symptomatic uncomplicated diverticular disease: results from an observational cohort study. BMC Gastroenterol 2023; 23:82. [PMID: 36959568 PMCID: PMC10037807 DOI: 10.1186/s12876-023-02690-x] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Accepted: 02/22/2023] [Indexed: 03/25/2023] Open
Abstract
BACKGROUND Rifaximin effectively treats symptomatic uncomplicated diverticular disease (SUDD) and has shown eubiotic potential (i.e., an increase in resident microbial elements with potential beneficial effects) in other diseases. This study investigated changes in the fecal microbiome of patients with SUDD after repeated monthly treatment with rifaximin and the association of these changes with the severity of abdominal pain. METHODS This was a single-center, prospective, observational, uncontrolled cohort study. Patients received rifaximin 400 mg twice a day for 7 days per month for 6 months. Abdominal pain (assessed on a 4-point scale from 0 [no pain] to 3 [severe pain]) and fecal microbiome (assessed using 16 S rRNA gene sequencing) were assessed at inclusion (baseline) and 3 and 6 months. The Spearman's rank test analyzed the relationship between changes in the gut microbiome and the severity of abdominal pain. A p-value ≤ 0.05 was considered statistically significant. RESULTS Of the 23 patients enrolled, 12 patients completed the study and were included in the analysis. Baseline abdominal pain levels decreased significantly after 3 (p = 0.036) and 6 (p = 0.008) months of treatment with rifaximin. The abundance of Akkermansia in the fecal microbiome was significantly higher at 3 (p = 0.017) and 6 (p = 0.015) months versus baseline. The abundance of Ruminococcaceae (p = 0.034), Veillonellaceae (p = 0.028), and Dialister (p = 0.036) were significantly increased at 6 months versus baseline, whereas Anaerostipes (p = 0.049) was significantly decreased. The severity of abdominal pain was negatively correlated with the abundance of Akkermansia (r=-0.482; p = 0.003) and Ruminococcaceae (r=-0.371; p = 0.026) but not with Veillonellaceae, Dialister, or Anaerostipes. After 3 months of rifaximin, abdominal pain was significantly less in patients with Akkermansia in their fecal microbiome than in patients without Akkermansia (p = 0.022). CONCLUSION The eubiotic effect of rifaximin was associated with decreased abdominal pain in patients with SUDD.
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Affiliation(s)
- Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russian Federation
- Scientific Community for the Human Microbiome Research, Moscow, Russian Federation
| | - Oleg Shifrin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russian Federation
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russian Federation
- Scientific Community for the Human Microbiome Research, Moscow, Russian Federation
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russian Federation
- Scientific Community for the Human Microbiome Research, Moscow, Russian Federation
| | - Alexander Korolev
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russian Federation
| | - Anna Kudryavtseva
- Laboratory of Postgenomic Research, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
| | - George Krasnov
- Laboratory of Postgenomic Research, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
| | - Nona Benuni
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow, Russian Federation
| | - Giovanni Barbara
- Department of Medical and Surgical Sciences, University of Bologna, IRCCS Azienda Ospedaliero-Universitaria, Bologna, Italy
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16
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Big Data in Gastroenterology Research. Int J Mol Sci 2023; 24:ijms24032458. [PMID: 36768780 PMCID: PMC9916510 DOI: 10.3390/ijms24032458] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/18/2023] [Accepted: 01/20/2023] [Indexed: 01/28/2023] Open
Abstract
Studying individual data types in isolation provides only limited and incomplete answers to complex biological questions and particularly falls short in revealing sufficient mechanistic and kinetic details. In contrast, multi-omics approaches to studying health and disease permit the generation and integration of multiple data types on a much larger scale, offering a comprehensive picture of biological and disease processes. Gastroenterology and hepatobiliary research are particularly well-suited to such analyses, given the unique position of the luminal gastrointestinal (GI) tract at the nexus between the gut (mucosa and luminal contents), brain, immune and endocrine systems, and GI microbiome. The generation of 'big data' from multi-omic, multi-site studies can enhance investigations into the connections between these organ systems and organisms and more broadly and accurately appraise the effects of dietary, pharmacological, and other therapeutic interventions. In this review, we describe a variety of useful omics approaches and how they can be integrated to provide a holistic depiction of the human and microbial genetic and proteomic changes underlying physiological and pathophysiological phenomena. We highlight the potential pitfalls and alternatives to help avoid the common errors in study design, execution, and analysis. We focus on the application, integration, and analysis of big data in gastroenterology and hepatobiliary research.
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17
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TURSI A, MASTROMARINO P, CAPOBIANCO D, ELISEI W, CAMPAGNA G, PICCHIO M, GIORGETTI G, FABIOCCHI F, BRANDIMARTE G. Faecalibacterium prausnitzii is not decreased in symptomatic uncomplicated diverticular disease of the colon. BIOSCIENCE OF MICROBIOTA, FOOD AND HEALTH 2023; 42:1-2. [PMID: 36660603 PMCID: PMC9816050 DOI: 10.12938/bmfh.2022-046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/13/2022] [Indexed: 01/22/2023]
Abstract
In this letter, assessment of the amount of fecal Faecalibacterium prausnitzii in symptomatic uncomplicated diverticular disease (SUDD) is described. Among 44 consecutive patients, comprising 15 SUDD patients, 13 patients with asymptomatic diverticulosis (AD), and 16 healthy controls (HC), the fecal amount of Faecalibacterium prausnitzii was not found to be significantly different between HC, AD and SUDD subjects (p=0.871). Moreover, its count in the HC microbiota (-4.57 ± 2.15) was lower compared with those in the AD (-4.11 ± 1.03) and SUDD subjects (-4.03 ± 1.299). This behavior seems to be different from that occurring in inflammatory bowel disease (IBD) and similar to that of other mucin-degrading species in a SUDD setting.
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Affiliation(s)
- Antonio TURSI
- Territorial Gastroenterology Service, Azienda Sanitaria
Locale, Barletta-Andria-Trani, Andria 76123, Italy,Department of Medical and Surgical Sciences, Catholic
University, Rome, Italy,*Corresponding author. Antonio Tursi (E-mail: )
| | - Paola MASTROMARINO
- Department of Public Health and Infectious Diseases, Section
of Microbiology, Sapienza University, Rome, Italy
| | - Daniela CAPOBIANCO
- Department of Public Health and Infectious Diseases, Section
of Microbiology, Sapienza University, Rome, Italy
| | - Walter ELISEI
- Division of Gastroenterology, S. Camillo-Forlanini Hospital,
Rome, Italy
| | - Giuseppe CAMPAGNA
- Department of Experimental Medicine, Sapienza University,
Rome, Italy
| | - Marcello PICCHIO
- Division of Surgery, P. Colombo Hospital, ASL Roma 6,
Velletri (Rome), Italy
| | | | - Federica FABIOCCHI
- Digestive Endoscopy and Nutrition Unit, S. Eugenio Hospital,
Rome, Italy
| | - Giovanni BRANDIMARTE
- Division of Internal Medicine and Gastroenterology, Cristo Re
Hospital, Rome, Italy
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18
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Tursi A, Papa V, Lopetuso LR, Settanni CR, Gasbarrini A, Papa A. Microbiota Composition in Diverticular Disease: Implications for Therapy. Int J Mol Sci 2022; 23:14799. [PMID: 36499127 PMCID: PMC9736941 DOI: 10.3390/ijms232314799] [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: 10/27/2022] [Revised: 11/21/2022] [Accepted: 11/23/2022] [Indexed: 12/05/2022] Open
Abstract
Gut microbiota (GM) composition and its imbalance are crucial in the pathogenesis of several diseases, mainly those affecting the gastrointestinal tract. Colon diverticulosis and its clinical manifestations (diverticular disease, DD) are among the most common digestive disorders in developed countries. In recent literature, the role of GM imbalance in the onset of the different manifestations within the clinical spectrum of DD has been highlighted. This narrative review aims to summarize and critically analyze the current knowledge on GM dysbiosis in diverticulosis and DD by comparing the available data with those found in inflammatory bowel disease (IBD). The rationale for using probiotics to rebalance dysbiosis in DD is also discussed.
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Affiliation(s)
- Antonio Tursi
- Territorial Gastroenterology Service, ASL BAT, 70031 Andria, Italy
- Department of Translational Medicine and Surgery, School of Medicine, Catholic University, 00168 Rome, Italy
| | - Valerio Papa
- Department of Translational Medicine and Surgery, School of Medicine, Catholic University, 00168 Rome, Italy
- Digestive Surgery, Fondazione Policlinico Universitario “A. Gemelli”, IRCCS, 00168 Rome, Italy
| | - Loris Riccardo Lopetuso
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Gastroenterology Department, Fondazione Policlinico Gemelli, IRCCS, 00168 Rome, Italy
- Department of Medicine and Ageing Sciences, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
- Center for Advanced Studies and Technology (CAST), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
| | - Carlo Romano Settanni
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Gastroenterology Department, Fondazione Policlinico Gemelli, IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, School of Medicine, Catholic University, 00168 Rome, Italy
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Gastroenterology Department, Fondazione Policlinico Gemelli, IRCCS, 00168 Rome, Italy
| | - Alfredo Papa
- Department of Translational Medicine and Surgery, School of Medicine, Catholic University, 00168 Rome, Italy
- Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Gastroenterology Department, Fondazione Policlinico Gemelli, IRCCS, 00168 Rome, Italy
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Șchiopu CG, Ștefănescu C, Boloș A, Diaconescu S, Gilca-Blanariu GE, Ștefănescu G. Functional Gastrointestinal Disorders with Psychiatric Symptoms: Involvement of the Microbiome-Gut-Brain Axis in the Pathophysiology and Case Management. Microorganisms 2022; 10:2199. [PMID: 36363791 PMCID: PMC9694215 DOI: 10.3390/microorganisms10112199] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 11/03/2022] [Accepted: 11/05/2022] [Indexed: 11/09/2022] Open
Abstract
Functional Gastrointestinal Disorders have been an important cause of poor life quality in affected populations. The unclear etiology and pathophysiological mechanism alter the clinical evolution of the patient. Although a strong connection with psychological stress has been observed, it was not until recently that the gut-brain axis involvement has been revealed. Furthermore, the current literature not only promotes the gut-brain axis modulation as a therapeutical target for functional digestive disorders but also states that the gut microbiome has a main role in this bi-directional mechanism. Psychiatric symptoms are currently recognized as an equally important aspect of the clinical manifestation and modulation of both the digestive and central nervous systems and could be the best approach in restoring the balance. As such, this article proposes a detailed description of the physiology of the microbiome-gut-brain axis, the pathophysiology of the functional gastrointestinal disorders with psychiatric symptoms and current perspectives for therapeutical management, as revealed by the latest studies in the scientific literature.
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Affiliation(s)
- Cristina Gabriela Șchiopu
- Department of Psychiatry, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
| | - Cristinel Ștefănescu
- Department of Psychiatry, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
| | - Alexandra Boloș
- Department of Psychiatry, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
| | - Smaranda Diaconescu
- Medical-Surgical Department, Faculty of Medicine, University “Titu Maiorescu”, 040441 Bucuresti, Romania
| | | | - Gabriela Ștefănescu
- Department of Gastroentereology, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iași, Romania
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Hong CT, Chan L, Chen KY, Lee HH, Huang LK, Yang YCSH, Liu YR, Hu CJ. Rifaximin Modifies Gut Microbiota and Attenuates Inflammation in Parkinson's Disease: Preclinical and Clinical Studies. Cells 2022; 11:3468. [PMID: 36359864 PMCID: PMC9656351 DOI: 10.3390/cells11213468] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 09/30/2022] [Accepted: 10/27/2022] [Indexed: 09/15/2023] Open
Abstract
Patients with Parkinson's disease (PD) exhibit distinct gut microbiota, which may promote gut-derived inflammation. Rifaximin is a nonabsorbable antibiotic that can modify gut microbiota. The present study investigated the effect of rifaximin on gut microbiota and inflammation status in PD. The study examined the effect of long-term rifaximin treatment on in vivo transgenic PD mice (MitoPark) and short-term rifaximin treatment on patients with PD. Rifaximin treatment caused a significant change in gut microbiota in the transgenic PD mice; in particular, it reduced the relative abundance of Prevotellaceae UCG-001 and increased the relative abundance of Bacteroides, Muribaculum, and Lachnospiraceae UCG-001. Rifaximin treatment attenuated serum interleukin-1β, interleukin-6 and tumor necrosis factor-α, claudin-5 and occludin, which indicated the reduction of systemic inflammation and the protection of the blood-brain barrier integrity. The rifaximin-treated MitoPark mice exhibited better motor and memory performance than did the control mice, with lower microglial activation and increased neuronal survival in the hippocampus. In the patients with PD, 7-day rifaximin treatment caused an increase in the relative abundance of Flavonifractor 6 months after treatment, and the change in plasma proinflammatory cytokine levels was negatively associated with the baseline plasma interleukin-1α level. In conclusion, the present study demonstrated that rifaximin exerted a neuroprotective effect on the transgenic PD mice by modulating gut microbiota. We observed that patients with higher baseline inflammation possibly benefited from rifaximin treatment. With consideration for the tolerability and safety of rifaximin, randomized controlled trials should investigate the disease-modification effect of long-term treatment on select patients with PD.
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Affiliation(s)
- Chien-Tai Hong
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Lung Chan
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Kai-Yun Chen
- Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
| | - Hsun-Hua Lee
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Li-Kai Huang
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
| | - Yu-Chen S. H. Yang
- Joint Biobank, Office of Human Research, Taipei Medical University, Taipei 11031, Taiwan
| | - Yun-Ru Liu
- Joint Biobank, Office of Human Research, Taipei Medical University, Taipei 11031, Taiwan
| | - Chaur-Jong Hu
- Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
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21
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Fan H, Gao L, Yin Z, Ye S, Zhao H, Peng Q. Probiotics and rifaximin for the prevention of travelers' diarrhea: A systematic review and network meta-analysis. Medicine (Baltimore) 2022; 101:e30921. [PMID: 36221413 PMCID: PMC9542755 DOI: 10.1097/md.0000000000030921] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Probiotics and rifaximin are treatments for gut microbiota dysbiosis in patients with traveler's diarrhea (TD), and they both proved beneficial for the prevention of TD. However, comparative effectiveness research between them has not been performed. A systematic review and network meta-analysis are to be performed to clarify which of them is more effective in the prevention of TD. METHODS Literature concerning the effectiveness of probiotics or rifaximin in the prevention of TD was searched in Medline, Embase, the Cochrane Central Register of Controlled Trials, and clinical registries for randomized controlled trials (RCTs) from inception of these databases to November 30, 2021 without any language restrictions. The primary efficacy outcome was the incidence of TD, and the safety outcome was the incidence of adverse events. The effect size of probiotics was measured by using relative ratio (RR), and the network meta-analysis was performed by using a frequentist approach and a random-effect model. RESULTS Totally 17 RCTs after screening 1119 retrieved records were included in analysis and 9 RCTs were with low risk of bias. Compared with placebo, both probiotics and rifaximin were associated with lower incidence of TD (probiotics, RR 0.85, 95% CI 0.76-0.95; rifaximin, RR 0.47, 95% CI 0.35-0.63), and rifaximin was more effective than probiotics (RR 0.56, 95% CI 0.4-0.78). Further analysis showed that sodium butyrate, rifaximin and L. acidophilus + L. bulgaricus + Bifido.bifidum + Strept. Thermophilus were the three most effective treatments for TD. CONCLUSIONS Both rifaximin and probiotics are superior over placebo, and rifaximin has better treatment effect than probiotics in reducing the incidence of TD. Different types of probiotics have heterogeneous treatment effects.
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Affiliation(s)
- Hao Fan
- School of Tourism and Service Management, Chongqing University of Education, Chongqing, China
- College of Humanities and Social Sciences, Yuan Ze University, Taoyuan, Taiwan
| | - Lei Gao
- School of Culture and Tourism, Chongqing City Management College, Chongqing, China
| | - Zidan Yin
- College of Humanities and Social Sciences, Yuan Ze University, Taoyuan, Taiwan
| | - Sheng Ye
- Chongqing Geomatics and Remote Sensing Center, Chongqing, China
| | - Hua Zhao
- School of Foreign Languages, Sichuan Normal University, Chengdu, China
| | - Qi Peng
- Department of Endoscopy, Longmatan District People’s Hospital, Luzhou City, China
- *Correspondence: Qi Peng, No. 2, guanyinbao Road, Shidong Town, Longmatan District, Luzhou City, China (e-mail: )
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22
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Forlano R, Sivakumar M, Mullish BH, Manousou P. Gut Microbiota—A Future Therapeutic Target for People with Non-Alcoholic Fatty Liver Disease: A Systematic Review. Int J Mol Sci 2022; 23:ijms23158307. [PMID: 35955434 PMCID: PMC9368436 DOI: 10.3390/ijms23158307] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 07/25/2022] [Accepted: 07/25/2022] [Indexed: 12/03/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease, affecting one-third of the population worldwide. Despite many medications being in the pipeline to treat the condition, there is still no pharmaceutical agent licensed to treat the disease. As intestinal bacteria play a crucial role in the pathogenesis and progression of liver damage in patients with NAFLD, it has been suggested that manipulating the microbiome may represent a therapeutical option. In this review, we summarise the latest evidence supporting the manipulation of the intestinal microbiome as a potential therapy for treating liver disease in patients with NAFLD.
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Affiliation(s)
- Roberta Forlano
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W2 1NY, UK; (R.F.); (B.H.M.)
| | - Mathuri Sivakumar
- Faculty of Medicine, University of Birmingham, Birmingham B15 2TT, UK;
| | - Benjamin H. Mullish
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W2 1NY, UK; (R.F.); (B.H.M.)
| | - Pinelopi Manousou
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W2 1NY, UK; (R.F.); (B.H.M.)
- Correspondence:
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23
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Jung JH, Kim SE, Suk KT, Kim DJ. Gut microbiota-modulating agents in alcoholic liver disease: Links between host metabolism and gut microbiota. Front Med (Lausanne) 2022; 9:913842. [PMID: 35935787 PMCID: PMC9354621 DOI: 10.3389/fmed.2022.913842] [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: 04/06/2022] [Accepted: 07/04/2022] [Indexed: 11/13/2022] Open
Abstract
Alcoholic liver disease (ALD) involves a wide spectrum of diseases, including asymptomatic hepatic steatosis, alcoholic hepatitis, hepatic fibrosis, and cirrhosis, which leads to morbidity and mortality and is responsible for 0.9% of global deaths. Alcohol consumption induces bacterial translocation and alteration of the gut microbiota composition. These changes in gut microbiota aggravate hepatic inflammation and fibrosis. Alteration of the gut microbiota leads to a weakened gut barrier and changes host immunity and metabolic function, especially related to bile acid metabolism. Modulation and treatment for the gut microbiota in ALD has been studied using probiotics, prebiotics, synbiotics, and fecal microbial transplantation with meaningful results. In this review, we focused on the interaction between alcohol and gut dysbiosis in ALD. Additionally, treatment approaches for gut dysbiosis, such as abstinence, diet, pro-, pre-, and synbiotics, antibiotics, and fecal microbial transplantation, are covered here under ALD. However, further research through human clinical trials is warranted to evaluate the appropriate gut microbiota-modulating agents for each condition related to ALD.
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Affiliation(s)
- Jang Han Jung
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
| | - Sung-Eun Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
| | - Ki Tae Suk
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
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24
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Wang L, Cao ZM, Zhang LL, Li JM, Lv WL. The Role of Gut Microbiota in Some Liver Diseases: From an Immunological Perspective. Front Immunol 2022; 13:923599. [PMID: 35911738 PMCID: PMC9326173 DOI: 10.3389/fimmu.2022.923599] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 06/20/2022] [Indexed: 12/12/2022] Open
Abstract
Gut microbiota is a microecosystem composed of various microorganisms. It plays an important role in human metabolism, and its metabolites affect different tissues and organs. Intestinal flora maintains the intestinal mucosal barrier and interacts with the immune system. The liver is closely linked to the intestine by the gut-liver axis. As the first organ that comes into contact with blood from the intestine, the liver will be deeply influenced by the gut microbiota and its metabolites, and the intestinal leakage and the imbalance of the flora are the trigger of the pathological reaction of the liver. In this paper, we discuss the role of gut microbiota and its metabolites in the pathogenesis and development of autoimmune liver diseases((including autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis), metabolic liver disease such as non-alcoholic fatty liver disease, cirrhosisits and its complications, and liver cancer from the perspective of immune mechanism. And the recent progress in the treatment of these diseases was reviewed from the perspective of gut microbiota.
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Affiliation(s)
- Li Wang
- *Correspondence: Li Wang, ; Zheng-Min Cao, ; Juan-mei Li, ; Wen-liang Lv,
| | - Zheng-Min Cao
- *Correspondence: Li Wang, ; Zheng-Min Cao, ; Juan-mei Li, ; Wen-liang Lv,
| | | | - Juan-mei Li
- Department of Infection, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Wen-liang Lv
- Department of Infection, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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25
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Gough EK. The impact of mass drug administration of antibiotics on the gut microbiota of target populations. Infect Dis Poverty 2022; 11:76. [PMID: 35773678 PMCID: PMC9245274 DOI: 10.1186/s40249-022-00999-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 06/09/2022] [Indexed: 12/15/2022] Open
Abstract
Antibiotics have become a mainstay of healthcare in the past century due to their activity against pathogens. This manuscript reviews the impact of antibiotic use on the intestinal microbiota in the context of mass drug administration (MDA). The importance of the gut microbiota to human metabolism and physiology is now well established, and antibiotic exposure may impact host health via collateral effects on the microbiota and its functions. To gain further insight into how gut microbiota respond to antibiotic perturbation and the implications for public health, factors that influence the impact of antibiotic exposure on the microbiota, potential health outcomes of antibiotic-induced microbiota alterations, and strategies that have the potential to ameliorate these wider antibiotic-associated microbiota perturbations are also reviewed.
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Affiliation(s)
- Ethan K Gough
- Department of International Health, Human Nutrition Program, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
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26
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Omar NN, Mosbah RA, Sarawi WS, Rashed MM, Badr AM. Rifaximin Protects against Malathion-Induced Rat Testicular Toxicity: A Possible Clue on Modulating Gut Microbiome and Inhibition of Oxidative Stress by Mitophagy. Molecules 2022; 27:4069. [PMID: 35807317 PMCID: PMC9267953 DOI: 10.3390/molecules27134069] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 06/17/2022] [Accepted: 06/20/2022] [Indexed: 02/04/2023] Open
Abstract
Testicular dysfunction is caused by chronic exposure to environmental pollution, such as malathion, which causes oxidative stress, promoting cell damage. Autophagy is a key cellular process for eliminating malfunctioning organelles, such as the mitochondria (mitophagy), an eminent source of reactive oxygen species (ROS). Autophagy is crucial for protection against testicular damage. Rifaximin (RFX) is a non-absorbable antibiotic that can reshape the gut microbiome, making it effective in different gastrointestinal disorders. Interestingly, the gut microbiome produces short chain fatty acids (SCFAs) in the circulation, which act as signal molecules to regulate the autophagy. In this study, we investigated the regulatory effects of RFX on gut microbiota and its circulating metabolites SCFA and linked them with the autophagy in testicular tissues in response to malathion administration. Moreover, we divided the groups of rats that used malathion and RFX into a two-week group to investigate the mitophagy process and a four-week group to study mitochondriogenesis. The current study revealed that after two weeks of cotreatment with RFX, apoptosis was inhibited, oxidative stress was improved, and autophagy was induced. More specifically, PINK1 was overexpressed, identifying mitophagy activation. After four weeks of cotreatment with RFX, there was an increase in acetate and propionate-producing microflora, as well as the circulating levels of SCFAs. In accordance with this, the expression of PGC-1α, a downstream to SCFAs action on their receptors, was activated. PGC-1α is an upstream activator of mitophagy and mitochondriogenesis. In this sense, the protein expression of TFAM, which regulates the mitochondrial genome, was upregulated along with a significant decrease in apoptosis and oxidative stress. Conclusion: we found that RFX has a positive regulatory effect on mitophagy and mitochondria biogenesis, which could explain the novel role played by RFX in preventing the adverse effects of malathion on testicular tissue.
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Affiliation(s)
- Nesreen Nabil Omar
- Department of Biochemistry, Faculty of Pharmacy, Modern University for Technology and Information, Cairo 11585, Egypt
| | - Rasha A. Mosbah
- Infection Control Unit, Zagazig University Hospital, Zagazig University, El Sharkia 44519, Egypt;
| | - Wedad S. Sarawi
- Department of Pharmacology and Toxicology, King Saud University, Riyadh 11362, Saudi Arabia; (W.S.S.); or (A.M.B.)
| | - Marwa Medhet Rashed
- National Center for Social & Criminological Research, Expert, Crime Investigation Department, Giza 3755153, Egypt;
| | - Amira M. Badr
- Department of Pharmacology and Toxicology, King Saud University, Riyadh 11362, Saudi Arabia; (W.S.S.); or (A.M.B.)
- Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt
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27
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Liu J, Yang D, Wang X, Asare PT, Zhang Q, Na L, Shao L. Gut Microbiota Targeted Approach in the Management of Chronic Liver Diseases. Front Cell Infect Microbiol 2022; 12:774335. [PMID: 35444959 PMCID: PMC9014089 DOI: 10.3389/fcimb.2022.774335] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 02/21/2022] [Indexed: 12/12/2022] Open
Abstract
The liver is directly connected to the intestines through the portal vein, which enables the gut microbiota and gut-derived products to influence liver health. There is accumulating evidence of decreased gut flora diversity and alcohol sensitivity in patients with various chronic liver diseases, including non-alcoholic/alcoholic liver disease, chronic hepatitis virus infection, primary sclerosing cholangitis and liver cirrhosis. Increased intestinal mucosal permeability and decline in barrier function were also found in these patients. Followed by bacteria translocation and endotoxin uptake, these will lead to systemic inflammation. Specific microbiota and microbiota-derived metabolites are altered in various chronic liver diseases studies, but the complex interaction between the gut microbiota and liver is missing. This review article discussed the bidirectional relationship between the gut and the liver, and explained the mechanisms of how the gut microbiota ecosystem alteration affects the pathogenesis of chronic liver diseases. We presented gut-microbiota targeted interventions that could be the new promising method to manage chronic liver diseases.
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Affiliation(s)
- Jing Liu
- Department of Research, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital; The College of Medical Technology, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Dakai Yang
- Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Xiaojing Wang
- School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Paul Tetteh Asare
- Human and Animal Health Unit, Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland
| | - Qingwen Zhang
- Department of Research, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital; The College of Medical Technology, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Lixin Na
- Department of Research, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital; The College of Medical Technology, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Lei Shao
- School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai, China
- *Correspondence: Lei Shao,
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28
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Kawaratani H, Kondo Y, Tatsumi R, Kawabe N, Tanabe N, Sakamaki A, Okumoto K, Uchida Y, Endo K, Kawaguchi T, Oikawa T, Ishizu Y, Hige S, Takami T, Terai S, Ueno Y, Mochida S, Takikawa Y, Torimura T, Matsuura T, Ishigami M, Koike K, Yoshiji H. Long-Term Efficacy and Safety of Rifaximin in Japanese Patients with Hepatic Encephalopathy: A Multicenter Retrospective Study. J Clin Med 2022; 11:1571. [PMID: 35329897 PMCID: PMC8948903 DOI: 10.3390/jcm11061571] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 03/02/2022] [Accepted: 03/08/2022] [Indexed: 01/06/2023] Open
Abstract
Background: Rifaximin is commonly used for hepatic encephalopathy (HE). However, the effects of long-term treatment for Japanese people are limited. Therefore, this study aimed to investigate the effects and safety of long-term treatment with rifaximin on HE. Methods: A total of 215 patients with cirrhosis administered with rifaximin developed overt or covert HE, which was diagnosed by an attending physician for >12 months. Laboratory data were extracted at pretreatment and 3, 6, and 12 months after rifaximin administration. The long-term effect of rifaximin was evaluated, and the incidence of overt HE during 12 months and adverse events was extracted. Results: Ammonia levels were significantly improved after 3 months of rifaximin administration and were continued until 12 months. There were no serious adverse events after rifaximin administration. The number of overt HE incidents was 9, 14, and 27 patients within 3, 6, and 12 months, respectively. Liver enzymes, renal function, and electrolytes did not change after rifaximin administration. Prothrombin activity is a significant risk factor for the occurrence of overt HE. The serum albumin, prothrombin activity, and albumin−bilirubin (ALBI) scores were statistically improved after 3 and 6 months of rifaximin administration. Moreover, the same results were obtained in patients with Child−Pugh C. Conclusions: The long-term rifaximin treatment was effective and safe for patients with HE, including Child−Pugh C.
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Affiliation(s)
- Hideto Kawaratani
- Department of Gastroenterology, Nara Medical University, Kashihara 634-8521, Japan;
| | - Yasuteru Kondo
- Department of Hepatology, Sendai Kousei Hospital, Sendai 980-0873, Japan;
| | - Ryoji Tatsumi
- Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo 060-0033, Japan; (R.T.); (S.H.)
| | - Naoto Kawabe
- Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, Aichi 470-1192, Japan;
| | - Norikazu Tanabe
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yamaguchi University, Ube 755-8505, Japan; (N.T.); (T.T.)
| | - Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; (A.S.); (S.T.)
| | - Kazuo Okumoto
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata 990-9585, Japan; (K.O.); (Y.U.)
| | - Yoshihito Uchida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan; (Y.U.); (S.M.)
| | - Kei Endo
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka 028-3694, Japan; (K.E.); (Y.T.)
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan; (T.K.); (T.T.)
| | - Tsunekazu Oikawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan; (T.O.); (T.M.)
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi 466-8550, Japan; (Y.I.); (M.I.)
| | - Shuhei Hige
- Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo 060-0033, Japan; (R.T.); (S.H.)
| | - Taro Takami
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yamaguchi University, Ube 755-8505, Japan; (N.T.); (T.T.)
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan; (A.S.); (S.T.)
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata 990-9585, Japan; (K.O.); (Y.U.)
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Saitama 350-0495, Japan; (Y.U.); (S.M.)
| | - Yasuhiro Takikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka 028-3694, Japan; (K.E.); (Y.T.)
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan; (T.K.); (T.T.)
| | - Tomokazu Matsuura
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan; (T.O.); (T.M.)
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi 466-8550, Japan; (Y.I.); (M.I.)
| | | | - Hitoshi Yoshiji
- Department of Gastroenterology, Nara Medical University, Kashihara 634-8521, Japan;
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Suhocki PV, Ronald JS, Diehl AME, Murdoch DM, Doraiswamy PM. Probing gut-brain links in Alzheimer's disease with rifaximin. ALZHEIMER'S & DEMENTIA (NEW YORK, N. Y.) 2022; 8:e12225. [PMID: 35128026 PMCID: PMC8804600 DOI: 10.1002/trc2.12225] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 11/05/2021] [Indexed: 12/12/2022]
Abstract
Gut-microbiome-inflammation interactions have been linked to neurodegeneration in Alzheimer's disease (AD) and other disorders. We hypothesized that treatment with rifaximin, a minimally absorbed gut-specific antibiotic, may modify the neurodegenerative process by changing gut flora and reducing neurotoxic microbial drivers of inflammation. In a pilot, open-label trial, we treated 10 subjects with mild to moderate probable AD dementia (Mini-Mental Status Examination (MMSE) = 17 ± 3) with rifaximin for 3 months. Treatment was associated with a significant reduction in serum neurofilament-light levels (P < .004) and a significant increase in fecal phylum Firmicutes microbiota. Serum phosphorylated tau (pTau)181 and glial fibrillary acidic protein (GFAP) levels were reduced (effect sizes of -0.41 and -0.48, respectively) but did not reach statistical significance. In addition, there was a nonsignificant downward trend in serum cytokine interleukin (IL)-6 and IL-13 levels. Cognition was unchanged. Increases in stool Erysipelatoclostridium were correlated significantly with reductions in serum pTau181 and serum GFAP. Insights from this pilot trial are being used to design a larger placebo-controlled clinical trial to determine if specific microbial flora/products underlie neurodegeneration, and whether rifaximin is clinically efficacious as a therapeutic.
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Affiliation(s)
| | | | | | | | - P. Murali Doraiswamy
- Duke University School of MedicineDurhamNorth CarolinaUSA
- Duke Institute for Brain SciencesDurhamNorth CarolinaUSA
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30
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Abstract
Environmental chemicals can alter gut microbial community composition, known as dysbiosis. However, the gut microbiota is a highly dynamic system and its functions are still largely underexplored. Likewise, it is unclear whether xenobiotic exposure affects host health through impairing host-microbiota interactions. Answers to this question not only can lead to a more precise understanding of the toxic effects of xenobiotics but also can provide new targets for the development of new therapeutic strategies. Here, we aim to identify the major challenges in the field of microbiota-exposure research and highlight the need to exam the health effects of xenobiotic-induced gut microbiota dysbiosis in host bodies. Although the changes of gut microbiota frequently co-occur with the xenobiotic exposure, the causal relationship of xenobiotic-induced microbiota dysbiosis and diseases is rarely established. The high dynamics of the gut microbiota and the complex interactions among exposure, microbiota, and host, are the major challenges to decipher the specific health effects of microbiota dysbiosis. The next stage of study needs to combine various technologies to precisely assess the xenobiotic-induced gut microbiota perturbation and the subsequent health effects in host bodies. The exposure, gut microbiota dysbiosis, and disease outcomes have to be causally linked. Many microbiota-host interactions are established by previous studies, including signaling metabolites and response pathways in the host, which may use as start points for future research to examine the mechanistic interactions of exposure, gut microbiota, and host health. In conclusion, to precisely understand the toxicity of xenobiotics and develop microbiota-based therapies, the causal and mechanistic links of exposure and microbiota dysbiosis have to be established in the next stage study.
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Affiliation(s)
- Liang Chi
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC, United States
| | - Pengcheng Tu
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC, United States
| | - Hongyu Ru
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC, United States
| | - Kun Lu
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC, United States,CONTACT Kun Lu Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC27599, United States
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Szychowiak P, Villageois-Tran K, Patrier J, Timsit JF, Ruppé É. The role of the microbiota in the management of intensive care patients. Ann Intensive Care 2022; 12:3. [PMID: 34985651 PMCID: PMC8728486 DOI: 10.1186/s13613-021-00976-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 12/15/2021] [Indexed: 12/13/2022] Open
Abstract
The composition of the gut microbiota is highly dynamic and changes according to various conditions. The gut microbiota mainly includes difficult-to-cultivate anaerobic bacteria, hence knowledge about its composition has significantly arisen from culture-independent methods based on next-generation sequencing (NGS) such as 16S profiling and shotgun metagenomics. The gut microbiota of patients hospitalized in intensive care units (ICU) undergoes many alterations because of critical illness, antibiotics, and other ICU-specific medications. It is then characterized by lower richness and diversity, and dominated by opportunistic pathogens such as Clostridioides difficile and multidrug-resistant bacteria. These alterations are associated with an increased risk of infectious complications or death. Specifically, at the time of writing, it appears possible to identify distinct microbiota patterns associated with severity or infectivity in COVID-19 patients, paving the way for the potential use of dysbiosis markers to predict patient outcomes. Correcting the microbiota disturbances to avoid their consequences is now possible. Fecal microbiota transplantation is recommended in recurrent C. difficile infections and microbiota-protecting treatments such as antibiotic inactivators are currently being developed. The growing interest in the microbiota and microbiota-associated therapies suggests that the control of the dysbiosis could be a key factor in the management of critically ill patients. The present narrative review aims to provide a synthetic overview of microbiota, from healthy individuals to critically ill patients. After an introduction to the different techniques used for studying the microbiota, we review the determinants involved in the alteration of the microbiota in ICU patients and the latter's consequences. Last, we assess the means to prevent or correct microbiota alteration.
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Affiliation(s)
- Piotr Szychowiak
- Université de Paris, IAME, INSERM, 75018, Paris, France
- Service de Médecine Intensive-Réanimation, Centre Hospitalier Régional Universitaire de Tours, 37000, Tours, France
| | - Khanh Villageois-Tran
- Université de Paris, IAME, INSERM, 75018, Paris, France
- Laboratoire de Bactériologie, AP-HP, Hôpital Beaujon, 92110, Paris, France
| | - Juliette Patrier
- Université de Paris, IAME, INSERM, 75018, Paris, France
- Service de Réanimation Médicale Et Infectieuse, AP-HP, Hôpital Bichat, 75018, Paris, France
| | - Jean-François Timsit
- Université de Paris, IAME, INSERM, 75018, Paris, France
- Service de Réanimation Médicale Et Infectieuse, AP-HP, Hôpital Bichat, 75018, Paris, France
| | - Étienne Ruppé
- Université de Paris, IAME, INSERM, 75018, Paris, France.
- Laboratoire de Bactériologie, AP-HP, Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, 75018, Paris, France.
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Biondo S, Bordin D, Golda T. Treatment for Uncomplicated Acute Diverticulitis. COLONIC DIVERTICULAR DISEASE 2022:273-289. [DOI: https:/doi.org/10.1007/978-3-030-93761-4_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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Biondo S, Bordin D, Golda T. Treatment for Uncomplicated Acute Diverticulitis. COLONIC DIVERTICULAR DISEASE 2022:273-289. [DOI: 10.1007/978-3-030-93761-4_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Scarpignato C, Stollman N. Non-Absorbable Antibiotics. COLONIC DIVERTICULAR DISEASE 2022:209-234. [DOI: 10.1007/978-3-030-93761-4_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Li H, Xiang Y, Zhu Z, Wang W, Jiang Z, Zhao M, Cheng S, Pan F, Liu D, Ho RCM, Ho CSH. Rifaximin-mediated gut microbiota regulation modulates the function of microglia and protects against CUMS-induced depression-like behaviors in adolescent rat. J Neuroinflammation 2021; 18:254. [PMID: 34736493 PMCID: PMC8567657 DOI: 10.1186/s12974-021-02303-y] [Citation(s) in RCA: 139] [Impact Index Per Article: 34.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 10/20/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Chronic unpredictable mild stress (CUMS) can not only lead to depression-like behavior but also change the composition of the gut microbiome. Regulating the gut microbiome can have an antidepressant effect, but the mechanism by which it improves depressive symptoms is not clear. Short-chain fatty acids (SCFAs) are small molecular compounds produced by the fermentation of non-digestible carbohydrates. SFCAs are ubiquitous in intestinal endocrine and immune cells, making them important mediators of gut microbiome-regulated body functions. The balance between the pro- and anti-inflammatory microglia plays an important role in the occurrence and treatment of depression caused by chronic stress. Non-absorbable antibiotic rifaximin can regulate the structure of the gut microbiome. We hypothesized that rifaximin protects against stress-induced inflammation and depression-like behaviors by regulating the abundance of fecal microbial metabolites and the microglial functions. METHODS We administered 150 mg/kg rifaximin intragastrically to rats exposed to CUMS for 4 weeks and investigated the composition of the fecal microbiome, the content of short-chain fatty acids in the serum and brain, the functional profiles of microglia and hippocampal neurogenesis. RESULTS Our results show that rifaximin ameliorated depressive-like behavior induced by CUMS, as reflected by sucrose preference, the open field test and the Morris water maze. Rifaximin increased the relative abundance of Ruminococcaceae and Lachnospiraceae, which were significantly positively correlated with the high level of butyrate in the brain. Rifaximin increased the content of anti-inflammatory factors released by microglia, and prevented the neurogenic abnormalities caused by CUMS. CONCLUSIONS These results suggest that rifaximin can regulate the inflammatory function of microglia and play a protective role in pubertal neurodevelopment during CUMS by regulating the gut microbiome and short-chain fatty acids.
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Affiliation(s)
- Haonan Li
- Department of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China
| | - Yujiao Xiang
- Cheeloo Hospital, Shandong University, Jinan, People's Republic of China
| | - Zemeng Zhu
- Department of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China
| | - Wei Wang
- Department of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China
| | - Zhijun Jiang
- Department of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China
| | - Mingyue Zhao
- Department of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China
| | - Shuyue Cheng
- Department of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China
| | - Fang Pan
- Department of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
| | - Dexiang Liu
- Department of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
| | - Roger C M Ho
- Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Institute of Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, Singapore
| | - Cyrus S H Ho
- Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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De Vincentis A, Santonico M, Del Chierico F, Altomare A, Marigliano B, Laudisio A, Reddel S, Grasso S, Zompanti A, Pennazza G, Putignani L, Guarino MPL, Cicala M, Antonelli Incalzi R. Gut Microbiota and Related Electronic Multisensorial System Changes in Subjects With Symptomatic Uncomplicated Diverticular Disease Undergoing Rifaximin Therapy. Front Med (Lausanne) 2021; 8:655474. [PMID: 34350192 PMCID: PMC8326398 DOI: 10.3389/fmed.2021.655474] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 06/11/2021] [Indexed: 01/07/2023] Open
Abstract
Background: Intestinal dysbiosis might play a pathogenetic role in subjects with symptomatic uncomplicated diverticular disease (SUDD), but the effect of rifaximin therapy has been scantly explored with regard to gut microbiota variations in patients with SUDD. Aims: To verify to which extent rifaximin treatment affects the gut microbiota and whether an electronic multisensorial assessment of stools and breath has the potential for detecting these changes. Methods: Breath and stool samples were collected from consecutive patients with SUDD before and after a 7 days' therapy with rifaximin. Stool microbiota was assessed, and the electronic multisensorial assessment was carried out by means of the BIONOTE electronic (e-)tongue in stools and (e-)nose in breath. Results: Forty-three subjects (female 60%, median age 66 years) were included, and 20 (47%) reported clinical improvement after rifaximin therapy. Alpha and beta diversity of stool microbiota did not significantly change after treatment, while a significant variation of selected taxa was shown (i.e., Citrobacter, Coprococcus, Anaerotruncus, Blautia, Eggerthella lenta, Dehalobacterium, SMB53, and Haemophilus parainfluenzae). Overall, the electronic multisensorial system suboptimally mirrored microbiota changes, but it was able to efficiently predict patients' clinical improvement after rifaximin with accuracies ranging from 0.81 to 0.98. Conclusions: In patients with SUDD, rifaximin administration is associated with significant variation of selected taxa. While inaccurate in predicting gut microbiota change, an electronic multisensorial system, made up of e-tongue and e-nose, was able to predict clinical improvement, thus potentially qualifying as an easy and cheap tool to forecast subjects taking most likely benefit from rifaximin therapy.
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Affiliation(s)
| | - Marco Santonico
- Unit of Electronics for Sensor Systems, Department of Science and Technology for Humans and the Environment, University Campus Bio-Medico di Roma, Rome, Italy
| | - Federica Del Chierico
- Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
| | - Annamaria Altomare
- Unit of Gastroenterology, University Campus Bio Medico of Rome, Rome, Italy
| | | | - Alice Laudisio
- Unit of Geriatrics, University Campus Bio Medico of Rome, Rome, Italy
| | - Sofia Reddel
- Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
| | - Simone Grasso
- Unit of Electronics for Sensor Systems, Department of Science and Technology for Humans and the Environment, University Campus Bio-Medico di Roma, Rome, Italy
| | - Alessandro Zompanti
- Unit of Electronics for Sensor Systems, Department of Engineering, University Campus Bio-Medico di Roma, Rome, Italy
| | - Giorgio Pennazza
- Unit of Electronics for Sensor Systems, Department of Engineering, University Campus Bio-Medico di Roma, Rome, Italy
| | - Lorenza Putignani
- Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
- Department of Diagnostic and Laboratory Medicine, Unit of Microbiology and Diagnostic Immunology, Unit of Parasitology and Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
| | | | - Michele Cicala
- Unit of Gastroenterology, University Campus Bio Medico of Rome, Rome, Italy
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Fianchi F, Liguori A, Gasbarrini A, Grieco A, Miele L. Nonalcoholic Fatty Liver Disease (NAFLD) as Model of Gut-Liver Axis Interaction: From Pathophysiology to Potential Target of Treatment for Personalized Therapy. Int J Mol Sci 2021; 22:6485. [PMID: 34204274 PMCID: PMC8233936 DOI: 10.3390/ijms22126485] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 06/13/2021] [Accepted: 06/14/2021] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide, affecting both adults and children and will result, in the near future, as the leading cause of end-stage liver disease. Indeed, its prevalence is rapidly increasing, and NAFLD is becoming a major public health concern. For this reason, great efforts are needed to identify its pathogenetic factors and new therapeutic approaches. In the past decade, enormous advances understanding the gut-liver axis-the complex network of cross-talking between the gut, microbiome and liver through the portal circulation-have elucidated its role as one of the main actors in the pathogenesis of NAFLD. Indeed, evidence shows that gut microbiota is involved in the development and progression of liver steatosis, inflammation and fibrosis seen in the context of NAFLD, as well as in the process of hepatocarcinogenesis. As a result, gut microbiota is currently emerging as a non-invasive biomarker for the diagnosis of disease and for the assessment of its severity. Additionally, to its enormous diagnostic potential, gut microbiota is currently studied as a therapeutic target in NAFLD: several different approaches targeting the gut homeostasis such as antibiotics, prebiotics, probiotics, symbiotics, adsorbents, bariatric surgery and fecal microbiota transplantation are emerging as promising therapeutic options.
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Affiliation(s)
- Francesca Fianchi
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (F.F.); (A.L.); (A.G.); (A.G.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del S. Cuore, 00168 Rome, Italy
| | - Antonio Liguori
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (F.F.); (A.L.); (A.G.); (A.G.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del S. Cuore, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (F.F.); (A.L.); (A.G.); (A.G.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del S. Cuore, 00168 Rome, Italy
| | - Antonio Grieco
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (F.F.); (A.L.); (A.G.); (A.G.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del S. Cuore, 00168 Rome, Italy
| | - Luca Miele
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (F.F.); (A.L.); (A.G.); (A.G.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del S. Cuore, 00168 Rome, Italy
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Piccioni A, Franza L, Brigida M, Zanza C, Torelli E, Petrucci M, Nicolò R, Covino M, Candelli M, Saviano A, Ojetti V, Franceschi F. Gut Microbiota and Acute Diverticulitis: Role of Probiotics in Management of This Delicate Pathophysiological Balance. J Pers Med 2021; 11:298. [PMID: 33919818 PMCID: PMC8070761 DOI: 10.3390/jpm11040298] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 04/05/2021] [Accepted: 04/11/2021] [Indexed: 02/05/2023] Open
Abstract
How can the knowledge of probiotics and their mechanisms of action be translated into clinical practice when treating patients with diverticular disease and acute diverticulitis? Changes in microbiota composition have been observed in patients who were developing acute diverticulitis, with a reduction of taxa with anti-inflammatory activity, such as Clostridium cluster IV, Lactobacilli and Bacteroides. Recent observations supported that a dysbiosis characterised by decreased presence of anti-inflammatory bacterial species might be linked to mucosal inflammation, and a vicious cycle results from a mucosal inflammation driving dysbiosis at the same time. An alteration in gut microbiota can lead to an altered activation of nerve fibres, and subsequent neuronal and muscular dysfunction, thus favoring abdominal symptoms' development. The possible role of dysbiosis and mucosal inflammation in leading to dysmotility is linked, in turn, to bacterial translocation from the lumen of the diverticulum to perivisceral area. There, a possible activation of Toll-like receptors has been described, with a subsequent inflammatory reaction at the level of the perivisceral tissues. Being aware that bacterial colonisation of diverticula is involved in the pathogenesis of acute diverticulitis, the rationale for the potential role of probiotics in the treatment of this disease becomes clearer. For this review, articles were identified using the electronic PubMed database through a comprehensive search conducted by combining key terms such as "gut microbiota", "probiotics and gut disease", "probiotics and acute diverticulitis", "probiotics and diverticular disease", "probiotics mechanism of action". However, the amount of data present on this matter is not sufficient to draw robust conclusions on the efficacy of probiotics for symptoms' management in diverticular disease.
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Affiliation(s)
- Andrea Piccioni
- Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, 1-00168 Rome, Italy; (M.C.); (M.C.); (V.O.); (F.F.)
| | - Laura Franza
- Università Cattolica del Sacro Cuore, 1-00168 Rome, Italy; (L.F.); (C.Z.); (E.T.); (M.P.); (R.N.); (A.S.)
| | - Mattia Brigida
- Unit of Gastroenterology, Department of Systems Medicine, Tor Vergata University, 2-00133 Rome, Italy;
| | - Christian Zanza
- Università Cattolica del Sacro Cuore, 1-00168 Rome, Italy; (L.F.); (C.Z.); (E.T.); (M.P.); (R.N.); (A.S.)
| | - Enrico Torelli
- Università Cattolica del Sacro Cuore, 1-00168 Rome, Italy; (L.F.); (C.Z.); (E.T.); (M.P.); (R.N.); (A.S.)
| | - Martina Petrucci
- Università Cattolica del Sacro Cuore, 1-00168 Rome, Italy; (L.F.); (C.Z.); (E.T.); (M.P.); (R.N.); (A.S.)
| | - Rebecca Nicolò
- Università Cattolica del Sacro Cuore, 1-00168 Rome, Italy; (L.F.); (C.Z.); (E.T.); (M.P.); (R.N.); (A.S.)
| | - Marcello Covino
- Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, 1-00168 Rome, Italy; (M.C.); (M.C.); (V.O.); (F.F.)
| | - Marcello Candelli
- Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, 1-00168 Rome, Italy; (M.C.); (M.C.); (V.O.); (F.F.)
| | - Angela Saviano
- Università Cattolica del Sacro Cuore, 1-00168 Rome, Italy; (L.F.); (C.Z.); (E.T.); (M.P.); (R.N.); (A.S.)
| | - Veronica Ojetti
- Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, 1-00168 Rome, Italy; (M.C.); (M.C.); (V.O.); (F.F.)
- Università Cattolica del Sacro Cuore, 1-00168 Rome, Italy; (L.F.); (C.Z.); (E.T.); (M.P.); (R.N.); (A.S.)
| | - Francesco Franceschi
- Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, 1-00168 Rome, Italy; (M.C.); (M.C.); (V.O.); (F.F.)
- Università Cattolica del Sacro Cuore, 1-00168 Rome, Italy; (L.F.); (C.Z.); (E.T.); (M.P.); (R.N.); (A.S.)
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Pancu DF, Scurtu A, Macasoi IG, Marti D, Mioc M, Soica C, Coricovac D, Horhat D, Poenaru M, Dehelean C. Antibiotics: Conventional Therapy and Natural Compounds with Antibacterial Activity-A Pharmaco-Toxicological Screening. Antibiotics (Basel) 2021; 10:401. [PMID: 33917092 PMCID: PMC8067816 DOI: 10.3390/antibiotics10040401] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 03/30/2021] [Accepted: 03/31/2021] [Indexed: 12/11/2022] Open
Abstract
Antibiotics are considered as a cornerstone of modern medicine and their discovery offers the resolution to the infectious diseases problem. However, the excessive use of antibiotics worldwide has generated a critical public health issue and the bacterial resistance correlated with antibiotics inefficiency is still unsolved. Finding novel therapeutic approaches to overcome bacterial resistance is imperative, and natural compounds with antibacterial effects could be considered a promising option. The role played by antibiotics in tumorigenesis and their interrelation with the microbiota are still debatable and are far from being elucidated. Thus, the present manuscript offers a global perspective on antibiotics in terms of evolution from a historical perspective with an emphasis on the main classes of antibiotics and their adverse effects. It also highlights the connection between antibiotics and microbiota, focusing on the dual role played by antibiotics in tumorigenesis. In addition, using the natural compounds with antibacterial properties as potential alternatives for the classical antibiotic therapy is discussed.
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Affiliation(s)
- Daniel Florin Pancu
- Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 1, 300041 Timisoara, Romania; (D.F.P.); (D.H.); (M.P.)
| | - Alexandra Scurtu
- Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (A.S.); (M.M.); (C.S.); (D.C.); (C.D.)
- Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Ioana Gabriela Macasoi
- Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (A.S.); (M.M.); (C.S.); (D.C.); (C.D.)
- Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Daniela Marti
- Faculty of Medicine, Western University Vasile Goldis Arad, 94 Revolutiei Blvd., 310025 Arad, Romania
| | - Marius Mioc
- Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (A.S.); (M.M.); (C.S.); (D.C.); (C.D.)
- Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Codruta Soica
- Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (A.S.); (M.M.); (C.S.); (D.C.); (C.D.)
- Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Dorina Coricovac
- Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (A.S.); (M.M.); (C.S.); (D.C.); (C.D.)
- Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
| | - Delia Horhat
- Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 1, 300041 Timisoara, Romania; (D.F.P.); (D.H.); (M.P.)
| | - Marioara Poenaru
- Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 1, 300041 Timisoara, Romania; (D.F.P.); (D.H.); (M.P.)
| | - Cristina Dehelean
- Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania; (A.S.); (M.M.); (C.S.); (D.C.); (C.D.)
- Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
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Beyaz Coşkun A, Sağdiçoğlu Celep AG. Therapeutic modulation methods of gut microbiota and gut-liver axis. Crit Rev Food Sci Nutr 2021; 62:6505-6515. [PMID: 33749411 DOI: 10.1080/10408398.2021.1902263] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Liver diseases are considered global health problems that cause more than 1 million deaths each year. Due to the increase in the prevalence of liver diseases worldwide, studies on different treatment methods have increased. Some of these methods is diagnostic and therapeutic applications based on the examination of the intestinal and intestinal microbiota. In this study, research articles, systematic review and review in the literature were examined in order to determine gut-liver axis relationship and treatment methods for liver diseases with gut modulation methods. Studies related to the subject have been searched in Google Scholar and Pubmed databases. The keywords "liver disease" and "gut-liver axis" and "microbiota" and "gut modulation methods" or "probiotic" or "prebiotic" or "symbiotic" or "antibiotic" or "bile acid regulation" or "adsorbent" or "fecal microbiota transplantation" were used in the searches. Improvements have been achieved in biomarkers of liver diseases by providing intestinal modulation with probiotic, prebiotic, symbiotic, antibiotic and adsorbents applications, bile acid regulation and fecal microbiota transplantation. In the results of experimental and clinical studies, it was seen that the therapeutic potential of the treatments performed by applying probiotics, prebiotics and symbiotics was higher.
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Affiliation(s)
- Ayfer Beyaz Coşkun
- Department of Nutrition and Dietetics, Faculty of Health Science, Fırat University, Elazığ, Turkey
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41
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Sometti D, Ballan C, Wang H, Braun C, Enck P. Effects of the antibiotic rifaximin on cortical functional connectivity are mediated through insular cortex. Sci Rep 2021; 11:4479. [PMID: 33627763 PMCID: PMC7904800 DOI: 10.1038/s41598-021-83994-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 01/18/2021] [Indexed: 12/19/2022] Open
Abstract
It is well-known that antibiotics affect commensal gut bacteria; however, only recently evidence accumulated that gut microbiota (GM) can influence the central nervous system functions. Preclinical animal studies have repeatedly highlighted the effects of antibiotics on brain activity; however, translational studies in humans are still missing. Here, we present a randomized, double-blind, placebo-controlled study investigating the effects of 7 days intake of Rifaximin (non-absorbable antibiotic) on functional brain connectivity (fc) using magnetoencephalography. Sixteen healthy volunteers were tested before and after the treatment, during resting state (rs), and during a social stressor paradigm (Cyberball game—CBG), designed to elicit feelings of exclusion. Results confirm the hypothesis of an involvement of the insular cortex as a common node of different functional networks, thus suggesting its potential role as a central mediator of cortical fc alterations, following modifications of GM. Also, the Rifaximin group displayed lower connectivity in slow and fast beta bands (15 and 25 Hz) during rest, and higher connectivity in theta (7 Hz) during the inclusion condition of the CBG, compared with controls. Altogether these results indicate a modulation of Rifaximin on frequency-specific functional connectivity that could involve cognitive flexibility and memory processing.
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Affiliation(s)
- Davide Sometti
- MEG-Center, University of Tübingen, Tübingen, Germany. .,Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. .,DiPSCo, Department of Psychology and Cognitive Science, University of Trento, Rovereto, Italy.
| | - Chiara Ballan
- MEG-Center, University of Tübingen, Tübingen, Germany.,DiPSCo, Department of Psychology and Cognitive Science, University of Trento, Rovereto, Italy
| | - Huiying Wang
- AAK, Department of Special Nutrition, AAK China Ltd, Shanghai, China
| | - Christoph Braun
- MEG-Center, University of Tübingen, Tübingen, Germany.,Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.,DiPSCo, Department of Psychology and Cognitive Science, University of Trento, Rovereto, Italy.,CIMeC, Center for Mind/Brain Research, University of Trento, Trento, Italy
| | - Paul Enck
- Department of Internal Medicine VI, University Hospital, Tübingen, Germany
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Lee NY, Suk KT. The Role of the Gut Microbiome in Liver Cirrhosis Treatment. Int J Mol Sci 2020; 22:E199. [PMID: 33379148 PMCID: PMC7796381 DOI: 10.3390/ijms22010199] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 12/22/2020] [Accepted: 12/24/2020] [Indexed: 02/07/2023] Open
Abstract
Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, diseases such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis and Wilson's disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease of other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver fibrosis.
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Affiliation(s)
| | - Ki Tae Suk
- Institute for Liver and Digestive Diseases, Hallym University College of Medicine, Chuncheon 24253, Korea;
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Zyryanov SK, Baybulatova EA. Rifaximin-Alpha and Other Crystalline Forms of Rifaximin: Are There Any Differences? ANTIBIOTICS AND CHEMOTHERAPY 2020; 65:52-62. [DOI: 10.37489/0235-2990-2020-65-7-8-52-62] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Rifaximin is an antibiotic characterized by polymorphism. It has various crystalline forms with different pharmacological characteristics. Rifaximin acts locally in the digestive tract, therefore it is important for the absorption to be minimal and for concentration in the intestinal lumen to be high. The absorption of other crystalline forms of rifaximin in the intestine is greater than that of rifaximin-α (Alpha Normix®). Differences in pharmacokinetics of the crystalline forms of rifaximin may affect its effectiveness and safety, especially in patients with chronic diseases (immunodeficiency and leaky gut against the background of liver cirrhosis) who require long courses of therapy. Rifaximin-α (Alpha Normix®) is unique as it has eubiotic and anti-inflammatory properties in addition to local antibacterial effect. Given its diverse mechanisms of action, rifaximin-α positively modulates gut microbiota.
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44
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Mutual Interplay of Host Immune System and Gut Microbiota in the Immunopathology of Atherosclerosis. Int J Mol Sci 2020; 21:ijms21228729. [PMID: 33227973 PMCID: PMC7699263 DOI: 10.3390/ijms21228729] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 11/17/2020] [Accepted: 11/17/2020] [Indexed: 12/14/2022] Open
Abstract
Inflammation is the key for the initiation and progression of atherosclerosis. Accumulating evidence has revealed that an altered gut microbiome (dysbiosis) triggers both local and systemic inflammation to cause chronic inflammatory diseases, including atherosclerosis. There have been some microbiome-relevant pro-inflammatory mechanisms proposed to link the relationships between dysbiosis and atherosclerosis such as gut permeability disruption, trigger of innate immunity from lipopolysaccharide (LPS), and generation of proatherogenic metabolites, such as trimethylamine N-oxide (TMAO). Meanwhile, immune responses, such as inflammasome activation and cytokine production, could reshape both composition and function of the microbiota. In fact, the immune system delicately modulates the interplay between microbiota and atherogenesis. Recent clinical trials have suggested the potential of immunomodulation as a treatment strategy of atherosclerosis. Here in this review, we present current knowledge regarding to the roles of microbiota in contributing atherosclerotic pathogenesis and highlight translational perspectives by discussing the mutual interplay between microbiota and immune system on atherogenesis.
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45
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Brown EG, Goldman SM. Modulation of the Microbiome in Parkinson's Disease: Diet, Drug, Stool Transplant, and Beyond. Neurotherapeutics 2020; 17:1406-1417. [PMID: 33034846 PMCID: PMC7851230 DOI: 10.1007/s13311-020-00942-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/28/2020] [Indexed: 12/13/2022] Open
Abstract
The gastrointestinal microbiome is altered in Parkinson's disease and likely plays a key role in its pathophysiology, affecting symptoms and response to therapy and perhaps modifying progression or even disease initiation. Gut dysbiosis therefore has a significant potential as a therapeutic target in Parkinson's disease, a condition elusive to disease-modifying therapy thus far. The gastrointestinal environment hosts a complex ecology, and efforts to modulate the relative abundance or function of established microorganisms are still in their infancy. Still, these techniques are being rapidly developed and have important implications for our understanding of Parkinson's disease. Currently, modulation of the microbiome can be achieved through non-pharmacologic means such as diet, pharmacologically through probiotic, prebiotic, or antibiotic use and procedurally through fecal transplant. Novel techniques being explored include the use of small molecules or genetically engineered organisms, with vast potential. Here, we review how some of these approaches have been used to date, important areas of ongoing research, and how microbiome modulation may play a role in the clinical management of Parkinson's disease in the future.
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Affiliation(s)
- Ethan G Brown
- Division of Movement Disorders and Neuromodulation, Weill Institute of Neurology, University of California, San Francisco, CA, USA.
| | - Samuel M Goldman
- Division of Movement Disorders and Neuromodulation, Weill Institute of Neurology, University of California, San Francisco, CA, USA
- Division of Occupational and Environmental Medicine, University of California, San Francisco, CA, USA
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Campanella B, Lomonaco T, Benedetti E, Onor M, Nieri R, Bramanti E. Validation and Application of a Derivatization-Free RP-HPLC-DAD Method for the Determination of Low Molecular Weight Salivary Metabolites. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E6158. [PMID: 32854235 PMCID: PMC7503734 DOI: 10.3390/ijerph17176158] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 08/12/2020] [Accepted: 08/20/2020] [Indexed: 12/13/2022]
Abstract
Saliva is an interesting, non-conventional, valuable diagnostic fluid. It can be collected using standardized sampling device; thus, its sampling is easy and non-invasive, it contains a variety of organic metabolites that reflect blood composition. The aim of this study was to validate a user-friendly method for the simultaneous determination of low molecular weight metabolites in saliva. We have optimized and validated a high throughput, direct, low-cost reversed phase liquid chromatographic method with diode array detection method without any pre- or post-column derivatization. We indexed salivary biomolecules in 35 whole non-stimulated saliva samples collected in 8 individuals in different days, including organic acids and amino acids and other carbonyl compounds. Among these, 16 whole saliva samples were collected by a single individual over three weeks before, during and after treatment with antibiotic in order to investigate the dynamics of metabolites. The concentrations of the metabolites were compared with the literature data. The multianalyte method here proposed requires a minimal sample handling and it is cost-effectiveness as it makes possible to analyze a high number of samples with basic instrumentation. The identification and quantitation of salivary metabolites may allow the definition of potential biomarkers for non-invasive "personal monitoring" during drug treatments, work out, or life habits over time.
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Affiliation(s)
- Beatrice Campanella
- National Research Council of Italy, C.N.R., Institute of Chemistry of Organometallic Compounds-ICCOM, 56124 Pisa, Italy; (B.C.); (M.O.); (R.N.)
| | - Tommaso Lomonaco
- Department of Chemistry and Industrial Chemistry, University of Pisa, 56124 Pisa, Italy;
| | - Edoardo Benedetti
- Hematology Unit, Department of Oncology, University of Pisa, 56100 Pisa, Italy;
| | - Massimo Onor
- National Research Council of Italy, C.N.R., Institute of Chemistry of Organometallic Compounds-ICCOM, 56124 Pisa, Italy; (B.C.); (M.O.); (R.N.)
| | - Riccardo Nieri
- National Research Council of Italy, C.N.R., Institute of Chemistry of Organometallic Compounds-ICCOM, 56124 Pisa, Italy; (B.C.); (M.O.); (R.N.)
| | - Emilia Bramanti
- National Research Council of Italy, C.N.R., Institute of Chemistry of Organometallic Compounds-ICCOM, 56124 Pisa, Italy; (B.C.); (M.O.); (R.N.)
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47
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Nasef NA, Mehta S. Role of Inflammation in Pathophysiology of Colonic Disease: An Update. Int J Mol Sci 2020; 21:E4748. [PMID: 32635383 PMCID: PMC7370289 DOI: 10.3390/ijms21134748] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/28/2020] [Accepted: 07/01/2020] [Indexed: 02/06/2023] Open
Abstract
Diseases of the colon are a big health burden in both men and women worldwide ranging from acute infection to cancer. Environmental and genetic factors influence disease onset and outcome in multiple colonic pathologies. The importance of inflammation in the onset, progression and outcome of multiple colonic pathologies is gaining more traction as the evidence from recent research is considered. In this review, we provide an update on the literature to understand how genetics, diet, and the gut microbiota influence the crosstalk between immune and non‑immune cells resulting in inflammation observed in multiple colonic pathologies. Specifically, we focus on four colonic diseases two of which have a more established association with inflammation (inflammatory bowel disease and colorectal cancer) while the other two have a less understood relationship with inflammation (diverticular disease and irritable bowel syndrome).
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Affiliation(s)
- Noha Ahmed Nasef
- Riddet Institute, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand
| | - Sunali Mehta
- Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand
- Maurice Wilkins Centre for Biodiscovery, University of Otago, Dunedin 9054, New Zealand
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48
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Gough EK, Bourke CD, Berejena C, Shonhai A, Bwakura-Dangarembizi M, Prendergast AJ, Manges AR. Strain-level analysis of gut-resident pro-inflammatory viridans group Streptococci suppressed by long-term cotrimoxazole prophylaxis among HIV-positive children in Zimbabwe. Gut Microbes 2020; 11:1104-1115. [PMID: 32024435 PMCID: PMC7524282 DOI: 10.1080/19490976.2020.1717299] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Antimicrobials have become a mainstay of healthcare in the past century due to their activity against pathogens. More recently, it has become clear that they can also affect health via their impact on the microbiota and inflammation. This may explain some of their clinical benefits despite global increases in antimicrobial resistance (AMR) and reduced antimicrobial effectiveness. We showed in a randomized controlled trial of stopping versus continuing cotrimoxazole prophylaxis among HIV-positive Zimbabwean children taking antiretroviral therapy (ART), that continuation of cotrimoxazole persistently suppressed gut-resident viridans group streptococcal species (VGS) that were associated with intestinal inflammation. In this addendum, we provide a broader overview of how antibiotics can shape the microbiota and use high read-depth whole metagenome sequencing data from our published study to investigate whether (i) the impact of cotrimoxazole on gut VGS and (ii) VGS associated inflammation, is attributable to strain-level variability. We focus on S. salivarius, the VGS species that was most prevalent in the cohort and for which there was sufficient genome coverage to differentiate strains. We demonstrate that suppression of S. salivarius by cotrimoxazole is not strain specific, nor did stool concentration of the pro-inflammatory mediator myeloperoxidase vary by S. salivarius strain. We also show that gut-resident S. salivarius strains present in this study population are distinct from common oral strains. This is the first analysis of how cotrimoxazole prophylaxis used according to international treatment guidelines for children living with HIV influences the gut microbiome at the strain-level. We also provide a detailed review of the literature on the mechanisms by which suppression of VGS may act synergistically with cotrimoxazole's anti-inflammatory effects to reduce gut inflammation. A greater understanding of the sub-clinical effects of antibiotics offers new insights into their responsible clinical use.
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Affiliation(s)
- Ethan K. Gough
- Department of International Health, Division of Human Nutrition, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA,CONTACT Ethan K. Gough Department of International Health, Division of Human Nutrition, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Claire D. Bourke
- Blizard Institute, Queen Mary University of London, London, UK,Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
| | - Chipo Berejena
- College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe
| | - Annie Shonhai
- College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe
| | | | - Andrew J. Prendergast
- Blizard Institute, Queen Mary University of London, London, UK,Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe,MRC Clinical Trials Unit at University College London, London, UK
| | - Amee R. Manges
- School of Population and Public Health, University of British Columbia, Vancouver, Canada
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49
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Weber D, Hiergeist A, Weber M, Dettmer K, Wolff D, Hahn J, Herr W, Gessner A, Holler E. Detrimental Effect of Broad-spectrum Antibiotics on Intestinal Microbiome Diversity in Patients After Allogeneic Stem Cell Transplantation: Lack of Commensal Sparing Antibiotics. Clin Infect Dis 2020; 68:1303-1310. [PMID: 30124813 DOI: 10.1093/cid/ciy711] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Accepted: 08/16/2018] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Maintaining gastrointestinal (GI) microbiome diversity plays a key role during allogeneic stem cell transplantation (ASCT), and loss of diversity correlates with acute GI graft versus host disease (GvHD) and poor outcomes. METHODS In this retrospective analysis of 161 ASCT patients, we used serial analyses of urinary 3-indoxyl sulfate (3-IS) levels and GI microbiome parameters within the first 10 days after ASCT to identify potential commensal microbiota-sparing antibiotics. Based on antibiotic activity, we formed 3 subgroups (Rifaximin without systemic antibiotics, Rifaximin with systemic antibiotics, and Ciprofloxacin/Metronidazole with/without systemic antibiotics). RESULTS Mono-antibiosis with Rifaximin revealed higher 3-IS levels (P < .001), higher Clostridium cluster XIVa (CCXIVa) abundance (P = .004), and higher Shannon indices (P = .01) compared to Ciprofloxacin/Metronidazole with/without systemic antibiotics. Rifaximin followed by systemic antibiotics maintained microbiome diversity compared to Ciprofloxacin/Metronidazole with/without systemic antibiotics, as these patients showed still higher 3-IS levels (P = .04), higher CCXIVa copy numbers (P = .01), and higher Shannon indexes (P = .01). Even for this larger cohort of patients, the outcome was superior with regard to GI GvHD (P = .05) and lower transplant-related mortality (P < .001) for patients receiving Rifaximin plus systemic antibiotics compared to other types of systemic antibiotic treatment. Antibiosis with Ciprofloxacin/Metronidazole (n = 12, P = .01), Piperacillin/Tazobactam (n = 52, P = .01), Meropenem/Vancomycin (n = 16, P = .003), Ceftazidime (n = 10, P = .03), or multiple systemic antibiotics (n = 53, P = .001) showed significantly lower 3-IS levels compared to mono-antibiosis with Rifaximin (n = 14) or intravenous Vancomycin (n = 4, not statistically significant). CONCLUSIONS Different types of antibiotic treatments show different impacts on markers of microbiome diversity. The identification of antibiotics sparing commensal bacteria remains an ongoing challenge. However, Rifaximin allowed a higher intestinal microbiome diversity, even in the presence of systemic broad-spectrum antibiotics.
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Affiliation(s)
- Daniela Weber
- Department of Hematology and Oncology, Internal Medicine III, University Medical Center, Regensburg, Germany
| | - Andreas Hiergeist
- Institute of Clinical Microbiology and Hygiene, University Medical Center, Regensburg, Germany
| | - Markus Weber
- Department of Orthopedic Surgery, University Medical Center, Regensburg, Germany
| | - Katja Dettmer
- Institute of Functional Genomics, University of Regensburg, Germany
| | - Daniel Wolff
- Department of Hematology and Oncology, Internal Medicine III, University Medical Center, Regensburg, Germany
| | - Joachim Hahn
- Department of Hematology and Oncology, Internal Medicine III, University Medical Center, Regensburg, Germany
| | - Wolfgang Herr
- Department of Hematology and Oncology, Internal Medicine III, University Medical Center, Regensburg, Germany
| | - André Gessner
- Institute of Clinical Microbiology and Hygiene, University Medical Center, Regensburg, Germany
| | - Ernst Holler
- Department of Hematology and Oncology, Internal Medicine III, University Medical Center, Regensburg, Germany
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50
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Yuan Y, Wang X, Xu X, Liu Y, Li C, Yang M, Yang Y, Ma Z. Evaluation of a Dual-Acting Antibacterial Agent, TNP-2092, on Gut Microbiota and Potential Application in the Treatment of Gastrointestinal and Liver Disorders. ACS Infect Dis 2020; 6:820-831. [PMID: 31849218 DOI: 10.1021/acsinfecdis.9b00374] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
TNP-2092 is a unique multitargeting drug conjugate with extremely low propensity for development of resistance. The in vitro activity of TNP-2092 against a panel of urease-producing bacteria was similar to that of rifaximin, a locally acting antibiotic approved for the treatment of hepatic encephalopathy, irritable bowel syndrome with diarrhea, and traveler's diarrhea. When given orally, TNP-2092 exhibited low absorption and the majority of compound was recovered in feces as parent. The impact of oral TNP-2092 on gut microbiota was investigated in rats. TNP-2092 was administered to rats by oral gavage for 7 days. Feces samples were collected and analyzed by 16S rRNA sequencing. Although the total amount of bacterial load appeared relatively unchanged before, during, and after treatment, significant changes in the relative abundance of certain gut bacteria at family and genus levels were observed. Some of the changes are known to be associated with improvement of symptoms associated with liver cirrhosis and hepatic encephalopathy. The observed effects of TNP-2092 on gut microbiota in rats were similar to those of rifaximin. In vivo, TNP-2092 demonstrated potent efficacy in a mouse Clostridium difficile infection model, superior to metronidazole and vancomycin, with no relapse observed after treatment. TNP-2092 is currently in clinical development for the treatment of symptoms associated with gastrointestinal and liver disorders.
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Affiliation(s)
- Ying Yuan
- TenNor Therapeutics Limited, 218 Xinghu Street, Suzhou Industrial Park, Suzhou 215123, China
| | - Xiaomei Wang
- TenNor Therapeutics Limited, 218 Xinghu Street, Suzhou Industrial Park, Suzhou 215123, China
| | - Xiangyi Xu
- TenNor Therapeutics Limited, 218 Xinghu Street, Suzhou Industrial Park, Suzhou 215123, China
| | - Yu Liu
- TenNor Therapeutics Limited, 218 Xinghu Street, Suzhou Industrial Park, Suzhou 215123, China
| | - Cancan Li
- WuXi AppTec (Shanghai) Co., Ltd., 288 Fute Zhong Road, Waigaoqiao, China (Shanghai) Pilot Free Trade Zone, Shanghai 200131, China
| | - Meng Yang
- WuXi AppTec (Shanghai) Co., Ltd., 288 Fute Zhong Road, Waigaoqiao, China (Shanghai) Pilot Free Trade Zone, Shanghai 200131, China
| | - Yiqing Yang
- BGI Genomics, BGI Park, No.21 Hongan 3rd Street, Yantian District, Shenzhen 518083, China
| | - Zhenkun Ma
- TenNor Therapeutics Limited, 218 Xinghu Street, Suzhou Industrial Park, Suzhou 215123, China
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