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Anton-Păduraru DT, Murgu AM, Bozomitu LI, Mîndru DE, Iliescu Halițchi CO, Trofin F, Ciongradi CI, Sârbu I, Eṣanu IM, Azoicăi AN. Diagnosis and Management of Gastrointestinal Manifestations in Children with Cystic Fibrosis. Diagnostics (Basel) 2024; 14:228. [PMID: 38275475 PMCID: PMC10814426 DOI: 10.3390/diagnostics14020228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 01/16/2024] [Accepted: 01/20/2024] [Indexed: 01/27/2024] Open
Abstract
Cystic fibrosis (CF) is primarily known for its pulmonary consequences, which are extensively explored in the existing literature. However, it is noteworthy that individuals with CF commonly display gastrointestinal (G-I) manifestations due to the substantial presence of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in the intestinal tract. Recognized as pivotal nonpulmonary aspects of CF, G-I manifestations exhibit a diverse spectrum. Identifying and effectively managing these manifestations are crucial for sustaining health and influencing the overall quality of life for CF patients. This review aims to synthesize existing knowledge, providing a comprehensive overview of the G-I manifestations associated with CF. Each specific G-I manifestation, along with the diagnostic methodologies and therapeutic approaches, is delineated, encompassing the impact of innovative treatments targeting the fundamental effects of CF on the G-I tract. The findings underscore the imperative for prompt diagnosis and meticulous management of G-I manifestations, necessitating a multidisciplinary team approach for optimal care and enhancement of the quality of life for affected individuals. In conclusion, the authors emphasize the urgency for further clinical studies to establish a more robust evidence base for managing G-I symptoms within the context of this chronic disease. Such endeavors are deemed essential for advancing understanding and refining the clinical care of CF patients with G-I manifestations.
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Affiliation(s)
- Dana-Teodora Anton-Păduraru
- Department of Mother and Child Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iaṣi, Romania; (D.-T.A.-P.); (L.I.B.); (D.E.M.); (C.O.I.H.); (A.N.A.)
- “Sf. Maria” Children Emergency Hospital, 700309 Iasi, Romania; (C.I.C.); (I.S.)
| | - Alina Mariela Murgu
- Department of Mother and Child Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iaṣi, Romania; (D.-T.A.-P.); (L.I.B.); (D.E.M.); (C.O.I.H.); (A.N.A.)
- “Sf. Maria” Children Emergency Hospital, 700309 Iasi, Romania; (C.I.C.); (I.S.)
| | - Laura Iulia Bozomitu
- Department of Mother and Child Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iaṣi, Romania; (D.-T.A.-P.); (L.I.B.); (D.E.M.); (C.O.I.H.); (A.N.A.)
- “Sf. Maria” Children Emergency Hospital, 700309 Iasi, Romania; (C.I.C.); (I.S.)
| | - Dana Elena Mîndru
- Department of Mother and Child Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iaṣi, Romania; (D.-T.A.-P.); (L.I.B.); (D.E.M.); (C.O.I.H.); (A.N.A.)
- “Sf. Maria” Children Emergency Hospital, 700309 Iasi, Romania; (C.I.C.); (I.S.)
| | - Codruța Olimpiada Iliescu Halițchi
- Department of Mother and Child Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iaṣi, Romania; (D.-T.A.-P.); (L.I.B.); (D.E.M.); (C.O.I.H.); (A.N.A.)
| | - Felicia Trofin
- Department of Preventive Medicine and Interdisciplinarity–Microbiology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iaṣi, Romania;
| | - Carmen Iulia Ciongradi
- “Sf. Maria” Children Emergency Hospital, 700309 Iasi, Romania; (C.I.C.); (I.S.)
- 2nd Department of Surgery, Pediatric Surgery and Orthopedics, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iaṣi, Romania
| | - Ioan Sârbu
- “Sf. Maria” Children Emergency Hospital, 700309 Iasi, Romania; (C.I.C.); (I.S.)
- 2nd Department of Surgery, Pediatric Surgery and Orthopedics, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iaṣi, Romania
| | - Irina Mihaela Eṣanu
- Medical Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iaṣi, Romania;
| | - Alice Nicoleta Azoicăi
- Department of Mother and Child Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iaṣi, Romania; (D.-T.A.-P.); (L.I.B.); (D.E.M.); (C.O.I.H.); (A.N.A.)
- “Sf. Maria” Children Emergency Hospital, 700309 Iasi, Romania; (C.I.C.); (I.S.)
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Fyntanidou B, Amaniti A, Soulioti E, Zagalioti SC, Gkarmiri S, Chorti A, Loukipoudi L, Ioannidis A, Dalakakis I, Menni AE, Shrewsbury AD, Kotzampassi K. Probiotics in Postoperative Pain Management. J Pers Med 2023; 13:1645. [PMID: 38138872 PMCID: PMC10745134 DOI: 10.3390/jpm13121645] [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: 10/30/2023] [Revised: 11/20/2023] [Accepted: 11/23/2023] [Indexed: 12/24/2023] Open
Abstract
Postoperative pain is the unpleasant sensory and emotional experience after surgery, its origin being both the inflammatory reaction induced by the surgical trauma on the abdominal wall and the splanchnic pain induced by the activation of nociceptors of the viscera, which are highly sensitive to distension, ischemia, and inflammation. Nowadays, it is well recognized that there is a close relationship between the gut microbiome and pain perception, and that microbiome is highly affected by both anesthesia and surgical manipulation. Thus, efforts to restore the disturbed microbiome via supplementation with beneficial bacteria, namely probiotics, seem to be effective. In this article, the knowledge gained mainly from experimental research on this topic is analyzed, the concluding message being that each probiotic strain works in its own way towards pain relief.
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Affiliation(s)
- Barbara Fyntanidou
- Department of Emergency Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (B.F.); (S.-C.Z.); (S.G.)
| | - Aikaterini Amaniti
- Department of Anesthesia & Intensive Care, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.A.); (L.L.); (I.D.)
| | - Eleftheria Soulioti
- Second Department of Anesthesiology, National and Kapodistrian University of Athens, Attikon University Hospital, 12462 Athens, Greece;
| | - Sofia-Chrysovalantou Zagalioti
- Department of Emergency Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (B.F.); (S.-C.Z.); (S.G.)
| | - Sofia Gkarmiri
- Department of Emergency Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (B.F.); (S.-C.Z.); (S.G.)
| | - Angeliki Chorti
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.C.); (A.I.); (A.-E.M.); (A.D.S.)
| | - Lamprini Loukipoudi
- Department of Anesthesia & Intensive Care, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.A.); (L.L.); (I.D.)
| | - Aris Ioannidis
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.C.); (A.I.); (A.-E.M.); (A.D.S.)
| | - Ioannis Dalakakis
- Department of Anesthesia & Intensive Care, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.A.); (L.L.); (I.D.)
| | - Alexandra-Eleftheria Menni
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.C.); (A.I.); (A.-E.M.); (A.D.S.)
| | - Anne D. Shrewsbury
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.C.); (A.I.); (A.-E.M.); (A.D.S.)
| | - Katerina Kotzampassi
- Department of Surgery, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (A.C.); (A.I.); (A.-E.M.); (A.D.S.)
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Nicolosi RM, Bonincontro G, Imperia E, Badiali C, De Vita D, Sciubba F, Dugo L, Guarino MPL, Altomare A, Simonetti G, Pasqua G. Protective Effect of Procyanidin-Rich Grape Seed Extract against Gram-Negative Virulence Factors. Antibiotics (Basel) 2023; 12:1615. [PMID: 37998817 PMCID: PMC10668874 DOI: 10.3390/antibiotics12111615] [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: 10/08/2023] [Revised: 11/08/2023] [Accepted: 11/09/2023] [Indexed: 11/25/2023] Open
Abstract
Biofilm formation and lipopolysaccharide (LPS) are implicated in the pathogenesis of gastrointestinal (GI) diseases caused by Gram-negative bacteria. Grape seeds, wine industry by-products, have antioxidant and antimicrobial activity. In the present study, the protective effect of procyanidin-rich grape seed extract (prGSE), from unfermented pomace of Vitis vinifera L. cv Bellone, on bacterial LPS-induced oxidative stress and epithelial barrier integrity damage has been studied in a model of Caco-2 cells. The prGSE was characterized at the molecular level using HPLC and NMR. The in vitro activity of prGSE against formation of biofilm of Salmonella enterica subsp. enterica serovar Typhimurium and Escherichia coli was investigated. In vivo, prGSE activity using infected Galleria mellonella larvae has been evaluated. The results show that the prGSE, if administered with LPS, can significantly reduce the LPS-induced permeability alteration. Moreover, the ability of the extract to prevent Reactive Oxygen Species (ROS) production induced by the LPS treatment of Caco-2 cells was demonstrated. prGSE inhibited the biofilm formation of E. coli and S. Typhimurium. In terms of in vivo activity, an increase in survival of infected G. mellonella larvae after treatment with prGSE was demonstrated. In conclusion, grape seed extracts could be used to reduce GI damage caused by bacterial endotoxin and biofilms of Gram-negative bacteria.
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Affiliation(s)
- Roberta Maria Nicolosi
- Department of Environmental Biology, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; (R.M.N.); (G.B.); (C.B.); (D.D.V.); (F.S.); (G.P.)
| | - Graziana Bonincontro
- Department of Environmental Biology, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; (R.M.N.); (G.B.); (C.B.); (D.D.V.); (F.S.); (G.P.)
| | - Elena Imperia
- Department of Science and Technology for Sustainable Development and One Health, University Campus Bio-Medico of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy; (E.I.); (L.D.)
| | - Camilla Badiali
- Department of Environmental Biology, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; (R.M.N.); (G.B.); (C.B.); (D.D.V.); (F.S.); (G.P.)
| | - Daniela De Vita
- Department of Environmental Biology, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; (R.M.N.); (G.B.); (C.B.); (D.D.V.); (F.S.); (G.P.)
| | - Fabio Sciubba
- Department of Environmental Biology, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; (R.M.N.); (G.B.); (C.B.); (D.D.V.); (F.S.); (G.P.)
- NMR-Based Metabolomics Laboratory (NMLab), Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy
| | - Laura Dugo
- Department of Science and Technology for Sustainable Development and One Health, University Campus Bio-Medico of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy; (E.I.); (L.D.)
| | - Michele Pier Luca Guarino
- Research Unit of Gastroenterology, Department of Medicine and Surgery, University Campus Bio-Medico of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy;
- Operative Research Unit of Gastroenterology, University Policlinico Foundation Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Rome, Italy
| | - Annamaria Altomare
- Department of Science and Technology for Sustainable Development and One Health, University Campus Bio-Medico of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy; (E.I.); (L.D.)
- Research Unit of Gastroenterology, Department of Medicine and Surgery, University Campus Bio-Medico of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy;
| | - Giovanna Simonetti
- Department of Environmental Biology, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; (R.M.N.); (G.B.); (C.B.); (D.D.V.); (F.S.); (G.P.)
| | - Gabriella Pasqua
- Department of Environmental Biology, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy; (R.M.N.); (G.B.); (C.B.); (D.D.V.); (F.S.); (G.P.)
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García-Santos JA, Nieto-Ruiz A, García-Ricobaraza M, Cerdó T, Campoy C. Impact of Probiotics on the Prevention and Treatment of Gastrointestinal Diseases in the Pediatric Population. Int J Mol Sci 2023; 24:9427. [PMID: 37298377 PMCID: PMC10253478 DOI: 10.3390/ijms24119427] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 05/22/2023] [Accepted: 05/25/2023] [Indexed: 06/12/2023] Open
Abstract
Despite the high prevalence of gastrointestinal disorders (GIDs) in infants and children, especially those categorized as functional GIDs (FGIDs), insufficient knowledge about their pathophysiology has limited both symptomatic diagnosis and the development of optimal therapies. Recent advances in the field of probiotics have made their potential use as an interesting therapeutic and preventive strategy against these disorders possible, but further efforts are still needed. In fact, there is great controversy surrounding this topic, generated by the high variety of potential probiotics strains with plausible therapeutic utility, the lack of consensus in their use as well as the few comparative studies available on probiotics that record their efficacy. Taking into account these limitations, and in the absence of clear guidelines about the dose and timeframe for successful probiotic therapy, our review aimed to evaluate current studies on potential use of probiotics for the prevention and treatment of the most common FGIDs and GIDs in the pediatric population. Furthermore, matters referring to know major action pathways and key safety recommendations for probiotic administration proposed by major pediatric health agencies shall also be discussed.
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Affiliation(s)
- José Antonio García-Santos
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain; (J.A.G.-S.); (A.N.-R.); (M.G.-R.)
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, Avda del Conocimiento 19, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs-GRANADA), Health Sciences Technological Park, Avda. de Madrid 15, 18012 Granada, Spain
| | - Ana Nieto-Ruiz
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain; (J.A.G.-S.); (A.N.-R.); (M.G.-R.)
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, Avda del Conocimiento 19, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs-GRANADA), Health Sciences Technological Park, Avda. de Madrid 15, 18012 Granada, Spain
| | - María García-Ricobaraza
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain; (J.A.G.-S.); (A.N.-R.); (M.G.-R.)
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, Avda del Conocimiento 19, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs-GRANADA), Health Sciences Technological Park, Avda. de Madrid 15, 18012 Granada, Spain
| | - Tomás Cerdó
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain; (J.A.G.-S.); (A.N.-R.); (M.G.-R.)
- Maimonides Institute for Research in Biomedicine of Córdoba (IMIBIC), Av. Menéndez Pidal, s/n, 14004 Córdoba, Spain
- Centre for Rheumatology Research, Division of Medicine, University College London, Gower Street, London WC1E 6BT, UK
| | - Cristina Campoy
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain; (J.A.G.-S.); (A.N.-R.); (M.G.-R.)
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, Avda del Conocimiento 19, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria de Granada (ibs-GRANADA), Health Sciences Technological Park, Avda. de Madrid 15, 18012 Granada, Spain
- Spanish Network of Biomedical Research in Epidemiology and Public Health (CIBERESP), Granada’s Node, Carlos III Health Institute, Avda. Monforte de Lemos 5, 28028 Madrid, Spain
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Lactobacillus rhamnosus GG normalizes gut dysmotility induced by environmental pollutants via affecting serotonin level in zebrafish larvae. World J Microbiol Biotechnol 2022; 38:222. [PMID: 36100774 DOI: 10.1007/s11274-022-03409-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 09/01/2022] [Indexed: 10/14/2022]
Abstract
Intestinal peristalsis is essential for gastrointestinal function, which could maintain the appropriate progression and digestion of food and reduce bacterial aggregation through mixing function. Even though certain ingredients of foodstuff are known to increase or decrease intestinal peristalsis, the role of environmental pollutants on intestinal peristalsis is relatively unknown. Therefore, the effects of four typical environmental pollutants (oxytetracycline, arsenic, polychlorinated biphenyls and chlorpyrifos) on intestinal peristalsis in the zebrafish model and then tested the recovery effect of the constipation-resistant probiotic. The results showed that 4-day environmental pollutants exposures on the zebrafish embryos at 1 day post fertilization clearly decreased the intestinal peristalsis through decreasing the serotonin (5-HT) production and down-regulating the expression of key genes involved in 5-HT synthesis. Pollutants-evoked change of gut motility could be normalized in the presence of Lactobacillus rhamnosus GG (LGG) via increasing 5-HT secretion. Exogenous 5-hydroxytryptophan (100 µg/L) could also rescue the dysfunction of gut motility in pollutants-treated zebrfish. The data identified that LGG normalized disorder of intestinal peristalsis induced by environmental pollutants through increasing 5-HT level. The stimulant effect of LGG on peristalsis may be associated with 5-HT system, which could provide references for the application of probiotics in regulation of gut dysmotility.
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Dargenio VN, Cristofori F, Dargenio C, Giordano P, Indrio F, Celano G, Francavilla R. Use of Limosilactobacillus reuteri DSM 17938 in paediatric gastrointestinal disorders: an updated review. Benef Microbes 2022; 13:221-242. [PMID: 35212258 DOI: 10.3920/bm2021.0151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Strains of lactobacilli are the most widely used probiotics and can be found in a large variety of food products and food supplements throughout the world. In this study, the evidence on Limosilactobacillus reuteri DSM 17938 (LR DSM 17938) has been reviewed. This species secretes reuterin and other substances singularly or in microvesicles, inhibiting pathogen growth and interacting with the intestinal microbiota and mucosa, restoring homeostasis. The use of LR DSM 17938 has been exploited in several pathological conditions. Preclinical research has shown that this probiotic can ameliorate dysbiosis and, by interacting with intestinal mucosal cells, can raise the pain threshold and promote gastrointestinal motility. These aspects are amongst the significant components in functional gastrointestinal disorders, such as colic and regurgitation in infants, functional abdominal pain and functional constipation in children and adolescents. This strain can decrease the duration of acute diarrhoea and hospitalization for acute gastroenteritis but does not seem to prevent nosocomial diarrhoea and antibiotic-associated diarrhoea. Because of its ability to survive in the gastric environment, it has been tested in Helicobacter pylori infection, showing a significant decrease of antibiotic-associated side effects and a tendency to increase the eradication rate. Finally, all these studies have shown the excellent safety of LR DSM 17938 even at higher dosages. In conclusion data from various clinical trials here reviewed can guide the clinician to find the correct dose, frequency of administration, and therapy duration.
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Affiliation(s)
- V N Dargenio
- Interdisciplinary Department of Medicine, Paediatric Section. University of Bari Aldo Moro, Children's Hospital 'Giovanni XXIII', Via Amendola 207, 70126 Bari, Italy
| | - F Cristofori
- Interdisciplinary Department of Medicine, Paediatric Section. University of Bari Aldo Moro, Children's Hospital 'Giovanni XXIII', Via Amendola 207, 70126 Bari, Italy
| | - C Dargenio
- Interdisciplinary Department of Medicine, Paediatric Section. University of Bari Aldo Moro, Children's Hospital 'Giovanni XXIII', Via Amendola 207, 70126 Bari, Italy
| | - P Giordano
- Interdisciplinary Department of Medicine, Paediatric Section. University of Bari Aldo Moro, Children's Hospital 'Giovanni XXIII', Via Amendola 207, 70126 Bari, Italy
| | - F Indrio
- Department of Paediatrics, University of Foggia, Via Pinto 1, 71100 Foggia, Italy
| | - G Celano
- Department of Soil, Plant and Food Science, University of Bari Aldo Moro, Via Amendola 265/a, 70126 Bari, Italy
| | - R Francavilla
- Interdisciplinary Department of Medicine, Paediatric Section. University of Bari Aldo Moro, Children's Hospital 'Giovanni XXIII', Via Amendola 207, 70126 Bari, Italy
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Layunta E, Forcén R, Grasa L. TLR2 and TLR4 Modulate Mouse Ileal Motility by the Interaction with Muscarinic and Nicotinic Receptors. Cells 2022; 11:cells11111791. [PMID: 35681486 PMCID: PMC9180263 DOI: 10.3390/cells11111791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 05/25/2022] [Accepted: 05/27/2022] [Indexed: 11/16/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic functional bowel disorder characterized by intestinal dysmotility. Changes in intestinal microbiota (dysbiosis) can lead to alterations in neuro-muscular functions in the gut. Toll-like receptors (TLRs) 2 and 4 recognize intestinal bacteria and are involved in the motor response induced by gastrointestinal (GI) neurotransmitters. Acetylcholine (ACh) is a well-known neurotransmitter involved in the regulation of GI motility. This study aimed to evaluate the role of TLR2 and TLR4 in the intestinal motor-response induced by ACh in the mouse ileum, as well as the expression and function of the muscarinic and nicotinic ACh receptors. Muscle contractility studies showed that the contractions induced by ACh were significantly lower in TLR2−/− and TLR4−/− with respect to WT mice. In WT mice, the contractions induced by ACh were reduced in the presence of AF-DX AF-DX 116 (a muscarinic ACh receptor (mAChR) M2 antagonist), 4-DAMP (a mAChR M3 antagonist), mecamylamine (a nicotinic AChR receptor (nAChR) α3β4 antagonist) and α-bungarotoxin (a nAChR α7 antagonist). In TLR2−/− mice, the contractions induced by ACh were increased by AF-DX 116 and mecamylamine. In TLR4−/− mice, the contractions induced by ACh were reduced by α-bungarotoxin and 4-DAMP. The mRNA and protein expressions of M3 and α3 receptors were diminished in the ileum from TLR2−/− and TLR4−/− with respect to WT mice. However, the levels of mRNA and protein of β4 were diminished only in TLR4−/− but not in TLR2−/− mice. In conclusion, our results show that TLR2 and TLR4 modulates the motor responses to ACh in the mouse ileum. TLR2 acts on muscarinic M2 and M3 and nicotinic α3β4 ACh receptors, while TLR4 acts on muscarinic M3 and nicotinic α3β4 and α7 ACh receptors.
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Affiliation(s)
- Elena Layunta
- Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Medicinaregatan 9C, 41390 Gothenburg, Sweden;
| | - Raquel Forcén
- Departamento de Farmacología, Fisiología y Medicina Legal y Forense, Facultad de Veterinaria, Universidad de Zaragoza, 50013 Zaragoza, Spain;
| | - Laura Grasa
- Departamento de Farmacología, Fisiología y Medicina Legal y Forense, Facultad de Veterinaria, Universidad de Zaragoza, 50013 Zaragoza, Spain;
- Instituto de Investigación Sanitaria de Aragón (IIS Aragón), 50009 Zaragoza, Spain
- Instituto Agroalimentario de Aragón—IA2—(Universidad de Zaragoza-CITA), 50013 Zaragoza, Spain
- Correspondence:
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Jomehzadeh N, Amin M, Javaherizadeh H, Rashno M. MOLECULAR ASSESSMENT OF FECAL LACTOBACILLI POPULATIONS IN CHILDREN WITH FUNCTIONAL CONSTIPATION. ARQUIVOS DE GASTROENTEROLOGIA 2022; 59:244-250. [PMID: 35830036 DOI: 10.1590/s0004-2803.202202000-44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 03/29/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Investigation of the gut-specific bacterial strains including lactobacilli is essential for understanding the bacterial etiology of constipation. OBJECTIVE This study aimed to compare the prevalence and quantity of intestinal lactobacilli in constipated children and healthy controls. METHODS Forty children fulfilling Rome IV criteria for functional constipation and 40 healthy controls were recruited. Fecal samples were analyzed using species-specific polymerase chain reaction followed by random amplified polymorphic DNA-PCR and quantitative real-time PCR. RESULTS Totally, seven different species of lactobacilli were detected. Out of 80 volunteers, 65 (81.3%) were culture and species-specific PCR positive from which 25 (38.46%) constipated children and 40 (61.54%) healthy subjects. The most prevalent species were L. paracasei 21 (32.3%) followed by L. plantarum 18 (27.7%) among both healthy and patient groups. Analysis of the RAPD dendrograms displayed that strains isolated from constipated and non-constipated children have similarity coefficients of more than 90%. The qPCR assays demonstrated constipated children had a lower amount of total lactobacilli population (per gram of feces) than healthy controls. CONCLUSION Our findings showed that the mere existence of various species of Lactobacillus in the gut does not enough to prevent some gastrointestinal disorders such as functional constipation, and their quantity plays a more important role.
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Affiliation(s)
- Nabi Jomehzadeh
- Department of Microbiology, School of Medicine, Abadan University of Medical Sciences, Abadan, Iran
- Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mansour Amin
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hazhir Javaherizadeh
- Alimentary Tract Research Center, Clinical Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammad Rashno
- Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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9
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Benjak Horvat I, Gobin I, Kresović A, Hauser G. How can probiotic improve irritable bowel syndrome symptoms? World J Gastrointest Surg 2021; 13:923-940. [PMID: 34621470 PMCID: PMC8462084 DOI: 10.4240/wjgs.v13.i9.923] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 03/22/2021] [Accepted: 08/06/2021] [Indexed: 02/06/2023] Open
Abstract
The onset and manifestations of irritable bowel syndrome (IBS) is associated with several factors, and the pathophysiology involves various central and peripheral mechanisms. Most studies indicate that the management of gut microbiota could significantly affect the improvement of subjective disorders in patients with IBS. Numerous clinical trials have assessed the efficacy of probiotics for IBS with controversial conclusions. Several clinical trials have suggested that probiotics can improve global IBS symptoms, while others only improve individual IBS symptoms, such as bloating scores and abdominal pain scores. Only a few clinical trials have found no apparent effect of probiotics on IBS symptoms. Generally, probiotics appear to be safe for patients with IBS. However, the question of which probiotics should be used for certain IBS subtypes remains unresolved. In everyday practice, the dose of the recommended probiotic remains questionable, as well as how long the probiotic should be used in therapy. The use of probiotics in the M subtype and non-classified IBS is particularly problematic, in which combination therapy should be recommended due to the change in symptoms. Therefore, new approaches are needed in the design of clinical studies that should address certain subtypes of IBS.
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Affiliation(s)
- Indira Benjak Horvat
- Department of Gastroenterology, Varaždin General Hospital, Varažin 42000, Croatia
| | - Ivana Gobin
- Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, Rijeka 51000, Croatia
| | - Andrea Kresović
- Department of Gastroenterology, Clinical Hospital Center Rijeka, Rijeka 51000, Croatia
| | - Goran Hauser
- Department of Gastroenterology, Faculty of Medicine, Clinical Hospital Center Rijeka, University of Rijeka, Rijeka 51000, Croatia
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10
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Palombo G, Merone M, Altomare A, Gori M, Terradura C, Bacco L, Del Chierico F, Putignani L, Cicala M, Guarino MPL, Piemonte V. The impact of the intestinal microbiota and the mucosal permeability on three different antibiotic drugs. Eur J Pharm Sci 2021; 164:105869. [PMID: 34020000 DOI: 10.1016/j.ejps.2021.105869] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 03/19/2021] [Accepted: 04/25/2021] [Indexed: 01/15/2023]
Abstract
BackgroundThe totality of bacteria, protozoa, viruses and fungi that lives in the human body is called microbiota. Human microbiota specifically colonizes the skin, the respiratory and urinary tract, the urogenital tract and the gastrointestinal system. This study focuses on the intestinal microbiota to explore the drug-microbiota relationship and, therefore, how the drug bioavailability changes in relation to the microbiota biodiversity to identify more personalized therapies, with the minimum risk of side effects. MethodsTo achieve this goal, we developed a new mathematical model with two compartments, the intestine and the blood, which takes into account the colonic mucosal permeability variation - measured by Ussing chamber system on human colonic mucosal biopsies - and the fecal microbiota composition, determined through microbiota 16S rRNA sequencing analysis. Both of the clinical parameters were evaluated in a group of Irritable Bowel Syndrome patients compared to a group of healthy controls. Key ResultsThe results show that plasma drug concentration increases as bacterial concentration decreases, while it decreases as intestinal length decreases too. ConclusionsThe study provides interesting data since in literature there are not yet mathematical models with these features, in which the importance of intestinal microbiota, the "forgotten organ", is considered both for the subject health state and in the nutrients and drugs metabolism.
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Affiliation(s)
- Giovanni Palombo
- Istituto di Analisi dei Sistemi ed Informatica "A. Ruberti", IASI-CNR (National Research Council of Italy), Rome, Italy; SYSBIO/ISBE.IT, Centre of System Biology, Rome, Italy
| | - Mario Merone
- Computer Systems and Bioinformatics Laboratory, Department of Engineering, University Campus Bio-Medico of Rome, Italy.
| | | | - Manuele Gori
- Unit of Gastroenterology Campus Bio-Medico University, Rome, Italy; Institute of Biochemistry and Cell Biology (IBBC) - National Research Council (CNR), Monterotondo Scalo, Rome, Italy
| | - Carlotta Terradura
- Unit of Chemical-physics Fundamentals in Chemical Engineering, Department of Engineering, University Campus Bio-Medico of Rome, Italy
| | - Luca Bacco
- Computer Systems and Bioinformatics Laboratory, Department of Engineering, University Campus Bio-Medico of Rome, Italy; Istituto di Linguistica Computazionale "Antonio Zampolli" (IL-CNR), ItaliaNLP Lab, Pisa, Italy
| | - Federica Del Chierico
- Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesú Children's Hospital, IRCCS, Rome, Italy
| | - Lorenza Putignani
- Department of Diagnostic and Laboratory Medicine, Unit of Parasitology and Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesú Children's Hospital, IRCCS, Rome, Italy
| | - Michele Cicala
- Unit of Gastroenterology Campus Bio-Medico University, Rome, Italy
| | | | - Vincenzo Piemonte
- Unit of Chemical-physics Fundamentals in Chemical Engineering, Department of Engineering, University Campus Bio-Medico of Rome, Italy
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11
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Simon E, Călinoiu LF, Mitrea L, Vodnar DC. Probiotics, Prebiotics, and Synbiotics: Implications and Beneficial Effects against Irritable Bowel Syndrome. Nutrients 2021; 13:nu13062112. [PMID: 34203002 PMCID: PMC8233736 DOI: 10.3390/nu13062112] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 06/05/2021] [Accepted: 06/16/2021] [Indexed: 12/12/2022] Open
Abstract
Irritable bowel syndrome (IBS) is still a common functional gastrointestinal disease that presents chronic abdominal symptoms but with a pathophysiology that is not yet fully elucidated. Moreover, the use of the synergistic combination of prebiotics and probiotics, known as synbiotics, for IBS therapy is still in the early stages. Advancements in technology led to determining the important role played by probiotics in IBS, whereas the present paper focuses on the detailed review of the various pathophysiologic mechanisms of action of probiotics, prebiotics, and synbiotics via multidisciplinary domains involving the gastroenterology (microbiota modulation, alteration of gut barrier function, visceral hypersensitivity, and gastrointestinal dysmotility) immunology (intestinal immunological modulation), and neurology (microbiota–gut–brain axis communication and co-morbidities) in mitigating the symptoms of IBS. In addition, this review synthesizes literature about the mechanisms involved in the beneficial effects of prebiotics and synbiotics for patients with IBS, discussing clinical studies testing the efficiency and outcomes of synbiotics used as therapy for IBS.
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Affiliation(s)
- Elemer Simon
- Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania; (E.S.); (L.F.C.)
| | - Lavinia Florina Călinoiu
- Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania; (E.S.); (L.F.C.)
- Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania;
| | - Laura Mitrea
- Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania;
| | - Dan Cristian Vodnar
- Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania; (E.S.); (L.F.C.)
- Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania;
- Correspondence: ; Tel.: +40-747-341-881
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12
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Altomare A, Gori M, Cocca S, Carotti S, Francesconi M, Ribolsi M, Emerenziani S, Perrone G, Morini S, Cicala M, Guarino MPL. Impaired Colonic Contractility and Intestinal Permeability in Symptomatic Uncomplicated Diverticular Disease. J Neurogastroenterol Motil 2021; 27:292-301. [PMID: 33594008 PMCID: PMC8026365 DOI: 10.5056/jnm20110] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 10/31/2020] [Accepted: 12/08/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND/AIMS Impaired intestinal motility seems to play a crucial role in symptomatic uncomplicated diverticular disease (SUDD), although the mechanism is not clear. The aim of the present study is to explore the contractility patterns of colonic smooth muscle strips (MS) and smooth muscle cells (SMCs) and to assess mucosal integrity in SUDD patients. METHODS MS or SMCs were isolated from specimens of human distal colon of 18 patients undergoing surgery for non-obstructive colonic cancer, among them 9 with SUDD. Spontaneous phasic contractions on strips and morpho-functional parameters on cells were evaluated in basal conditions and in response to acetylcholine (ACh). Mucosal integrity of SUDD colonic biopsies was evaluated by the Ussing Chamber system. Immunohistochemical staining for tight junction protein complex and for Toll-like receptor 4 (TLR4) was performed. RESULTS Colonic MS of SUDD group showed a significant reduced basal tone and ACh-elicited contraction, compared to the control group (9.5 g and 47.0% in the SUDD group; 14.16 g and 69.0% in the control group; P < 0.05). SMCs of SUDD group showed a maximal contractile response to ACh significantly reduced compared to control group (8.8% vs 16.5%, P < 0.05). SUDD patients displayed lower transepithelial electrical resistance and increased paracellular permeability compared to control group. Immunohistochemical expression of TLR4 was not different in both groups, while tight junction protein complex expression was lower in SUDD patients compared to control group patients. CONCLUSION It could be hypothesized that in SUDD, in absence of severe inflammation, an increased intestinal mucosal permeability is related to altered colonic motility probably responsible for symptoms genesis.
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Affiliation(s)
- Annamaria Altomare
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Manuele Gori
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
- Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Monterotondo Scalo, Rome, Italy
| | - Silvia Cocca
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Simone Carotti
- Microscopic and Ultrastructural Anatomy Unit, Università Campus Bio-Medico di Roma, Rome, Italy
- Predictive Molecular Diagnostic Division, Department of Pathology, Campus Bio-Medico University Hospital, Rome, Italy
| | - Maria Francesconi
- Microscopic and Ultrastructural Anatomy Unit, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Mentore Ribolsi
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Sara Emerenziani
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Giuseppe Perrone
- Predictive Molecular Diagnostic Division, Department of Pathology, Campus Bio-Medico University Hospital, Rome, Italy
| | - Sergio Morini
- Microscopic and Ultrastructural Anatomy Unit, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Michele Cicala
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
| | - Michele P L Guarino
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy
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13
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Ivashkin KV, Grechishnikova VR, Reshetova MS, Ivashkin VT. Irritable Bowel and Bacterial Overgrowth Syndromes: a Bacterial Link Hypothesis of Functional Disease. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2021; 31:54-63. [DOI: 10.22416/1382-4376-2021-31-1-54-63] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Aim. Assessment of the irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth syndrome (SIBO) interlinkage.Key points. SIBO may represent a "peripheral" mechanism of IBS, aside to nonspecific inflammation, increased epithelial permeability and local immune system activation. In various assays, the SIBO rate in IBS patients was 4-46% vs. 0-13% in an intact cohort. A limited diagnosability of SIBO obscures the SIBO-IBS causal interplay. Impaired motility in IBS may predispose to the SIBO development. Proinflammatory cytokines and mediators in SIBO, in turn, provoke visceral hypersensitivity and intense motility, the key IBS factors. Both conditions relate to qualitative and quantitative changes in microbiota, which warrants the application of probiotic Lactobacillus and Bifidobacterium strains.Conclusion. Further research into the SIBO-IBS interface is required for developing optimal probiotic-based therapies.
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Affiliation(s)
- K. V. Ivashkin
- Sechenov First Moscow State Medical University (Sechenov University)
| | | | - M. S. Reshetova
- Sechenov First Moscow State Medical University (Sechenov University)
| | - V. T. Ivashkin
- Sechenov First Moscow State Medical University (Sechenov University)
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14
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Uhlig F, Grundy L, Garcia-Caraballo S, Brierley SM, Foster SJ, Grundy D. Identification of a Quorum Sensing-Dependent Communication Pathway Mediating Bacteria-Gut-Brain Cross Talk. iScience 2020; 23:101695. [PMID: 33163947 PMCID: PMC7607502 DOI: 10.1016/j.isci.2020.101695] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 07/03/2020] [Accepted: 10/14/2020] [Indexed: 12/12/2022] Open
Abstract
Despite recently established contributions of the intestinal microbiome to human health and disease, our understanding of bacteria-host communication pathways with regard to the gut-brain axis remains limited. Here we provide evidence that intestinal neurons are able to "sense" bacteria independently of the host immune system. Using supernatants from cultures of the opportunistic pathogen Staphylococcus aureus (S. aureus) we demonstrate the release of mediators with neuromodulatory properties at high population density. These mediators induced a biphasic response in extrinsic sensory afferent nerves, increased membrane permeability in cultured sensory neurons, and altered intestinal motility and secretion. Genetic manipulation of S. aureus revealed two key quorum sensing-regulated classes of pore forming toxins that mediate excitation and inhibition of extrinsic sensory nerves, respectively. As such, bacterial mediators have the potential to directly modulate gut-brain communication to influence intestinal symptoms and reflex function in vivo, contributing to homeostatic, behavioral, and sensory consequences of infection.
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Affiliation(s)
- Friederike Uhlig
- Department of Biomedical Science, University of Sheffield, Sheffield, UK
| | - Luke Grundy
- Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI), Flinders University, Bedford Park, SA, Australia
- Hopwood Centre for Neurobiology, Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), North Terrace, Adelaide, SA, Australia
- Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia
| | - Sonia Garcia-Caraballo
- Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI), Flinders University, Bedford Park, SA, Australia
- Hopwood Centre for Neurobiology, Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), North Terrace, Adelaide, SA, Australia
- Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia
| | - Stuart M. Brierley
- Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI), Flinders University, Bedford Park, SA, Australia
- Hopwood Centre for Neurobiology, Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), North Terrace, Adelaide, SA, Australia
- Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia
| | - Simon J. Foster
- Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK
- Florey Institute, University of Sheffield, Sheffield, UK
| | - David Grundy
- Department of Biomedical Science, University of Sheffield, Sheffield, UK
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15
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Drago L, Meroni G, Chiaretti A, Laforgia N, Cucchiara S, Baldassarre ME. Effect of Limosilactobacillus reuteri LRE02- Lacticaseibacillus rhamnosus LR04 Combination on Antibiotic-Associated Diarrhea in a Pediatric Population: A National Survey. J Clin Med 2020; 9:jcm9103080. [PMID: 32987822 PMCID: PMC7650601 DOI: 10.3390/jcm9103080] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 09/16/2020] [Accepted: 09/22/2020] [Indexed: 11/16/2022] Open
Abstract
Probiotics are living microorganisms, which, upon oral ingestion, may prevent antibiotic-associated diarrhea (AAD) through the normalization of an unbalanced gastrointestinal flora. The objective of this study was to evaluate the benefits of a probiotic combination (Limosilactibacillus reuteri LRE02-DSM 23878 and Lacticaseibacillus rhamnosus LR04-DSM 16605) on the prevention of AAD in an outpatient pediatric setting. Questionnaires were delivered to pediatricians by each patient/parent during the visits after antibiotics and probiotics treatment to monitor physiological parameters. The primary outcome of both groups (probiotics and no probiotics treated) was the evaluation of the prevalence of AAD between the two groups. Evaluation of stool consistency using the Bristol Stool Scale (BSS) score was performed, as well as the evaluation of AAD duration, frequencies of daily evacuation, and the beginning of diarrhea and weight loss during AAD in both groups and related to antibiotic categories. Results indicated that probiotics, at the recommended dosage of 1.2 × 109 CFU (Colony Forming Unit) per day for 30 days, are associated with lower rates of AAD and a decreased number of days with diarrhea, independent of the type of antibiotic used. Moreover, the use of probiotics resulted in a normal stool consistency in a shorter time period, as evaluated by the BSS.
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Affiliation(s)
- Lorenzo Drago
- Laboratory of Clinical Microbiology and Microbial Metagenomic Unit, Department of Biomedical Sciences, University of Milan, 20133 Milan, Italy;
- Pediatric Research Center Romeo and Enrica Invernizzi, University of Milan, 20122 Milan, Italy
- Correspondence:
| | - Gabriele Meroni
- Laboratory of Clinical Microbiology and Microbial Metagenomic Unit, Department of Biomedical Sciences, University of Milan, 20133 Milan, Italy;
| | - Antonio Chiaretti
- Pediatric Emergency Department, Fondazione Policlinico Universitario A. Gemelli, IRCCS–Rome, 00168 Rome, Italy;
| | - Nicola Laforgia
- Department of Biomedical Science and Human Oncology-Section of Neonatology and NICU, University “Aldo Moro” of Bari, 70124 Bari, Italy; (N.L.); (M.E.B.)
| | - Salvatore Cucchiara
- Pediatric Gastroenterology and Liver Unit, Department of Women’s and Children’s Health, Sapienza University of Rome, 00161 Rome, Italy;
| | - Maria Elisabetta Baldassarre
- Department of Biomedical Science and Human Oncology-Section of Neonatology and NICU, University “Aldo Moro” of Bari, 70124 Bari, Italy; (N.L.); (M.E.B.)
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16
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Probiotics and constipation: mechanisms of action, evidence for effectiveness and utilisation by patients and healthcare professionals. Proc Nutr Soc 2019; 79:147-157. [PMID: 31262376 DOI: 10.1017/s0029665119000934] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The aim of this narrative review is to assess and present evidence on the mechanisms of action of probiotics in constipation, their effectiveness and their utilisation by patients and healthcare professionals. Chronic constipation is a common bothersome disorder that has a considerable impact on patients' quality of life. Probiotics have been increasingly investigated for their effectiveness in various disorders, including chronic constipation. Probiotics may affect gut motility and constipation through their impact on the gut microbiota and fermentation, the central and enteric nervous system and the immune system. However, evidence for the effectiveness of probiotics in the management of constipation remains varied, with some strains demonstrating improvements, while others show no effect. Despite the uncertainty in evidence and the fact that the majority of healthcare professionals do not recommend probiotics for constipation, an increased prevalence of probiotic use by people with constipation has been shown. Therefore, there is a need for public health strategies to inform the public about where strong evidence of probiotic effectiveness exist, and where evidence is still weak. Education of healthcare professionals on the increased utilisation of probiotics for constipation by the public and on current evidence for the effectiveness of specific strains is also required.
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Abstract
Aim:to review available data confirming the pathogenetic role of the intestinal microbiota in the formation of irritable bowel syndrome (IBS).Key findings.Changes in the intestinal biotope cause the development of visceral hypersensitivity and impaired intestinal motor activity, as well as neuroimmune transmission. This article discusses the main aspects of the biological properties of probiotic bacteria in terms of their action within the “brain — intestine — microbiota” chain. The results of experimental and clinical studies elucidating the mechanisms of action of probiotic cultures have been generalized. The understanding of these mechanisms allows practitioners to make informed decisions in prescribing probiotics to IBS patients. Key concepts concerning fecal microbiota transplantation, as well as the prospects and difficulties of implementing this approach are considered.Conclusions.The term “microbiota — intestine — brain” clearly demonstrates the correlation between the main functional components of IBS. Meta-analyses and systematic reviews confirm the efficacy of probiotics in IBS. However, further research into probiotic therapy options is needed to identify specific bacterial strains with proven clinical efficacy. The fecal microbiota transplantation method also requires further research, since many issues associated with this approach remain unclear.
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Gong J, Bai T, Zhang L, Qian W, Song J, Hou X. Inhibition effect of Bifidobacterium longum, Lactobacillus acidophilus, Streptococcus thermophilus and Enterococcus faecalis and their related products on human colonic smooth muscle in vitro. PLoS One 2017; 12:e0189257. [PMID: 29216305 PMCID: PMC5720742 DOI: 10.1371/journal.pone.0189257] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2017] [Accepted: 11/22/2017] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE To investigate the effects of four strains, generally used in clinic, including Bifidobacterium longum, Lactobacillus acidophilus, Streptococcus thermophilus and Enterococcus faecalis, and their related products on human colonic smooth muscle in vitro. METHODS Human colonic circular muscle strips obtained from disease-free margins of resected segments from 25 patients with colorectal cancer were isometrically examined in a constant-temperature organ bath and exposed to different concentrations of living bacteria, sonicated cell fractions and cell-free supernatant (CFS). The area under the curve (AUC) representing the contractility of smooth muscle strips was calculated. RESULTS (1) The four living probiotics inhibited the contractility of human colonic muscle strips only at high concentration (1010 CFUs/mL, all P<0.05). (2) The sonicated cell fractions from the four probiotics obviously inhibited human colonic smooth muscle strips in a dose-dependent manner (P<0.01). (3) The CFS from the four probiotics also inhibited colonic smooth muscle strips in a dose-dependent manner (all P<0.05). (4) The inhibition effect of CFS from Streptococcus thermophilus and Enterococcus faecalis decreased obviously when pretreated with NG-nitro-L-arginine (L-NNA, 10-5 mol/L) (P<0.05), but not the Bifidobacterium longum and Lactobacillus acidophilus (P>0.05). CONCLUSION Four common probiotics related products, including the sonicated cell fractions and the CFS, obviously inhibited human colonic smooth muscles strips contraction in a dose-dependent manner. Only high concentration living probiotics (1010 CFUs/mL) can inhibit the colonic smooth muscles strips contraction. The NO pathway may be partly involved in the inhibitory effect of CFS from Streptococcus thermophilus and Enterococcus faecalis.
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Affiliation(s)
- Jing Gong
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Bai
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lei Zhang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Qian
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jun Song
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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19
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Dimidi E, Christodoulides S, Scott SM, Whelan K. Mechanisms of Action of Probiotics and the Gastrointestinal Microbiota on Gut Motility and Constipation. Adv Nutr 2017; 8:484-494. [PMID: 28507013 PMCID: PMC5421123 DOI: 10.3945/an.116.014407] [Citation(s) in RCA: 297] [Impact Index Per Article: 37.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Constipation is a common and burdensome gastrointestinal disorder that may result from altered gastrointestinal motility. The effect of probiotics on constipation has been increasingly investigated in both animal and human studies, showing promising results. However, there is still uncertainty regarding the mechanisms of action of probiotics on gut motility and constipation. Several factors are vital to normal gut motility, including immune and nervous system function, bile acid metabolism and mucus secretion, and the gastrointestinal microbiota and fermentation; an imbalance or dysfunction in any of these components may contribute to aberrant gut motility and, consequently, symptoms of constipation. For example, adults with functional constipation have significantly decreased numbers of bifidobacteria (with one study showing a mean difference of 1 log10/g) and lactobacilli (mean difference, 1.4 log10/g) in stool samples, as well as higher breath methane, compared with control subjects. Modifying the gut luminal environment with certain probiotic strains may affect motility and secretion in the gut and, hence, provide a benefit for patients with constipation. Therefore, this review explores the mechanisms through which probiotics may exert an effect on gut motility and constipation. Nevertheless, the majority of current evidence is derived from animal studies, and therefore, further human studies are needed to determine the mechanisms through specific probiotic strains that might be effective in constipation.
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Affiliation(s)
- Eirini Dimidi
- Faculty of Life Sciences and Medicine, Diabetes and Nutritional Sciences Division, King’s College London, London, United Kingdom; and,Centre for Neuroscience and Trauma, Neurogastroenterology Group and GI Physiology Unit, Queen Mary University of London, London, United Kingdom
| | - Stephanos Christodoulides
- Faculty of Life Sciences and Medicine, Diabetes and Nutritional Sciences Division, King’s College London, London, United Kingdom; and,Centre for Neuroscience and Trauma, Neurogastroenterology Group and GI Physiology Unit, Queen Mary University of London, London, United Kingdom
| | - S Mark Scott
- Centre for Neuroscience and Trauma, Neurogastroenterology Group and GI Physiology Unit, Queen Mary University of London, London, United Kingdom
| | - Kevin Whelan
- Faculty of Life Sciences and Medicine, Diabetes and Nutritional Sciences Division, King's College London, London, United Kingdom; and
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Effects of Synbiotic2000™ Forte on the Intestinal Motility and Interstitial Cells of Cajal in TBI Mouse Model. Probiotics Antimicrob Proteins 2017; 9:172-181. [PMID: 28303478 DOI: 10.1007/s12602-017-9266-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The main objective of this study was to investigate the effects of Synbiotic2000™ Forte on the intestinal motility and interstitial cells of Cajal (ICC) in traumatic brain injury (TBI) mouse model. Kunming mice were randomly divided into sham operation group (S group), enteral nutrition group with TBI (E group), and Synbiotic2000™ Forte group with TBI (P group). The contractile activity of the intestinal smooth muscle, densities and ultrastructure of the ICC, kit protein concentration, weight, and defecation of mice were monitored and analyzed. TBI markedly suppressed contractile activity of the intestinal smooth muscle (P < 0.01), which led to a reduction of defecation (P < 0.01) and weight (P < 0.01). However, application of Synbiotic2000™ Forte significantly improved contractile activity of the small intestine (P < 0.01), which may be related to protective effects to the interstitial cells of Cajal, smooth muscle cells, and enteric neurons. TBI impaired ICC networks and densities (P < 0.01), events that were protected by the application of Synbiotic2000™ Forte. Synbiotic2000™ Forte may attenuate TBI-mediated inhibition of the kit protein pathway. Synbiotic2000™ Forte may improve intestinal motility and protect the ICC in the TBI mouse. These findings provide a novel support for the application of Synbiotic2000™ Forte in intestinal motility disturbance after TBI.
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Abstract
PURPOSE OF REVIEW The importance of the gut microbiome in human health is being increasingly recognized. The purpose of this review is to examine the existing literature pertaining to alterations in the gut microbiome and the utility of microbiome restoration therapies in gastrointestinal disorders. RECENT FINDINGS Imbalance and maladaptation of the microbiome, termed dysbiosis, has been associated with several disease states such as irritable bowel syndrome, Clostridium difficile infection, inflammatory bowel diseases, nonalcoholic fatty liver disease, and obesity among others. The possibility of restoration of normal microbiota has become an attractive concept for diseases in which the normal microbiome is perturbed. The rationale of using fecal microbiota transplantation to treat disease has been validated by its successful use in treating recurrent Clostridium difficile infection, which occurs as a result of decreased microbial diversity in the gut, most often in the setting of recent antibiotic treatment. Similar strategies may be applicable to other disorders. SUMMARY Alterations in the gut microbiome are associated with several disorders, and microbiome restoration based therapies such as fecal microbiota transplantation may be an adjunct to conventional treatments but more investigation is needed.
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Affiliation(s)
- Thomas Malikowski
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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de Meij TGJ, de Groot EFJ, Eck A, Budding AE, Kneepkens CMF, Benninga MA, van Bodegraven AA, Savelkoul PHM. Characterization of Microbiota in Children with Chronic Functional Constipation. PLoS One 2016; 11:e0164731. [PMID: 27760208 PMCID: PMC5070844 DOI: 10.1371/journal.pone.0164731] [Citation(s) in RCA: 89] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Accepted: 09/29/2016] [Indexed: 12/18/2022] Open
Abstract
Objectives Disruption of the intestinal microbiota is considered an etiological factor in pediatric functional constipation. Scientifically based selection of potential beneficial probiotic strains in functional constipation therapy is not feasible due to insufficient knowledge of microbiota composition in affected subjects. The aim of this study was to describe microbial composition and diversity in children with functional constipation, compared to healthy controls. Study Design Fecal samples from 76 children diagnosed with functional constipation according to the Rome III criteria (median age 8.0 years; range 4.2–17.8) were analyzed by IS-pro, a PCR-based microbiota profiling method. Outcome was compared with intestinal microbiota profiles of 61 healthy children (median 8.6 years; range 4.1–17.9). Microbiota dissimilarity was depicted by principal coordinate analysis (PCoA), diversity was calculated by Shannon diversity index. To determine the most discriminative species, cross validated logistic ridge regression was performed. Results Applying total microbiota profiles (all phyla together) or per phylum analysis, no disease-specific separation was observed by PCoA and by calculation of diversity indices. By ridge regression, however, functional constipation and controls could be discriminated with 82% accuracy. Most discriminative species were Bacteroides fragilis, Bacteroides ovatus, Bifidobacterium longum, Parabacteroides species (increased in functional constipation) and Alistipes finegoldii (decreased in functional constipation). Conclusions None of the commonly used unsupervised statistical methods allowed for microbiota-based discrimination of children with functional constipation and controls. By ridge regression, however, both groups could be discriminated with 82% accuracy. Optimization of microbiota-based interventions in constipated children warrants further characterization of microbial signatures linked to clinical subgroups of functional constipation.
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Affiliation(s)
- Tim G. J. de Meij
- Department of Pediatric Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands
- * E-mail:
| | - Evelien F. J. de Groot
- Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands
| | - Anat Eck
- Department of Medical Microbiology & Infection Control, VU University Medical Center, Amsterdam, The Netherlands
| | - Andries E. Budding
- Department of Medical Microbiology & Infection Control, VU University Medical Center, Amsterdam, The Netherlands
| | - C. M. Frank Kneepkens
- Department of Pediatric Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands
| | - Marc A. Benninga
- Department of Pediatric Gastroenterology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The Netherlands
| | - Adriaan A. van Bodegraven
- Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands
- Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (Co-MIK), Zuyderland Medical Center, Heerlen-Sittard-Geleen, The Netherlands
| | - Paul H. M. Savelkoul
- Department of Medical Microbiology & Infection Control, VU University Medical Center, Amsterdam, The Netherlands
- Department of Medical Microbiology, Maastricht University Medical Center, Maastricht, The Netherlands
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Distrutti E, Monaldi L, Ricci P, Fiorucci S. Gut microbiota role in irritable bowel syndrome: New therapeutic strategies. World J Gastroenterol 2016; 22:2219-2241. [PMID: 26900286 PMCID: PMC4734998 DOI: 10.3748/wjg.v22.i7.2219] [Citation(s) in RCA: 192] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 12/05/2015] [Accepted: 12/30/2015] [Indexed: 02/07/2023] Open
Abstract
In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome (IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial (Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful (Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required.
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Carotti S, Guarino MPL, Vespasiani-Gentilucci U, Morini S. Starring role of toll-like receptor-4 activation in the gut-liver axis. World J Gastrointest Pathophysiol 2015; 6:99-109. [PMID: 26600967 PMCID: PMC4644892 DOI: 10.4291/wjgp.v6.i4.99] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 07/21/2015] [Accepted: 10/19/2015] [Indexed: 02/06/2023] Open
Abstract
Since the introduction of the term “gut-liver axis”, many studies have focused on the functional links of intestinal microbiota, barrier function and immune responses to liver physiology. Intestinal and extra-intestinal diseases alter microbiota composition and lead to dysbiosis, which aggravates impaired intestinal barrier function via increased lipopolysaccharide translocation. The subsequent increased passage of gut-derived product from the intestinal lumen to the organ wall and bloodstream affects gut motility and liver biology. The activation of the toll-like receptor 4 (TLR-4) likely plays a key role in both cases. This review analyzed the most recent literature on the gut-liver axis, with a particular focus on the role of TLR-4 activation. Findings that linked liver disease with dysbiosis are evaluated, and links between dysbiosis and alterations of intestinal permeability and motility are discussed. We also examine the mechanisms of translocated gut bacteria and/or the bacterial product activation of liver inflammation and fibrogenesis via activity on different hepatic cell types.
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Pasqualetti V, Altomare A, Guarino MPL, Locato V, Cocca S, Cimini S, Palma R, Alloni R, De Gara L, Cicala M. Antioxidant activity of inulin and its role in the prevention of human colonic muscle cell impairment induced by lipopolysaccharide mucosal exposure. PLoS One 2014; 9:e98031. [PMID: 24837182 PMCID: PMC4024047 DOI: 10.1371/journal.pone.0098031] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Accepted: 04/28/2014] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Fructans, such as inulin, are dietary fibers which stimulate gastro-intestinal (GI) function acting as prebiotics. Lipopolysaccharide (LPS) impairs GI motility, through production of reactive oxygen species. The antioxidant activity of various fructans was tested and the protective effect of inulin on colonic smooth muscle cell (SMC) impairment, induced by exposure of human mucosa to LPS, was assessed in an ex vivo experimental model. METHODS The antioxidant capacity of fructans was measured in an in vitro system that simulates cooking and digestion processes. Human colonic mucosa and submucosa, obtained from disease-free margins of resected segments for cancer, were sealed between two chambers, with the mucosal side facing upwards with Krebs solution with or without purified LPS from a pathogenic strain of Escherichia coli (O111:B4) and inulin (Frutafit IQ), and the submucosal side facing downwards into Krebs solution. The solutions on the submucosal side were collected following mucosal exposure to Krebs in the absence (N-undernatant) or presence of LPS (LPS-undernatant) or LPS+inulin (LPS+INU-undernatant). Undernatants were tested for their antioxidant activity and the effects on SMCs contractility. Inulin protective effects on mucosa and submucosa layers were assessed measuring the protein oxidation level in the experimental conditions analyzed. RESULTS Antioxidant activity of inulin, which was significantly higher compared to simple sugars, remained unaltered despite cooking and digestion processes. Inulin protected the mucosal and submucosal layers against protein oxidation. Following exposure to LPS-undernatant, a significant decrease in maximal acetylcholine (Ach)-induced contraction was observed when compared to the contraction induced in cells incubated with the N-undernatant (4±1% vs 25±5% respectively, P<0.005) and this effect was completely prevented by pre-incubation of LPS with Inulin (35±5%). CONCLUSIONS Inulin protects the human colon mucosa from LPS-induced damage and this effect appears to be related to the protective effect of inulin against LPS-induced oxidative stress.
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Affiliation(s)
- Valentina Pasqualetti
- Food Sciences and Human Nutrition Unit, University Campus Bio-Medico of Rome, Rome, Italy
| | - Annamaria Altomare
- Gastroenterology Unit, University Campus Bio-Medico of Rome, Rome, Italy
| | | | - Vittoria Locato
- Food Sciences and Human Nutrition Unit, University Campus Bio-Medico of Rome, Rome, Italy
| | - Silvia Cocca
- Gastroenterology Unit, University Campus Bio-Medico of Rome, Rome, Italy
| | - Sara Cimini
- Food Sciences and Human Nutrition Unit, University Campus Bio-Medico of Rome, Rome, Italy
| | - Rossella Palma
- Gastroenterology Unit, University Campus Bio-Medico of Rome, Rome, Italy
| | - Rossana Alloni
- Surgery Unit, University Campus Bio-Medico of Rome, Rome, Italy
| | - Laura De Gara
- Food Sciences and Human Nutrition Unit, University Campus Bio-Medico of Rome, Rome, Italy
| | - Michele Cicala
- Gastroenterology Unit, University Campus Bio-Medico of Rome, Rome, Italy
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Ammoscato F, Scirocco A, Altomare A, Matarrese P, Petitta C, Ascione B, Caronna R, Guarino M, Marignani M, Cicala M, Chirletti P, Malorni W, Severi C. Lactobacillus rhamnosus protects human colonic muscle from pathogen lipopolysaccharide-induced damage. Neurogastroenterol Motil 2013; 25:984-e777. [PMID: 24118564 DOI: 10.1111/nmo.12232] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2013] [Accepted: 08/15/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Lactobacillus species might positively affect gastrointestinal motility. These Gram-positive bacteria bind Toll-like receptor 2 (TLR2) that elicits anti-inflammatory activity and exerts protective effects on damage induced by lipopolysaccharide (LPS). Whether such effect occurs in gastrointestinal smooth muscle has not been established yet. Aim of this study was to characterize the effects of Lactobacillus rhamnosus GG (LGG) and of supernatants harvested from LGG cultures on human colonic smooth muscle and to explore their protective activity against LPS-induced myogenic morpho-functional alterations. METHODS The effects of LGG (ATCC 53103 strain) and of supernatants have been tested on both human colonic smooth muscle strips and isolated cells in the absence or presence of LPS obtained from a pathogenic strain of Escherichia coli. Their effects on myogenic morpho-functional properties, on LPS-induced NFκB activation, and on cytokine production have been evaluated. Toll-like receptor 2 expression has been analyzed by qPCR and flow cytometry. KEY RESULTS Lactobacillus rhamnosus GG exerted negligible transient effects per se whereas it was capable of activating an intrinsic myogenic response counteracting LPS-induced alterations. In particular, both LGG and supernatants significantly reduced the LPS-induced morpho-functional alterations of muscle cells, i.e. cell shortening and inhibition of contractile response. They also hindered LPS-induced pro-inflammatory effects by decreasing pro-inflammatory transcription factor NFκB activation and pro-inflammatory cytokine IL-6 secretion, and restored the secretion levels of anti-inflammatory cytokine IL10. CONCLUSIONS & INFERENCES Taken together these data demonstrate that LGG protects human colonic smooth muscle from LPS-induced myogenic damage and might be beneficial on intestinal motor disorders due to bacterial infection.
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Affiliation(s)
- F Ammoscato
- Department of Internal Medicine and Medical Specialties, University Sapienza, Rome, Italy
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Scalera A, Di Minno MND, Tarantino G. What does irritable bowel syndrome share with non-alcoholic fatty liver disease? World J Gastroenterol 2013; 19:5402-5420. [PMID: 24023483 PMCID: PMC3761093 DOI: 10.3748/wjg.v19.i33.5402] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2013] [Revised: 06/05/2013] [Accepted: 07/23/2013] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS) are two very common diseases in the general population. To date, there are no studies that highlight a direct link between NAFLD and IBS, but some recent reports have found an interesting correlation between obesity and IBS. A systematic PubMed database search was conducted highlighting that common mechanisms are involved in many of the local and systemic manifestations of NAFLD, leading to an increased cardiovascular risk, and IBS, leading to microbial dysbiosis, impaired intestinal barrier and altered intestinal motility. It is not known when considering local and systemic inflammation/immune system activation, which one has greater importance in NAFLD and IBS pathogenesis. Also, the nervous system is implicated. In fact, inflammation participates in the development of mood disorders, such as anxiety and depression, characteristics of obesity and consequently of NAFLD and, on the other hand, in intestinal hypersensitivity and dysmotility.
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Abstract
AIM To test the activities of culture-extracted or commercially available toll-like receptors (TLRs) ligands to establish their direct impact on target gastrointestinal motor cells. METHODS Short-term and long-term effects of Shigella flexneri M90T and Escherichia coli K-2 strains-extracted lipopolysaccharides (LPS), commercially highly purified LPS (E. coli O111:B4 and EH100), and Pam2CSK4 and Pam3CSK4, which bind TLR2/6 and TLR1/2 heterodimers, respectively, have been assessed on pure primary cultures of colonic human smooth muscle cells (HSMC). RESULTS Pathogenic Shigella-LPS and nonpathogenic E. coli K-2-LPS induced a time-dependent decrease of resting cell length and acetylcholine-induced contraction, with both alterations occurring rapidly and being more pronounced in response to the former. However, their effects differed, prolonging HSMC exposure with Shigella-LPS effects maintained throughout the 4 hours of observation compared with E. coli K-2-LPS, which disappeared after 60 minutes of incubation. Similar differences in magnitude and time dependency of myogenic effects were observed between pure TLR4 and TLR2/1 or TLR2/6 ligands. The specific activation of TLR4 with LPS from pathogen or nonpathogen E. coli, O111:B4 and EH100, respectively, induced smooth muscle alterations that progressively increased, prolonging incubation, whereas TLR2 ligands induced short-term alterations, of a lesser magnitude, which decreased over time. The real-time polymerase chain reaction analysis showed that HSMC express mRNA for TLR1, 2, 4, and 6, substantiating a direct effect of TLR ligands on human colonic smooth muscle. CONCLUSIONS This study highlights that bacterial products can directly affect gastrointestinal motility and that TLRs subtypes may differ in their cellular activity.
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Lee BJ, Bak YT. Irritable bowel syndrome, gut microbiota and probiotics. J Neurogastroenterol Motil 2011; 17:252-66. [PMID: 21860817 PMCID: PMC3155061 DOI: 10.5056/jnm.2011.17.3.252] [Citation(s) in RCA: 146] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2011] [Revised: 06/09/2011] [Accepted: 06/11/2011] [Indexed: 12/13/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a complex disorder characterized by abdominal symptoms including chronic abdominal pain or discomfort and altered bowel habits. The etiology of IBS is multifactorial, as abnormal gut motility, visceral hypersensitivity, disturbed neural function of the brain-gut axis and an abnormal autonomic nervous system are all implicated in disease progression. Based on recent experimental and clinical studies, it has been suggested that additional etiological factors including low-grade inflammation, altered gut microbiota and alteration in the gut immune system play important roles in the pathogenesis of IBS. Therefore, therapeutic restoration of altered intestinal microbiota may be an ideal treatment for IBS. Probiotics are live organisms that are believed to cause no harm and result in health benefits for the host. Clinical efficacy of probiotics has been shown in the treatment or prevention of some gastrointestinal inflammation-associated disorders including traveler's diarrhea, antibiotics-associated diarrhea, pouchitis of the restorative ileal pouch and necrotizing enterocolitis. The molecular mechanisms, as cause of IBS pathogenesis, affected by altered gut microbiota and gut inflammation-immunity are reviewed. The effect of probiotics on the gut inflammation-immune systems and the results from clinical trials of probiotics for the treatment of IBS are also summarized.
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Affiliation(s)
- Beom Jae Lee
- Department of Gastroenterology, Korea University Guro Hospital, Seoul, Korea
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Shu XC, Wang SD, Wang FY. Advances in understanding the relationship between irritable bowel syndrome and intestinal bacteria. Shijie Huaren Xiaohua Zazhi 2011; 19:1808-1812. [DOI: 10.11569/wcjd.v19.i17.1808] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a multifactorial functional disorder of unknown cause and pathophysiology. Commensal bacteria in the digestive tract and host co-exist in a mutually beneficial relationship. If this relationship is interrupted, various types of diseases will be caused. In recent years, the development of microecology has led to a better understanding of the relationship between intestinal bacterial flora and IBS. Many studies have suggested a close relationship between intestinal bacteria and IBS. In this article, we will review the role of alterations in intestinal bacterial flora in the pathogenesis of IBS.
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Rhee SH. Basic and translational understandings of microbial recognition by toll-like receptors in the intestine. J Neurogastroenterol Motil 2011; 17:28-34. [PMID: 21369489 PMCID: PMC3042215 DOI: 10.5056/jnm.2011.17.1.28] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2010] [Revised: 12/22/2010] [Accepted: 12/28/2010] [Indexed: 12/16/2022] Open
Abstract
Microbial recognition by multicellular organisms is initially accomplished by a group of pattern recognition receptors which are specialized to recognize microbe-associated molecular patterns (MAMPs) such as lipopolysaccharide, bacterial lipoprotein, CpG DNA motif, double strand RNA and flagellin. Toll-like receptors (TLRs) are the representative pattern recognition receptors, and microbial recognition by TLRs elicits innate and inflammatory responses. Ten TLR family members have been presently identified in human genome, and numerous studies discovered that intracellular responses from MAMPs-TLR engagements are mediated by a participation of at least 4 immediate adaptor molecules such as myeloid differentiation primary response gene-88 (MyD88), MyD88 adaptor-like (Mal) (also known as Toll/IL-1 receptor domain-containing adaptor protein [TIRAP]), Toll/IL-1 receptor domain-containing adaptor-inducing interferon-β (TRIF) and TRIF-related adaptor molecule (TRAM) leading to activate transcription factors including nuclear factor κB, activator protein-1 and interferon-regulatory factors. Given that large amounts of commensal microbiota constantly reside in the intestinal lumen, enteric microbial recognition by TLRs at the intestinal epithelium provides a critical impact on regulating intestinal homeostasis. Indeed, aberrant TLR4 and TLR5 activations are etiologically associated with the development and progress of intestinal inflammatory diseases including inflammatory bowel disease and necrotizing enterocolitis. In this review article, we present the molecular mechanism by which TLRs elicit intracellular signal transduction, and summarize the physiological relevance of TLRs related to the gastrointestinal tract.
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Affiliation(s)
- Sang Hoon Rhee
- Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
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Amit-Romach E, Uni Z, Reifen R. Multistep mechanism of probiotic bacterium, the effect on innate immune system. Mol Nutr Food Res 2010; 54:277-84. [PMID: 19998380 DOI: 10.1002/mnfr.200800591] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The etiology and pathogenesis of inflammatory bowel disease are still not fully understood. However, evidence from both animal models and clinical observations suggests luminal bacteria as the most probable inducer of this disease. The intestinal bacterial microbiota may be modified by dietary addition of viable probiotic bacteria, thereby constituting an alternative approach to disease prevention and treatment. The aim of this study was to evaluate and compare the effects of two probiotic regiments; Lactobacillus GG and a mixture of Streptococcus thermophilus, Lactobacillus acidophilus, and Bifidobacterium lactis (YO-MIX Y 109 FRO 1000) in both normal and trinitrobenzenesulfonic acid colitis-induced rats. Colon morphology and damage were evaluated histologically; colonic tissues were used for mRNA analysis, using real-time PCR. Administration of both probiotics reduced the expression of proinflammatory cytokines tumor necrosis factor-alpha and IL-6 and increased the expression of mucin 2 in compared with colitis group and reduced the inflammatory response. These results provide additional support for the positive effect of probiotics in the gut and may shed light on the mechanism by which probiotic bacteria exert their action in an animal model.
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Affiliation(s)
- Einat Amit-Romach
- Department of Animal Science, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel
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Scirocco A, Matarrese P, Petitta C, Cicenia A, Ascione B, Mannironi C, Ammoscato F, Cardi M, Fanello G, Guarino MPL, Malorni W, Severi C. Exposure of Toll-like receptors 4 to bacterial lipopolysaccharide (LPS) impairs human colonic smooth muscle cell function. J Cell Physiol 2010; 223:442-50. [PMID: 20112289 DOI: 10.1002/jcp.22053] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Endotoxemia by bacterial lipopolysaccharide (LPS) has been reported to affect gut motility specifically depending on Toll-like receptor 4 activation (TLR4). However, the direct impact of LPS ligation to TLR4 on human smooth muscle cells (HSMC) activity still remains to be elucidated. The present study shows that TLR4, its associated molecule MD2, and TLR2 are constitutively expressed on cultured HSMC and that, once activated, they impair HSMC function. The stimulation of TLR4 by LPS induced a time- and dose-dependent contractile dysfunction, which was associated with a decrease of TLR2 messenger, a rearrangement of microfilament cytoskeleton and an oxidative imbalance, i.e., the formation of reactive oxygen species (ROS) together with the depletion of GSH content. An alteration of mitochondria, namely a hyperpolarization of their membrane potential, was also detected. Most of these effects were partially prevented by the NADPH oxidase inhibitor apocynin or the NFkappaB inhibitor MG132. Finally, a 24 h washout in LPS-free medium almost completely restored morphofunctional and biochemical HSMC resting parameters, even if GSH levels remained significantly lower and no recovery was observed in TLR2 expression. Thus, the exposure to bacterial endotoxin directly and persistently impaired gastrointestinal smooth muscle activity indicating that HSMC actively participate to dysmotility during infective burst. The knowledge of these interactions might provide novel information on the pathogenesis of infection-associated gut dysmotility and further clues for the development of new therapeutic strategies.
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Collins SM, Denou E, Verdu EF, Bercik P. The putative role of the intestinal microbiota in the irritable bowel syndrome. Dig Liver Dis 2009; 41:850-3. [PMID: 19740713 DOI: 10.1016/j.dld.2009.07.023] [Citation(s) in RCA: 84] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2009] [Accepted: 07/30/2009] [Indexed: 02/08/2023]
Abstract
The irritable bowel syndrome (IBS) is a chronic abdominal symptom complex that is heterogeneous in terms of its clinical presentation and underlying pathophysiology and pathogenesis. It is now established that enteric infection can trigger the syndrome in at least a subset of patients. In addition, there is growing evidence of low grade inflammation and immune activation in the distal bowel of some IBS patients. These observations now prompt the question as to what maintains gut dysfunction in these patients. The intestinal microbiota influences a broad array of host organs that include the gut and the brain, and is an important determinant of normal function in these systems. Disruption of the delicate balance between the host and its intestinal microbiota (termed dysbiosis) results in changes in the mucosal immune system that range from overt inflammation as seen in Crohn's Disease, to low grade inflammation without tissue injury, as seen in a subset of IBS patients. Under experimental conditions, disruption of the microbiota also produces changes in gut sensory-motor function and immune activity. Thus, dysbiosis induced by infection, dietary change or drugs such as antibiotics could produce low grade inflammation and chronic gut dysfunction, reminiscent of that seen in IBS. Fluctuations in gut physiology destabilize the habitat of commensal bacteria and provide a basis for chronic dysbiosis. Recent observations in animal models that changes in gut flora influence behavior provide a basis for a novel unifying hypothesis that accommodates both gut dysfunction and behavioral changes that characterize many IBS patients. This hypothesis states that dysbiosis exists in at least a subset of IBS patients, as a result of infection, dietary change or drugs and contributes to gut inflammatory and functional change in addition to psychiatric co-morbidity.
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Affiliation(s)
- S M Collins
- The Farncombe Digestive Health Research Institute, The Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
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Kunze WA, Mao YK, Wang B, Huizinga JD, Ma X, Forsythe P, Bienenstock J. Lactobacillus reuteri enhances excitability of colonic AH neurons by inhibiting calcium-dependent potassium channel opening. J Cell Mol Med 2009; 13:2261-2270. [PMID: 19210574 DOI: 10.1111/j.1582-4934.2009.00686.x] [Citation(s) in RCA: 241] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Probiotics are live non-pathogenic commensal organisms that exert therapeutic effects in travellers' diarrhea, irritable bowel syndrome and inflammatory bowel disease. Little is known about mechanisms of action of commensal bacteria on intestinal motility and motility-induced pain. It has been proposed that probiotics affect intestinal nerve function, but direct evidence for this has thus far been lacking. We hypothesized that probiotic effects might be mediated by actions on colonic intrinsic sensory neurons. We first determined whether sensory neurons were present in rat colon by their responses to chemical mucosal stimulation and identified them in terms of physiological phenotype and soma morphotype. Enteric neuron excitability and ion channel activity were measured using patch clamp recordings. We fed 10(9)Lactobacillus reuteri (LR) or vehicle control to rats for 9 days. LR ingestion increased excitability (threshold for evoking action potentials) and number of action potentials per depolarizing pulse, decreased calcium-dependent potassium channel (IK(Ca)) opening and decreased the slow afterhyperpolarization (sAHP) in sensory AH neurons, similar to the IK(Ca) antagonists Tram-34 and clotrimazole. LR did not affect threshold for action potential generation in S neurons. Our results demonstrate that LR targets an ion channel in enteric sensory nerves through which LR may affect gut motility and pain perception.
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Affiliation(s)
- Wolfgang A Kunze
- The Brain-Body Institute, St. Joseph's Healthcare, Hamilton, ON, Canada.,Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, ON, Canada
| | - Yu-Kang Mao
- The Brain-Body Institute, St. Joseph's Healthcare, Hamilton, ON, Canada
| | - Bingxian Wang
- Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Jan D Huizinga
- Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Xuelian Ma
- The Brain-Body Institute, St. Joseph's Healthcare, Hamilton, ON, Canada
| | - Paul Forsythe
- The Brain-Body Institute, St. Joseph's Healthcare, Hamilton, ON, Canada.,Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - John Bienenstock
- The Brain-Body Institute, St. Joseph's Healthcare, Hamilton, ON, Canada.,Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
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