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Strzelec M, Kubicka E, Kuliczkowska-Płaksej J, Kolačkov K, Janek Ł, Bolanowski M, Jawiarczyk-Przybyłowska A. Copeptin and Mid-Regional Proadrenomedullin Are Not Useful Biomarkers of Cardiometabolic Disease in Patients with Acromegaly-A Preliminary Study. Biomedicines 2025; 13:666. [PMID: 40149642 PMCID: PMC11939899 DOI: 10.3390/biomedicines13030666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 02/19/2025] [Accepted: 02/28/2025] [Indexed: 03/29/2025] Open
Abstract
Background/Objectives: Cardiovascular complications are a leading cause of premature mortality in patients with acromegaly. Copeptin (CPP) correlates strongly with plasma osmolality and is regulated by non-osmotic stimuli involved in the pathophysiology of cardiovascular disease. Mid-regional proadrenomedullin (MR-proADM), synthesized mainly in the adrenal medulla, vascular endothelial cells, and the heart, has vasodilatory effects. The study aimed to assess two cardiovascular biomarkers (CPP and MR-proADM) in acromegaly patients in relation to disease activity and compare findings with a control group. Methods: The study examined CPP and MR-proADM levels alongside hormonal and biochemical parameters and cardiovascular and metabolic disease prevalence in 53 acromegaly patients and 26 controls. Results: No significant differences in CPP or MR-proADM concentrations were observed between the two groups. However, a positive correlation occurred between growth hormone (GH) and CPP concentrations, and there was a negative correlation between fasting glucose and CPP concentrations in acromegaly patients. The study also found a positive correlation between low-density lipoprotein (LDL) cholesterol and MR-proADM concentrations and between high-density lipoprotein (HDL) cholesterol and MR-proADM levels in the study group. Moreover, atherogenic dyslipidemia was significantly more common in the active form of acromegaly and pituitary macroadenoma patients than in the control group. Acromegaly patients had significantly higher fasting glucose and fasting insulin levels compared to controls, and the homeostasis model assessment of the insulin resistance (HOMA-IR) index was significantly lower in the study group than in the controls. Conclusions: Neither CPP or MR-proADM are significant diagnostic or monitoring indicators of cardiovascular or metabolic complications in acromegaly.
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Affiliation(s)
- Martyna Strzelec
- Department and Clinic of Endocrinology and Internal Medicine, Wroclaw Medical University, Wybrzeże Pasteura 4, 50-367 Wroclaw, Poland; (M.S.)
| | - Eliza Kubicka
- Department of Nuclear Medicine, Tadeusz Marciniak Lower Silesia Specialist Hospital-Centre for Medical Emergency, 54-049 Wroclaw, Poland
| | - Justyna Kuliczkowska-Płaksej
- Department and Clinic of Endocrinology and Internal Medicine, Wroclaw Medical University, Wybrzeże Pasteura 4, 50-367 Wroclaw, Poland; (M.S.)
| | - Katarzyna Kolačkov
- Department and Clinic of Endocrinology and Internal Medicine, Wroclaw Medical University, Wybrzeże Pasteura 4, 50-367 Wroclaw, Poland; (M.S.)
| | - Łucja Janek
- Statistical Analysis Centre, Wroclaw Medical University, 50-368 Wroclaw, Poland
| | - Marek Bolanowski
- Department and Clinic of Endocrinology and Internal Medicine, Wroclaw Medical University, Wybrzeże Pasteura 4, 50-367 Wroclaw, Poland; (M.S.)
| | - Aleksandra Jawiarczyk-Przybyłowska
- Department and Clinic of Endocrinology and Internal Medicine, Wroclaw Medical University, Wybrzeże Pasteura 4, 50-367 Wroclaw, Poland; (M.S.)
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Maslennikov R, Alieva A, Poluektova E, Zharikov Y, Suslov A, Letyagina Y, Vasileva E, Levshina A, Kozlov E, Ivashkin V. Sarcopenia in cirrhosis: Prospects for therapy targeted to gut microbiota. World J Gastroenterol 2023; 29:4236-4251. [PMID: 37545638 PMCID: PMC10401661 DOI: 10.3748/wjg.v29.i27.4236] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 05/25/2023] [Accepted: 06/21/2023] [Indexed: 07/13/2023] Open
Abstract
Decreased muscle mass and function, also known as sarcopenia, is common in patients with cirrhosis and is associated with a poor prognosis. Although the pathogenesis of this disorder has not been fully elucidated, a disordered gut-muscle axis probably plays an important role. Decreased barrier function of the gut and liver, gut dysbiosis, and small intestinal bacterial overgrowth (SIBO) can lead to increased blood levels of ammonia, lipopolysaccharides, pro-inflammatory mediators, and myostatin. These factors have complex negative effects on muscle mass and function. Drug interventions that target the gut microbiota (long-term use of rifaximin, lactulose, lactitol, or probiotics) positively affect most links of the compromised gut-muscle axis in patients with cirrhosis by decreasing the levels of hyperammonemia, bacterial translocation, and systemic inflammation and correcting gut dysbiosis and SIBO. However, although these drugs are promising, they have not yet been investigated in randomized controlled trials specifically for the treatment and prevention of sarcopenia in patients with cirrhosis. No data exist on the effects of fecal transplantation on most links of gut-muscle axis in cirrhosis; however, the results of animal experimental studies are promising.
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Affiliation(s)
- Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Aliya Alieva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Yury Zharikov
- Department of Human Anatomy and Histology, Sechenov University, Moscow 119435, Russia
| | - Andrey Suslov
- Department of Human Anatomy and Histology, Sechenov University, Moscow 119435, Russia
| | - Yana Letyagina
- Department of Human Anatomy and Histology, Sechenov University, Moscow 119435, Russia
| | - Ekaterina Vasileva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Anna Levshina
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov University, Moscow 119991, Russia
| | - Evgenii Kozlov
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov University, Moscow 119991, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
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Efremova I, Maslennikov R, Poluektova E, Vasilieva E, Zharikov Y, Suslov A, Letyagina Y, Kozlov E, Levshina A, Ivashkin V. Epidemiology of small intestinal bacterial overgrowth. World J Gastroenterol 2023; 29:3400-3421. [PMID: 37389240 PMCID: PMC10303511 DOI: 10.3748/wjg.v29.i22.3400] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 03/31/2023] [Accepted: 05/11/2023] [Indexed: 06/06/2023] Open
Abstract
Small intestinal bacterial overgrowth (SIBO) is defined as an increase in the bacterial content of the small intestine above normal values. The presence of SIBO is detected in 33.8% of patients with gastroenterological complaints who underwent a breath test, and is significantly associated with smoking, bloating, abdominal pain, and anemia. Proton pump inhibitor therapy is a significant risk factor for SIBO. The risk of SIBO increases with age and does not depend on gender or race. SIBO complicates the course of a number of diseases and may be of pathogenetic significance in the development of their symptoms. SIBO is significantly associated with functional dyspepsia, irritable bowel syndrome, functional abdominal bloating, functional constipation, functional diarrhea, short bowel syndrome, chronic intestinal pseudo-obstruction, lactase deficiency, diverticular and celiac diseases, ulcerative colitis, Crohn's disease, cirrhosis, metabolic-associated fatty liver disease (MAFLD), primary biliary cholangitis, gastroparesis, pancreatitis, cystic fibrosis, gallstone disease, diabetes, hypothyroidism, hyperlipidemia, acromegaly, multiple sclerosis, autism, Parkinson's disease, systemic sclerosis, spondylarthropathy, fibromyalgia, asthma, heart failure, and other diseases. The development of SIBO is often associated with a slowdown in orocecal transit time that decreases the normal clearance of bacteria from the small intestine. The slowdown of this transit may be due to motor dysfunction of the intestine in diseases of the gut, autonomic diabetic polyneuropathy, and portal hypertension, or a decrease in the motor-stimulating influence of thyroid hormones. In a number of diseases, including cirrhosis, MAFLD, diabetes, and pancreatitis, an association was found between disease severity and the presence of SIBO. Further work on the effect of SIBO eradication on the condition and prognosis of patients with various diseases is required.
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Affiliation(s)
- Irina Efremova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Roman Maslennikov
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Elena Poluektova
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
| | - Ekaterina Vasilieva
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
| | - Yury Zharikov
- Department of Human Anatomy and Histology, Sechenov University, Moscow 125009, Russia
| | - Andrey Suslov
- Department of Human Anatomy and Histology, Sechenov University, Moscow 125009, Russia
| | - Yana Letyagina
- N.V. Sklifosovsky Institute of Clinical Medicine, Sechenov University, Moscow 119991, Russia
| | - Evgenii Kozlov
- Department of Clinical Immunology and Allergy, Sechenov University, Moscow 119991, Russia
| | - Anna Levshina
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- Department of Clinical Immunology and Allergy, Sechenov University, Moscow 119991, Russia
| | - Vladimir Ivashkin
- Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
- The Scientific Community for Human Microbiome Research, Moscow 119435, Russia
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Jensen EA, Young JA, Jackson Z, Busken J, Kuhn J, Onusko M, Carroll RK, List EO, Brown JM, Kopchick JJ, Murphy ER, Berryman DE. Excess Growth Hormone Alters the Male Mouse Gut Microbiome in an Age-dependent Manner. Endocrinology 2022; 163:bqac074. [PMID: 35617141 PMCID: PMC9167039 DOI: 10.1210/endocr/bqac074] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Indexed: 11/19/2022]
Abstract
The gut microbiome has an important role in host development, metabolism, growth, and aging. Recent research points toward potential crosstalk between the gut microbiota and the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. Our laboratory previously showed that GH excess and deficiency are associated with an altered gut microbial composition in adult mice. Yet, no study to date has examined the influence of GH on the gut microbiome over time. Our study thus tracked the effect of excess GH action on the longitudinal changes in the gut microbial profile (ie, abundance, diversity/maturity, predictive metabolic function, and short-chain fatty acid [SCFA] levels) of bovine GH (bGH) transgenic mice at age 3, 6, and 12 months compared to littermate controls in the context of metabolism, intestinal phenotype, and premature aging. The bGH mice displayed age-dependent changes in microbial abundance, richness, and evenness. Microbial maturity was significantly explained by genotype and age. Moreover, several bacteria (ie, Lactobacillus, Lachnospiraceae, Bifidobacterium, and Faecalibaculum), predictive metabolic pathways (such as SCFA, vitamin B12, folate, menaquinol, peptidoglycan, and heme B biosynthesis), and SCFA levels (acetate, butyrate, lactate, and propionate) were consistently altered across all 3 time points, differentiating the longitudinal bGH microbiome from controls. Of note, the bGH mice also had significantly impaired intestinal fat absorption with increased fecal output. Collectively, these findings suggest that excess GH alters the gut microbiome in an age-dependent manner with distinct longitudinal microbial and predicted metabolic pathway signatures.
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Affiliation(s)
- Elizabeth A Jensen
- Translational Biomedical Sciences Graduate Program, Graduate College, Ohio University, Athens, Ohio 45701, USA
- Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio 45701, USA
| | - Jonathan A Young
- Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio 45701, USA
- Edison Biotechnology Institute, Konneker Research Labs, Athens, Ohio 45701, USA
| | - Zachary Jackson
- Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio 45701, USA
| | - Joshua Busken
- Edison Biotechnology Institute, Konneker Research Labs, Athens, Ohio 45701, USA
| | - Jaycie Kuhn
- Edison Biotechnology Institute, Konneker Research Labs, Athens, Ohio 45701, USA
- The Diabetes Institute, Parks Hall, Ohio University, Athens, Ohio 45701, USA
| | - Maria Onusko
- The Diabetes Institute, Parks Hall, Ohio University, Athens, Ohio 45701, USA
- Department of Biological Sciences, College of Arts and Sciences, Ohio University, Athens, Ohio 45701, USA
| | - Ronan K Carroll
- Department of Biological Sciences, College of Arts and Sciences, Ohio University, Athens, Ohio 45701, USA
- Molecular and Cellular Biology Program, Ohio University, Athens, Ohio 45701, USA
- Infectious and Tropical Diseases Institute, Irvine Hall, Ohio University, Athens, Ohio 45701, USA
| | - Edward O List
- Translational Biomedical Sciences Graduate Program, Graduate College, Ohio University, Athens, Ohio 45701, USA
- Edison Biotechnology Institute, Konneker Research Labs, Athens, Ohio 45701, USA
- The Diabetes Institute, Parks Hall, Ohio University, Athens, Ohio 45701, USA
| | - J Mark Brown
- Department of Cardiovascular & Metabolic Sciences, and The Center for Microbiome & Human Health, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio 44195, USA
| | - John J Kopchick
- Translational Biomedical Sciences Graduate Program, Graduate College, Ohio University, Athens, Ohio 45701, USA
- Edison Biotechnology Institute, Konneker Research Labs, Athens, Ohio 45701, USA
- The Diabetes Institute, Parks Hall, Ohio University, Athens, Ohio 45701, USA
- Molecular and Cellular Biology Program, Ohio University, Athens, Ohio 45701, USA
- Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, 45701USA
| | - Erin R Murphy
- Translational Biomedical Sciences Graduate Program, Graduate College, Ohio University, Athens, Ohio 45701, USA
- Molecular and Cellular Biology Program, Ohio University, Athens, Ohio 45701, USA
- Infectious and Tropical Diseases Institute, Irvine Hall, Ohio University, Athens, Ohio 45701, USA
- Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, 45701USA
| | - Darlene E Berryman
- Translational Biomedical Sciences Graduate Program, Graduate College, Ohio University, Athens, Ohio 45701, USA
- Edison Biotechnology Institute, Konneker Research Labs, Athens, Ohio 45701, USA
- The Diabetes Institute, Parks Hall, Ohio University, Athens, Ohio 45701, USA
- Molecular and Cellular Biology Program, Ohio University, Athens, Ohio 45701, USA
- Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, 45701USA
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Hammer HF, Fox MR, Keller J, Salvatore S, Basilisco G, Hammer J, Lopetuso L, Benninga M, Borrelli O, Dumitrascu D, Hauser B, Herszenyi L, Nakov R, Pohl D, Thapar N, Sonyi M, European H 2‐CH 4‐breath test group. European guideline on indications, performance, and clinical impact of hydrogen and methane breath tests in adult and pediatric patients: European Association for Gastroenterology, Endoscopy and Nutrition, European Society of Neurogastroenterology and Motility, and European Society for Paediatric Gastroenterology Hepatology and Nutrition consensus. United European Gastroenterol J 2022; 10:15-40. [PMID: 34431620 PMCID: PMC8830282 DOI: 10.1002/ueg2.12133] [Citation(s) in RCA: 82] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 06/18/2021] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION Measurement of breath hydrogen (H2 ) and methane (CH4 ) excretion after ingestion of test-carbohydrates is used for different diagnostic purposes. There is a lack of standardization among centers performing these tests and this, together with recent technical developments and evidence from clinical studies, highlight the need for a European guideline. METHODS This consensus-based clinical practice guideline defines the clinical indications, performance, and interpretation of H2 -CH4 -breath tests in adult and pediatric patients. A balance between scientific evidence and clinical experience was achieved by a Delphi consensus that involved 44 experts from 18 European countries. Eighty eight statements and recommendations were drafted based on a review of the literature. Consensus (≥80% agreement) was reached for 82. Quality of evidence was evaluated using validated criteria. RESULTS The guideline incorporates new insights into the role of symptom assessment to diagnose carbohydrate (e.g., lactose) intolerances and recommends that breath tests for carbohydrate malabsorption require additional validated concurrent symptom evaluation to establish carbohydrate intolerance. Regarding the use of breath tests for the evaluation of oro-cecal transit time and suspected small bowel bacterial overgrowth, this guideline highlights confounding factors associated with the interpretation of H2 -CH4 -breath tests in these indications and recommends approaches to mitigate these issues. CONCLUSION This clinical practice guideline should facilitate pan-European harmonization of diagnostic approaches to symptoms and disorders, which are very common in specialist and primary care gastroenterology practice, both in adult and pediatric patients. In addition, it identifies areas of future research needs to clarify diagnostic and therapeutic approaches.
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Affiliation(s)
- Heinz F. Hammer
- Division of Gastroenterology and HepatologyDepartment of Internal MedicineMedical UniversityGrazAustria
| | - Mark R. Fox
- Centre for Integrative GastroenterologyDigestive Function: BaselLaboratory and Clinic for Motility Disorders and Functional Gastrointestinal DiseasesKlinik ArlesheimArlesheimSwitzerland
- Division of Gastroenterology and HepatologyUniversity Hospital ZurichZurichSwitzerland
| | - Jutta Keller
- Department of Internal MedicineIsraelitic HospitalAcademic Hospital of the University of HamburgHamburgGermany
| | - Silvia Salvatore
- Pediatric DepartmentHospital “F. Del Ponte”University of InsubriaVareseItaly
| | - Guido Basilisco
- Gastroenterology and Endoscopy UnitFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanoItaly
| | - Johann Hammer
- Department of Gastroenterology and HepatologyUniversity Hospital of Internal Medicine 3Medical University of ViennaViennaAustria
| | - Loris Lopetuso
- UOC Medicina Interna e GastroenterologiaDipartimento di Scienze Mediche e ChirurgicheFondazione Policlinico Universitario A. Gemelli IRCCSRomeItalia
- Department of Medicine and Ageing Sciences“G. d'Annunzio” University of Chieti‐PescaraChietiItaly
| | - Marc Benninga
- Department of Pediatric Gastroenterology, Hepatology and NutritionEmma Children's HospitalAmsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands
| | - Osvaldo Borrelli
- UCL Great Ormond Street Institute of Child Health and Department of GastroenterologyNeurogastroenterology and MotilityGreat Ormond Street HospitalLondonUK
| | - Dan Dumitrascu
- Department of GastroenterologyClinica Medicala 2Cluj‐NapocaRomania
| | - Bruno Hauser
- Department of Paediatric Gastroenterology, Hepatology and NutritionKidZ Health Castle UZ BrusselBrusselsBelgium
| | - Laszlo Herszenyi
- Department of GastroenterologyMedical CentreHungarian Defence ForcesBudapestHungary
| | - Radislav Nakov
- Clinic of GastroenterologyTsaritsa Yoanna University HospitalMedical University of SofiaSofiaBulgaria
| | - Daniel Pohl
- Division of Gastroenterology and HepatologyUniversity Hospital ZurichZurichSwitzerland
| | - Nikhil Thapar
- UCL Great Ormond Street Institute of Child Health and Department of GastroenterologyNeurogastroenterology and MotilityGreat Ormond Street HospitalLondonUK
- Gastroenterology, Hepatology and Liver TransplantQueensland Children's HospitalBrisbaneAustralia
| | - Marc Sonyi
- Division of Gastroenterology and HepatologyDepartment of Internal MedicineMedical UniversityGrazAustria
- Clinic for General Medicine, Gastroenterology, and Infectious DiseasesAugustinerinnen HospitalCologneGermany
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Jensen EA, Young JA, Kuhn J, Onusko M, Busken J, List EO, Kopchick JJ, Berryman DE. Growth hormone alters gross anatomy and morphology of the small and large intestines in age- and sex-dependent manners. Pituitary 2022; 25:116-130. [PMID: 34373994 PMCID: PMC8905484 DOI: 10.1007/s11102-021-01179-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/27/2021] [Indexed: 02/03/2023]
Abstract
PURPOSE Growth hormone (GH) has an important role in intestinal barrier function, and abnormalities in GH action have been associated with intestinal complications. Yet, the impact of altered GH on intestinal gross anatomy and morphology remains unclear. METHODS This study investigated the influence of GH signaling on gross anatomy, morphology, and fibrosis by characterizing the small and large intestines in male and female bovine growth hormone transgenic (bGH) mice and GH receptor gene-disrupted (GHR-/-) mice at multiple timepoints. RESULTS The length, weight, and circumference of the small and large intestines were increased in bGH mice and decreased in GHR-/- mice across all ages. Colon circumference was significantly increased in bGH mice in a sex-dependent manner while significantly decreased in male GHR-/- mice. Villus height, crypt depth, and muscle thickness of the small intestine were generally increased in bGH mice and decreased in GHR-/- mice compared to controls with age- and sex-dependent exceptions. Colonic crypt depth and muscle thickness in bGH and GHR-/- mice were significantly altered in an age- and sex-dependent manner. Fibrosis was increased in the small intestine of bGH males at 4 months of age, but no significant differences were seen between genotypes at other timepoints. CONCLUSION This study observed notable opposing findings in the intestinal phenotype between mouse lines with GH action positively associated with intestinal gross anatomy (i.e. length, weight, and circumference). Moreover, GH action appears to alter morphology of the small and large intestines in an age- and sex-dependent manner.
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Affiliation(s)
- Elizabeth A Jensen
- Translational Biomedical Sciences Program, Graduate College, Ohio University, Athens, OH, USA
- Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA
| | - Jonathan A Young
- Edison Biotechnology Institute, Ohio University, Athens, OH, USA
- Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA
| | - Jaycie Kuhn
- Edison Biotechnology Institute, Ohio University, Athens, OH, USA
- College of Arts and Sciences, Ohio University, Athens, OH, USA
| | - Maria Onusko
- The Diabetes Institute, Ohio University, Parks Hall Suite 142, Athens, OH, USA
- College of Arts and Sciences, Ohio University, Athens, OH, USA
| | - Joshua Busken
- Edison Biotechnology Institute, Ohio University, Athens, OH, USA
| | - Edward O List
- Translational Biomedical Sciences Program, Graduate College, Ohio University, Athens, OH, USA
- Edison Biotechnology Institute, Ohio University, Athens, OH, USA
- The Diabetes Institute, Ohio University, Parks Hall Suite 142, Athens, OH, USA
| | - John J Kopchick
- Translational Biomedical Sciences Program, Graduate College, Ohio University, Athens, OH, USA
- Edison Biotechnology Institute, Ohio University, Athens, OH, USA
- The Diabetes Institute, Ohio University, Parks Hall Suite 142, Athens, OH, USA
- Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA
| | - Darlene E Berryman
- Translational Biomedical Sciences Program, Graduate College, Ohio University, Athens, OH, USA.
- Edison Biotechnology Institute, Ohio University, Athens, OH, USA.
- The Diabetes Institute, Ohio University, Parks Hall Suite 142, Athens, OH, USA.
- Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA.
- Office of Research and Grants, Heritage College of Osteopathic Medicine, Ohio University, Irvine Hall 220B, Athens, OH, 45701, USA.
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Jensen EA, Young JA, Mathes SC, List EO, Carroll RK, Kuhn J, Onusko M, Kopchick JJ, Murphy ER, Berryman DE. Crosstalk between the growth hormone/insulin-like growth factor-1 axis and the gut microbiome: A new frontier for microbial endocrinology. Growth Horm IGF Res 2020; 53-54:101333. [PMID: 32717585 PMCID: PMC7938704 DOI: 10.1016/j.ghir.2020.101333] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 06/11/2020] [Accepted: 06/12/2020] [Indexed: 12/16/2022]
Abstract
Both the GH/IGF-1 axis and the gut microbiota independently play an important role in host growth, metabolism, and intestinal homeostasis. Inversely, abnormalities in GH action and microbial dysbiosis (or a lack of diversity) in the gut have been implicated in restricted growth, metabolic disorders (such as chronic undernutrition, anorexia nervosa, obesity, and diabetes), and intestinal dysfunction (such as pediatric Crohn's disease, colonic polyps, and colon cancer). Over the last decade, studies have demonstrated that the microbial impact on growth may be mediated through the GH/IGF-1 axis, pointing toward a potential relationship between GH and the gut microbiota. This review covers current research on the GH/IGF-1 axis and the gut microbiome and its influence on overall host growth, metabolism, and intestinal health, proposing a bidirectional relationship between GH and the gut microbiome.
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Affiliation(s)
- Elizabeth A Jensen
- Translational Biomedical Sciences Graduate Program, Graduate College, Ohio University, Athens, OH, United States of America; Ohio University Heritage College of Osteopathic Medicine, Athens, OH, United States of America
| | - Jonathan A Young
- Ohio University Heritage College of Osteopathic Medicine, Athens, OH, United States of America; Edison Biotechnology Institute, Konneker Research Labs, Athens, OH, United States of America
| | - Samuel C Mathes
- Edison Biotechnology Institute, Konneker Research Labs, Athens, OH, United States of America
| | - Edward O List
- Translational Biomedical Sciences Graduate Program, Graduate College, Ohio University, Athens, OH, United States of America; Edison Biotechnology Institute, Konneker Research Labs, Athens, OH, United States of America; The Diabetes Institute, Parks Hall Suite 142, Ohio University, Athens, OH, United States of America
| | - Ronan K Carroll
- Department of Biological Sciences, College of Arts and Sciences, Ohio University, Athens, OH, United States of America; Molecular and Cellular Biology Program, Ohio University, Athens, OH, United States of America
| | - Jaycie Kuhn
- Edison Biotechnology Institute, Konneker Research Labs, Athens, OH, United States of America
| | - Maria Onusko
- The Diabetes Institute, Parks Hall Suite 142, Ohio University, Athens, OH, United States of America; Department of Biological Sciences, College of Arts and Sciences, Ohio University, Athens, OH, United States of America
| | - John J Kopchick
- Translational Biomedical Sciences Graduate Program, Graduate College, Ohio University, Athens, OH, United States of America; Edison Biotechnology Institute, Konneker Research Labs, Athens, OH, United States of America; The Diabetes Institute, Parks Hall Suite 142, Ohio University, Athens, OH, United States of America; Molecular and Cellular Biology Program, Ohio University, Athens, OH, United States of America; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, United States of America
| | - Erin R Murphy
- Translational Biomedical Sciences Graduate Program, Graduate College, Ohio University, Athens, OH, United States of America; Molecular and Cellular Biology Program, Ohio University, Athens, OH, United States of America; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, United States of America; Infectious and Tropical Diseases Institute, Irvine Hall, Ohio University, Athens, OH, United States of America
| | - Darlene E Berryman
- Translational Biomedical Sciences Graduate Program, Graduate College, Ohio University, Athens, OH, United States of America; Edison Biotechnology Institute, Konneker Research Labs, Athens, OH, United States of America; The Diabetes Institute, Parks Hall Suite 142, Ohio University, Athens, OH, United States of America; Molecular and Cellular Biology Program, Ohio University, Athens, OH, United States of America; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, United States of America.
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Inayet N, Hayat J, Bano G, Poullis A. Gastrointestinal symptoms in acromegaly: A case control study. World J Gastrointest Pharmacol Ther 2020; 11:17-24. [PMID: 32550042 PMCID: PMC7288728 DOI: 10.4292/wjgpt.v11.i2.17] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 05/19/2020] [Accepted: 05/30/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acromegaly is a chronic disease caused by a pituitary somatotroph adenoma resulting in excess secretion of growth hormone, which leads to excess secretion of Insulin like growth factor 1 from the liver, causing abnormal soft tissue growth. There is increasing awareness that diseases affecting connective tissue are associated with an increase in functional gastrointestinal symptoms. Data was collected from patients with a confirmed diagnosis of acromegaly to evaluate the intensity, variety and impact of abdominal symptoms in comparison with a control group who were healthy participants recruited from the local fracture clinic.
AIM To evaluate the frequency type and burden of abdominal symptoms in acromegaly in comparison with a control group.
METHODS Medical documentation of patients with a diagnosis of acromegaly treated in one tertiary medical centre between 2010 and 2017 has been analysed. Data was collected from patients with confirmed acromegaly, using the Short Form Health Survey (SF36) and Rome IV Diagnostic questionnaire for Functional Gastrointestinal Disorders in Adults (R4DQ) and compared to a sex- and age-matched control group, to assess the burden of abdominal symptoms. Microsoft Excel and IBM SPSS v 25 were used for data analysis.
RESULTS Fifty patients with acromegaly (24 male and 26 females; age range 23-64 years, mean 43) and 200 controls (96 male and 104 females; age range 18-84, mean 42.4) were recruited. 92% (46 out of 50) of patients with acromegaly reported abdominal symptoms and 78% (39 out of 50) had at least one functional gastrointestinal disorder according to the Rome IV diagnostic criteria, compared to 16% of controls (OR > 1, P < 0.0001). The most commonly reported symptom was constipation (69% acromegaly vs 21% of controls OR > 1, P < 0.0001, 95%CI: 4.4–15.8). 34 out of 50 (68%) respondents met the criteria for functional constipation according to Rome IV. Upper gastrointestinal disorders were also more prevalent in the acromegaly group. There was no statistically significant difference in the prevalence of biliary and anorectal symptoms between the two groups. Patients in acromegaly group scored lower on the mean scores of the eight parameters of SF36 Quality of Life questionnaire (mean scores 60.04 vs 71.23, 95%CI: -13.6829 to -8.6971, OR > 1, P < 0.001) as compared to the control group.
CONCLUSION Upper and lower functional gastrointestinal tract disorders (defined by Rome IV diagnostic criteria) are significantly more prevalent in patients with acromegaly compared with healthy age and sex matched controls in our study. Functional constipation is the most commonly reported problem. Poorer quality of life may in part be attributable to the increased prevalence of abdominal symptoms.
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Affiliation(s)
- Nashiz Inayet
- Department of Gastroenterology, St Georges Hospital and St Georges, University of London, London SW17 0QT, United Kingdom
| | - Jamal Hayat
- Department of Gastroenterology, St Georges Hospital and St Georges, University of London, London SW17 0QT, United Kingdom
| | - Gul Bano
- Department of Endocrinology, St Georges Hospital and St Georges, University of London, London SW17 0QT, United Kingdom
| | - Andrew Poullis
- Department of Gastroenterology, St Georges Hospital and St Georges, University of London, London SW17 0QT, United Kingdom
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Young JA, Jensen EA, Stevens A, Duran-Ortiz S, List EO, Berryman DE, Kopchick JJ. Characterization of an intestine-specific GH receptor knockout (IntGHRKO) mouse. Growth Horm IGF Res 2019; 46-47:5-15. [PMID: 31078722 PMCID: PMC6646076 DOI: 10.1016/j.ghir.2019.05.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 04/15/2019] [Accepted: 05/01/2019] [Indexed: 12/29/2022]
Abstract
OBJECTIVE Growth hormone (GH) has been reported to enhance the intestinal barrier; as such, recombinant GH has been administered for several intestinal diseases. However, excess GH action has been implicated in increasing the risk of intestinal dysfunction. The goal of this study was to examine the direct effects of GH on the small and large intestines to clarify the role GH plays in intestinal function through the use of a mouse model. DESIGN An intestinal epithelial-specific GH receptor (GHR) knockout (IntGHRKO) mouse line was generated using Cre-lox with the villin promoter driving Cre expression. The generated mice were characterized with respect to growth and intestinal phenotypes. RESULTS IntGHRKO mice showed no significant changes in body length, weight, or composition compared to floxed controls. Male IntGHRKO mice had significantly shorter large intestines at 4 and 12 months of age. Intestinal barrier function was assessed by measuring the expression of tight junction related genes, as well as levels of serum endotoxin and fecal albumin. Results showed sex differences as males had an increase in occludin levels but normal serum endotoxin and fecal albumin; while, females had changes in fecal albumin levels with normal occludin and serum endotoxin. Evaluation of glucose tolerance and fat absorption also showed sex differences as females were glucose intolerant, while males had impaired fat absorption. Histopathology revealed a trend towards decreased villus height in males, which could explain the sex difference in glucose homeostasis. CONCLUSIONS Overall, the data demonstrate that disruption of GH on the intestinal epithelial cells modestly affects the intestinal gross anatomy, morphology, and function in a sex-specific manner.
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Affiliation(s)
- Jonathan A Young
- Edison Biotechnology Institute, Ohio University, Athens, OH, United States of America; Molecular and Cellular Biology Program, Ohio University, Athens, OH, United States of America
| | - Elizabeth A Jensen
- Edison Biotechnology Institute, Ohio University, Athens, OH, United States of America; Heritage College of Osteopathic Medicine, Athens, OH, United States of America; Translational Biomedical Sciences Program, Graduate College, Ohio University, Athens, OH, United States of America
| | - Austin Stevens
- Edison Biotechnology Institute, Ohio University, Athens, OH, United States of America
| | - Silvana Duran-Ortiz
- Edison Biotechnology Institute, Ohio University, Athens, OH, United States of America; Molecular and Cellular Biology Program, Ohio University, Athens, OH, United States of America
| | - Edward O List
- Edison Biotechnology Institute, Ohio University, Athens, OH, United States of America; Department of Specialty Medicine, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, United States of America
| | - Darlene E Berryman
- Edison Biotechnology Institute, Ohio University, Athens, OH, United States of America; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, United States of America; Diabetes Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, United States of America
| | - John J Kopchick
- Edison Biotechnology Institute, Ohio University, Athens, OH, United States of America; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, United States of America.
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Sisman P, Pekgoz M, Bayrakci I, Sisman M, Cander S, Oz Gul O, Erturk E, Ersoy C. Evaluation of upper gastrointestinal system in acromegaly. ANNALES D'ENDOCRINOLOGIE 2019; 80:196-201. [PMID: 31227172 DOI: 10.1016/j.ando.2019.03.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Revised: 12/11/2018] [Accepted: 03/15/2019] [Indexed: 12/30/2022]
Abstract
PURPOSE Acromegaly causes multiple comorbidities, including gastrointestinal disorders. The present study evaluated the frequency of hiatal hernia and other upper gastrointestinal pathologies in patients with acromegaly, given that visceromegaly and reduced nitric oxide levels in acromegaly may impact diaphragm and lower esophageal sphincter function and thus possibly the development of hiatal hernia. METHODS Thirty-nine acromegaly patients followed our center for the previous 6months were recruited. Upper gastrointestinal endoscopy was performed once in all patients to evaluate hiatal hernia, esophagitis, gastroduodenitis and ulcer. RESULTS Twenty-three patients were male and 16 female. Upper gastrointestinal endoscopy found hiatal hernia, esophagitis and gastroduodenitis or gastric ulcer in 3 (7.6%), 2 (1.7%) and 31 (79.4%) patients, respectively. Pathologic examination of gastric antrum biopsy found intestinal metaplasia in 12 (30.7%) patients, and Helicobacter pylori was positive in 13 (33.3%). There were no significant correlations between age, gender, disease duration or preoperative adenoma size on the one hand and hiatal hernia or other endoscopic findings on the other. Similarly, neither surgical success nor recurrence was associated with endoscopic findings. CONCLUSIONS The study showed that prevalence of gastritis, duodenitis, peptic ulcer and intestinal metaplasia is higher and prevalence of hiatal hernia lower in acromegaly patients than in the healthy population. Various unknown disease-related pathophysiological conditions may play a role; there is a need for further studies.
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Affiliation(s)
- Pinar Sisman
- Medicana Hospital, Endocrinology and Metabolism Clinic, Bursa, Turkey.
| | - Murat Pekgoz
- Izzet Baysal State Hospital, Gastroenterology Clinic, Bolu, Turkey.
| | - Ismail Bayrakci
- Viransehir State Hospital, Internal Medicine Clinic, Urfa, Turkey.
| | - Mete Sisman
- Muradiye State Hospital, General Surgery Clinic, Bursa, Turkey.
| | - Soner Cander
- Uludag University Medical School, Department Of Endocrinology and Metabolism, Bursa, Turkey.
| | - Ozen Oz Gul
- Uludag University Medical School, Department Of Endocrinology and Metabolism, Bursa, Turkey.
| | - Erdinc Erturk
- Uludag University Medical School, Department Of Endocrinology and Metabolism, Bursa, Turkey.
| | - Canan Ersoy
- Uludag University Medical School, Department Of Endocrinology and Metabolism, Bursa, Turkey.
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Gatta L, Scarpignato C. Systematic review with meta-analysis: rifaximin is effective and safe for the treatment of small intestine bacterial overgrowth. Aliment Pharmacol Ther 2017; 45:604-616. [PMID: 28078798 PMCID: PMC5299503 DOI: 10.1111/apt.13928] [Citation(s) in RCA: 159] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Revised: 09/02/2016] [Accepted: 12/12/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND Small intestinal bacterial overgrowth (SIBO) is a heterogeneous syndrome, characterised by an increased number and/or abnormal type of bacteria in the small bowel. Over the past decades, rifaximin has gained popularity for this indication despite its use is not evidence based. AIM To perform a systematic review and meta-analysis to summarise evidence about the efficacy and safety of rifaximin to eradicate SIBO in adult patients. METHODS MEDLINE, EMBASE, CCRCT, Scopus and Web of Science were searched from inception to March 16, 2015 for RCTs and observational studies. Furthermore, abstract books of major European, American and Asian gastroenterological meetings were also examined. RESULTS Thirty-two studies involving 1331 patients were included. The overall eradication rate according to intention-to-treat analysis was 70.8% (95% CI: 61.4-78.2; I2 = 89.4%) and to per protocol analysis 72.9% (95% CI: 65.5-79.8; I2 = 87.5%). Meta-regression identified three covariates (drug dose, study design and co-therapy) independently associated with an increased eradication rate. The overall rate of adverse events was 4.6% (95% CI: 2.3-7.5; I2 = 63.6%). In the subset of studies (n= 10) allowing the analysis, improvement or resolution of symptoms in patients with eradicated SIBO was found to be 67.7% (95% CI: 44.7-86.9; I2 = 91.3%). CONCLUSIONS Rifaximin treatment seems to be effective and safe for the treatment of SIBO. However, the quality of the available studies is generally poor. Well-designed RCTs are needed to substantiate these findings and to establish the optimal regimen.
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Affiliation(s)
- L. Gatta
- Clinical Pharmacology and Digestive Pathophysiology UnitDepartment of Clinical and Experimental MedicineUniversity of ParmaParmaItaly,Gastroenterology and Endoscopy UnitVersilia HospitalAzienda USL Toscana Nord‐OvestLido di CamaioreItaly
| | - C. Scarpignato
- Clinical Pharmacology and Digestive Pathophysiology UnitDepartment of Clinical and Experimental MedicineUniversity of ParmaParmaItaly
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12
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Caglar E, Hatipoglu E, Atasoy D, Niyazoglu M, Çağlar A, Tuncer M, Dobrucali A, Kadioglu P. LONGER CECUM INSERTION TIME AND MORE INADEQUATE COLONIC PREPARATION IN PATIENTS WITH ACROMEGALY: IS A DIFFERENT COLONOSCOPY PREPARATION NEEDED? ACTA ENDOCRINOLOGICA (BUCHAREST, ROMANIA : 2005) 2017; 13:60-64. [PMID: 31149149 PMCID: PMC6525746 DOI: 10.4183/aeb.2017.60] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
PURPOSE To investigate whether there is a difference between acromegalic and non-acromegalic cases in terms of bowel preparation and colonoscopic intervention. METHODS Patients with controlled and uncontrolled acromegaly and as a control group (CG) patients without acromegaly between January 2010 and March 2014 were included. Groups were compared regarding adequacy of bowel preparation, cecal insertion time (CIT) and colonoscopy results. RESULTS Fifty-nine patients with acromegaly (controlled n=30, uncontrolled n=29) and 73 age and gender matched volunteers without acromegaly were evaluated. CIT in cases with controlled, uncontrolled acromegaly cases and in CG was 5.33 [4.00-6.00], 7.00 [4.91-11.31], and 3.10 [2.35-4.65] minutes, respectively (p<0.001). Cases in CG had shorter CIT compared to controlled and uncontrolled acromegaly cases ( p=0.014 and p<0.001, respectively). There was no significant difference regarding CIT between controlled and uncontrolled acromegaly cases (p=0.247). Six (20%) of controlled acromegaly patients, 10 (35%) of uncontrolled acromegaly patients and three (4%) of CG had inadequate bowel cleansing (p<0.001). Although statistically insignificant, cases with inadequate bowel cleansing had tendency towards having prolonged CIT in comparison to cases with adequate bowel cleansing (6.00 [3.87-9.00] and 4.16 [2.95-5.70] minutes, respectively, p=0.07). CONCLUSION Inadequate bowel cleansing is one of the main problems encountered during colonoscopic investigation/surveillance in acromegalic patients. Therefore, a different protocol for colonoscopy preparation may be needed for these cases.
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Affiliation(s)
- E. Caglar
- Kayseri Education and Research Hospital, Gastroenterology and Hepatology, Kayseri, Istanbul, Turkey
| | - E. Hatipoglu
- Istanbul University, Cerrahpasa Medical School, Endocrinology and Metabolism, Istanbul, Turkey
| | - D. Atasoy
- Acıbadem University, School of Medicine, Atakent Hospital, General Surgery, Istanbul, Turkey
| | - M. Niyazoglu
- Istanbul University, Cerrahpasa Medical School, Endocrinology and Metabolism, Istanbul, Turkey
| | - A.S. Çağlar
- Endocrinology and Metabolism, Erciyes University, Medical School, Kayseri, Istanbul, Turkey
| | - M. Tuncer
- Istanbul University, Cerrahpasa Medical School, Gastroenterology and Hepatology, Istanbul, Turkey
| | - A. Dobrucali
- Istanbul University, Cerrahpasa Medical School, Gastroenterology and Hepatology, Istanbul, Turkey
| | - P. Kadioglu
- Istanbul University, Cerrahpasa Medical School, Endocrinology and Metabolism, Istanbul, Turkey
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13
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Briskey D, Tucker P, Johnson DW, Coombes JS. The role of the gastrointestinal tract and microbiota on uremic toxins and chronic kidney disease development. Clin Exp Nephrol 2016; 21:7-15. [DOI: 10.1007/s10157-016-1255-y] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 02/26/2016] [Indexed: 12/17/2022]
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Ghoshal UC, Srivastava D. Irritable bowel syndrome and small intestinal bacterial overgrowth: Meaningful association or unnecessary hype. World J Gastroenterol 2014; 20:2482-2491. [PMID: 24627585 PMCID: PMC3949258 DOI: 10.3748/wjg.v20.i10.2482] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2013] [Revised: 01/07/2014] [Accepted: 02/20/2014] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common condition characterized by abdominal pain or discomfort, bloating, and altered stool form and passage. Small intestinal bacterial overgrowth (SIBO) is a condition in which there is overgrowth of bacteria in small bowel in excess of 105 colony forming units per milliliter on culture of the upper gut aspirate. Frequency of SIBO varied from 4%-78% among patients with IBS and from 1%-40% among controls. Higher frequency in some studies might be due to fallacious criteria [post-lactulose breath-hydrogen rise 20 PPM above basal within 90 min (early-peak)]. Glucose hydrogen breath test (GHBT) has a low sensitivity to diagnose SIBO. Hence, studies based on GHBT might have under-estimated frequency of SIBO. Therefore, it is important to analyze these studies carefully to evaluate whether the reported association between IBS and SIBO is over or under-projected. This review evaluates studies on association between SIBO and IBS, discordance between different studies, their strength and weakness including methodological issues and evidence on therapeutic manipulation of gut flora on symptoms of IBS.
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15
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Paine P, McLaughlin J, Lal S. Review article: the assessment and management of chronic severe gastrointestinal dysmotility in adults. Aliment Pharmacol Ther 2013; 38:1209-29. [PMID: 24102305 DOI: 10.1111/apt.12496] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2013] [Revised: 02/27/2013] [Accepted: 08/30/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND The characterisation and management of chronic severe gastrointestinal (GI) dysmotility are challenging. It may cause intestinal failure requiring home parenteral nutrition (HPN). AIMS To review the presentation, aetiology, characterisation, management and outcome of chronic severe GI dysmotility, and to suggest a pragmatic management algorithm. METHODS PubMed search was performed up to December 2012 using appropriate search terms, restricted to human articles and reviewed for relevance. Segmental dysmotility, acute ileus, functional syndromes and non-English articles were excluded. Evidence and recommendations were evaluated using the GRADE system. RESULTS In total, 721 relevant articles were reviewed. A coherent and definitive picture is hampered by overlapping classification systems using multi-modal characterisation methods, subject to pitfalls and some requiring further validation. The literature is confined to case series with no randomised trials. Fewer than 20% undergo full thickness jejunal biopsy, which are otherwise labelled idiopathic. However, in studies with up to 80% biopsy rates, neuromuscular abnormalities may be found in 90%. Between 14% and 50% will require HPN, comprising 8-14% of all HPN patients, of which 2/3 are primary/idiopathic and 1/3 secondary, with scleroderma being the leading secondary cause. Ten-year mortality ranges from 13% to 35% and is worst in elderly scleroderma patients. Management includes limited treatments for secondary causes, prokinetics, symptom palliation, psychological support, nutrition, hydration and judicious surgery. CONCLUSIONS Severe dysmotility often remains idiopathic. It is rarely possible to alter disease trajectory; consequently, prognosis may be poor. Multi-disciplinary teams in a specialist setting can improve outcomes. Graded recommendations are enumerated and a pragmatic algorithm is suggested.
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Affiliation(s)
- P Paine
- Department of Gastroenterology, Salford Royal NHS Foundation Trust, Salford, UK; Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK
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Savarino E, Mei F, Parodi A, Ghio M, Furnari M, Gentile A, Berdini M, Di Sario A, Bendia E, Bonazzi P, Scarpellini E, Laterza L, Savarino V, Gasbarrini A. Gastrointestinal motility disorder assessment in systemic sclerosis. Rheumatology (Oxford) 2013; 52:1095-100. [PMID: 23382360 DOI: 10.1093/rheumatology/kes429] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVES SSc is a clinically heterogeneous and generalized disease, characterized by thickness of the connective tissue of the skin and internal organs, such as the digestive tract, impairing gastrointestinal (GI) motility. Our aim is to evaluate retrospectively abnormalities of oesophageal motility, gastric emptying, oro-cecal transit time (OCTT) and small intestine bacterial overgrowth (SIBO) in a large cohort of SSc patients. METHODS Ninety-nine SSc patients were included in the study. Forty-two patients underwent oesophageal conventional manometry, 45 performed a [(13)C]octanoic acid breath test to measure gastric emptying time and all 99 patients performed a lactulose breath test in order to evaluate OCTT and SIBO. Data were compared with healthy controls. RESULTS In SSc patients, median lower oesophageal sphincter (LOS) pressure [14 mmHg (25th-75th; 8-19) vs 24 mmHg (19-28); P < 0.01] and median wave amplitude [30 mmHg (16-70) vs 72 mmHg (48-96); P < 0.01] were lower than in controls. Oesophageal involvement, defined as reduced LOS pressure and ineffective oesophageal motility pattern, was encountered in 70% of SSc patients. A delayed gastric emptying time was present in 38% of SSc patients: mean t½ was 141 ± 79 min vs 90 ± 40 min of controls (P < 0.01). Also, OCTT was significantly delayed in SSc: median OCTT was 160 min (25th-75th; 135-180) vs 105 min (25th-75th; 90-135) of controls (P < 0.01). SIBO was observed in 46% of SSc compared with 5% of controls (P < 0.01). CONCLUSION GI involvement is very frequent in SSc patients. Oesophagus and small bowel are more frequently impaired, whereas delayed gastric emptying is less common.
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Weinstock LB, Walters AS, Paueksakon P. Restless legs syndrome--theoretical roles of inflammatory and immune mechanisms. Sleep Med Rev 2012; 16:341-54. [PMID: 22258033 DOI: 10.1016/j.smrv.2011.09.003] [Citation(s) in RCA: 114] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2011] [Revised: 09/22/2011] [Accepted: 09/26/2011] [Indexed: 12/13/2022]
Abstract
Theories for restless legs syndrome (RLS) pathogenesis include iron deficiency, dopamine dysregulation and peripheral neuropathy. Increased prevalence of small intestinal bacterial overgrowth (SIBO) in controlled studies in RLS and case reports of post-infectious RLS suggest potential roles for inflammation and immunological alterations. A literature search for all conditions associated with RLS was performed. These included secondary RLS disorders and factors that may exacerbate RLS. All of these conditions were reviewed with respect to potential pathogenesis including reports of iron deficiency, neuropathy, SIBO, inflammation and immune changes. A condition was defined as highly-associated if there was a prevalence study that utilized an appropriate control group. Small case reports were recorded but not included as definite RLS-associated conditions. Fifty four diseases, syndromes and conditions have been reported to cause and/or exacerbate RLS. Of these, 38 have been reported to have a higher prevalence than age-matched controls, 9 have adequate sized reports and have general acceptance as RLS-associated conditions and 7 have been reported in case report form. Overall, 42 of the 47 RLS-associated conditions (89%) have also been associated with inflammatory and/or immune changes. In addition, 43% have been associated with peripheral iron deficiency, 40% with peripheral neuropathy and 32% with SIBO. Most of the remaining conditions have yet to be studied for these factors. The fact that 95% of the 38 highly-associated RLS conditions are also associated with inflammatory/immune changes suggests the possibility that RLS may be mediated or affected through these mechanisms. Inflammation can be responsible for iron deficiency and hypothetically could cause central nervous system iron deficiency-induced RLS. Alternatively, an immune reaction to gastrointestinal bacteria or other antigens may hypothetically cause RLS by a direct immunological attack on the central or peripheral nervous system.
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Affiliation(s)
- Leonard B Weinstock
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA
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Biller S, Baumgarten D, Haueisen J. A novel marker design for magnetic marker monitoring in the human gastrointestinal tract. IEEE Trans Biomed Eng 2011; 58:3368-75. [PMID: 21968707 DOI: 10.1109/tbme.2011.2166074] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Magnetic marker monitoring (MMM) is a technique to determine the motility of the gastrointestinal tract and to observe the dissolution of pharmaceutical compounds. Today's magnetic markers usually consist of magnetized magnetite. Because of their weak magnetic fields, highly sensitive sensor systems are required. For a wider class of applications, stronger markers and more flexible measurement setups are necessary. In this paper, a novel marker design is introduced. This marker comprises one permanent magnet and a compartment of iron powder in a magnetically unstable configuration. During dissolution of the pharmaceuticals, the powder is redistributed around the magnet, thereby altering the externally measured magnetic induction. Based on this design, magnetically marked tablets and capsules were prepared and their magnetic field during dissolution was observed. Magnetic induction values were between 16 and 0.2 μT at distances of 5-30 cm, which is considerably higher compared to the pico-Tesla range of conventional markers. During dissolution, the magnetic induction decreased by between 14% and 27%. These values could be confirmed in detailed finite element method simulations. In conclusion, the present results indicate that our novel marker design is well suited for MMM with more flexible sensor technologies, such as magnetoresistive sensors.
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Affiliation(s)
- Sebastian Biller
- Institute of Biomedical Engineering and Informatics, Ilmenau University of Technology, Ilmenau D-98684, Germany.
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19
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Furnari M, Parodi A, Gemignani L, Giannini EG, Marenco S, Savarino E, Assandri L, Fazio V, Bonfanti D, Inferrera S, Savarino V. Clinical trial: the combination of rifaximin with partially hydrolysed guar gum is more effective than rifaximin alone in eradicating small intestinal bacterial overgrowth. Aliment Pharmacol Ther 2010; 32:1000-6. [PMID: 20937045 DOI: 10.1111/j.1365-2036.2010.04436.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Abnormal intestinal clearance is involved in the pathogenesis of small intestinal bacterial overgrowth (SIBO). It is known that partially hydrolysed guar gum affects intestinal motility. Eradication therapy of SIBO is based on antibiotic treatment: no data are available on the role of fibre supplementation in eradicating SIBO. AIM To assess whether the combination of partially hydrolysed guar gum and rifaximin is more effective than rifaximin alone in the treatment of SIBO. METHODS A 50 g-glucose breath test was given to 500 consecutive patients. Patients with a positive glucose breath test and predisposing conditions to SIBO entered into the study, and were randomized to receive rifaximin 1200 mg/day or rifaximin 1200 mg/day plus partially hydrolysed guar gum 5 g/day for 10 days. Patients completed a symptom questionnaire and glucose breath test both in basal condition and 1 month after withdrawal of therapy. RESULTS Seventy-seven patients had SIBO. Eradication rate of SIBO was 62.1% in the rifaximin group (both on per-protocol and intention-to-treat analyses), and 87.1% (per-protocol, P=0.017) and 85.0% (intention-to-treat, P=0.036) in the rifaximin-plus-partially hydrolysed guar gum group. Clinical improvement was observed in 86.9% and 91.1% of eradicated cases in rifaximin and rifaximin-plus-partially hydrolysed guar gum groups respectively (P=0.677). CONCLUSION The combination of rifaximin with partially hydrolysed guar gum seems to be more useful in eradicating SIBO compared with rifaximin alone.
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Affiliation(s)
- M Furnari
- Department of Internal Medicine, University of Genoa, Italy
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Bures J, Cyrany J, Kohoutova D, Förstl M, Rejchrt S, Kvetina J, Vorisek V, Kopacova M. Small intestinal bacterial overgrowth syndrome. World J Gastroenterol 2010; 16:2978-90. [PMID: 20572300 PMCID: PMC2890937 DOI: 10.3748/wjg.v16.i24.2978] [Citation(s) in RCA: 358] [Impact Index Per Article: 23.9] [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
Human intestinal microbiota create a complex polymicrobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO). SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacteriostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insufficiency, immunodeficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, fistulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Non-invasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be complex, addressing all causes, symptoms and complications, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO.
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Lappinga PJ, Abraham SC, Murray JA, Vetter EA, Patel R, Wu TT. Small intestinal bacterial overgrowth: histopathologic features and clinical correlates in an underrecognized entity. Arch Pathol Lab Med 2010; 134:264-70. [PMID: 20121616 DOI: 10.5858/134.2.264] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT Small intestinal bacterial overgrowth (SIBO) is a common cause of chronic diarrhea and malabsorption. Morphologic changes associated with this condition have not, to our knowledge, been studied in detail. OBJECTIVE To better characterize the histopathologic changes associated with SIBO by comparing the clinicopathologic features of patients with SIBO (duodenal aspirate cultures with > or =10(5) colony-forming units [CFUs]/mL) to controls with cultures found to be negative (<10(5) CFUs/mL). DESIGN We included 67 consecutive patients with SIBO and 55 controls in the series. Each duodenal biopsy was assessed for the following features: villous to crypt ratio, intraepithelial lymphocytosis, crypt apoptoses, basal plasmacytosis, cryptitis/villitis, peptic duodenitis, erosions/ulcers, eosinophilia, and absence of goblet and Paneth cells; and correlated with clinical features and culture results. RESULTS Decreased villous to crypt ratio (<3ratio1) was more frequent in SIBO than controls (24% versus 7%; P = .01). Duodenal biopsies from patients with SIBO were slightly less likely to be judged within reference range than were controls (52% versus 64%; P = .27). There were no significant differences in any of the other histologic features. Clinically, patients in the SIBO group were older than the age of controls (mean, 60 years versus 52 years; P = .02), and they were more likely to have one of the known predisposing factors for bacterial overgrowth (66% versus 36%; P = .002). Other clinical features, including presenting symptoms, were similar. CONCLUSIONS Villous blunting is the only feature more common to SIBO than to controls. More than half of biopsies from SIBO patients are histologically unremarkable. Therefore, SIBO needs to be considered as a potential etiology for gastrointestinal symptoms even when duodenal biopsies are found to be normal.
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Affiliation(s)
- Paul J Lappinga
- Departments of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA
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Ojetti V, Lauritano EC, Barbaro F, Migneco A, Ainora ME, Fontana L, Gabrielli M, Gasbarrini A. Rifaximin pharmacology and clinical implications. Expert Opin Drug Metab Toxicol 2009; 5:675-82. [PMID: 19442033 DOI: 10.1517/17425250902973695] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Rifaximin is a semisynthetic, rifamycin-based non-systemic antibiotic, with a low gastrointestinal absorption and a good antibacterial activity. The antibacterial action covers Gram-positive and Gram-negative organisms, both aerobes and anaerobes. Its antimicrobial action is based on its property to bind to the beta-subunit of bacterial DNA-dependent RNA polymerase inhibiting, thereby, the bacterial RNA synthesis. Rifaximin contributes to restore gut microflora imbalance, becoming an important therapeutic agent in several organic and functional gastrointestinal diseases such as hepatic encephalopathy, small intestine bacterial overgrowth, inflammatory bowel disease and colonic diverticular disease. This antibiotic has the advantage of low microbial resistance and few systemic adverse events and is safe in all patient populations, including young children.
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Affiliation(s)
- Veronica Ojetti
- Internal Medicine Department, Catholic University of Sacred Heart, Gemelli Hospital, Rome, Italy. veronica.ojetti tin.it
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Bibliography. Current world literature. Diabetes and the endocrine pancreas II. Curr Opin Endocrinol Diabetes Obes 2008; 15:383-93. [PMID: 18594281 DOI: 10.1097/med.0b013e32830c6b8e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Abstract
PURPOSE OF REVIEW To review recently published studies presenting novel and relevant information on small intestinal motility. RECENT FINDINGS The reviewed studies covered a variety of topics with several themes emerging. Our understanding of the influence of systemic disorders, intestinal and extraintestinal infections and enteric bacteria on digestive motor function continues to involve. Elegant and important new studies have been published that better define the physiology of intestinal gas handling along with the genesis of symptoms commonly attributed to excessive intestinal gas. While interest in small intestinal bacterial overgrowth in irritable bowel syndrome continues, the utility and specificity of lactulose hydrogen breath testing is yet again questioned and further data are needed before the practice of routinely prescribing antibiotics to patients with irritable bowel syndrome can be endorsed. SUMMARY Small intestinal motility remains an understudied area. Recent publications provide additional new information related to physiology and pathophysiology of small bowel motility. These findings should be of interest to clinician and investigator alike.
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Ziegler TR, Cole CR. Small bowel bacterial overgrowth in adults: a potential contributor to intestinal failure. Curr Gastroenterol Rep 2007; 9:463-467. [PMID: 18377796 DOI: 10.1007/s11894-007-0060-x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
Small bowel bacterial overgrowth (SBBO), in which colon-derived bacteria colonize the upper small bowel, is found in a wide variety of adult diseases associated with intestinal failure and dysfunction, including short bowel syndrome and other conditions following massive bowel resection, dysmotility disorders, and inflammatory bowel disease. SBBO also appears to be relatively common in the elderly, in whom it often goes unrecognized. SBBO is an important cause of malabsorption and thus may contribute to diarrhea and malnutrition. Elevated upper small intestinal aspirate colony counts remain the gold standard diagnostic test; a variety of noninvasive tests that detect elevated levels of breath hydrogen produced by bacterial fermentation of oral carbohydrate loads are also performed for diagnosis. Physicians commonly prescribe a variety of oral antibiotic regimens for documented or presumed SBBO. Additional research is needed to define the epidemiology, optimal diagnostic test(s), and therapeutic regimens for this condition.
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Affiliation(s)
- Thomas R Ziegler
- Department of Medicine, Center for Clinical and Molecular Nutrition, Suite GG-23, General Clinical Research Center, Emory University Hospital, 1364 Clifton Road, Atlanta, GA 30322, USA.
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