Clostridioides difficile is well-known for its potential to cause healthcare-associated diarrhea in patients with previous antibiotic use. However, C. difficile can also be found as an asymptomatic... Show moreClostridioides difficile is well-known for its potential to cause healthcare-associated diarrhea in patients with previous antibiotic use. However, C. difficile can also be found as an asymptomatic colonizer of the gut. This thesis focuses on C. difficile colonization with the aim to better understand this condition and its role in epidemioloy of C. difficile infections. Investigations included microbiota analyses and transmission analyses. Show less
Vendrik, K.E.W.; Chernova, V.O.; Kuijper, E.J.; Terveer, E.M.; Hilten, J.J. van; Contarino, M.F.; FMT4PD Study Group 2023
Introduction Experimental studies suggest a role of gut microbiota in the pathophysiology of Parkinson’s disease (PD) via the gut–brain axis. The gut microbiota can also influence the metabolism of... Show moreIntroduction Experimental studies suggest a role of gut microbiota in the pathophysiology of Parkinson’s disease (PD) via the gut–brain axis. The gut microbiota can also influence the metabolism of levodopa, which is the mainstay of treatment of PD. Therefore, modifying the gut microbiota by faecal microbiota transplantation (FMT) could be a supportive treatment strategy.Methods and analysis We have developed a study protocol for a single-centre, prospective, self-controlled, interventional, safety and feasibility donor-FMT pilot study with randomisation and double-blinded allocation of donor faeces. The primary objectives are feasibility and safety of FMT in patients with PD. Secondary objectives include exploring whether FMT leads to alterations in motor complications (fluctuations and dyskinesias) and PD motor and non-motor symptoms (including constipation), determining alterations in gut microbiota composition, assessing donor–recipient microbiota similarities and their association with PD symptoms and motor complications, evaluating the ease of the study protocol and examining FMT-related adverse events in patients with PD. The study population will consist of 16 patients with idiopathic PD that use levodopa and experience motor complications. They will receive FMT with faeces from one of two selected healthy human donors. FMT will be administered via a gastroscope into the duodenum, after treatment with oral vancomycin, bowel lavage and domperidone. There will be seven follow-up moments during 12 months.Ethics and dissemination This study was approved by the Medical Ethical Committee Leiden Den Haag Delft (ref. P20.087). Study results will be disseminated through publication in peer-reviewed journals and international conferences.Trial registration number International Clinical Trial Registry Platform: NL9438. Show less
The global obesity pandemic is one of the most significant long-term challenges for healthcare in the current era. Obesity is strongly associated with disrupted glucose and lipid metabolism, a pro... Show moreThe global obesity pandemic is one of the most significant long-term challenges for healthcare in the current era. Obesity is strongly associated with disrupted glucose and lipid metabolism, a pro-inflammatory state of the immune system, and has a causal role in the development of cardiometabolic diseases. The medical science is challenged to find new targets in the fight against this worldwide silent pandemic.We investigated how the gut microbiota influences local and systemic lipid metabolism and immune system of the host and the relationship to pathophysiology of atherosclerosis. The central question was "Does the gut microbiota have a anti-atherogenic potential?" Our studies have shown that oral administration of the bacterium A. muciniphila positively influences the host's lipid metabolism. In addition, oral administration of this bacterium triggers an anti-inflammatory immune response. These findings suggest that A. muciniphila has anti-atherogenic potential. Furthermore, we provided critical insights into two commonly accepted and widely used research methods in cardiometabolic and microbiome research, namely Bone Marrow Transplantation (BMT) and 16S rRNA sequencing. These insights should be taken into account in the research design and interpretation of the research data when applied. In another study, we demonstrated that the gut microbiota increases the cytokine reactions of immune cells after BMT. This phenotype can be transferred to immune cells of healthy controls through Fecal Microbiota Transplantation, implying that this phenotype is independent of BMT-induced gut damage, leaky gut syndrome, and microbiota-mediated. In summary, our studies show that the gut microbiota has anti-atherogenic potential by playing a causal role in the modulation of lipid metabolism and the host's immune system. Show less
Reigadas, E.; Prehn, J. van; Falcone, M.; Fitzpatrick, F.; Vehreschild, M.J.G.T.; Kuijper, E.J.; ... ; Study Grp Host Microbiota Interact 2021
Background: Clostridioides difficile infection (CDI) remains the leading cause of healthcare-associated diarrhoea, despite existing guidelines for infection control measures and antimicrobial... Show moreBackground: Clostridioides difficile infection (CDI) remains the leading cause of healthcare-associated diarrhoea, despite existing guidelines for infection control measures and antimicrobial stewardship. The high associated health and economic burden of CDI calls for novel strategies to prevent the development and spread of CDI in susceptible patients. Objectives: We aim to review CDI prophylactic treatment strategies and their implementation in clinical practice. Sources: We searched PubMed, Embase, Emcare, Web of Science, and the COCHRANE Library databases to identify prophylactic interventions aimed at prevention of CDI. The search was restricted to articles published in English since 2012. Content: A toxin-based vaccine candidate is currently being investigated in a phase III clinical trial. However, a recent attempt to develop a toxin-based vaccine has failed. Conventional probiotics have not yet proved to be an effective strategy for prevention of CDI. New promising microbiota-based interventions that bind and inactivate concomitantly administered antibiotics, such as ribaxamase and DAV-132, have been developed. Prophylaxis of CDI with C. difficile antibiotics should not be performed routinely and should be considered only for secondary prophylaxis in very selected patients who are at the highest imminent risk for recurrent CDI (R-CDI) after a thorough evaluation. Faecal microbiota transplantation (FMT) has proved to be a very effective treatment for patients with multiple recurrences. Bezlotoxumab provides protection against R-CDI, mainly in patients with primary episodes and a high risk of relapse. Implications: There are no proven effective, evidenced-based prophylaxis options for primary CDI. As for secondary prevention, FMT is considered the option of choice in patients with multiple recurrences. Bezlotoxumab can be added to standard treatment for patients at high risk for R-CDI. The most promising strategies are those aimed at reducing changes in intestinal microbiota and development of a new effective non-toxin-based vaccine. Elena Reigadas, Clin Microbiol Infect 2021;27:1777 (c) 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved. Show less
Bacterial vaginosis (BV) is perceived as a condition of disrupted vaginal microbiota, but remains of unknown aetiology. In this study, vaginal microbiota composition was determined in twenty-one... Show moreBacterial vaginosis (BV) is perceived as a condition of disrupted vaginal microbiota, but remains of unknown aetiology. In this study, vaginal microbiota composition was determined in twenty-one women with BV, before and after treatment with metronidazole or clindamycin. Microbiota composition varied greatly between women and defining a (un)healthy vaginal microbiota state remains elusive, challenging BV diagnosis and treatment. While relative abundance ofLactobacillusincreased after antibiotic treatment in two-third of women, its abundance was not associated with treatment outcome. Instead, remaining complaints of abnormal vaginal discharge were more common after metronidazole treatment and associated with increased relative abundance ofUreaplasma. Show less
Munckhof, E.H.A. van den; Hafkamp, H.C.; Kluijver, J. de; Kuijper, E.J.; Koning, M.N.C. de; Quint, W.G.V.; Knetsch, C.W. 2020
BackgroundThe elderly (>= 65years) are one of the populations most at risk for respiratory tract infections (RTIs). The aim of this study was to determine whether nasal and/or oropharyngeal... Show moreBackgroundThe elderly (>= 65years) are one of the populations most at risk for respiratory tract infections (RTIs). The aim of this study was to determine whether nasal and/or oropharyngeal microbiota profiles are associated with age and RTIs.MethodsNasal and oropharyngeal swabs of 152 controls and 152 patients with an RTI were included. The latter group consisted of 72 patients with an upper respiratory tract infection (URTI) and 80 with a lower respiratory tract infection (LRTI). Both nasal and oropharyngeal swabs were subjected to microbiota profiling using amplicon sequencing of the 16S rRNA gene. Moraxella species were determined using quantitative real-time PCR and culture.ResultsBased on the microbiota profiles of the controls and the patients with an RTI, eight nasal and nine oropharyngeal microbiota clusters were defined. Nasal microbiota dominated by either Moraxella catarrhalis or Moraxella nonliquefaciens was significantly more prevalent in elderly compared to mid-aged adults in the control group (p=0.002). Dominance by M. catarrhalis/nonliquefaciens was significantly less prevalent in elderly with an LRTI (p=0.001) compared to controls with similar age.ConclusionsNasal microbiota dominated by M. catarrhalis/nonliquefaciens is associated with respiratory health in the elderly population. Show less
Cardiometabolic disease such as obesity, type 2 diabetes, and atherosclerosis, are a leading cause of morbidity and mortality in the Western world. Two important risk factors for the development of... Show moreCardiometabolic disease such as obesity, type 2 diabetes, and atherosclerosis, are a leading cause of morbidity and mortality in the Western world. Two important risk factors for the development of cardiometabolic disease are hyperlipidemia and inflammation. Recently, evidence strongly indicates a role for the gut microbiota in the development of cardiometabolic disease. Therapeutic approaches are therefore aimed at modifying the gut microbiota composition and function to beneficially affect the development of cardiometabolic disease and its underlying risk factors. A potential candidate to modify gut microbiota composition are indigestible carbohydrates, or prebiotics. In this thesis, we aimed to understand the interplay between various indigestible carbohydrates, gut microbiota composition and function, and the development of obesity, type 2 diabetes, and atherosclerosis. Together, the studies described in this thesis increased our knowledge on the potential of various indigestible carbohydrates in the modulation of the gut microbiota to affect the development of cardiometabolic disease, suggesting a promising strategy to further pursue with some caution. Show less
Since a decade, Clostridium difficile infection (CDI) has increased progressively in incidence and severity of disease. Currently, CDI is considered the leading cause of nosocomial diarrhoea,... Show moreSince a decade, Clostridium difficile infection (CDI) has increased progressively in incidence and severity of disease. Currently, CDI is considered the leading cause of nosocomial diarrhoea, associated with an increased duration of hospitalization, healthcare expenses, morbidity and mortality. This thesis describes our findings with outbreak control, diagnosis, identification of specific risk factors and treatment of CDI after the discovery of the emergence of C. difficile PCR-ribotype 027 in the Netherlands. The studies illustrate the role of antibiotics in relation to persistence, severeness and spreading of CDI. Antibiotics are shown to be a primary risk factor for the development of (ribotype-specific) CDI and an essential part of the outbreak control measures (__bundle-approach__), namely antibiotic stewardship. The use of antibacterials is a risk for selection of novel endemic C. difficile strains in e.g. animals, which introduce an increasing risk of alternative zoonotic transmission routes. Except for very mild CDI, which is clearly induced by usage of specific antibiotics, antibacterial treatment is advised. This thesis reviews the comparative effectiveness of the currently available treatment modalities, thereby providing evidence-based recommendations for CDI remedies. Treatment options include: oral and non-oral antibiotics, toxin-binding resins and polymers, immunotherapy, probiotics, faecal or bacterial intestinal transplantation. Show less
