Browsing by Subject "Medizin"

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Einfluss der mediterranen Ernährung auf das Fettsäuremuster von Erythrozytenmembranen sowie auf Darmmikrobiota- und Darmbarriere-assoziierte Biomarker : Mechanismen und klinische Anwendungen
(2022) Seethaler, Benjamin; Bischoff, Stephan C.
Dissertation from Benjamin Seethaler: "Effect of the Mediterranean diet on the fatty acid pattern of erythrocyte membranes and on gut microbiota- and gut barrier-associated biomarkers - mechanisms and clinical applications". In summary, the results of the PhD project offer new insights into the biomedical mechanisms of action and health effects of the Mediterranean diet. Of particular importance is the relationship we have shown between dietary fiber from the Mediterranean diet, its fermentation to short-chain fatty acids, and its beneficial influence on impaired intestinal barrier function. In the future, our studies may provide the basis for personalized nutritional therapy to improve impaired gut barrier function in high-risk breast cancer patients. Furthermore, we were able to establish LBP and zonulin as biomarkers to detect gut barrier function and to determine and assess gut barrier disorders. This method validation simplifies or enables the assessment of intestinal barrier function in clinical practice or clinical trials.
Selektivverträge in der medizinischen Versorgung
(2017) Arnegger, Silke; Ernst, Christian
In the past fifteen years, Germany has introduced several types of medical care and cooperation opportunities between actors in the healthcare market. The gatekeeper model known as Hausarztzentrierte Versorgung (HZV) is a primary physician model and is an example of selective or individual contracting that is now possible between physicians in private practice and health insurance companies. It is also an example of new policy instruments intended to increase competition in the healthcare system (e.g. between insurance companies, amongst physicians in private practice). Increased competition should lead to improvements in the quality of patient care and economic efficiencies in the provision of that care. The latter is an especially important goal in light of the fact that there are a growing number of patients with chronic diseases. Selective medical care contracts like the HZV are situated at this pivot point. Going forward, German health insurance companies and other healthcare market actors – in particular, physicians in private practice – are allowed to enter into individual contracts for the provision of medical care to a group of patients. For this purpose, physicians specializing in a particular field mandate their professional associations to negotiate contracts. Thereafter physicians who want to participate in these contracts can offer the applicable provisions to their patients. Previously, all insurance companies and all registered doctors in private practice were required to enter into collective agreements. Contracts like the HZV mean it should now be possible to study the individual patient care models of different health insurance companies and offer medical care that is better tailored to patients. Additionally, these contracts should encourage communication amongst different actors in the healthcare system and incentivize their behaviour to generate efficiencies. This empirical study aims to explain whether the HZV, namely the selective contracts for primary care physicians in the state of Baden-Württemberg, contain the right incentives for participating doctors (agents) to produce efficient results for the insurance companies with which they have contracted (principals). Data on the quality and efficiency of care provided under these contracts is compared to data on their financial impact on participating doctors. New Institutional Economics inform the theoretical framework used in this study. Its theories of social contract, especially agency, and transaction costs play a central role in interpreting and analysing the data collected. Many studies of selective contracting in the field of healthcare economics focus on legal issues arising from actual and proposed changes to the law. By providing an empirical healthcare oriented economic account of such contracts for primary care physicians in Germany, this study supplements that literature with data and analysis that has been lacking on this important development.
Strain-resolved analysis of the human intestinal microbiota
(2022) Podlesny, Daniel; Fricke, Florian W.
The gut microbiota is ascribed a crucial role in human health, particularly in regulating immune and inflammatory responses, which is why it is being associated with a wide range of diseases, including obesity, diabetes, and cancer. Nonetheless, fundamental ecological questions of microbiome establishment, stability and resilience, as well as its transmission across hosts and generations remain incompletely understood, partly due to the lack of methods for high-resolution microbiome profiling. New insights in this field can therefore directly contribute to the development of bacterial and microbiota-based therapies. This work introduces SameStr, a novel bioinformatic program for strain-resolved metagenomics that allows for the specific tracking of microbes across samples, enabling the detection and quantification of microbial transmission and persistence, as well as the observation of direct strain competition. Deployed across cohorts to process over 4200 metagenomes, SameStr enabled analysis of the microbiome with unprecedented phylogenetic resolution. The data included both publicly available metagenomes and sequence data generated in collaboration with our research partners, and was examined using multivariate statistics and machine learning frameworks. First, the establishment and development of the neonatal microbiota was studied, revealing a birth mode-dependent vertical transmission of the maternal microbiota. The microbiota of neonates born by cesarean section was characterized by increased relative abundance of oxygen-tolerant and atypical organisms and showed signs of a delayed establishment of a strictly anaerobic gut environment in these children. Such birth mode-dependent differences diminished over time, yet were measurable within the first two years of life. Furthermore, strain analysis verified the transmission and colonization of parental microbes, which indicated a possible lifelong colonization by microbes from selected species. The temporal persistence of microbes was also characterized in healthy adults, revealing similar taxonomy-dependent patterns of stability. For some species, persistence has been demonstrated both in children and in adults over a period of at least two years. These species are known for their capability to metabolize host-derived glycans found both in breastmilk and intestinal mucus, pointing to a potential strategy for effective cross-generational microbiota transmission, and warranting additional research to assess the implications of their disturbed transfer for long-term health. Since their specificity allows assignment to individual hosts, fingerprints of individual microbial strains offer the potential to be used in forensics and data quality control applications. Finally, to gain new insights into the microbiota dynamics during Fecal Microbiota Transplantation (FMT), microbial strain transmission was analyzed in the context of a diverse set of patient, microbiome, and clinical conditions. In the analyzed studies, FMT was used for the experimental treatment of a variety of diseases, including colonization with drug-resistant and pathogenic microbes, metabolic and inflammatory bowel diseases, and as an adjunct to the immunotherapeutic treatment of cancer. Analyses uncovered what appear to be the universal drivers of post-FMT microbiota assembly, including clinical and ecological factors that are important for successful transplantation of donor strains. In particular, the relevance of the microbiota dysbiosis of the recipient was emphasized, which was inducible by pre-treating the patient with antibiotics or laxatives. Presumably, this can open up ecological niches in the patients intestines, which favors colonization with donor strains. Colonization rates did not play a role for the treatment success of recurrent C. difficile infections and inflammatory bowel disease, but indicated a trend associated with an improved immune response in cancer patients. Concerningly, the transfer of an atypical and potentially pro-inflammatory microbial community from one donor was also observed, calling for further investigations into the immediate and long-term clinical consequences of FMT. These analyses demonstrate the advantages of a strain-based microbiome analysis. Due to the achieved methodological accuracy, strain-resolved microbial dynamics could be precisely disentangled when comparing longitudinal samples from healthy adults as well as parent-child and patient-donor pairs. This revealed taxonomic, clinical, and ecological factors that are critical to microbiome assembly, including microbial transmission, persistence, and competition. Together, these findings lay the groundwork for future developments of precision personalized microbiota modulation therapies.