Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in severe COVID-19

The clinical course of the 2019 coronavirus disease (COVID-19) is variable and to a substantial degree still unpredictable, especially in persons who have neither been vaccinated nor recovered from previous infection. We hypothesized that disease progression and inflammatory responses were associated with alterations in the microbiome and metabolome. To test this, we integrated metagenome, metabolome, cytokine, and transcriptome profiles of longitudinally collected samples from hospitalized COVID-19 patients at the beginning of the pandemic (before vaccines or variants of concern) and non-infected controls, and leveraged detailed clinical information and post-hoc confounder analysis to identify robust within- and cross-omics associations. Severe COVID-19 was directly associated with a depletion of potentially beneficial intestinal microbes mainly belonging to Clostridiales, whereas oropharyngeal microbiota disturbance appeared to be mainly driven by antibiotic use. COVID-19 severity was also associated with enhanced plasma concentrations of kynurenine, and reduced levels of various other tryptophan metabolites, lysophosphatidylcholines, and secondary bile acids. Decreased abundance of Clostridiales potentially mediated the observed reduction in 5-hydroxytryptophan levels. Moreover, altered plasma levels of various tryptophan metabolites and lower abundances of Clostridiales explained significant increases in the production of IL-6, IFNγ and/or TNFα. Collectively, our study identifies correlated microbiome and metabolome alterations as a potential contributor to inflammatory dysregulation in severe COVID-19

A time-resolved proteomic and prognostic map of COVID-19

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease

Lysimeterversuche zum Langzeitverhalten der Herbizide Metamitron (GOLTIXR^{R}) und Methabenzthiazuron (TRIBUNILR^{R}) in einer Parabraunerde mit besonderer Berücksichtigung der Transport- und Verlagerungsprozesse unter Einbeziehung von Detailuntersuchungen

The demands made on the ecological compatibility of pesticides continue to increase. The intention on the part of the legislature to promote this development has been documented in the past few years by two far-reaching amendments. In the amended German Pesticides Act (Pflanzenschutzgesetz, 1986) the natural environment ("Natural Environment : Its Components of Soil, Water, Air, Animal and Plant Species and also their Mutual Interactions") has been recognized as requiring special protection on the same level as human and animal health. In the same year, a new extremely low threshold concentration for pesticides was laid down in the Drinking Water Ordinance (Trinkwasserverordnung, 1986), which since then has also been applied to the protection of the ground water against pesticide contaminations (FEDERAL DEPARTMENT OF HEALTH (BGA), 1989, KLEIN and DIETER, 1989; KLEIN, 1987). These legal standards require a comprehensive estimate and assessment of the behaviour of pesticides and their residues in soils, which proves to be particularly difficult due to the extremely complicated interactions of soil, plant and climate factors in their impact on the processes of bonding, sorption, degradation/mineralization, translocation and volatilization. Precise knowledge of the extent and velocity of these processes and the influencing factors are necessary in order to obtain a reliable evaluation. This requires extensive study programmes taking into consideration the very different conditions of natural sites under the influence of agricultural land use. Lysimeter experiments with $^{14}$C-labelled active ingredients represent one approach (FÜHR et al., 1989 and 1991). The intellectual combination and analysis of all these results to achieve an overall assessment is a further problem as reflected in this quotation from Prof. G. Miehlich (1989) in an essay on the subject "What is Soil?", "The human brain is only capable of dealing with relationship networks to a very limited extent, and traditional training in the natural sciences promotes monocausal thinking. The system of relationships between the processes taking place within the soil and also their interactions with the entire ecosystem can be only be recognized by means of an approach considering the whole ecosystem, which has to be carried out on an interdisciplinary basis including the application of computer modelling", However, itshould be noted here that from the present point of view computer models are unable to provide accurate forecasts due to a number of simplifications and destrictions, as [...

Lysimeterversuche zum Langzeitverhalten der Herbizide Metamitron (GOLTIX"R) und Methabenzthiazuron (TRIBUNIL"R) in einer Parabraunerde mit besonderer Beruecksichtigung der Transport- und Verlagerungsprozesse unter Einbeziehung von Detailuntersuchungen

SIGLEAvailable from TIB Hannover: RA 831(2465) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman