Christoph Kaleta

Christian-Albrechts-Universität zu Kiel | CAU · Research Group Medical Systems Biology

Introduction By 2050, the worldwide percentage of people 65 years and older is assumed to have doubled compared to current numbers. Therefore, finding ways of promoting healthy (cognitive) aging is crucial. Physical activity is considered an effective approach to counteract not only physical but also cognitive decline. However, the underlying mecha...

Current classifications (World Health Organization-HAEM5/ICC) define up to 26 molecular B-cell precursor acute lymphoblastic leukemia (BCP-ALL) disease subtypes by genomic driver aberrations and corresponding gene expression signatures. Identification of driver aberrations by transcriptome sequencing (RNA-Seq) is well established, while systematic...

Objective Inflammatory bowel disease (IBD) is a persistent inflammatory condition affecting the gastrointestinal tract, presenting significant challenges in its management and treatment. Despite the knowledge that within-host bacterial evolution occurs in the intestine, the disease has so far rarely been studied from an evolutionary perspective. In...

The microbiome expresses a variety of functions that influence host biology. The range of functions depends on composition of the microbiome, which itself can change during the lifetime of the host as a consequence of neutral assembly processes, host-mediated selection, and/or environmental conditions. To date, the exact dynamics of microbiome asse...

The microbiome is increasingly receiving attention as an important modulator of host health and disease. However, while numerous mechanisms through which the microbiome influences its host have been identified, there is still a lack of approaches that allow to specifically modulate the abundance of individual microbes or microbial functions of inte...

Current classifications (WHO-HAEM5 / ICC) define up to 26 molecular B-cell precursor acute lymphoblastic leukemia (BCP-ALL) disease subtypes, which are defined by genomic driver aberrations and corresponding gene expression signatures. Identification of driver aberrations by RNA-Seq is well established, while systematic approaches for gene expressi...

Recent rodent microbiome experiments suggest that besides Akkermansia, Parasutterella sp. are important in type 2 diabetes and obesity development. In the present translational human study, we aimed to characterize Parasutterella in our European cross-sectional FoCus cohort (n = 1,544) followed by validation of the major results in an independent C...

The microbiota of multicellular organisms undergoes considerable changes during development but the general mechanisms that control community assembly and succession are poorly understood. Here, we use bacterial recolonization experiments in Nematostella vectensis as a model to understand general mechanisms determining bacterial establishment and s...

Neurodegenerative diseases such as Parkinson’s (PD) and Alzheimer’s disease (AD), the prevalence of which is rapidly rising due to an aging world population and westernization of lifestyles, are expected to put a strong socioeconomic burden on health systems worldwide. Clinical trials of therapies against PD and AD have only shown limited success s...

Cognitive decline is one of the greatest health threats of old age and the maintenance of optimal brain function across a lifespan remains a big challenge. The hippocampus is considered particularly vulnerable but there is cross-species consensus that its functional integrity benefits from the early and continuous exercise of demanding physical, so...

Due to the aging of the world population and westernization of lifestyles, the prevalence of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) is rapidly rising and is expected to put a strong socioeconomic burden on health systems worldwide. Due to the limited success of clinical trials of therapies against n...

Inflammation is considered a possible cause of cognitive decline during aging. This study investigates the influence of physical activity and social isolation in old mice on their cognitive functions and inflammation. The Barnes maze task was performed to assess spatial learning and memory in 3, 9, 15, 24, and 28 months old male C57BL/6 mice as wel...

Parkinson’s Disease (PD) is a neurodegenerative disease, leading to motor and non-motor complications. Autonomic alterations, including gastrointestinal symptoms, precede motor defects and act as early warning signs. Chronic exposure to dietary, environmental heavy metals impacts the gastrointestinal system and host-associated microbiome, eventuall...

Aspergillus fumigatus is an important human fungal pathogen and its conidia are constantly inhaled by humans. In immunocompromised individuals, conidia can grow out as hyphae that damage lung epithelium. The resulting invasive aspergillosis is associated with devastating mortality rates. Since infection is a race between the innate immune system an...

A key challenge in microbiome research is to predict the functionality of microbial communities based on community membership and (meta)-genomic data. As central microbiota functions are determined by bacterial community networks, it is important to gain insight into the principles that govern bacteria-bacteria interactions. Here, we focused on the...

Hexokinases (HK) catalyze the first step of glycolysis limiting its pace. HK2 is highly expressed in gut epithelium, contributes to immune responses, and is upregulated during inflammation. We examined the microbial regulation of HK2 and its impact on inflammation using mice lacking HK2 in intestinal epithelial cells (Hk2ΔIEC). Hk2ΔIEC mice were le...

The exchange of metabolites among different bacterial genotypes profoundly impacts the structure and function of microbial communities. However, the factors governing the establishment of these cross-feeding interactions remain poorly understood. While shared physiological features may facilitate interactions among more closely related individuals,...

The exchange of metabolites among different bacterial genotypes profoundly impacts the structure and function of microbial communities. However, the factors governing the establishment of these cross-feeding interactions remain poorly understood. While shared physiological features may facilitate interactions among more closely related individuals,...

The burden of fungal infections for humans, animals and plants is widely underestimated and comprises deadly infections as well as great conomic costs. Despite that, antifungal drugs are scarce and emergence of resistance in fungal strains contributes to a high mortality. To overcome this shortage, we propose toxic intermediates and their controlli...

Urinary tract infections (UTIs) are frequent in humans, affecting the upper and lower urinary tract. Present diagnosis relies on the positive culture of uropathogenic bacteria from urine and clinical markers of inflammation of the urinary tract. The bladder is constantly challenged by adverse environmental stimuli which influence urinary tract phys...

Aspergillus fumigatus is an important human fungal pathogen and its conidia are constantly inhaled by humans. In immunocompromised individuals, conidia can grow out as hyphae that damage lung epithelium. The resulting invasive aspergillosis is associated with devastating mortality rates. Since infection is a race between the innate immune system an...

In this review, we summarize and briefly discuss various approaches to modeling the metabolism in human immune cells, with a focus on energy metabolism. These approaches include metabolic reconstruction, elementary modes, and flux balance analysis, which are often subsumed under constraint-based modeling. Further approaches are evolutionary game th...

There is a strong connection between microbiome composition and human health. Recent studies have shown that beyond an influence of medication on microbiome composition, the microbiome is capable of metabolizing a large number of approved drugs. This includes the degradation of drugs, the production of more potent derivatives, and also the synthesi...

Genome-scale metabolic models of microorganisms are powerful frameworks to predict phenotypes from an organism’s genotype. While manual reconstructions are laborious, automated reconstructions often fail to recapitulate known metabolic processes. Here we present gapseq (https://github.com/jotech/gapseq), a new tool to predict metabolic pathways and...

Background The intestinal microbiota plays a crucial role in protecting the host from pathogenic microbes, modulating immunity and regulating metabolic processes. We studied the simplified human intestinal microbiota (SIHUMIx) consisting of eight bacterial species with a particular focus on the discovery of novel small proteins with less than 100 a...

Hexokinases (HK) catalyze the first step of glycolysis and thereby limit its pace. HK2 is highly expressed in the gut epithelium, plays a role in immune responses and is upregulated in inflammation and ulcerative colitis. Here, we examined the microbial regulation of HK2 and its impact on intestinal inflammation by generating mice lacking HK2 speci...

Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed the bulk transcriptome, bulk DNA methylome, and single-cell tr...

Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed the bulk transcriptome, bulk DNA methylome, and single-cell tr...

The molecular foundation of chronic inflammatory diseases (CIDs) can differ markedly between individuals. As our understanding of the biochemical mechanisms underlying individual disease manifestations and progressions expands, new strategies to adjust treatments to the patient's characteristics will continue to profoundly transform clinical practi...

The exchange of metabolites among different bacterial genotypes profoundly impacts the structure and function of microbial communities. However, the factors governing the establishment of these cross-feeding interactions remain poorly understood. While shared physiological features may facilitate interactions among more closely related individuals,...

The pandemic spread of the potentially life-threatening disease COVID-19 requires a thorough understanding of the longitudinal dynamics of host responses. Temporal resolution of cellular features associated with a severe disease trajectory will be a pre-requisite for finding disease outcome predictors. Here, we performed a longitudinal multi-omics...

Both intrinsic and extrinsic mechanisms regulating bacterial expression have been elucidated and described, however, such studies have mainly focused on local effects on the two-dimensional structure of the prokaryote genome while long-range as well as spatial interactions influencing gene expression are still only poorly understood. In this paper,...

The reconstruction and application of genome-scale metabolic network models is a central topic in the field of systems biology with numerous applications in biotechnology, ecology, and medicine. However, there is no agreed upon standard for the definition of the nutritional environment for these models. The objective of this article is to provide a...

The study of microbiomes by sequencing has revealed a plethora of correlations between microbial community composition and various life-history characteristics of the corresponding host species. However, inferring causation from correlation is often hampered by the sheer compositional complexity of microbiomes, even in simple organisms. Synthetic c...

The study of microbiomes by sequencing has revealed a plethora of correlations between microbial community composition and various life-history characteristics of the corresponding host species. However, inferring causation from correlation is often hampered by the sheer compositional complexity of microbiomes, even in simple organisms. Synthetic c...

Microbial metabolic processes greatly impact ecosystem functioning and the physiology of multi-cellular host organisms. The inference of metabolic capabilities and phenotypes from genome sequences with the help of prior biomolecular knowledge stored in online databases remains a major challenge in systems biology. Here, we present gapseq: a novel t...

High-sugar diets cause thirst, obesity, and metabolic dysregulation, leading to diseases including type 2 diabetes and shortened lifespan. However, the impact of obesity and water imbalance on health and survival is complex and difficult to disentangle. Here, we show that high sugar induces dehydration in adult Drosophila, and water supplementation...

The microbiota is generally assumed to have a substantial influence on the biology of multicellular organisms. The exact functional contributions of the microbes are often unclear and cannot be inferred easily from 16S rRNA genotyping, which is commonly used for taxonomic characterization of bacterial associates. In order to bridge this knowledge g...

The biology of all organisms is influenced by the associated community of microorganisms. In spite of its importance, it is usually not well understood how exactly this microbiota affects host functions and what are the underlying molecular processes. To rectify this knowledge gap, we took advantage of the nematode Caenorhabditis elegans as a tract...

Metformin is the first-line therapy for treating type 2 diabetes and a promising anti-aging drug. We set out to address the fundamental question of how gut microbes and nutrition, key regulators of host physiology, affect the effects of metformin. Combining two tractable genetic models, the bacterium E. coli and the nematode C. elegans, we develope...

Background & aims: Altered interactions between the mucosal immune system and intestinal microbiota contribute to pathogenesis of inflammatory bowel diseases (IBD). It is not clear how inhibitors of cytokines, such as antagonists of tumor necrosis factor (anti-TNF), affect the intestinal microbiome. We investigated the effects of anti-TNF agents o...

E. coli are a flexible group of bacteria that thrive in various niches by tuning gene expression to tolerate or rapidly grow for sustained virulence. E. coli metabolic trade-offs to maintain homeostasis can be taken advantage of treatments for human disease by assessing E. coli mechanisms of rapid growth (short intensive antibiotic treatment) or re...

In order to survive and reproduce, organisms must perform a multitude of tasks. However, trade-offs limit their ability to allocate energy and resources to all of these different processes. One strategy to solve this problem is to specialize in some traits and team up with other organisms that can help by providing additional, complementary functio...

The original version of this Article contained an error in the spelling of the author Jule Müller, which was incorrectly given as Julia Müller. Additionally, in Fig. 4a, the blue-red colour scale for fold change in ageing/disease regulation included a blue stripe in place of a red stripe at the right-hand end of the scale. These errors have been co...

Background Human diseases are often associated with changes in the microbiome.Objectives The goal of the work was to investigate the contribution of the microbiome to diseases associated with aging and their treatment.ResultsThere are considerable changes in the microbiome and its environment in the context of aging. In the treatment of diseases as...

Caenorhabditis elegans is associated in nature with a species-rich, distinct microbiota, which was characterized only recently [1]. Thus, our understanding of the relevance of the microbiota for nematode fitness is still at its infancy. One major benefit that the intestinal microbiota can provide to its host is protection against pathogen infection...

The microbiome is generally assumed to have a substantial influence on the biology of multicellular organisms. The exact functional contributions of the microbes are often unclear and cannot be inferred easily from 16S rRNA genotyping, which is commonly used for taxonomic characterization of the bacterial associates. In order to bridge this knowled...

The biology of all organisms is influenced by the associated community of microorganisms. In spite of its importance, it is usually not well understood how exactly this microbiome affects host functions and what are the underlying molecular processes. To rectify this knowledge gap, we took advantage of the nematode C. elegans as a tractable, experi...

Metabolites curated from literature.

Background & aims: RNase H2 is a holoenzyme comprising 3 subunits (ribonuclease H2 subunits A, B, and C) that cleaves RNA:DNA hybrids and removes misincorporated ribonucleotides from genomic DNA via ribonucleotide excision repair. Ribonucleotide incorporation by eukaryotic DNA polymerases occurs during every round of genome duplication and produce...

The bacterial nucleoid is highly condensed and forms compartment-like structures within the cell. Much attention has been devoted to investigating the dynamic topology and organization of the nucleoid. In contrast, the specific nucleoid organization, and the relationship between nucleoid structure and function is often neglected with regard to impo...