Anouk C. Tengeler

Bio: Anouk C. Tengeler is an academic researcher from Radboud University Nijmegen. The author has contributed to research in topics: Gut flora & Circadian rhythm. The author has an hindex of 7, co-authored 8 publications receiving 1196 citations. Previous affiliations of Anouk C. Tengeler include Weizmann Institute of Science & Leiden University.

Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection.

Abstract: Obesity, diabetes, and related manifestations are associated with an enhanced, but poorly understood, risk for mucosal infection and systemic inflammation. Here, we show in mouse models of obesity and diabetes that hyperglycemia drives intestinal barrier permeability, through GLUT2-dependent transcriptional reprogramming of intestinal epithelial cells and alteration of tight and adherence junction integrity. Consequently, hyperglycemia-mediated barrier disruption leads to systemic influx of microbial products and enhanced dissemination of enteric infection. Treatment of hyperglycemia, intestinal epithelial-specific GLUT2 deletion, or inhibition of glucose metabolism restores barrier function and bacterial containment. In humans, systemic influx of intestinal microbiome products correlates with individualized glycemic control, indicated by glycated hemoglobin levels. Together, our results mechanistically link hyperglycemia and intestinal barrier function with systemic infectious and inflammatory consequences of obesity and diabetes.

Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice.

Abstract: The impact of the gut microbiota on host physiology and behavior has been relatively well established. Whether changes in microbial composition affect brain structure and function is largely elusive, however. This is important as altered brain structure and function have been implicated in various neurodevelopmental disorders, like attention-deficit/hyperactivity disorder (ADHD). We hypothesized that gut microbiota of persons with and without ADHD, when transplanted into mice, would differentially modify brain function and/or structure. We investigated this by colonizing young, male, germ-free C57BL/6JOlaHsd mice with microbiota from individuals with and without ADHD. We generated and analyzed microbiome data, assessed brain structure and function by magnetic resonance imaging (MRI), and studied mouse behavior in a behavioral test battery. Principal coordinate analysis showed a clear separation of fecal microbiota of mice colonized with ADHD and control microbiota. With diffusion tensor imaging, we observed a decreased structural integrity of both white and gray matter regions (i.e., internal capsule, hippocampus) in mice that were colonized with ADHD microbiota. We also found significant correlations between white matter integrity and the differentially expressed microbiota. Mice colonized with ADHD microbiota additionally showed decreased resting-state functional MRI-based connectivity between right motor and right visual cortices. These regions, as well as the hippocampus and internal capsule, have previously been reported to be altered in several neurodevelopmental disorders. Furthermore, we also show that mice colonized with ADHD microbiota were more anxious in the open-field test. Taken together, we demonstrate that altered microbial composition could be a driver of altered brain structure and function and concomitant changes in the animals’ behavior. These findings may help to understand the mechanisms through which the gut microbiota contributes to the pathobiology of neurodevelopmental disorders.

Relationship between diet, the gut microbiota, and brain function

Abstract: The human intestinal microbiota, comprising trillions of microorganisms, exerts a substantial effect on the host. The microbiota plays essential roles in the function and development of several physiological processes, including those in the brain. A disruption in the microbial composition of the gut has been associated with many metabolic, inflammatory, neurodevelopmental, and neurodegenerative disorders. Nutrition is one of several key factors that shape the microbial composition during infancy and throughout life, thereby affecting brain structure and function. This review examines the effect of the gut microbiota on brain function. The ability of external factors, such as diet, to influence the microbial composition implies a certain vulnerability of the gut microbiota. However, it also offers a potential therapeutic strategy for ameliorating symptoms of mental and physical disorders. Therefore, this review examines the potential effect of nutritional components on gut microbial composition and brain function.

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

High-performance medicine: the convergence of human and artificial intelligence

Abstract: The use of artificial intelligence, and the deep-learning subtype in particular, has been enabled by the use of labeled big data, along with markedly enhanced computing power and cloud storage, across all sectors. In medicine, this is beginning to have an impact at three levels: for clinicians, predominantly via rapid, accurate image interpretation; for health systems, by improving workflow and the potential for reducing medical errors; and for patients, by enabling them to process their own data to promote health. The current limitations, including bias, privacy and security, and lack of transparency, along with the future directions of these applications will be discussed in this article. Over time, marked improvements in accuracy, productivity, and workflow will likely be actualized, but whether that will be used to improve the patient-doctor relationship or facilitate its erosion remains to be seen.

The Human Intestinal Microbiome in Health and Disease

Abstract: The large majority of studies on the role of the microbiome in the pathogenesis of disease are correlative and preclinical; several have influenced clinical practice.

The Microbiota-Gut-Brain Axis

Abstract: The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within ...