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Widmer, G.

Publications and source records attributed to Widmer, G..

5 recordsLinked to original sources

Ingestible Osmotic Pill for In-vivo Sampling of Gut Microbiome

Technologies capable of non-invasively sampling different locations in the gut upstream of the colon will enable new insights into the role of organ-specific microbiota in human health. We present an ingestible, biocompatible, battery-less, 3D-printed micro-engineered pill with integrated osmotic sampler and microfluidic channels for in vivo sampling of the gut lumen and its microbiome upstream of the colon. The pills sampling performance was characterized using realistic in vitro models and validated in vivo in pigs and primates. Our results show that the bacterial populations recovered from the pills microfluidic channels closely resemble the bacterial population demographics of the microenvironment to which the pill was exposed. We believe such lab-on-a-pill devices will revolutionize our understanding of the spatial diversity of the gut microbiome and its response to medical conditions and treatments.

bioengineering↗

Deprivation of dietary fiber enhances susceptibility of mice to cryptosporidiosis

Based on our initial observations showing that mice consuming a probiotic product develop more severe cryptosporidiosis, we investigated the impact of other dietary interventions on the intracellular proliferation of Cryptosporidium parvum and C. tyzzeri in the mouse. Mice were orally infected with oocysts and parasite multiplication measured by quantifying fecal oocyst output. High-throughput sequencing of 16S ribosomal RNA amplicons was used to correlate oocyst output with diet and with the composition of the intestinal microbiota. On average, mice fed a diet without fiber (cellulose, pectin and inulin) developed more severe infections. As expected, a diet without fibers also significantly altered the fecal microbiota. Consistent with these observations, mice fed a prebiotic product sold for human consumption excreted significantly fewer oocysts. The fecal microbiota of mice consuming no plant polysaccharides was characterized by a lower relative abundance of Bacteroidetes bacteria. Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host. This model is consistent with the metabolic dependence of intracellular stages of the parasite on the host cell. These observations underscore the potential of dietary interventions to alleviate the impact of cryptosporidiosis, particularly in infants at risk of recurrent enteric infections.\n\nAUTHOR SUMMARYThe infection with Cryptosporidium parasite, a condition known as cryptosporidiosis, is a common cause of infant diarrhea in developing countries. We have previously shown that mice infected with C. parvum, one of the main cause of human cryptosporidiosis, develop a more severe infection if given probiotics. To investigate the mechanism of this effect, we fed mice prebiotics and diet lacking plant fiber. We found that fermentable fiber, whether administered as a prebiotic supplement or is part of the diet, has a protective effect against cryptosporidiosis in mice. We also observed a significant association between the severity of infection and the composition of the gut microbiota. A significant inverse correlation was found between severity of cryptosporidiosis and the ratio between the abundance of bacteria belonging to the phylum Bacteroidetes and the abundance of Firmicute bacteria. This ratio is frequently viewed as a marker of a healthy microbiota. These results raise the possibility that dietary interventions could be used to alleviate the impact of cryptosporidiosis.

microbiology↗

Deep SNP: An End-to-end Deep Neural Network with Attention-based Localization for Break-point Detection in SNP Array Genomic data

Diagnosis and risk stratification of cancer and many other diseases require the detection of genomic breakpoints as a prerequisite of calling copy number alterations (CNA). This, however, is still challenging and requires time-consuming manual curation. As deep-learning methods outperformed classical state-of-the-art algorithms in various domains and have also been successfully applied to life science problems including medicine and biology, we here propose Deep SNP, a novel Deep Neural Network to learn from genomic data. Specifically, we used a manually curated dataset from 12 genomic single nucleotide polymorphism array (SNPa) profiles as truth-set and aimed at predicting the presence or absence of genomic breakpoints, an indicator of structural chromosomal variations, in windows of 40,000 probes. We compare our results with well-known neural network models as well as Rawcopy though this tool is designed to predict breakpoints and in addition genomic segments with high sensitivity. We show, that Deep SNP is capable of successfully predicting the presence or absence of a breakpoint in large genomic windows and outperforms state-of-the-art neural network models. Qualitative examples suggest that integration of a localization unit may enable breakpoint detection and prediction of genomic segments, even if the breakpoint coordinates were not provided for network training. These results warrant further evaluation of DeepSNP for breakpoint localization and subsequent calling of genomic segments.

genomics↗

Cryopreservation of Infectious Cryptosporidium parvum Oocysts

Cryptosporidiosis in an enteric infection caused by Cryptosporidium parasites and is a major cause of acute infant diarrhea in the developing world. A major bottleneck to research progress is the lack of methods to cryopreserve Cryptosporidium oocysts, thus requiring routine propagation in laboratory animals. Here, we report a method to cryopreserve C. parvum oocysts by ultra-fast cooling. Cryopreserved oocysts exhibits high viability and robust in vitro excystation, and are infectious to interferon-{gamma} knockout mice. The course of the infection is comparable to what we observe with unfrozen oocysts. Oocyst viability and infectivity is not visibly changed after several weeks of cryogenic storage. Cryopreservation will facilitate the sharing of oocysts from well characterized isolates and transgenic strains among different laboratories.

microbiology↗

Probiotics enhance susceptibility of mice to cryptosporidiosis

Cryptosporidiosis is a leading cause of diarrhea in infants and immune-compromised individuals. The lack of effective drugs against this enteric infection is motivating research to develop alternative treatments. To this aim, the impact of probiotics on the course of cryptosporidiosis was explored. The native intestinal microbiota of specific pathogen-free immunosuppressed mice was initially depleted with orally administered antibiotics. Then, a commercially available probiotic product intended for human consumption was added (or not) to the drinking water. Probiotic treated and untreated mice were orally infected with Cryptosporidium parvum oocysts. On average, mice treated with probiotic excreted more oocysts, indicative of a more severe infection. The probiotic treatment significantly altered the fecal microbiota, but taxonomic analyses showed no direct association between ingestion of probiotic bacteria and their abundance in fecal microbiota. These results suggest that probiotics indirectly alter the intestinal microenvironment in such a way that favors proliferation of C. parvum. The increase in the relative abundance of facultative anaerobes observed in mice with severe cryptosporidiosis indicates that dysbiosis is a consequence of severe cryptosporidiosis. The increase in the abundance of facultative anaerobes observed in severely infected animals is consistent with analyses of microbiota from individuals infected with other enteric pathogens. The results are significant because they show that C. parvum responds to changes in the intestinal microenvironment induced by a nutritional supplement.\n\nOne Sentence SummaryMice treated with probiotics develop more severe symptoms of cryptosporidiosis.

microbiology↗