Biology subjects

Estaki, M.

Publications and source records attributed to Estaki, M..

7 recordsLinked to original sources

bioRxiv2024

Bio-engineering a common probiotic to exploit colonic inflammation promotes reliable efficacy in translational models of colitis

The intricate balance between the gut microbiome and host health inspires innovations in drug development. Commensal bacteria provide a multi-targeted approach ideal for treating complex medical conditions, like inflammatory bowel disease (IBD). These bacteria are self-replicating factories with broad targets that promote balanced intestinal inflammation, mucosal barrier function, and eubiosis. Yet, the lack of superiority to gold-standard treatments and their clinical inconsistency makes most probiotics unreliable for disease treatments. Intestinal inflammation, a driving factor in many diseases, often overwhelms commensal bacteria, which lack the stress-resistance mechanisms necessary to withstand host immune defenses. To address this, we introduced a persistence platform BioPersist into E. coli Nissle 1917. We hypothesized that a bio-engineered probiotic, or genetically engineered microbial medicine (GEMM), designed to persist during inflammation would enhance probiotic bioavailability during colitis, leading to sustained therapeutic outcomes. We evaluated BioPersist in multiple translational colitis models such as in mice and pigs. BioPersist delayed the onset and reduced the severity of both chronic and acute colitis, proving more effective than 5-aminosalicylate. BioPersist thrived during inflammation promoting tolerogenic immune responses that limited infiltrating leukocyte activity and decreased TNF- from resident myeloid cells in the mesentery. The persistence feature of BioPersist allowed the probiotic to overcome the damaging inflammatory response, eliciting mucosal healing evident by the increase in microbially-derived butyric acid. Based on these preclinical results, BioPersist may be a novel therapeutic option for both human and veterinary applications that sustains efficacy during colitis. One Sentence SummaryAdding a persistence feature to a probiotic enhances its efficacy for colitis treatment, enhancing future human and veterinary therapeutic applications.

microbiology↗

bioRxiv2024

Medication Use is Associated with Distinct Microbial Features in Anxiety and Depression

This study investigated the relationship between gut microbiota and neuropsychiatric disorders (NPDs), specifically anxiety disorder (ANXD) and/or major depressive disorder (MDD), as defined by DSM-IV or V criteria. The study also examined the influence of medication use, particularly antidepressants and/or anxiolytics, classified through the Anatomical Therapeutic Chemical (ATC) Classification System, on the gut microbiota. Both 16S rRNA gene amplicon sequencing and shallow shotgun sequencing were performed on DNA extracted from 666 fecal samples from the Tulsa-1000 and NeuroMAP CoBRE cohorts. The results highlight the significant influence of medication use; antidepressant use is associated with significant differences in gut microbiota beta diversity and has a larger effect size than NPD diagnosis. Next, specific microbes were associated with ANXD and MDD, highlighting their potential for non-pharmacological intervention. Finally, the study demonstrated the capability of Random Forest classifiers to predict diagnoses of NPD and medication use from microbial profiles, suggesting a promising direction for the use of gut microbiota as biomarkers for NPD. The findings suggest that future research on the gut microbiotas role in NPD and its interactions with pharmacological treatments are needed.

microbiology↗

bioRxiv2023

BIRDMAn: A Bayesian differential abundance framework that enables robust inference of host-microbe associations

Quantifying the differential abundance (DA) of specific taxa among experimental groups in microbiome studies is challenging due to data characteristics (e.g., compositionality, sparsity) and specific study designs (e.g., repeated measures, meta-analysis, cross-over). Here we present BIRDMAn (Bayesian Inferential Regression for Differential Microbiome Analysis), a flexible DA method that can account for microbiome data characteristics and diverse experimental designs. Simulations show that BIRDMAn models are robust to uneven sequencing depth and provide a >20-fold improvement in statistical power over existing methods. We then use BIRDMAn to identify antibiotic-mediated perturbations undetected by other DA methods due to subject-level heterogeneity. Finally, we demonstrate how BIRDMAn can construct state-of-the-art cancer-type classifiers using The Cancer Genome Atlas (TCGA) dataset, with substantial accuracy improvements over random forests and existing DA tools across multiple sequencing centers. Collectively, BIRDMAn extracts more informative biological signals while accounting for study-specific experimental conditions than existing approaches.

bioinformatics↗

bioRxiv2021

A Mediterranean-like fat blend protects against the development of severe colitis in the mucin-2 deficient murine model

The Mediterranean diet (MD) is a health-promoting, moderate fat diet (~ 40% energy). It is not known if the blend of fats found in the MD contribute to the beneficial protective effects. We compared the MD fat blend (high monounsaturated, 2:1 n-6:n-3 polyunsaturated and moderate saturated fat) to isocaloric diets composed with corn oil (CO, n-6 polyunsaturated-rich), olive oil (high monounsaturated-rich) or milk fat (MF, saturated-rich) on spontaneous colitis development in Muc2-/- mice. The MD resulted in lower clinical and histopathological scores, and induced tolerogenic CD103+CD11b+ dendritic, Th22 and IL-17+IL-22+ cells important for intestinal barrier repair. MD also reduced attendant insulin resistance and a shift to a higher health-promoting gut microbes including Lactobacillus B. animalis and Muribaculaceae, whereas CO showed higher prevalence of mucin-degraders (Akkermansia muciniphila) and colitis promoters (Enterobacteriaceae). Our findings suggest that the MD fat blend could be recommended as a maintenance diet for colitis.

immunology↗

bioRxiv2020

A comparison of DNA/RNA extraction protocols for high-throughput sequencing of microbial communities

One goal among microbial ecology researchers is to capture the maximum amount of information from all organisms in a sample. The recent COVID-19 pandemic, caused by the RNA virus SARS-CoV-2, has highlighted a gap in traditional DNA-based protocols, including the high-throughput methods we previously established as field standards. To enable simultaneous SARS-CoV-2 and microbial community profiling, we compare the relative performance of two total nucleic acid extraction protocols and our previously benchmarked protocol. We included a diverse panel of environmental and host-associated sample types, including body sites commonly swabbed for COVID-19 testing. Here we present results comparing the cost, processing time, DNA and RNA yield, microbial community composition, limit of detection, and well-to-well contamination, between these protocols. Accession numbersRaw sequence data were deposited at the European Nucleotide Archive (accession#: ERP124610) and raw and processed data are available at Qiita (Study ID: 12201). All processing and analysis code is available on GitHub (github.com/justinshaffer/Extraction_test_MagMAX). Methods summaryTo allow for downstream applications involving RNA-based organisms such as SARS-CoV-2, we compared the two extraction protocols designed to extract DNA and RNA against our previously established protocol for extracting only DNA for microbial community analyses. Across 10 diverse sample types, one of the two protocols was equivalent or better than our established DNA-based protocol. Our conclusion is based on per-sample comparisons of DNA and RNA yield, the number of quality sequences generated, microbial community alpha- and beta-diversity and taxonomic composition, the limit of detection, and extent of well-to-well contamination.

ecology↗

bioRxiv2020

EMPress enables tree-guided, interactive, and exploratory analyses of multi-omic datasets

Standard workflows for analyzing microbiomes often include the creation and curation of phylogenetic trees. Here we present EMPress, an interactive tool for visualizing trees in the context of microbiome, metabolome, etc. community data scalable beyond modern large datasets like the Earth Microbiome Project. EMPress provides novel functionality--including ordination integration and animations--alongside many standard tree visualization features, and thus simplifies exploratory analyses of many forms of omic data.

bioinformatics↗

bioRxiv2020

Physical activity shapes the intestinal microbiome and immunity of healthy mice but has no protective effects against colitis in MUC2-/- mice

The interactions among humans, their environment, and the trillions of microbes residing within the human intestinal tract form a tripartite relationship that is fundamental to the overall health of the host. Disruptions in the delicate balance between the intestinal microbiota and their host immunity are implicated in various chronic diseases including inflammatory bowel disease (IBD). There is no known cure for IBD, therefore, novel therapeutics targeting prevention and symptoms management are of great interest. Recently, physical activity in healthy mice was shown to be protective against chemically-induced colitis, however the benefits of physical activity during or following disease onset is not known. In this study, we examine whether voluntary wheel running is protective against primary disease symptoms in a mucin 2 deficient (Muc2-/-) life-long model of murine colitis. We show that 6 weeks of wheel running in healthy C57BL/6 mice leads to distinct changes in fecal bacteriome, increased butyrate production, and modulation in colonic gene expression of various cytokines, suggesting an overall primed anti-inflammatory state. However, these physical activity-derived benefits are not present in Muc2-/- mice harboring a dysfunctional mucosal layer from birth, ultimately showing no improvements in clinical signs. We extrapolate from our findings that while physical activity in healthy individuals may be an important preventative measure against IBD, for those with a compromised intestinal mucosa, a commonality in IBD patients, these benefits are lost.

microbiology↗