Acarbose impairs gut growth by targeting intracellular glucosidases.

Unlabelled: Acarbose is a type 2 diabetes medicine that prevents dietary starch breakdown into glucose by inhibiting host amylase and glucosidase enzymes. Numerous gut species in the genus enzymatically break down starch and change in relative abundance within the gut microbiome in acarbose-treated individuals. To mechanistically explain this observation, we used two model starch-degrading , (Bo), and (Bt).

Why Symptoms Linger in Quiescent Crohn's Disease: Investigating the Impact of Sulfidogenic Microbes and Sulfur Metabolic Pathways.

Introduction: Even in the absence of inflammation, persistent symptoms in patients with Crohn's disease (CD) are prevalent and worsen quality of life. We previously demonstrated enrichment in sulfidogenic microbes in quiescent Crohn's disease patients with (qCD + S) vs without persistent GI symptoms (qCD-S). Thus, we hypothesized that sulfur metabolic pathways would be enriched in stool while differentially abundant microbes would be associated with important sulfur metabolic pathways in qCD + S.

VMAP: Vaginal Microbiome Atlas during Pregnancy.

Objectives: To enable interactive visualization of the vaginal microbiome across the pregnancy and facilitate discovery of novel insights and generation of new hypotheses.

Material And Methods: Vaginal Microbiome Atlas during Pregnancy (VMAP) was created with R shiny to generate visualizations of structured vaginal microbiome data from multiple studies.

Results: VMAP (http://vmapapp.

Why Symptoms Linger in Quiescent Crohn's Disease: Investigating the Impact of Sulfidogenic Microbes and Sulfur Metabolic Pathways.

Introduction: Even in the absence of inflammation, persistent symptoms in patients with Crohn's disease (CD) are prevalent and worsen quality of life. We previously demonstrated enrichment in sulfidogenic microbes in quiescent Crohn's disease patients with ( ) vs. without persistent GI symptoms ( ).

The Microbiome in Quiescent Crohn's Disease With Persistent Symptoms Show Disruptions in Microbial Sulfur and Tryptophan Pathways.

Background And Aims: Even in the absence of inflammation, persistent symptoms in Crohn's disease (CD) are prevalent and worsen quality of life. Amongst patients without inflammation (quiescent CD), we hypothesized that microbial community structure and function, including tryptophan metabolism, would differ between patients with persistent symptoms () and without persistent symptoms ().

Methods: We performed a multicenter observational study nested within the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease.

Acarbose Impairs Gut Growth by Targeting Intracellular GH97 Enzymes.

Acarbose is a type-2 diabetes medicine that inhibits dietary starch breakdown into glucose by inhibiting host amylase and glucosidase enzymes. Numerous gut species in the genus enzymatically break down starch and change in relative abundance within the gut microbiome in acarbose-treated individuals. To mechanistically explain this observation, we used two model starch-degrading , (Bo) and (Bt).

Host factors are associated with vaginal microbiome structure in pregnancy in the ECHO Cohort Consortium.

Using pooled vaginal microbiota data from pregnancy cohorts (N = 683 participants) in the Environmental influences on Child Health Outcomes (ECHO) Program, we analyzed 16S rRNA gene amplicon sequences to identify clinical and demographic host factors that associate with vaginal microbiota structure in pregnancy both within and across diverse cohorts. Using PERMANOVA models, we assessed factors associated with vaginal community structure in pregnancy, examined whether host factors were conserved across populations, and tested the independent and combined effects of host factors on vaginal community state types (CSTs) using multinomial logistic regression models. Demographic and social factors explained a larger amount of variation in the vaginal microbiome in pregnancy than clinical factors.

Discovery of sparse, reliable omic biomarkers with Stabl.

Adoption of high-content omic technologies in clinical studies, coupled with computational methods, has yielded an abundance of candidate biomarkers. However, translating such findings into bona fide clinical biomarkers remains challenging. To facilitate this process, we introduce Stabl, a general machine learning method that identifies a sparse, reliable set of biomarkers by integrating noise injection and a data-driven signal-to-noise threshold into multivariable predictive modeling.

Microbiome preterm birth DREAM challenge: Crowdsourcing machine learning approaches to advance preterm birth research.

Every year, 11% of infants are born preterm with significant health consequences, with the vaginal microbiome a risk factor for preterm birth. We crowdsource models to predict (1) preterm birth (PTB; <37 weeks) or (2) early preterm birth (ePTB; <32 weeks) from 9 vaginal microbiome studies representing 3,578 samples from 1,268 pregnant individuals, aggregated from public raw data via phylogenetic harmonization. The predictive models are validated on two independent unpublished datasets representing 331 samples from 148 pregnant individuals.

MaLiAmPi enables generalizable and taxonomy-independent microbiome features from technically diverse 16S-based microbiome studies.

For studies using microbiome data, the ability to robustly combine data from technically and biologically distinct microbiome studies is a crucial means of supporting more robust and clinically relevant inferences. Formidable technical challenges arise when attempting to combine data from technically diverse 16S rRNA gene variable region amplicon sequencing (16S) studies. Closed operational taxonomic units and taxonomy are criticized as being heavily dependent upon reference sets and with limited precision relative to the underlying biology.

The Fecal Microbiome in Quiescent Crohn's Disease with Persistent Gastrointestinal Symptoms Show Enrichment of Oral Microbes But Depletion of Butyrate and Indole Producers.

Background And Aims: Even in the absence of inflammation, persistent symptoms in Crohn's disease (CD) are prevalent and negatively impact quality of life. We aimed to determine whether quiescent CD patients with persistent symptoms ( ) have changes in microbial structure and functional potential compared to those without symptoms ( ).

Methods: We performed a prospective multi-center observational study nested within the SPARC IBD study.

Human Microbiomes and Disease for the Biomedical Data Scientist.

The human microbiome is complex, variable from person to person, essential for health, and related to both the risk for disease and the efficacy of our treatments. There are robust techniques to describe microbiota with high-throughput sequencing, and there are hundreds of thousands of already-sequenced specimens in public archives. The promise remains to use the microbiome both as a prognostic factor and as a target for precision medicine.

VMAP: Vaginal Microbiome Atlas During Pregnancy.

The vaginal microbiome has been shown to be associated with pregnancy outcomes including preterm birth (PTB) risk. Here we present VMAP: Vaginal Microbiome Atlas during Pregnancy (http://vmapapp.org), an application to visualize features of 3,909 vaginal microbiome samples of 1,416 pregnant individuals from 11 studies, aggregated from raw public and newly generated sequences via an open-source tool, MaLiAmPi.

Microbiome Preterm Birth DREAM Challenge: Crowdsourcing Machine Learning Approaches to Advance Preterm Birth Research.

Globally, every year about 11% of infants are born preterm, defined as a birth prior to 37 weeks of gestation, with significant and lingering health consequences. Multiple studies have related the vaginal microbiome to preterm birth. We present a crowdsourcing approach to predict: (a) preterm or (b) early preterm birth from 9 publicly available vaginal microbiome studies representing 3,578 samples from 1,268 pregnant individuals, aggregated from raw sequences via an open-source tool, MaLiAmPi.

A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome from COVID-19.

There are limited therapeutic options for patients with coronavirus disease (COVID-19)-related acute respiratory distress syndrome with inflammation-mediated lung injury. Mesenchymal stromal cells offer promise as immunomodulatory agents. Evaluation of efficacy and safety of allogeneic mesenchymal cells in mechanically-ventilated patients with moderate or severe COVID-19-induced respiratory failure.

Exposure to antibiotics with anaerobic activity before respiratory viral infection is associated with respiratory disease progression after hematopoietic cell transplant.

We examined associations between specific antibiotic exposures and progression to lower respiratory tract disease (LRTD) following individual respiratory viral infections (RVIs) after hematopoietic cell transplantation (HCT). We analyzed allogeneic HCT recipients of all ages with their first RVI during the first 100 days post-HCT. For the 21 days before RVI onset, we recorded any receipt of specific groups of antibiotics, and the cumulative sum of the number of antibiotics received for each day (antibiotic-days).

Mucolytic bacteria license pathobionts to acquire host-derived nutrients during dietary nutrient restriction.

Pathobionts employ unique metabolic adaptation mechanisms to maximize their growth in disease conditions. Adherent-invasive Escherichia coli (AIEC), a pathobiont enriched in the gut mucosa of patients with inflammatory bowel disease (IBD), utilizes diet-derived L-serine to adapt to the inflamed gut. Therefore, the restriction of dietary L-serine starves AIEC and limits its fitness advantage.

Host-microbe interactions and outcomes in multiple myeloma and hematopoietic stem cell transplantation.

Microbiota are essential to normal immune development and there is growing recognition of its importance to human health and disease and deepening understanding of the complexity of host-microbe interactions in the human gut and other tissues. Commensal microbes not only can influence host immunity locally through impacts of bioactive microbial metabolites and direct interactions with epithelial cells and innate immune receptors but also can exert systemic immunomodulatory effects via impacts on host immune cells capable of trafficking beyond the gut. Emerging data suggest microbiota influence the development of multiple myeloma (MM), a malignancy of the immune system derived from immunoglobulin-producing bone marrow plasma cells, through the promotion of inflammation.

Comparative Analysis of Public RNA-Sequencing Data from Human Intestinal Enteroid (HIEs) Infected with Enteric RNA Viruses Identifies Universal and Virus-Specific Epithelial Responses.

Acute gastroenteritis (AGE) has a significant disease burden on society. Noroviruses, rotaviruses, and astroviruses are important viral causes of AGE but are relatively understudied enteric pathogens. Recent developments in novel biomimetic human models of enteric disease are opening new possibilities for studying human-specific host-microbe interactions.

geneshot: gene-level metagenomics identifies genome islands associated with immunotherapy response.

Researchers must be able to generate experimentally testable hypotheses from sequencing-based observational microbiome experiments to discover the mechanisms underlying the influence of gut microbes on human health. We describe geneshot, a novel bioinformatics tool for identifying testable hypotheses based on gene-level metagenomic analysis of WGS microbiome data. By applying geneshot to two independent previously published cohorts, we identify microbial genomic islands consistently associated with response to immune checkpoint inhibitor (ICI)-based cancer treatment in culturable type strains.

Signal Versus Noise: How to Analyze the Microbiome and Make Progress on Antimicrobial Resistance.

Antimicrobial resistance has become a worldwide medical challenge [1], so impactful that vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) have entered the common vernacular. We have attempted to reduce the selective pressure through antimicrobial stewardship, curtail the spread by identifying and isolating carriers and individuals with symptomatic infection, and treat antibiotic-resistant organisms (AROs) by developing novel antimicrobials. Despite these extraordinary measures, the challenge of AROs continues to grow.

SARS-CoV-2 vaccines: a triumph of science and collaboration.

Roughly 1 year after the first case of COVID-19 was identified and less than 1 year after the sequencing of SARS-CoV-2, multiple SARS-CoV-2 vaccines with demonstrated safety and efficacy in phase III clinical trials are available. The most promising vaccines have targeted the surface glycoprotein (S-protein) of SARS-CoV-2 and achieved an approximate 85%-95% reduction in the risk of symptomatic COVID-19, while retaining excellent safety profiles and modest side effects in the phase III clinical trials. The mRNA, replication-incompetent viral vector, and protein subunit vaccine technologies have all been successfully employed.

Targeting the Gut Microbiome to Mitigate Immunotherapy-Induced Colitis in Cancer.

Immune checkpoint inhibitors (ICIs) have been a transformational advance in cancer therapy in the past decade. However, ICIs can produce immune-related adverse effects (irAEs), which can lead to both morbidity and premature termination of therapy. Recent studies suggest that the gut microbiota and its metabolites affect ICI efficacy and toxicity.