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Biology subjects

Patridge, E.

Publications and source records attributed to Patridge, E..

4 recordsLinked to original sources

The human gut microbiome activity is resilient and stable for up to six months: a large stool metatranscriptomic study

The human microbiome influences health and disease through diverse biochemical and functional outputs (e.g. enzymes, structural proteins, metabolites, and other cellular components) that affect nearly every aspect of human physiology. Metatranscriptomics (MT), an unbiased RNA sequencing approach, is a high-throughput and high-content method that quantifies both gut microbial taxonomy and active biochemical functions. Because microbial community composition and gene expression are dynamic, understanding temporal variation in the gut metatranscriptome across multiple time scales is essential. Here, we report the temporal dynamics of gut microbiome species and functions using a large cohort (n=6,157) with a clinically validated stool MT test. We quantified microbiome stability from hours to years and assessed taxonomic and functional resilience to major luminal perturbations, such as colonoscopy bowel preparation. Longitudinal analyses of samples collected within the same day, and across days, weeks, months, and years, revealed consistently high stability in both composition and gene expression within a single day and, importantly, across an approximate six-month period. Among individuals reporting stable diets and no antibiotic exposure, taxonomic and functional profiles remained stable for up to three years. Following colonoscopy preparation, our preliminary study of the microbiome demonstrated strong resilience, returning to its pre-procedure state within one week. Overall, these findings demonstrate that the gut microbiome is generally stable over a six-month time frame, with longer-term changes occurring gradually. These findings support the robustness of stool-based MT profiling for species-level and pathway-resolved functional analysis in longitudinal research and health applications.

microbiology↗

Sub-optimal activity of gut microbiome functional pathways increases the odds of Irritable Bowel Syndrome in a large adult human population

Functional gastrointestinal disorders present diagnostic and therapeutic challenges, and there is a strong need for molecular markers that enable early health insights and intervention. Herein, we present an approach to assess the gut microbiome with stool-based gut metatranscriptome data from a large adult human population (n = 80,570), using irritable bowel syndrome as an example that features both an abnormal gut microbiome and a spectrum of distinct conditions. We develop a suite of eight gut microbial functional pathway scores, each of which represents the activity of a set of interacting microbial functional features (based on KEGG orthology) relevant to known gut biochemical activities. We use a normative approach within a subpopulation (n = 9,350) to define "Good" and "Not Optimal" activities for these transcriptome-based gut pathway scores. We hypothesize that Not Optimal scores are associated with irritable bowel syndrome (IBS) and its subtypes (i.e., IBS-Constipation, IBS-Diarrhea, IBS-Mixed Type). We show that Not Optimal functional pathway scores are associated with higher odds of IBS or its subtypes within an independent cohort (n = 71,220) using both the Rome IV Diagnostic Questionnaire as well as self-reported phenotypes. Rather than waiting to diagnose IBS after symptoms appear, these functional pathway scores can help to provide early health insights into molecular pathways that may contribute to IBS. These molecular endpoints could also assist with measuring the efficacy of practical interventions, developing related algorithms, providing personalized nutritional recommendations, diagnostic support, and treatments for gastrointestinal disorders like IBS. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=68 SRC="FIGDIR/small/580548v4_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@d84aaeorg.highwire.dtl.DTLVardef@f2276org.highwire.dtl.DTLVardef@19fab7aorg.highwire.dtl.DTLVardef@1b2f738_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Microbial functional pathways based on metatranscriptomic profiling enable effective saliva-based health assessments for precision wellness

It is increasingly recognized that an important step towards improving overall health is to accurately measure biomarkers of health from the molecular activities prevalent in the oral cavity. We present a general methodology for computationally quantifying the activity of microbial functional pathways using metatranscriptomic data. We describe their implementation as a collection of eight oral pathway scores using a large salivary sample dataset (n=9,350), and we evaluate score associations with oropharyngeal disease phenotypes within an unseen independent cohort (n=14,129). As clinical validation, we show that the relevant oral pathway scores are significantly worse in individuals with periodontal disease, acid reflux, and nicotine addiction, compared with controls. Given these associations, we make the case to use these oral pathway scores to provide molecular health insights from simple, non-invasive saliva samples, and as molecular endpoints for actionable interventions to address the associated conditions. HighlightsO_LIMicrobial functional pathways in the oral cavity are quantified as eight oral scores C_LIO_LIScores are significantly worse for individuals with oropharyngeal disease phenotypes C_LIO_LIThis methodology may be generalized to other pathways and other sample types C_LIO_LIThese scores provide longitudinal health insights in a precision wellness application C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=72 SRC="FIGDIR/small/565122v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@12fb7bdorg.highwire.dtl.DTLVardef@1c7dbf3org.highwire.dtl.DTLVardef@39700forg.highwire.dtl.DTLVardef@ebf63c_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

Gut microbiome activity contributes to individual variation in glycemic response in adults

Limiting post-meal glycemic response is an important factor in reducing the risk of chronic metabolic diseases, and contributes to significant health benefits in people with elevated levels of blood sugar. In this study, we collected gut microbiome activity (i.e., metatranscriptomic) data and measured the glycemic responses of 550 adults who consumed more than 30,000 meals from omnivore or vegetarian/gluten-free diets. We demonstrate that gut microbiome activity makes a statistically significant contribution to individual variation in glycemic response, in addition to anthropometric factors and the nutritional composition of foods. We describe predictive models (multilevel mixed-effects regression and gradient boosting machine) of variation in glycemic response among individuals ingesting the same foods. We introduce functional features aggregated from microbial activity data as candidates for association with mechanisms of glycemic control. In summary, we demonstrate for the first time that metatranscriptomic activity of the gut microbiome is correlated with glycemic response among adults.

systems biology↗