Understanding artificial mouse-microbiome heterogeneity and six actionable themes to increase study power

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>The negative effects of data clustering due to (intra-class/spatial) correlations are well-known in statistics to interfere with interpretation and study power. Therefore, it is unclear why housing many laboratory mice (≥4), instead of one-or-two per cage, with the improper use/reporting of clustered-data statistics, abound in the literature. Among other sources of ‘artificial’ confounding, including cyclical oscillations of the ‘cage microbiome’, we quantified the heterogeneity of modern husbandry practices/perceptions. The objective was to identify actionable themes to re-launch emerging protocols and intuitive statistical strategies to increase study power. Amenable for interventions, ‘cost-vs-science’ discordance was a major aspect explaining heterogeneity and the reluctance to change. Combined, four sources of information (scoping-reviews, professional-surveys, expert-opinion, and ‘implementability-score-statistics’) indicate that a six-actionable-theme framework could minimize ‘artificial’ heterogeneity. With a ‘Housing Density Cost Simulator’ in Excel and fully annotated statistical examples, this framework could reignite the use of ‘study power’ to monitor the success/reproducibility of mouse-microbiome studies.</jats:p>

Investigation of Host–Microbe–Parasite Interactions in an In Vitro 3D Model of the Vertebrate Gut

“…[ 12,13 ] Furthermore, data generated from studies of the structure and function of the gut microbiome of live animals are often inconsistent and irreproducible across laboratories, due to the strict association between gut microbiome and surrounding environmental variables. [ 14,15 ] Therefore, over the last decade, the search for robust, reliable, and sustainable alternative in vitro technologies for gut microbiome research has been intense. [ 12,13,16,17 ]…”

“…[12,13] Furthermore, data generated from studies of the structure and function of the gut microbiome of live animals are often inconsistent and irreproducible across laboratories, due to the strict association between gut microbiome and surrounding environmental variables. [14,15] Therefore, over the last decade, the search for robust, reliable, and sustainable alternative in vitro technologies for gut microbiome research has been intense. [12,13,16,17] Currently, several reductionist in vitro models are available for systematic investigations of the complex crosstalk between (commensal and/or pathogenic) microbes and vertebrate tissues, under well-controlled and reproducible conditions.…”