Impact of PepT1 deletion on microbiota composition and colitis requires multiple generations.

NPJ Biofilms and Microbiomes
Emilie ViennoisDidier Merlin

Abstract

Numerous studies of knockout mice find impacts on microbiota composition that influence host phenotype. However, such differences can vanish when KO mice are compared directly to WT littermates, suggesting these differences do not reflect the genetic deletion per se but microbiota composition drifting over generations. Hence, our hypothesis that absence of di/tri-peptide transporter PepT1 altered microbiota composition resulting in resistance to colitis compelled scrutiny. In this study, we used PepT1-/- and WT founder mice bred separately for multiple generations. Such mice were then bred to each other to generate F1 PepT1-/- and WT littermates, which were then bred within their genotype to generate F2, F3, and F4, offspring. Here we report that founder PepT1-/- mice were, relative to their WT counterparts, resistant to DSS colitis. Such resistance was associated with alterations in gut microbiota, which, when transplanted to germfree mice, was sufficient to transfer resistance to colitis. Such differences were not observed when comparing F1 PepT1-/- to F1 WT littermates but rather, returned gradually over subsequent generations such that, relative to their F4 WT controls, F4 PepT1-/- displayed microbiota composition and colit...Continue Reading

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Citations

Mar 25, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·Junsik SungDidier Merlin

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Methods Mentioned

BETA
biopsies
confocal microscopy
dissecting
Lysozyme
Assay

Software Mentioned

LEfSE
PICRUSt
UCLUST
PICRUSt ( Phylogenetic Investigation of Communities by Reconst...
FastTree
Quantitative Insights Into Microbial Ecology ( QIIME
QIIME
Morpheus
GraphPad Prism

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