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In vivo transcriptome of Lactobacillus acidophilus and colonization impact on murine host intestinal gene expression


Goh, Yong Jun; Barrangou, Rodolphe; Klaenhammer, Todd (2021), In vivo transcriptome of Lactobacillus acidophilus and colonization impact on murine host intestinal gene expression, Dryad, Dataset,


Lactobacillus acidophilus NCFM is a probiotic strain commonly used in dairy products and dietary supplements. Post-genome in vitro studies of NCFM thus far have linked potential key genotypes to its probiotic-relevant attributes including gut survival, prebiotic utilization, host interactions and immunomodulatory activities. To corroborate and extend beyond previous in vivo and in vitro functional studies, we employed a dual RNA-seq transcriptomic approach to identify genes potentially driving the gut fitness and activities of L. acidophilus NCFM in vivo, and in parallel, examine the ileal transcriptional response of its murine hosts during monocolonization. Spatial expression profiling of NCFM from the ileum through the colon revealed a set of 134 core genes that were consistently overexpressed during gut transit. These in vivo core genes are predominantly involved in the metabolism of carbohydrates, amino acids and nucleotides, along with mucus-binding proteins and adhesion factors, confirming their functionally important roles in nutrient acquisition and gut retention.  Functional characterization of the highly expressed major S-layer encoding gene established its indispensable role as a cell shape determinant and maintenance of cell surface integrity, essential for viability and probiotic attributes.  Host colonization by L. acidophilus resulted in significant down-regulation of several pro-inflammatory cytokines and tight junction proteins. Genes related to redox signaling, mucin glycosylation and circadian rhythm modulation were induced, suggesting impacts on intestinal development and immune functions. Metagenomic analysis of NCFM populations post-colonization demonstrated the genomic stability of L. acidophilus as a gut transient and further established its safety as a probiotic and biotherapeutic delivery platform.


North Carolina Agricultural Foundation