In Vivo Transcriptome of Lactobacillus acidophilus and Colonization Impact on Murine Host Intestinal Gene Expression

Area of Science:

• Microbiology
• Genomics
• Host-Microbe Interactions

Background:

• Lactobacillus acidophilus NCFM is a widely used probiotic with known in vitro attributes.
• Previous studies relied on in vitro data, limiting understanding of in vivo mechanisms.

Purpose of the Study:

• To identify genes essential for L. acidophilus NCFM gut survival and activity in vivo.
• To investigate the host's transcriptional response to L. acidophilus NCFM colonization in the ileum.

Main Methods:

• Dual RNA sequencing (RNA-seq) transcriptomic approach.
• Germfree murine colonization model for in vivo studies.
• Metagenomic analysis of post-colonization NCFM populations.

Main Results:

• Identified 134 core genes overexpressed by NCFM during gut transit, involved in metabolism and adhesion.
• Demonstrated the S-layer gene's critical role in cell integrity and probiotic function.
• Observed host downregulation of pro-inflammatory cytokines and tight junction proteins.
• Detected induction of host genes related to redox signaling, mucin glycosylation, and circadian rhythm.

Conclusions:

• Provides the first in vivo view of L. acidophilus NCFM gut survival mechanisms and gene expression.
• Highlights the probiotic's role in nutrient acquisition, stress adaptation, and host interaction.
• Suggests L. acidophilus NCFM influences host immunity, intestinal homeostasis, and circadian-metabolic axis.