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Postnatal intestinal mucosa and gut microbial composition develop hand in hand: A mouse study
1School of Biological Sciences, National Institute of Science Education and Research (NISER), P.O. Jatni, Khurda, Odisha, India; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, India.
Insights
The developing gut microbiome and host factors interact to mature the intestinal barrier during early life. This study reveals the critical role of microbial composition, like Bacteroidetes, in forming gut defense mechanisms.
Area of Science:
- Microbiology
- Developmental Biology
- Immunology
Background:
- Postnatal gut microbiota undergoes dynamic structural and functional changes.
- Intestinal mucosal barrier integrity is crucial for host defense against pathogens.
- The co-development of gut microbes, barrier integrity, and epithelial cells is not fully understood.
Purpose of the Study:
- To investigate the age-dependent relationship between gut microbial composition and intestinal development in mice.
- To elucidate the kinetics of microbial colonization and barrier formation during the critical postnatal window.
Main Methods:
- 16S rRNA gene sequencing for gut microbial composition and diversity analysis.
- In vivo gut permeability assays, gene expression analysis of tight junction proteins and epithelial cell markers.
- Assessment of goblet cell populations, villus length, and cecal IgA levels.
Main Results:
- Significant shifts in gut microbial composition observed from postnatal day 14, with initial Proteobacteria and peak Verrucomicrobia abundance.
- Age-dependent biphasic pattern in intestinal barrier integrity and intestinal epithelial cell differentiation.
- Bacteroidetes phylum correlated with mucosal barrier formation, while early barrier improvement (days 1-7) was linked to host factors.
Conclusions:
- Host factors and the gut microbiome are crucial for intestinal development and mucosal homeostasis.
- Microbial composition, particularly Bacteroidetes, plays a significant role in postnatal gut barrier maturation.
- Understanding these interactions is key to developing strategies for gut health.
Background:
During the early postnatal life, gut microbiota development experiences dynamic changes in their structural and functional composition. The postnatal period is the critical window to develop a host defense mechanism. The maturation of intestinal mucosal barrier integrity is one of the essential defense mechanisms to prevent the entry of pathogens. However, the co-development of intestinal microbial colonization, formation of barrier integrity, and intestinal epithelial cell layer is not entirely understood.
Methods:
We studied the gut microbial composition and diversity using 16S rRNA marker gene-based sequencing in mice to understand postnatal age-dependent association kinetics between gut microbial and intestinal development. Next, we assessed the intestinal development by in vivo gut permeability assay, mRNA gene expression of different tight junction proteins and intestinal epithelial cell markers, goblet cells population, villus length, and cecal IgA quantification.
Results:
Our results showed a significant shift in gut microbial structural and functional composition from postnatal day 14 onwards with early life Proteobacteria abundance. Relative abundance of Verrucomicrobia was maximum at postnatal day 14 and showed a gradual decrease over time. We also observed an age-dependent biphasic pattern in barrier integrity improvement and differentiation of intestinal epithelial cells (IECs). A significant improvement in barrier integrity between days 1 and 7 showed the host factor contribution, while that beyond day 14 revealed an association with changes in microbiota composition. Our temporal correlation analysis associated Bacteroidetes phylum with the mucosal barrier formation during postnatal development.
Conclusions:
The present study revealed the importance and interplay of host factors and the microbiome in gut development and intestinal mucosal homeostasis.
