Altering Early Life Gut Microbiota Has Long-Term Effect on Immune System and Hypertension in Spontaneously...

Area of Science:

• Immunology
• Microbiology
• Cardiovascular Science

Background:

• Hypertension is linked to immunological factors, with Spontaneously Hypertensive Rats (SHR) exhibiting elevated proinflammatory CD161+ immune cells.
• The early-life gut microbiome's role in immune system development and its impact on hypertension is not fully understood.

Purpose of the Study:

• To investigate the effect of early postnatal gut microbiota on immune system development and hypertension in SHR.
• To determine if altering gut microbiota composition in neonatal SHR can mitigate hypertension and associated immune dysregulation.

Main Methods:

• 16S rDNA sequencing was used to analyze fecal microbial populations in SHR and normotensive WKY rats.
• Cross-fostering experiments were performed, where newborn SHR pups were raised by WKY dams to alter their early gut microbiota.
• Flow cytometry and blood pressure measurements were used to assess immune cell populations and systolic blood pressure in adult rats.

Main Results:

• Neonatal SHR exhibited distinct gut microbiota compared to WKY, with lower Proteobacteria and different Enterobacteriaceae/Pasteurellaceae profiles.
• Cross-fostering SHR pups by WKY dams significantly shifted their gut microbiota towards the WKY profile, reducing specific bacterial taxa.
• Cross-fostered SHR showed reduced proinflammatory CD161+ immune cells in spleen and aorta and lower systolic blood pressure at adulthood.

Conclusions:

• Early-life gut microbiota composition significantly impacts immune system development and hypertension in SHR.
• Modulating the gut microbiome in early life can lead to long-lasting effects, reducing inflammation and lowering blood pressure.
• Targeting the gut microbiome presents a potential therapeutic strategy for managing hypertension.