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

Francois M Abboud,Aaron Ericsson,Mark W Chapleau,Michael Z Cicha,Madhu V Singh

doi:10.3389/fphys.2021.752924

Francois M Abboud, Aaron Ericsson + Show 3 more

Open Access

https://doi.org/10.3389/fphys.2021.752924

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Abstract

Hypertension is regulated by immunological components. Spontaneously hypertensive rats (SHR) display a large population of proinflammatory CD161 + immune cells. We investigated the effect of early post-natal gut microbiota on the development of the immune system and resulting hypertension in the SHR. We first examined the microbial populations in the fecal samples of SHR and normotensive control WKY using 16S rDNA sequencing. We found that in the newborn SHR (1-week old) the gut microbiota was qualitatively and quantitatively different from the newborns of normotensive WKY. The representation of the predominant bacterial phylum Proteobacteria was significantly less in 1-week old SHR pups than in WKY (94.5% Proteobacteria in WKY vs. 65.2% in SHR neonates). Even within the phylum Proteobacteria, the colonizing genera in WKY and SHR differed dramatically. Whereas WKY microbiota was predominantly comprised of Escherichia-Shigella, SHR microbiota was represented by other taxa of Enterobacteriaceae and Pasteurellaceae. In contrast, the representation of phylum Firmicutes in the neonatal SHR gut was greater than WKY. Cross-fostering newborn SHR pups by lactating WKY dams caused a dramatic shift in 1-week old cross-fostered SHR gut microbiota. The two major bacterial taxa of phylum Proteobacteria, Enterobacteriaceae and Pasteurellaceae as well as Lactobacillus intestinalis, Proteus, Romboustia and Rothia were depleted after cross-fostering and were replaced by the predominant genera of WKY (Escherichia-Shigella). A proinflammatory IL-17F producing CD161 + immune cell population in the spleen and aorta of cross-fostered SHR was also reduced (30.7% in self-fostered SHR vs. 12.6% in cross-fostered SHR at 30 weeks of age) as was the systolic blood pressure in adult cross-fostered SHR at 10 weeks of age. Thus, altered composition of gut microbiota of SHR toward WKY at early neonatal age had a long-lasting effect on immune system by reducing proinflammatory immune cells and lowering systolic blood pressure.

Highlights

Gut microbes exert profound effects on health and disease by assisting in development of the gut, maintaining gut barrier function, providing energy and protecting against pathogenic invasion
We examined the gut microbiome using 16S rDNA sequencing from the fecal samples of neonatal (1 week), of weanlings (5 weeks), and of adult (12 weeks) male spontaneously hypertensive rat (SHR) and WKY rats
The phylum Proteobacteria was more dominant in WKY than in SHR (Figure 1D) and consisted primarily of Escherichia-Shigella (93.2%), whereas in neonatal SHR there was a total lack of EscherichiaShigella, and instead the Proteobacteria of Enterobacteriaceae and Pasteurellaceae prevailed at 35.0 and 27.9%, respectively (Figure 1D)

Summary

Introduction

Gut microbes exert profound effects on health and disease by assisting in development of the gut, maintaining gut barrier function, providing energy and protecting against pathogenic invasion. Use of angiotensin II (Ang II) was correlated with change in gut microbiome (Yang et al, 2015), oral administration of minocycline antibiotic reduced blood pressure presumably by altering the gut microbiome and fecal transplants from normotensive rats to stroke-prone SHR (SHRSP) reduced blood pressure (Adnan et al, 2017). These models have inherent limitations; considering the quick effect of Ang II on hypertension, it is not clear whether in Ang II-induced hypertension the change in gut microbiota was a consequence of Ang II administration. It appears that gut microbiome may affect hypertension at different stages through different mechanisms

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