Early and late gut microbiota signatures of stroke in high salt-fed stroke-prone spontaneously hypertensive rats

The high salt-fed stroke-prone spontaneously hypertensive rat (SHRSP) is a suitable tool to study the mechanisms underlying stroke pathogenesis. Alterations of the gut microbiota (GM) have previously been associated with increased stroke occurrence. Salt intake modifies GM in rats and humans. We aimed to identify GM changes in high salt-fed SHRSPs compared to stroke-resistant SHR controls as a potential contributor to stroke.SHRSPs and SHRSRs were fed a regular or stroke-permissive diet (Japanese diet, JD) for 4 weeks (T0). Separate groups underwent prolonged JD exposure (T1). Body weight, proteinuria levels and stroke occurrence were assessed throughout experiments. Calprotectin levels, gut barrier integrity and GM profiling were evaluated at T0 and T1. Stroke occurred in JD-fed SHRSPs, preceded by proteinuria and diarrhoea. The GM of JD-fed SHRSPs underwent early and late compositional changes compared to SHRSRs. An overrepresentation of Streptococcaceae and an underrepresentation of Lachnospiraceae were observed at T0, while at T1 short-chain fatty acid producers, e.g. Lachnobacterium and Faecalibacterium, decreased and pathobionts such as Coriobacteriaceae and Desulfovibrio increased. Occludin gene expression behaved differently in SHRSPs and SHRSRs. Calprotectin levels remained unchanged.In conclusion, the altered GM in JD-fed SHRSPs may be detrimental to gut homeostasis and contribute to stroke occurrence.