Maternal
chronic kidney disease (CKD) is linked to offspring
hypertension. The gut microbiome and its
tryptophan metabolites,
nitric oxide (NO), and renin-angiotensin system (RAS) are closely related to the development of
hypertension.
Hydrogen sulfide (H2S) has shown an
anti-hypertensive effect. Our objective was to test whether l- or d-
cysteine supplementation in pregnancy can prevent
hypertension programmed by maternal CKD in adult offspring and to explore the protective mechanisms. CKD was induced in pregnant Sprague Dawley rats by a 0.5%
adenine diet for 3 weeks. l- or d-
cysteine was supplemented at 8 mmol/kg
body weight/day during pregnancy. Male offspring were sacrificed at the age of 12 weeks (n = 8 per group). Maternal CKD-induced
hypertension was similarly prevented by l- or d-
cysteine supplementation. The protective effects of l- and d-
cysteine are related to reducing oxidative stress, rebalancing the RAS, and reshaping the gut microbiome.
l-cysteine therapy protected adult offspring against
hypertension and was associated with enhanced H2S production, restoration of NO bioavailability, enhancement of beneficial genera Oscillibacter and Butyricicoccus, depletion of
indole-producing genera Alistipes and Akkermansia, and the reduction of several
indole metabolites. d-
cysteine treatment increased
kynurenic acid,
3-hydroxykynurenine, and
xanthurenic acid in the
kynurenine pathway, decreased
5-hydroxytryptophan and
serotonin in the
serotonin pathway, and enriched genera Bacteroides and Odoribacter abundance. In summary, these results suggest that l- and d-
cysteine protect against maternal CKD-induced offspring
hypertension, likely by enhancing H2S production, modulating gut microbiota and its derived metabolites, and the restoration of NO and RAS.