Maternal tryptophan supplementation protects adult rat offspring against hypertension programmed by maternal chronic kidney disease: Implication of tryptophan-metabolizing microbiome and aryl hydrocarbon receptor

Chien Ning Hsu, I. Chun Lin, Hong Ren Yu, Li Tung Huang, Mao Meng Tiao, You Lin Tain*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

22 Scopus citations

Abstract

Hypertension and chronic kidney disease (CKD) can originate during early-life. Tryptophan metabolites generated by different pathways have both detrimental and beneficial effects. In CKD, uremic toxins from the tryptophan-generating metabolites are endogenous ligands of the aryl hydrocarbon receptor (AHR). The interplay between AHR, nitric oxide (NO), the renin–angiotensin system (RAS), and gut microbiota is involved in the development of hypertension. We examined whether tryptophan supplementation in pregnancy can prevent hypertension and kidney disease programmed by maternal CKD in adult offspring via the aforementioned mechanisms. Sprague–Dawley (SD) female rats received regular chow or chow supplemented with 0.5% adenine for 3 weeks to induce CKD before pregnancy. Pregnant controls or CKD rats received vehicle or tryptophan 200 mg/kg per day via oral gavage during pregnancy. Male offspring were divided into four groups (n = 8/group): control, CKD, tryptophan supplementation (Trp), and CKD plus tryptophan supplementation (CKDTrp). All rats were sacrificed at the age of 12 weeks. We found maternal CKD induced hypertension in adult offspring, which tryptophan supplementation prevented. Maternal CKD-induced hypertension is related to impaired NO bioavailability and non-classical RAS axis. Maternal CKD and tryptophan supplementation differentially shaped distinct gut microbiota profile in adult offspring. The protective effect of tryptophan supplementation against maternal CKD-induced programmed hypertension is relevant to alterations to several tryptophan-metabolizing microbes and AHR signaling pathway. Our findings support interplay among tryptophan-metabolizing microbiome, AHR, NO, and the RAS in hypertension of developmental origins. Furthermore, tryptophan supplementation in pregnancy could be a potential approach to prevent hypertension programmed by maternal CKD.

Original languageEnglish
Article number4552
Pages (from-to)1-16
Number of pages16
JournalInternational Journal of Molecular Sciences
Volume21
Issue number12
DOIs
StatePublished - 06 2020

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Keywords

  • Aryl hydrocarbon receptor
  • Chronic kidney disease
  • Developmental origins of health and disease (DOHaD)
  • Gut microbiota
  • Hypertension
  • Nitric oxide
  • Pregnancy
  • Renin–angiotensin system
  • Tryptophan

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