Abstract
The concept that hypertension and chronic kidney disease (CKD) originate in early life has emerged recently. During pregnancy, tryptophan is crucial for maternal protein synthesis and fetal development. On one hand, impaired tryptophan metabolic pathway in pregnancy impacts fetal programming, resulting in the developmental programming of hypertension and kidney disease in adult offspring. On the other hand, tryptophan-related interventions might serve as reprogramming strategies to prevent a disease from occurring. In the present review, we aim to summarize (1) the three major tryptophan metabolic pathways, (2) the impact of tryptophan metabolism in pregnancy, (3) the interplay occurring between tryptophan metabolites and gut microbiota on the production of uremic toxins, (4) the role of tryptophan-derived metabolites-induced hypertension and CKD of developmental origin, (5) the therapeutic options in pregnancy that could aid in reprogramming adverse effects to protect offspring against hypertension and CKD, and (6) possible mechanisms linking tryptophan metabolism to developmental programming of hypertension and kidney disease.
Highlights
Hypertension affects more than one fourth of the global population [1]
We searched the PubMed/MEDLINE databases for studies published in English between January 1990 and July 2020, using the following search terms: “blood pressure,” ”chronic kidney disease” “developmental programming,” “developmental origins of health and disease” (DOHaD),” “gestation” “hypertension,” “indole,” “indoxyl sulfate,” “kynurenine,” “melatonin,” “mother,” “maternal,” “offspring,” “progeny,” “pregnancy,” “perinatal,” “serotonin,” and “tryptophan.” Relevant studies were assessed for inclusion by combining the title and abstract screening, followed by a review of full-text studies
We recently reported that maternal tryptophan supplementation protects offspring against hypertension programmed by maternal chronic kidney disease (CKD) is associated with alterations to several tryptophan-metabolizing microbes, including Lactobacillus, Ruminococcus, and Clostridium [69]
Summary
Hypertension affects more than one fourth of the global population [1]. Despite pharmacotherapy advances over the past decades, the prevalence of hypertension is still rising globally [2]. Hypertension and CKD are more common in adults, both of which can be driven by environmental insults in early life [4,5] This has given rise to the concept of “developmental origins of health and disease” (DOHaD) [6]. Imbalanced maternal nutrition during pregnancy and lactation produces fetal programming that permanently alter the body’s morphology and function and leads to many adult diseases, including hypertension and CKD [7]. This review, highlights evidence on the impact of tryptophan metabolism during pregnancy on offspring hypertension and kidney disease, as well as the role of tryptophan-related interventions as a reprogramming strategy in the prevention of hypertension of CKD in adult offspring. We searched the PubMed/MEDLINE databases for studies published in English between January 1990 and July 2020, using the following search terms: “blood pressure,” ”chronic kidney disease” “developmental programming,” “DOHaD,” “gestation” “hypertension,” “indole,” “indoxyl sulfate,” “kynurenine,” “melatonin,” “mother,” “maternal,” “offspring,” “progeny,” “pregnancy,” “perinatal,” “serotonin,” and “tryptophan.” Relevant studies were assessed for inclusion by combining the title and abstract screening, followed by a review of full-text studies
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