Short-Chain Fatty Acids and Preeclampsia: A Scoping Review

Preeclampsia (PE) is a pregnancy-associated hypertension disorder with high morbidity and mortality. Short-chain fatty acids (SCFAs)-molecules produced by gut microbes-have been associated with hypertension, yet their relation to PE remains uncertain.

The aim was to review existing human studies that examined associations of the major SCFAs (acetate, propionate, butyrate) in pregnancy with PE development.

Two reviewers independently searched online databases (EMBASE, PubMed, Web of Science, and Cochrane Database of Systematic Reviews) in January 2024 using the following terms: "short-chain fatty acids," "acetic acid," "butyric acid," "propionic acid," and "preeclampsia." The final set of included studies had to report associations of SCFAs with PE, be peer-reviewed, be written in English, and be conducted in humans.

The abstracts of 907 studies were screened; 43 underwent full-text screening and 11 (1318 total participants, 352 with PE) were included in the final review. All studies used a case-control design. SCFAs were measured in a range of biospecimens (eg, serum, plasma, feces, placentas, and amniotic fluid) that were collected at distinct time points in pregnancy. All 7 studies that investigated butyrate found that it was lower in PE cases than in controls, with 6 of these showing statistical significance (P < .05). Five studies showed that acetate was significantly lower in individuals with PE compared with healthy individuals, while 1 study found that acetate was significantly higher in PE cases. One study reported significantly higher propionate among PE cases vs controls, while 2 studies reported significantly lower propionate levels in PE cases. The nuance in results for acetate and propionate may owe to reasons such as differences in distributions of population characteristics associated with SCFA level and PE or type of PE (early vs late).

Current epidemiologic evidence, which derives only from case-control studies, suggests that SCFAs, particularly butyrate (protective), in pregnancy are related to the development of PE. Large-cohort studies are warranted to investigate the temporality and potential causality of these associations.