Treatment outcomes of meningitis and its associated factors among neonates admitted to public hospitals in Harar Town, Ethiopia: Cross-sectional study.

Hypertensive disorders of pregnancy (HDP), including gestational hypertension, preeclampsia and eclampsia, are a leading cause of maternal and perinatal morbidity and mortality worldwide, affecting 5–10% of all pregnancies (). Beyond the immediate adverse outcomes (), including preterm birth, fetal growth restriction and perinatal mortality, affected women face markedly elevated long-term risks of cardiovascular disease (including ischemic heart disease, heart failure, stroke and cardiomyopathy) (), metabolic syndrome (characterized by hypertension, obesity, dyslipidemia and insulin resistance) () and chronic kidney disease, whereas offspring exhibit increased susceptibility to neurodevelopmental disorders such as autism spectrum disorder, attention-deficit/hyperactivity disorder, cerebral palsy and cognitive impairments (,), as well as cardiometabolic disorders, including elevated blood pressure and obesity in childhood and adolescence across the life course (). Despite decades of research, the precise pathogenic mechanisms underlying HDPs remain incompletely understood and current clinical management largely focuses on blood pressure control and timely delivery rather than on disease-modifying interventions. The recognition that HDP pathogenesis involves complex interactions among maternal vascular dysfunction, placental ischemia, systemic inflammation and immune dysregulation has prompted growing interest in the role of the gut microbiota as an upstream modulator of these processes (). The gut microbiota undergoes notable physiological remodeling during pregnancy, with longitudinal studies demonstrating gestational stage-specific shifts in microbial composition, diversity and functional capacity that support maternal metabolic adaptation and immune modulation (,). Using bibliometric analysis of 1,268 publications, Chen () mapped global research trends and identified that the gut microbiota during pregnancy shifts toward increased Proteobacteria and reduced in the third trimester, supporting its role in metabolic adaptation. These pregnancy-induced microbial changes are characterized by increased inter-subject variability and altered abundances of taxa involved in short-chain fatty acids (SCFAs) production (). Notably, disruptions in this normal remodeling process have been documented in women who develop HDP, with reduced α-diversity and distinct taxonomic signatures reported in affected pregnancies (,). A systematic review and meta-analysis by Colonetti () pooled data from 11 case-control studies (total n=1,020) and reported that preeclamptic women had notably lower gut microbial α-diversity (standardized mean difference, −0.67; 95% CI, −1.02–0.32) and a higher Firmicutes/Bacteroidetes ratio, confirming a consistent association between dysbiosis and preeclampsia. Similarly, Jordan () conducted a scoping review concluding that microbiota dysbiosis is reproducibly associated with increased preeclampsia risk, although the directionality of this relationship remains a topic of debate, as multiple studies have explicitly questioned whether microbial alterations represent a causative factor or merely an epiphenomenon secondary to disease pathophysiology (,). The importance of understanding site-specific microbial changes during pregnancy has been emphasized in the study by Flores Ventura (), which highlighted opportunities for targeted interventions based on distinct microbial signatures. Specifically, distinct site-specific signatures in the gut, vaginal and oral microbiotas are differentially associated with pregnancy outcomes (for example, preterm birth, pre-eclampsia and gestational diabetes), providing a rational basis for the development of site-specific probiotic interventions tailored to each biological niche. Notably, the functional consequences of microbiota-host interactions are primarily mediated through microbial-derived metabolites rather than microbial composition Among these, SCFAs and tryptophan metabolites have emerged as particularly notable signaling molecules at the maternal-fetal interface (,,). SCFAs, generated through bacterial fermentation of dietary fiber, exert pleiotropic effects on host physiology through activation of G protein-coupled receptors and histone deacetylase (HDAC) inhibition, thereby modulating vascular tone, inflammatory responses and immune cell function (,). A scoping review by Zhao () synthesized evidence from 11 case-control studies (total of 2,314 participants) and concluded that reduced SCFAs concentrations, particularly butyrate (median reduction, 37%; range, 22–54%), are consistently associated with preeclampsia. The tryptophan pathway represents another major route of host-microbiota metabolic interaction, with gut bacteria metabolizing dietary tryptophan to generate indole derivatives, while host enzymes process the majority through the kynurenine pathway (). A systematic review by van Zundert () examined 42 studies (18 human and 24 animal studies)