Hypertension Shifts Gut Microbiota and Tryptophan Metabolism in Women

BackgroundHypertension affects over 1.28 billion adults worldwide, including a significant number of women. Although the gut microbiome is implicated in the onset and progression of hypertension, few studies have examined the relationship in middle-aged women. MethodsWithin an established cohort, we investigated the relationship between gut microbiota and its metabolites in normotensive vs. hypertensive middle-aged women (n=108) matched for age (56.6{+/-}0.91 years) and body mass index (24.3{+/-}0.24 kg/m{superscript 2}). Fecal microbiota analysis was performed using 16S rRNA sequencing and serum metabolites were analyzed using LC-MS/QTOF. Associations between the microbiota, metabolomic alterations and systemic inflammatory cytokines were statistically examined to uncover their interrelationships and potential role in disease progression. ResultsWomen with hypertension had gut dysbiosis with an increased Firmicutes/Bacteroidetes ratio and higher abundances of inflammatory taxa including Anaerostipes and Collinsella. Untargeted serum metabolomics demonstrated that hypertensive participants had elevated levels of tryptophan, the pro-inflammatory metabolite kynurenine and lower levels of health-promoting indoles produced by the action of gut microbiota on tryptophan (p<0.05). These findings were confirmed in microbiota analysis showing a reduced abundance of indole-producing species (Alistipes shahii, Bacteroides faecichinchillae, Bacteroides stercoris)(p<0.05) suggesting a lower microbial activity of tryptophan-indole metabolism. Furthermore, hypertension increased inflammatory markers including an elevated IL12/IL10 ratio, interferon-{gamma} and tumor necrosis factor-. The IL-12/IL-10 ratio demonstrated a positive correlation with kynurenine levels, emphasizing the involvement of cytokines and gut microbiota in driving systemic inflammation in hypertension. ConclusionImbalances in microbiota-regulated tryptophan metabolism contribute to systemic inflammation in hypertensive, middle-aged women, presenting a potentially modifiable target for intervention. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/25321440v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1a40928org.highwire.dtl.DTLVardef@555954org.highwire.dtl.DTLVardef@15bb089org.highwire.dtl.DTLVardef@a2fe5a_HPS_FORMAT_FIGEXP M_FIG C_FIG