Aldosterone is a mineralocorticoid hormone produced by the adrenal cortex whose primary action is to regulate Na+ handling in the distal nephron and control blood pressure. Primary aldosteronism (PA), characterized by inappropriately elevated aldosterone secretion, is a prevalent yet underdiagnosed cause of hypertension. Our group recently reported that plasma aldosterone increases in mice when microbes are suppressed (by oral antibiotics) or absent (germ-free mice). This finding uncovered a novel regulatory axis between the microbiota and aldosterone secretion; however, the underlying mechanisms driving the aldosterone change remain unknown. This research aims to examine how gut microbes regulate aldosterone. We reasoned that microbes could alter aldosterone by modifying one of the two primary regulators of aldosterone: angiotensin II, or, plasma K+. Alternatively, microbes could more generally affect adrenal hormones, leading to changes in multiple hormones, including aldosterone. In our previously published work, we reported that angiotensin II levels did not correlate with the aldosterone change in antibiotic-treated mice, implying that angiotensin II is not responsible for the change in aldosterone. In the current study, we tested the two remaining hypotheses: whether changes in either plasma K+ correlate with the changes in aldosterone after antibiotics treatment, or, whether another major adrenal hormone (corticosterone) also correlates with the changes in aldosterone after antibiotics treatment.We examined 3 separate cohorts of 7-week-old male C57BL/6J mice (n=6-7): cohort1 (baseline), cohort2 (1 day on antibiotics), and cohort3 (7 days on antibiotics). For cohort2 and 3, conventional mice were treated with mixtures of 3 antibiotics (1g/L ampicillin, 1g/L neomycin, and 0.5g/L vancomycin) in drinking water to dramatically reduce gut microbes. Each cohort was subject to blood collection during the light cycle via submandibular bleeding. To measure plasma levels of aldosterone and corticosterone, we centrifuged the blood at 2600rpm for 16min and ran ELISA. To measure plasma K+, we ran i-STAT analyzer using whole blood.Plasma aldosterone increases with antibiotics treatment, confirming our previous finding. This increase was seen at day 1 on antibiotics (cohort1 185.5±8.6 vs cohort2 613.8±131.1, p=0.02) and had largely resolved by day 7 on antibiotics (cohort2 613.8±131.1 vs cohort3 215.1±44.7, p=0.01; cohort1 185.5±8.6 vs cohort3 215.1±44.7, p >0.99). However, this increase in aldosterone is not corelated with plasma K+ (cohort1 4.3±0.1 vs cohort2 4.4±0.1, p=0.54; cohort2 4.4±0.1 vs cohort3 4.5±0.1, p=0.94; cohort1 4.3±0.1 vs cohort3 4.5±0.1, p=0.36). Instead, corresponding to changes in aldosterone, plasma corticosterone increases after 1 day of antibiotics treatment (cohort1 158,870±19,686 vs cohort2 288,657±41,151, p=0.013) and returns to the baseline after 7 days of antibiotics treatment (cohort2 288,657±41 vs cohort3 80,869±12,780, p=0.0001; cohort1 158,870±19,686 vs cohort3 80,869±12,780, p=0.16).In sum, this evidence suggests that general upregulation of adrenal hormones is correlated with changes in aldosterone in antibiotic-treated mice, indicating microbiota as a potential regulator of adrenal hormones and a possible therapeutic target for PA and/or other forms of hypertension. The same experiments using female mice are currently underway. Future studies include identification of specific bacterial species driving the aldosterone phenotype and testing whether this increase in aldosterone upon microbial depletion is controlled centrally (through hypothalamic-pituitary-adrenal (HPA) axis) or locally. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Jeong et al. (Fri,) studied this question.