Protective Effects of Female Gut Microbiota Transplantation on Hypertension and Renal Damage in Male Dahl Salt-Sensitive Rats

Abstract

We have previously demonstrated through microbiota transplantation studies that the gut microbiota importantly contributes to the development of hypertension, renal damage, and renal inflammation in the Dahl Salt-Sensitive (SS) rat fed a 4.0% NaCl high salt diet (HS). We also know that female SS rats are significantly protected from salt-induced hypertension, renal injury, and renal immune cell infiltration compared to males. One potential explanation for this sex difference is the substantial divergence we have observed in gut microbiota composition between male and female SS rats. Therefore, we hypothesized that gut microbiota transplantation between males and females would modulate the observed sex differences in salt-sensitivity. At 8 weeks of age, we first suppressed the native gut microbiota of male SS rat recipients via broad-spectrum antibiotics treatment (bacitracin and streptomycin, 2 g each/L, p.o.) for 3 days, followed by inoculation with either male or female donor cecal contents (oral gavage, 1 mL) for 7 consecutive days. Thus, our experimental groups are 1) male recipient rats repopulated with male donor microbiota (M+M, n=4) and 2) male recipient rats repopulated with female donor microbiota (M+F, n=3). Donor rats were maintained on the 0.4% NaCl low salt diet (LS) to more closely mimic the intrinsic microbiota of each sex. Telemeters were implanted at 10 weeks to allow for the continuous monitoring of blood pressure, followed by 3 weeks of HS challenge. At baseline, there were no differences in mean arterial pressure (MAP) between groups (123.4±1.3 vs 124.5±3.6 mmHg, M+M vs M+F on HS day 0, p=0.765). However, during the last week of HS challenge, males receiving female cecal microbiota transplantation had significantly reduced MAP compared to controls (153.6±3.4 vs 144.1±4.8 mmHg, M+M versus M+F on HS day 19, p=0.013). At the conclusion of the study, this reduction in blood pressure also coincided with a protection from renal damage, indicated by reduced urinary albumin excretion (209.0±37.1 vs 143.7±19.2 mg/day, M+M vs M+F, p=0.035), and an improvement in renal function, indicated by an increase in creatinine clearance (0.36±0.02 vs 0.48±0.01 ml/min/g kidney, M+M vs M+F, p=0.002). However, there appeared to be no effects on renal inflammation, with no changes to either the circulating or renal immune cell profile between rats receiving male or female microbiota. Furthermore, in female SS rat recipients that were subsequently transplanted with either male or female donor cecal contents, we observed no significant effects related to sex of donor microbiota in terms of blood pressure, renal damage, or renal inflammation. Together, these data demonstrate the anti-hypertensive and renoprotective effects of the female gut microbiota to recipient male SS rats. Moreover, there are additional factors within the female host that appear to be protective against the male microbiota. 19CDA34660184, HL161231 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.