Researchers from the Cardiovascular Pharmacology group at the Granada Institute for Biomedical Research (ibs.GRANADA) have demonstrated in a preclinical study that a probiotic can enhance the effect of one of the most commonly used treatments for high blood pressure without increasing its adverse effects. This finding opens new avenues for the development of complementary therapeutic strategies to help improve the management of this disease, especially in the most difficult-to-treat cases.

High blood pressure remains one of the leading public health problems worldwide. It is the most significant risk factor for developing cardiovascular diseases, such as heart attacks and strokes. Although various medications exist to treat it, maintaining blood pressure within appropriate levels is not always easy. In fact, some patients are unable to achieve adequate control even when taking multiple medications simultaneously.

In recent years, science has increasingly focused on the gut microbiota, the collection of microorganisms that naturally live in our intestines. These microorganisms are known to influence many bodily processes, including inflammation, metabolism, and vascular health. It has also been observed that the gut microbiota can be altered in people with hypertension.

Based on this idea, the research team analyzed whether the probiotic Limosilactobacillus fermentum (LC40) could improve the response to hydrochlorothiazide (HCTZ), a diuretic widely used to treat hypertension. Researchers from the University of Granada, the University of Münster (Germany), the National Center for Cardiovascular Research (CNIC), the Center for Biomedical Research, and the company Biosearch Life also participated in the study.

The study was conducted on spontaneously hypertensive rats, a widely used experimental model for studying this disease. The results show that combining the probiotic with hydrochlorothiazide achieved a greater reduction in blood pressure than the drug treatment alone. Furthermore, it improved blood vessel function, which is essential for maintaining good cardiovascular health.

One of the most significant findings is that the probiotic did not increase the drug's adverse effects. Specifically, it did not alter blood levels of the drug nor worsen the electrolyte imbalances that this type of treatment can cause. This suggests that its benefit is not due to an increased amount of medication in the body, but rather to its action through other complementary mechanisms.

The study also observed that this strategy helped restore alterations in the gut microbiota associated with hypertension. In the treated animals, some potentially harmful bacteria decreased, while microorganisms capable of producing beneficial compounds, such as acetate, which is linked to protective effects on the gut and cardiovascular system, increased.

Along with these changes in the gut microbiota, the researchers detected a reduction in intestinal inflammation, endotoxemia, and neuroinflammation. They also observed lower sympathetic activity—a nervous system response that is typically increased in hypertension—and a decrease in vascular oxidative stress, a process that promotes damage to blood vessels.

Furthermore, the study suggests a potential beneficial effect on the immune system. Specifically, an increase in regulatory T cells was observed, which help to curb excessive inflammatory responses. Overall, the results indicate that the probiotic does not act on just one specific point, but rather contributes to improving several mechanisms involved in hypertension.

Another important finding is that these effects depended on the gut microbiota, as they could be reproduced through fecal microbiota transplantation. This reinforces the idea that gut bacteria are not a secondary factor, but can directly influence how the body responds to certain treatments.

“These results indicate that the gut microbiota can become an ally in improving the treatment of hypertension. We have seen that a probiotic is able to reinforce the action of a widely used drug without increasing its adverse effects, which opens a promising line of research for patients with poor blood pressure control,” says Dr. Juan Duarte, principal investigator of the MP02 Cardiovascular Pharmacology group at ibs.GRANADA, professor at the University of Granada, and lead author of this study.

Overall, the study provides initial evidence that probiotics could improve the effectiveness of an antihypertensive drug without increasing its side effects. The researchers emphasize, however, that this is a preclinical study. Therefore, these results will need to be confirmed in patients before this strategy can be implemented in clinical practice.

The research has been funded by the State Research Agency (AEI), the Ministry of Science and Innovation (MCIN), the Junta de Andalucía with European funds and the Carlos III Health Institute.

Bibliographic reference:

González-Correa C, Miñano S, Moleón J, Toral M, Robles-Vera I, Sánchez M, Jiménez R, Olivares M, Martín-Morales N, O'Valle F, Guerra-Hernández E, Romero M, Gómez-Guzmán M, Duarte J. The probiotic Limosilactobacillus fermentum CECT5716 enhances the antihypertensive response to hydrochlorothiazide in spontaneously hypertensive rats. Gut Microbes. 2025 Dec 31;17(1):2586324. Doi: 10.1080/19490976.2025.2586324. Epub 2025 Nov 18. PMID: 41254951; PMCID: PMC12645898.

About the group:

El grupo MP02-Cardiovascular Pharmacology The research team at ibs.GRANADA, led by Dr. Juan Manuel Duarte, investigates the mechanisms involved in high blood pressure, with a particular focus on the role of the immune system in endothelial dysfunction and the influence of the gut microbiota on blood pressure control. Their work combines basic and applied research and is carried out in collaboration with the Virgen de las Nieves University Hospital and with companies and centers involved in the development of functional foods and health innovation.

More information: https://www.ibsgranada.es/grupos-de-investigacion/mp02-farmacologia-cardiovascular/

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