The National Heart, Lung, and Blood Institute (NHLBI) convened a working group of multidisciplinary researchers on June 10, 2016, in Bethesda, MD to share current scientific knowledge regarding the role of microbiota in blood pressure regulation, and to explore and identify scientific gaps and challenges.
The working group is responsive to NHLBI Strategic Plan Objectives 1, 2, 3, and 4.
Dysregulation of commensal microbiota can contribute to the pathophysiology of a variety of disorders, including obesity, colitis, metabolic syndrome, cardiovascular disease, and kidney disease. A few recent studies have suggested that gut and oral microbiota may also play a role in the maintenance of blood pressure homeostasis. The microbiota can be altered or potentially corrected in response to various factors, such as diet, thus providing a promising base to develop innovative intervention strategies for treating hypertension. Furthermore, several studies have suggested the existence of cross-talk between gut microbiota and brain (gut-brain axis), gut microbiota and vasculature (gut-vascular axis), gut microbiota and kidney (gut-kidney axis), and oral microbiota and circulating nitrate and nitrite levels (entero-salivary axis). At present, the role of these axes on blood pressure regulation is poorly understood, and it is unknown whether other interactions exist.
Working Group Discussion
The working group brought together 16 experts from diverse backgrounds in hypertension, cancer, cardiovascular, renal, nutritional, inflammatory, gastrointestinal, and oral diseases. NIH staff from the NHLBI, NIDDK, and NIDCR organized and participated in the meeting. The working group reviewed existing and emerging scientific evidence connecting gut and oral microbiota to blood pressure regulation. Four thematic sessions were followed by general group discussion at the end of the meeting. During the first session, speakers reviewed and discussed the current link between the gut microbiota and hypertension. During the second session, speakers discussed the role of the microbiota in human diseases, such as metabolic syndrome, cardiovascular, and renal diseases. The theme of the third session was the oral microbiota and blood pressure regulation. The final session discussed the topic of the microbiome as a potential therapeutic target. Since the working group members came from diverse backgrounds, and most had not collaborated before, the meeting provided an excellent opportunity for cross-disciplinary thinking and discussions, and highlighted the potential for future collaborations.
Working Group Recommendations
The working group concluded that both gut and oral microbiota play an important role in the maintenance of normal blood pressure. An alteration of microbiota by various factors (i.e., genetic predisposition, diet, environment, emotion, aging, etc.) can result in abnormal blood pressure regulation, leading to various human diseases including hypertension. The working group suggested the following recommendations to address the identified knowledge gaps and challenges. These include:
- New hypotheses that could be tested experimentally in animal models:
- Blood pressure is influenced by host genome-microbiome cross-talk.
- Specific changes to the microbiota (e.g., microbe composition or metabolite production) associate with aging or age-related diseases such as hypertension and chronic kidney disease.
- High blood pressure develops due to contributions from the gut-brain-kidney axis.
- Gut microbiota plays an important role in resistant hypertension.
- Bacteria in the gut, on the tongue dorsum, and elsewhere (e.g., skin) associate with the development of high blood pressure.
- Interactions between bacteria and viruses (or fungi) contribute to another level of complexity in human health, such as hypertension.
- Nutritional factors, including salt sensitivity, affect blood pressure regulation via altered microbiota.
New hypotheses that could be tested in early clinical studies:
- Gut and oral microbial composition influence blood pressure, which may explain differences in ethnicity and efficacy of anti-hypertensive drugs.
- Anti-inflammatory drugs, antibiotics, and/or lifestyle factors (e.g., exercise and diet) influence blood pressure via altered microbiota.
- Microbial dysbiosis links metabolism to high blood pressure and kidney disease.
- New preventive or therapeutic strategies can target the microbiota (microbe composition or metabolite production) to mitigate arterial dysfunction.
- Microbial metabolites and nucleotides guide can act as biomarkers towards the practice of personalized medicine for hypertension.
During the general discussion, some working group members noted that organizing a national research initiative on microbiota and hypertension could be helpful to benefit a large population of uncontrolled hypertensive patients, especially those with resistant hypertension. In addition, it was noted that it will be important going forward to identify specific microbial metabolites which contribute to blood pressure regulation as well as kidney disease and renal control of blood pressure. Finally, creating animal resources to conduct studies using germ-free, genetic hypertensive model organisms was suggested to test the proposed hypotheses.
The working group plans to prepare a manuscript for publication in a peer-reviewed journal.
Young S. Oh, PhD
Working Group Members
- Mohan K. Raizada, PhD, University of Florida
- Bina Joe, PhD, University of Toledo
- Nathan S. Bryan, PhD, Baylor College of Medicine
- Eugene B. Chang, MD, University of Chicago
- Floyd Dewhirst, DDS, PhD, Harvard School of Dental Medicine
- Andrew T. Gewirtz, PhD, Georgia State University
- Wendy A. Henderson, PhD, MSN, CRNP, NINR, NIH
- Kenneth A. Jamerson, MD, University of Michigan
- Pedro A. Jose, MD, PhD, George Washington University
- John R. Kirby, PhD, University of Iowa
- Johanna W. Lampe, PhD, RD, Fred Hutchinson Cancer Research Center
- Carl J. Pepine, MD, MACC, University of Florida
- Jennifer L. Pluznick, PhD, Johns Hopkins University
- Dominic S. Raj, MD, George Washington University
- Douglas R. Seals, PhD, University of Colorado
- W.H. Wilson Tang, MD, Cleveland Clinic Lerner College of Medicine
- Zorina Galis, PhD, Vascular Biology & Hypertension Branch, DCVS, NHLBI
- Christine Maric-Bilkan, PhD, Vascular Biology & Hypertension Branch, DCVS, NHLBI
- Young Oh, PhD, Vascular Biology & Hypertension Branch, DCVS, NHLBI
- Pothur Srinivas, PhD, Epidemiology Branch, DCVS, NHLBI
- Chris Ketchum, PhD, Division of Kidney, Urologic, and Hematologic Diseases, NIDDK
- Paul L. Kimmel, MD, Division of Kidney, Urologic, and Hematologic Diseases, NIDDK
- R. Dwayne Lunsford, PhD, Division of Microbiology Program, NIDCR