Microbiome medicine: Scientists engineer gut bacteria to treat hypertension

Scientists have successfully modified Lactobacillus paracasei, a beneficial gut bacterium, to produce a protein called ACE2 and demonstrated its role in lowering blood pressure. The finding opens new doors in using the microbiome to treat hypertension.

“The question we always ask is, can we exploit microbiota to help our health, for which optimal blood pressure is a cardinal sign. Until now, we have simply said changes in microbiota play a role in elevated blood pressure or hypertension,” says Dr. Bina Joe, hypertension researcher and chair of the department of physiology and pharmacology, University of Toledo (UToledo)  College of Medicine and Life Sciences.

“Those are important findings, but they don’t always have an immediate translational application. This is the first time we have shown that we really can do this. It’s a proof of principle that you can use microbiota to make products that measurably improve your health.”

Blood pressure modulating protein
According to the US Centers for Disease Control and Prevention, nearly half of US adults have hypertension and about one in four of those manage their blood pressure. Uncontrolled blood pressure is a major risk factor for heart attack, stroke and kidney disease.

The current study, published in the Pharmacological Research journal and conducted by researchers at UToledo, showed how the specially modified Lactobacillus paracasei bacterium produces ACE2 in lab rats predisposed to hypertension and that are unable to naturally produce ACE2.

By feeding rats the engineered bacterium as a probiotic, researchers introduced human ACE2 in their guts, which specifically reduced their gut angiotensin II and lowered their blood pressure. ACE2 has drawn considerable interest in recent years because of its role as a critical receptor for the virus that causes COVID-19.

“It is a real possibility that we can use bacteria to correct hypertension. This is a big deal, and the concept could be applied to other diseases,” she says. “For example, if you are unable to control your sugar, can we have a bacteria make a protein that can lower your blood glucose? There are still a lot of questions that need to be answered, but now we know the paradigm works.”

Female vs male treatment receptivityResearchers are certain that modifying the ACE2 gene can produce a viable treatment for hypertension.
There is an anomaly that the scientists are still trying to figure out. The blood-pressure-lowering effects were only seen in female rats despite no visible difference in ACE2 expression between male and female rats. According to Joe, this could be because females have two functional copies of ACE2 and males do not.

The gene encoding ACE2 is located in a region of the X-chromosome, which escapes a genetic phenomenon called X-inactivation. According to Joe, having two functional copies of ACE2 is extremely important for females because when both copies were lost, females had a much higher level of hypertension compared to males.

“Females, therefore, appear to readily accept all the help they can get from gut microbiota supplying ACE. For now, this is a theory that requires further experimental proof,” explains Joe.

Even with the differing results between male and female rats, however, Joe says the findings are an essential stepping stone between the theory of leveraging bacteria to treat hypertension and other chronic conditions and practically being able to bring it into the clinic.

Managing microbiome medicine
More research is needed in this field of study, including studies about what happens when ACE2-producing bacteria are introduced in animals that make the protein naturally and the side effects that might come with boosting ACE2 levels in the gut.

However, this first-of-its-kind research from UToledo opens a window into the substantial potential of exploiting the bacteria living in our gut for our benefit.

“There have been questions about microbiome medicine — is it a fad, or is it real? This is an extremely exciting demonstration that we can exploit bacteria to work for us, and it works for high blood pressure, something that affects a significant portion of the population,” says Joe.

“It’s that ray of hope that you may not need traditional medications to keep your blood pressure in check.”

Meanwhile, nutrition brands highlight a sustained demand for products that target the gut-brain axis — the bidirectional communication system between the human digestive system and the brain — as research builds a better understanding of the links between the intestinal microflora and other health areas.