The microbiome and health: Sniffing out hypertension THE role of the microbiome, the complement of bacterial passengers carried around by every human being, gets more intriguing by the month. Recent papers have confirmed that having the wrong microbiome can cause malnutrition, and that transplanting bugs from one person to another, in the form of small amounts of faeces, can abolish Clostridium difficile infection, a potentially fatal gut disease, even when antibiotics have failed to do so. The latest connection to be investigated between the microbiome and health is that of gut bacteria to blood pressure. Work by Jennifer Pluznick of Johns Hopkins University, in Baltimore, and her colleagues, published in the Proceedings of the National Academy of Sciences, confirms that this link exists - at least, in mice and thus probably also in men. And an intriguing aside is that, in essence, the reason is that the kidneys have a sense of smell. What they are smelling is propionic acid, a substance that several species of gut bacteria produce in quantity. Earlier work, by researchers at Imperial College, London, suggests that formic acid - a similar but smaller molecule - acts on the kidneys to alter blood pressure, but the details are obscure. Dr Pluznick has shown that as far as propionic acid is concerned, one of the detectors which regulates the process is an olfactory-receptor protein of a type more familiarly seen in people's noses. Dr Pluznick had previously shown that at least six such nasal proteins are made by kidney cells, too. Preliminary experiments led her to focus on one, called Olfr78, and also on a second receptor protein, Gpr41, that is not found in the nose. The kidneys help to control blood pressure via an enzyme called renin, which increases it. Dr Pluznick found that in normal, healthy mice propionic acid regulates this process, causing blood pressure to drop. She then looked at the role of Olfr78 and Gpr41, and the link with the microbiome, by comparing normal mice with those that have been genetically engineered to eliminate one or other of the genes for the proteins in question. She found, first, that when she injected engineered mice with propionic acid, the blood pressure of those in which Olfr78 had been knocked out dropped more than it did in normal mice. In those in which the knocked-out gene was Gpr41, by contrast, it did not fall at all. The two proteins thus seem to be acting in opposite ways. That was intriguing, but did not absolutely prove the connection with gut bacteria. The clincher was when she treated some mice with an antibiotic, to kill off their gut bacteria. Mice so treated that had no gene for Olfr78 showed a significant rise in blood pressure. Those that were genetically normal did not. She has yet to do the experiment on Gpr41-deficient mice. These results, it must be acknowledged, are confusing - indicating as they do that propionic acid can push blood pressure in either direction, depending on which receptor is involved. Almost certainly, other as-yet-unidentified receptors are part of the picture, too. It does look, though, as if something produced by gut bacteria, probably propionic acid or a related molecule, is acting like a hormone and regulating blood pressure. If the same were to prove true in people, it would add a new layer of complexity to the relationship between humans and their microbiomes. How evolution came to give bugs the power to regulate the blood pressure of their hosts is a fascinating question. A more pressing one, though, is whether what seems true in mice really is true in people, and if so, how big the effect is. Given the amount of hypertension seen in modern humanity, knowing the answer to that is really rather important.