Kidney Function

How Gut Bacteria Talk Directly to the Kidney

The evidence here is strong in animals and increasingly supported in people. The kidney filters blood, balances salt and water, and controls blood pressure through a hormone system of its own. None of that sounds like it should involve the intestine. It does, because the kidney carries receptors built to detect compounds that nothing in the human body makes.

Compounds with a single source

Short-chain fatty acids are produced when gut bacteria ferment fibre. Acetate, propionate and butyrate are the main ones.

They don't stay in the gut. They're absorbed and circulate in the bloodstream, where acetate alone usually sits above 100 micromolar.

The evidence that they come from bacteria and nothing else is unusually clean. In germ-free animals, raised with no gut bacteria at all, these compounds are virtually undetectable in the blood.

So the body has a class of circulating signal that exists only because of what lives in the intestine.

A smell receptor working inside the kidney

What makes this more than a curiosity is where the body listens for them.

Olfactory receptor 78 was first identified as a smell receptor. It also sits in the juxtaglomerular apparatus, the cluster of cells in the kidney that release renin, the hormone starting the cascade that raises blood pressure.

Isolated kidney filtering units from normal mice release renin when propionate is applied. Units from mice lacking that receptor don't. Those animals also have lower renin activity in their blood.

A second receptor, GPR41, sits in the lining of blood vessels, and an intact vessel lining is needed for these compounds to widen them.

So the kidney's blood pressure machinery has a sensor tuned to a bacterial product.

Source: Olfactory receptor 78 modulates renin but not baseline blood pressure

What happens when the sensors are removed

Receptors matter most when you take them away.

Researchers bred mice lacking both GPR41 and GPR43, the two receptors immune cells use to detect these compounds.

Even without any other insult, those mice had significantly larger kidneys and more collagen deposited in kidney and heart tissue, meaning more scarring. They had more inflammatory immune cells in the kidney.

The route was traceable. Without the receptors, the gut barrier was weaker, letting bacterial fragments into the bloodstream and triggering inflammation. Blocking the receptor that detects those fragments reversed the damage.

These same receptors turned out to be partly responsible for the blood pressure benefits of a high-fibre diet, which means the diet works through them rather than around them.

The human data points the same way. In UK Biobank, genetic variants producing lower levels of both receptors were more common in people with high blood pressure.

Source: Gut Microbiota Metabolites Sensed by Host GPR41/43 Protect Against Hypertension

Why blood pressure is the kidney story

Connecting this back to kidney function needs one more step, and it's a short one.

High blood pressure is one of the two leading causes of kidney failure worldwide. The kidney's tiny filtering units are damaged by sustained pressure, and once enough are lost, function declines permanently.

So a mechanism affecting blood pressure is a mechanism affecting kidney function over time.

The animals lacking these receptors made that concrete. They didn't only have higher pressure. Their kidneys were enlarged and scarred directly.

Source: Gut microbiota-derived short-chain fatty acids and kidney diseases

What this means for you

Kidney function is checked with a simple blood and urine test, and anyone with high blood pressure, diabetes or a family history should ask their doctor about being monitored. In addition, the research above shows the kidney carrying receptors specifically for compounds that only gut bacteria produce, with animals lacking those receptors developing enlarged, scarred kidneys. A varied, plant-rich diet supports the same gut bacteria this research ties to those signals reaching the kidney at all. That's the same idea behind GutLab, everyday gut health starts with regularly feeding the microbiome a broad range of plant-rich ingredients.