Leaky gut

"Leaky gut" means a gut wall that lets bacterial products slip into the blood, where they can switch on inflammation. In old mice it is well shown and helps drive the body-wide inflammation of aging. In healthy older people, the one direct test found the barrier working about as well as in the young; the leak-and-inflame link shows up mainly in people who are already frail or ill, and the proposed leak markers, such as zonulin, give inconsistent results.

Don't treat ordinary aging as a leaky gut, and don't build decisions on a single leak marker. The sensible habits are the ordinary ones for the gut community as a whole: plenty of fibre, a varied plant-rich diet, and not taking antibiotics you don't need.

What the barrier is

The gut lining is sealed by tight-junction proteins between its cells. Butyrate, made by gut bacteria from fibre, is the main fuel of the cells lining the colon, and in cultured human intestinal cells it helps assemble those tight-junction proteins.^[1] The idea behind "leaky gut" in aging is that as the butyrate-making bacteria decline, the lining is starved of fuel, the seal weakens and the barrier lets things through. More on butyrate is on short-chain fatty acids.

In mice: a clear chain from leak to inflammation

As mice age, their gut wall becomes leakier and a bacterial cell-wall fragment shows up in their blood alongside a rise in inflammatory signals. Germ-free mice show neither, and housing germ-free mice with old conventional mice is enough to raise those signals.^[2] Transplanting gut microbes from old mice into young ones made the gut wall leakier and sped up inflammation in the brain and retina, and microbes from young donors reversed those changes.^[3]

What leaks is not only cell-wall fragments. In ageing mice, gut bacterial DNA travels in the blood and builds up in heart-muscle cells, where it inflames the heart through cGAS-STING, the cell's sensor for stray DNA. Bacterial DNA is also enriched in the heart-muscle cells of older people, though that human finding is descriptive only.^[4]

In people: mainly in the frail and ill

A direct test of gut permeability in 48 healthy 65–75-year-olds and 52 healthy 18–40-year-olds found the barrier working about as well in the older group, including in the colon, where butyrate does its work. Only among people with irritable bowel syndrome (IBS), 21 older and 27 younger, did the older patients leak more, and then in the small intestine rather than the colon, mainly in the diarrhoea-predominant type. The authors found no sign that ageing on its own weakens the barrier, though they noted that medicines and other illnesses may still affect it.^[5]

Where a link with inflammation does appear, it is in people who are already frail. A review of 11 studies found that frail older adults had higher blood levels of zonulin, a proposed marker of a leaky gut, and of inflammatory signals than healthy peers.^[6]

The markers are shaky

Even in illness the leak markers don't line up. A 2024 meta-analysis of 10 studies in older people with Parkinson's, Alzheimer's and related conditions found no difference in stool zonulin in Parkinson's; another stool leak marker, alpha-1-antitrypsin, was higher in Parkinson's, but the authors judged the evidence for it too limited to rely on yet.^[7] With the markers this inconsistent even in disease, a single result says little about an individual.

The same logic in the mouth

The leak-and-inflame idea is not confined to the gut: periodontal disease lets mouth bacteria seed body-wide inflammation, which is part of why oral health tracks with longevity.

What to do

Don't assume aging has made your gut leaky. In the one direct test in healthy 65–75-year-olds, it hadn't.
Feed the butyrate makers the ordinary way: fibre and a varied, plant-rich diet, and no antibiotics you don't need.
Treat the conditions that do go with a leakier gut with your doctor, such as gut disease, and frailty, where markers point the same way, rather than chasing a marker.

The wider picture of the aging gut is on Dysbiosis; its role in body-wide inflammation is on chronic inflammation.