Intermittent fasting might protect eyes in Sjögren’s by shifting gut bacteria

Intermittent fasting may offer a new way to ease the dry eye symptoms that commonly affect people with Sjögren’s disease, according to a new study in mice.

The alternating fasting and eating regimen was found to restore a healthier gut environment in the animals. This shift ultimately reduced immune cell attacks on the tear-producing glands, helping restore tear production and limit damage to the eye’s surface.

Specifically, researchers found that the fasting regimen increased levels of certain liver-produced bile acids, which drove the growth of Akkermansia muciniphila, a beneficial gut bacterium.

“By establishing a healthier gut milieu and rebalancing lacrimal gland immunity, [intermittent fasting] represents a safe, system-level strategy with translational potential for long-term management of [Sjogren’s disease]-associated dry eye,” researchers wrote.

The study, “Intermittent fasting ameliorates Sjögren’s syndrome-related dry eye through a preponderant bile acid-Akkermansia homeostasis establishment,” was published in the Journal of Autoimmunity.

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The link between Sjögren’s disease and dry eye

Sjögren’s disease occurs when the immune system mistakenly attacks the body’s own tissues, primarily moisture-producing glands such as the salivary and tear glands. As a result, more than 60% of people diagnosed with the disease develop persistent dry eye, which can cause burning, irritation, blurred vision, and damage to the eye’s surface.

Unlike more common forms of dry eye disease, Sjögren’s-related dry eye is driven by widespread immune dysfunction throughout the body. Because of this, local treatments such as artificial tears often provide only limited relief.

“Therefore, exploring a safe, effective, and long-term therapeutic strategy to regulate abnormal [bodywide] immune state and alleviate dry eye symptoms remains a crucial goal for the comprehensive management of [Sjögren’s disease],” the researchers wrote.

Intermittent fasting has previously shown promising benefits in several metabolic and immune-related diseases. It is also known to reshape the gut microbiome, the community of bacteria and other microorganisms living in the intestine, which is often altered in people with Sjögren’s disease.

The researchers, therefore, wondered whether modulating these factors through intermittent fasting could be a promising therapeutic strategy to alleviate Sjögren’s-related dry eye symptoms.

To test the idea, the researchers turned to a mouse model of Sjögren’s disease in which dry eye disease had been induced. One group of mice followed an alternate-day fasting regimen, eating normally every other day and fasting on the intervening days, while another group of mice with Sjögren’s disease-related dry eye continued eating normally. Healthy mice fed a normal diet served as controls.

Compared with the reduced tear production seen in Sjögren’s disease mice that ate normally, those on intermittent fasting produced significantly more tears and showed less dry eye-induced damage to the cornea, the transparent outer layer of the eye. They also had fewer dying cells and markedly less infiltration of immune cells into the tear-producing glands, suggesting the fasting regimen protected the glands from autoimmune attacks.

When the mice’s gut bacteria were depleted with antibiotics, however, intermittent fasting no longer improved tear production or reduced corneal damage, indicating that the diet’s protective effects depended on the gut microbiome.

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How gut bacteria and bile acids protect the eyes

Consistent with this finding, intermittent fasting substantially reshaped the gut microbiome. Among the bacterial groups altered by intermittent fasting, Akkermansia stood out as the most responsive. Within this group, Akkermansia muciniphila, a beneficial bacterium naturally found in the intestine and associated with metabolic health, emerged as the bacterial species most strongly associated with the fasting response.

Supporting its role as a key mediator of the diet’s protective effects, providing Sjögren’s disease mice with a heat-treated form of Akkermansia muciniphila significantly improved tear production and reduced corneal damage.

Looking for factors that might explain the expansion of Akkermansia, the researchers found that intermittent fasting markedly increased levels of certain bile acids, including ursodeoxycholic acid (UDCA). These are molecules produced by the liver that help digest fats and regulate the gut microbiome, and their higher levels were associated with greater Akkermansia abundance. Giving UDCA to Sjögren’s disease mice reproduced many of the benefits of intermittent fasting, suggesting that increased bile acids may help drive Akkermansia expansion and contribute to the diet’s protective effects.

The gut changes were accompanied by broad effects on the immune system. Intermittent fasting reduced the number of inflammatory Th17 cells, which fuel autoimmune attacks, while increasing regulatory immune cells that help prevent excessive immune responses.

“Our findings highlight the potential of targeting the gut-eye axis in autoimmune diseases and open up new avenues for developing diet-based therapies for [Sjogren’s disease] and other autoimmune disorders,” the researchers concluded.