The immune system and gut work closely together to keep the body healthy, but as we age, this balance breaks. Now, researchers have found that functional T cells can strengthen the gut barrier, rebalance gut bacteria and reduce harmful inflammation.

The findings, published in Science Immunology, suggest that maintaining healthy T cells is key to preserving gut health and preventing chronic inflammation that drives aging-related diseases.

As we age, specific immune cells called CD4 T cells build up in the gut, altering immune responses. This causes the gut barrier to weaken, allowing harmful bacteria to trigger inflammation, which contributes to aging and related diseases. However, it’s still unclear how exactly CD4 T cells drive this process.

To address this question, Manuel Gómez de las Heras at the Universidad Autónoma de Madrid and his colleagues studied mice with defective CD4 T cells caused by a mitochondrial problem that mimics aging.

Increased inflammation

As mice with faulty CD4 T cells aged, their gut lining became damaged, leading to a “leaky gut” that let harmful bacteria and toxins enter the body. This weakening of the gut barrier was associated with changes in the gut microbiota. 

While the overall number of different microbial species stayed similar to that of healthy mice, harmful bacteria linked to inflammation grew more in mice with faulty T cells, and helpful bacteria that support gut health decreased. These changes influenced how the bacteria broke down nutrients and produced beneficial molecules such as short-chain fatty acids.

Mice with faulty T cells showed symptoms such as weight loss and diarrhea, with their guts becoming swollen and inflamed, before becoming sick and dying. The loss of gut barrier integrity played a key role in the animals’ health problems, the researchers found.

Gut barrier

In mice with faulty T cells, anti-inflammatory immune cells were reduced, while cells that promote inflammation increased. These changes disrupted normal immune responses and led to increased antibody production, causing damage to the gut. Although similar problems happen naturally during aging, they appeared earlier and were more severe in these mice, the researchers found. 

Transplanting healthy CD4 T cells into the mice restored gut immune balance, strengthened the gut barrier, reduced harmful bacteria, and lowered inflammation. This treatment also delayed signs of aging-related diseases. 

The work, the authors say, “provides insights into the potential applications of T cell-based therapies to delay age-associated pathologies through the strengthening of intestinal barrier integrity.”