From your gut to your brain?

We have been connecting the gut microbiome to a bunch of functions in our body for some time now, however until now, you could mostly come across healing teas and such. But don’t worry, science dove in head first and scientists are exploring all the ties between the gut and and the brain in hopes of discovering new underlying mechanisms and connections. 

Historically, the brain has been viewed as "immune privileged", meaning for example immune cells (like T cells) were thought to stay out unless there was an acute problem requiring a solution. However, a new study shows that αβ T cells, which are considered key players in the adaptive immune system, are permanently stationed in a specific brain region called the subfornical organ (SFO).

Using imaging techniques, RNA sequencing, and both mouse and human brain tissue, researchers found that these brain-resident T cells aren’t magically lost there, nor are they temporarily visiting. They're functionally differentiated from those in surrounding membranes (the meninges), highly active, producing inflammatory molecules like interferon-gamma (already linked to Alzheimer’s disease pathology), and dependent on signals from the gut microbiome and white fat to form and function.

The subfornical organ is a brain region known for sensing bodily signals like thirst, hunger, and inflammation. It's also highly accessible by the bloodstream, making it a natural checkpoint for incoming immune cells, so overall it makes sense that the highest density of resident T cells in both mice and humans was in this region. It might even suggest it could act as a network for immune-brain communication.

In this study, they attempted to trace the origins of the T cells and found they come from the gut and adipose (fat) tissue, where they are primed by microbiota (gut bacteria) and environmental cues like our diet. The proof was in the pathology of mice-when they were fed a high-fat diet, their brains showed increased T cell presence, when the microbiome was altered (for example by antibiotics), T cell levels in the brain lowered. And if that wasn’t enough, they showed that T cells literally move from the gut and fat into the brain using advanced tracking techniques. All this evidence supports the existence of two immune axes, firstly the gut-brain axis, and secondly, the fat-brain axis, from which both are involved in T cell migration.

These resident T cells in our brain now appear to be critical for regulating normal behavior (so far proven in mice). Disrupting their numbers, either by depleting them or blocking their migration, resulted in behavioral changes, including increased anxiety and stress responses during tests (like novelty-suppressed feeding).

This research shifts how we think about immune presence in the brain, even in a healthy state, and highlights the gut and fat as remote controllers of certain brain functions.It opens new doors for treating neuroinflammatory and neuropsychiatric disorders—not by acting directly on the brain, but by targeting the immune system in the gut or fat, but as per usual, we need to wait for more and more research…

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Resources:

Yoshida T. M., et al. (2025) The subfornical organ is a nucleus for gut-derived T cells that regulate behaviour

www.nature.com

magazine.publichealth.jhu.edu