Crosstalking circuits of the gut-metabolic-lung-brain axis

2026: ERS Barcelona

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Can a healthy gut shape lung immunity? Can the gut communicate with the lungs, and if so, how? This was covered in a session about the cross-talking circuits of the gut-metabolic-lung-brain axis, shaping injury and repair.

Gut microbiota is an intergral part of our immune system

The gut is host to a wide variety of microorganisms, known as gut microbiota, facilitating digestion and nutrition uptake and preventing pathological organisms from colonising. A biodiverse microbiota is more resilient to pathogens. Gut dysbiosis, i.e. an imbalance in the composition of the microbiota, has been identified as a driver for immune-mediated chronic diseases, including lung injury and inflammation.

Immune modulation: not only driven by bacteria

Research has mainly focused on bacteria, but other guests, like fungi, protozoa and viruses also modulate the immune system. One protozoa of interest for dr Kyle Burrows and colleagues is the Tritrichomonas musculis (T.mu). They showed that introducing T.mu in the gut lead to a significant and sustained increase in lung eosinophils, due to gut-derived innate lymphoid cells (ILCs) connecting to T- and B-cells in the lung. This exacerbated allergic airway inflammation but on the other hand limited the impact of an induced tuberculosis infection.¹ Gut microbes can remotely shape pulmonary immunity via inter-organ trafficking of ILC2s, which, depending on disease context, can be protective or pathogenic.

Immune signalling from lung to brain

Francesca Odoardi talked about the lung-to-brain immune signalling and its impact on neuroinflammation. She touched upon Mulitple Sclerosis, the most common auto-immune disease targeting the CNS, a disease that is characterized by inflammation, demyelination and neurodegeneration in the CNS. The pathogenicity of the disease is still under discussion, but given that smoking is a strong risk factor, it is believed that immune reactions in the lung can play a key role.

Odoardi’s research group have performed experimental animal studies, showing that induced lung dysbiosis altered the susceptibility for autoimmune inflammation in CNS.² Following the induced dysbiosis, the microglia changed, both in morphology and gene expression and thus changing odds of CNS inflammation.

With the lungs’ constant exposure to environment, the lung microbiota can be a part of an early warning system to protect the sensitive brain tissue. The T-cell activation in the lung is also highly efficient, using both the regular IP3 mediated pathway and the oxygen-dependent NAADP pathway. It is possible that the lungs play a much bigger role in neurological disease than previously thought.

Metabolic signals

Looking further to metabolic signalling, it has been seen in epidemiological studies, such as the HUNT study,³ that elevated glucose levels were associated with higher risk of incident asthma. Type 2 diabetes and asthma are common comorbidities but the mechanisms linking them are still not fully understood. Chronic systemic inflammation drive both airway hyperresponsiveness and insulin resistance, but is insulin resistance a cause of asthma or a consequence of the chronic airway inflammation?

Consider metabolic impact of treatment

Treatments for one disease can also have a clinical impact for other diseases. For instance: high ICS doses may raise glucose levels for the diabetic patient and using oral corticosteroids drive incident T2DM. On the other hand, antidiabetic agents have been associated with improvement in asthma outcomes, independently of glycaemic control.⁴ GLP-1 receptors are present in the airway and their activation induces bronchodilation, but the clinical relevance in asthma is not established.

A coordinated approach to treating comorbidities may bring synergistic effects to improve outcomes in asthma.

24257-09.09.2026