In the process of researching last month's newsletter, I discovered that the idea of a "gut-lung axis" (similar to the well-established gut-brain axis) is much more developed than I had realized. Last month we focused on the gut in post-viral syndromes, including ones that affect the lungs. Since then, I have been noticing other reports of gut symptoms in lung diseases, such as the hantavirus outbreak on the cruise ship that was exploring remote locations. Passengers on the cruise presented with both gastrointestinal symptoms and respiratory distress. Hantavirus is believed to occur following inhalation of (dried) feces from infected rodents, which in this case likely occurred off the ship during an excursion. Even inhaled pathogens can affect the gut.
Last month we talked about the role of imbalanced microbes in post-infection syndromes, and the patterns described in these conditions are seen in lung conditions generally. Indeed, gut microbial dysbiosis (imbalance of microbe populations) is clearly a hallmark of lung diseases, from asthma and chronic obstructive pulmonary disease (COPD) to cystic fibrosis (Dang 2019; Lv 2025; Ozcam 2024; Wang 2025; Zhu 2025).
In addition to gut microbial dysbiosis, people with asthma often have IBS or food sensitivities (Deshmukh 2019; Kumari 2018), as do people with other chronic lung disorders, such as COPD and cystic fibrosis (CF) (Dang 2019). So far, though, we don't understand this relationship. Perhaps having a gut problem worsens a lung problem, or that lung problems adversely the gut. I'm guessing the relationship is dynamic, perhaps something like a "vicious cycle."
The gut-lung axis operates via signals coming from the gut to reach the lungs via blood and lymph vessels (Dang 2018; Ziaka 2024; Zhu 2025). There is some evidence that this communication is bidirectional, but the mechanisms by which things happening in the lung, such as infection or asthma, influence gut functions are not as well understood.
The list of gut-derived signals that can influence lung function is expanding but now includes immune-regulating short-chain fatty acids such as butyrate (Zhu 2025), and some other microbe metabolites such as desaminotyrosine (DAT, made from flavonoids, which are polyphenol antioxidants found in fruits and vegetables), which boosts viral immunity (Dang 2019; Esirito Santo 2021). Substances microbes make via protein metabolism (polyamines such as spermidine) also seem to have immunoregulatory actions in the lung, reducing inflammation (Wawrzyniak 2021). It also seems that immune cells living in the gut can also, via lymph and blood, migrate to the lung, and either act to improve immunity, downregulate inflammation, or worsen it (Ziakis 2024; Zhao 2026).
Another way that gut microbes can influence lung function can be through influencing immune cell development. Gut microbes can influence the production of immune cells (hematopoiesis) via release of short-chain fatty acids (e.g., butyrate, acetate) that are absorbed into the lymphatic system or blood to reach the bone marrow. This is where baby immune cells are born (Dang 2019). Short-chain fatty acids can influence just what type of cell a baby immune cell becomes, and affect such things as the effectiveness of immune responses to lung viruses, or development of inappropriate inflammatory conditions such as asthma.
One key mechanism of the badness of dysbiosis is that it causes or enhances intestinal permeability (leaky gut). A leaky gut can allow pathogenic microbes and microbe products into the body and systemic circulation to reach lungs (Zhu 2025). These microbial products can activate or worsen inflammation in the lungs.
Taken together, this developing story of the gut-lung axis highlights a key role of gut microbes and immune system in regulation of lung function. It is a key example of, as we like to say… what happens in the gut does not stay in the gut!