Gut-lung axis: Scientists connect cruciferous vegetables to lung health in infections

18 Aug 2023 --- Molecules in cruciferous vegetables such as broccoli or kale may help maintain a healthy lung barrier and ease infection, according to new research on mice. These molecules help to activate the aryl hydrocarbon receptor (AHR), a protein that signals cells to respond to environmental stressors or infections. AHR helps to prevent tissue damage, which is impacted by infection.

The researchers found that AHR was highly active in lung endothelial cells, which form a single cell layer that lines all blood vessels and regulates exchanges between the bloodstream and the surrounding tissue. AHR is often expressed in body parts exposed to external stimuli, such as the lungs and gut. 

“I hope the study will strengthen interest in the gut-lung axis, i.e., how do these two barrier organs communicate,’’ co-author Andreas Wack, group leader of the Immunoregulation Laboratory at the Francis Crick Institute, UK, tells Nutrition Insight. 

“We have shown one way (via AHR ligands produced in the gut, traveling through the circulation, taken up by endothelial). A few others are described already, but a more comprehensive view will be very interesting.” 

In addition to lung health support, Wack suggests that AHR activation could also support vascular health, as the activity is high in endothelial in many organs. He notes vascular health is often a critical parameter of disease severity. 

The research team notes more studies are needed to determine whether regular diets could have the same impact as the purified experimental diets used in the study. 

Enhancing AHR activity  
The lung barrier between the body and outside air comprises only two layers of cells, allowing oxygen to enter, but it has to be kept strong against pollution and infections. 

In mice infected with a flu virus, the researchers found blood in airspaces in the lungs, as this had leaked across the damaged lung barrier. When AHR was overactivated, the research team observed less blood in the lung spaces. 

In addition, mice with enhanced AHR activity could better fight off a bacterial infection on top of the original virus. They didn’t lose as much weight when infected with the flu. 

Cruciferous vegetables like broccoli or kale contain molecules that activate AHR.Flu infection in mice consuming AHR ligands – molecules that activate AHR activity – caused a decrease in protective lung AHR activity. The researchers note that these findings link food consumption to AHR activity. 

Infected mice didn’t eat as much food when ill, so their intake of AHR ligands was reduced, leading to a less active AHR system and more lung damage. 

The researchers noted that it was beneficial for mice to be on an AHR ligand-rich diet. These mice had better barrier integrity and less lung damage during infection than mice on the control diet. 

Additional research needed 
Although the study’s results, published in Nature, indicate that an altered diet could activate AHR in lung endothelial cells and help protect lung barrier function after infection, Wack emphasizes that the research used highly-controlled conditions to make clear statements. “Translating this into the messy conditions of human life is less obvious.” 

Experts welcome the study and its outcomes but note more work is needed to show that the pathways identified could be a valid therapeutic target in people with viral lung infections. 

“It is too early to say whether such a study would translate to human disease,” notes Sheena Cruickshank, immunologist and professor in biomedical sciences at the University of Manchester, UK. 

“Further validation would need to be done as mouse diets and microbiomes differ. Furthermore, the mice – as is standard – were kept in pathogen-free conditions with a standardized external environment.” 

She continues that it is unclear what might happen in the presence of environmental stressors that may impact the AHR, such as other infections or pollution. 

“If this does translate to humans, it provides real hope for future cheap ways that people can improve their outcome to infection. It also reinforces the idea that our diet and microbiome are also very important in the function of our immune systems.”

Health implications 
Though more research is needed, the researchers note that therapeutic intervention strategies that activate AHR or lifestyle modifications relating to a balanced dietary intake may effectively ameliorate lung damage clinically. 

“People may be less likely to maintain a good diet when they’re ill, so aren’t taking in the molecules from vegetables which make this system work,” notes Wack.

The study’s authors note research is needed to validate the outcomes in humans.“We do not aim to turn this immediately into a therapy. We rather try to work out more generally the effects of the gut-lung axis on lung barrier integrity,” he continues. “We certainly do not make big claims that broccoli will heal your lung infection or anything. It is rather about barrier maintenance: how does AHR activity support barrier maintenance?”

Research has also indicated that nutrients in broccoli can reduce the risk, rate and severity of prostate cancer by protecting cells in the prostate gland. 

Gut-lung axis 
First author Jack Major, visiting scientist at the Francis Crick Institute, notes that the research identifies a gut-lung axis, “linking diet to protection against lung infection via endothelial cells.” 

“We looked at flu in this research, but other research has shown that COVID-19 may also reduce AHR activity in the lung. It will be interesting to investigate the impact of other respiratory viruses on AHR and whether different molecules in our diet use other pathways than AHR to affect lung function via endothelial cells.”

Postbiotics to support lung health also use this connection between the gut and lungs. For example, Swedish BioGaia has unveiled results from a study that indicates its probiotic Protectis could increase the human body’s immune response to COVID-19 as a supplement to vaccination.

Moreover, supplementation with a probiotic and herbal blend by ResBiotic Nutrition increased the lung function of asthmatic patients due to increased short-chain fatty acids production in the participants of a clinical trial.

By Jolanda van Hal