Gut–Lung Axis and Pulmonary Fibrosis: Can Gut Health Affect Lung Fibrosis?
Can the Health of Your Gut Affect Your Lungs?
At first glance, the intestine and lungs appear to be completely separate organs. One processes food and houses trillions of microorganisms; the other exchanges oxygen and carbon dioxide.
Yet these two organs are biologically connected.
Researchers increasingly use the term gut–lung axis to describe the bidirectional communication between the gastrointestinal tract, its microbiome, the immune system, microbial metabolites, and the respiratory system.
This emerging field has become particularly interesting in chronic inflammatory lung diseases and, more recently, in interstitial lung disease (ILD) and pulmonary fibrosis.
Pulmonary fibrosis is characterized by abnormal repair of injured lung tissue, activation of fibroblasts and myofibroblasts, excessive extracellular-matrix deposition, and progressive architectural distortion of the lung. In idiopathic pulmonary fibrosis (IPF), this process can lead to progressive loss of lung function.
Traditional models of pulmonary fibrosis have focused primarily on what happens inside the lung. That remains essential. However, newer research raises an additional question:
Could biological signals originating in the gut influence inflammation, immune regulation, epithelial injury, or fibrotic signaling in the lung?
The answer is increasingly intriguing—but it requires scientific caution.
Current evidence supports an association between the intestinal microbiome and pulmonary fibrosis, and experimental studies provide several plausible mechanisms linking the two. Importantly, recent human data have strengthened this association. However, we do not yet have sufficient evidence to conclude that correcting gut dysbiosis can prevent, stop, or reverse pulmonary fibrosis.
Understanding that distinction is central to an evidence-based functional and integrative approach.
What Is the Gut–Lung Axis?
The gut–lung axis is a bidirectional communication network between the gastrointestinal tract and the respiratory system.
Communication can occur through several interconnected pathways:
the immune system
microbial metabolites
systemic circulation
intestinal and pulmonary barrier function
inflammatory mediators
neuroendocrine signaling
migration or translocation of microbial products
interactions with the bone marrow and immune-cell production
The intestine contains one of the largest microbial ecosystems in the human body. Collectively, these microorganisms and their genetic material are referred to as the gut microbiome.
Gut bacteria metabolize dietary components—particularly fiber, amino acids, and other substrates—and produce biologically active molecules.
These include:
short-chain fatty acids such as butyrate, acetate, and propionate
tryptophan-derived metabolites
secondary bile acids
microbial cell-wall products such as lipopolysaccharide (LPS)
other signaling molecules capable of influencing immune and metabolic pathways
Some of these molecules can enter the circulation and potentially influence distant organs, including the lungs.
The relationship also works in the opposite direction. Lung disease, systemic inflammation, medications, antibiotics, altered diet, reduced physical activity, hypoxemia, and other physiological stresses may influence the intestinal environment.
This is why the concept is called an axis rather than a one-way pathway.
What Is Gut Dysbiosis?
A healthy microbiome is not defined by the presence of one particular “good bacterium.” It is a complex ecological community.
Gut dysbiosis broadly refers to an alteration in the composition or function of this microbial ecosystem.
It may involve:
loss of microbial diversity
depletion of potentially beneficial organisms
expansion of potentially harmful or pro-inflammatory organisms
changes in microbial metabolic activity
disruption of normal host–microbe interactions
Dysbiosis has been studied extensively in inflammatory bowel disease, metabolic disease, autoimmune disorders, asthma, COPD, and several other conditions.
Pulmonary fibrosis is now being added to this research landscape.
What Does the Human Evidence Show?
This is where the field has recently become much more interesting.
Earlier pulmonary-fibrosis microbiome research focused heavily on the lung microbiome. Studies demonstrated that the lungs are not sterile and that alterations in pulmonary microbial burden and composition can occur in IPF.
The gut microbiome was much less well studied.
That is changing.
A 2024 study comparing stool microbiota from patients with IPF and healthy controls identified differences in multiple bacterial groups. The study was small, so its findings should be regarded as exploratory rather than definitive. (pubmed.ncbi.nlm.nih.gov)
More importantly, a much larger recent analysis evaluated gut microbiota in 411 participants with IPF from the CleanUP-IPF trial.
Researchers found that gut microbial diversity and community composition were associated with impaired gas exchange as measured by DLCO. Certain bacterial genera were also associated with transplant-free survival, and microbiome characteristics appeared to interact with antimicrobial and antifibrotic treatment exposure.
This does not prove that the gut microbiome causes IPF progression. But it provides substantial human evidence that the intestinal microbial ecosystem is associated with clinically meaningful characteristics of IPF. (pubmed.ncbi.nlm.nih.gov)
This distinction matters:
Association is not causation.
A different microbiome in advanced pulmonary fibrosis could be a contributor to disease, a consequence of disease, or both.
How Could Gut Dysbiosis Influence Pulmonary Fibrosis?
Current research proposes several interconnected mechanisms.
1. Immune Dysregulation
The intestine is one of the body’s largest immune interfaces.
Gut microorganisms continuously interact with intestinal epithelial cells, macrophages, dendritic cells, regulatory T cells, Th17 cells, innate lymphoid cells, and many other components of mucosal immunity.
Changes in gut microbial composition may therefore alter systemic immune signaling.
This becomes relevant to pulmonary fibrosis because abnormal immune activation and inflammatory signaling can interact with epithelial injury and fibroblast activation.
The microbiome may potentially influence the balance between pro-inflammatory and regulatory immune responses, thereby changing the environment in which fibrotic signaling occurs.
Recent mechanistic reviews identify immune dysregulation as one of the principal pathways potentially connecting intestinal dysbiosis with pulmonary fibrosis. (pmc.ncbi.nlm.nih.gov)
2. Intestinal Barrier Dysfunction: The “Leaky Gut” Question
The intestinal lining forms a sophisticated biological barrier.
Its role is not simply to prevent substances from entering the bloodstream. It selectively regulates the interaction between nutrients, microorganisms, microbial molecules, immune cells, and systemic circulation.
When this barrier becomes dysfunctional, intestinal permeability may increase.
The popular term “leaky gut” refers broadly to this phenomenon, although the term is frequently oversimplified in wellness marketing.
Increased permeability may allow greater systemic exposure to microbial components such as LPS.
These signals can potentially promote:
systemic inflammation
innate immune activation
oxidative stress
cytokine production
All of these processes could theoretically influence a susceptible lung.
However, there is currently insufficient clinical evidence to claim that “leaky gut causes pulmonary fibrosis.”
A more scientifically accurate statement is:
Intestinal barrier dysfunction is a plausible component of gut–lung signaling and is being investigated as a potential contributor to inflammatory and fibrotic pathways.
3. Short-Chain Fatty Acids: Butyrate, Acetate and Propionate
One of the most fascinating links between diet, microbiome, immunity, and the lungs involves short-chain fatty acids (SCFAs).
The principal SCFAs include:
acetate
propionate
butyrate
They are produced primarily when intestinal bacteria ferment dietary fibers and resistant starches.
Butyrate is particularly important for intestinal health because it serves as an energy source for colonocytes and contributes to intestinal barrier integrity.
SCFAs can also exert systemic immunological effects.
Their mechanisms include:
activation of G-protein-coupled receptors
regulation of immune-cell differentiation
modulation of inflammatory signaling
histone deacetylase inhibition
effects on epithelial barrier function
These mechanisms have generated interest in whether reduced production of beneficial microbial metabolites could contribute to a systemic environment favoring inflammation or fibrosis.
Experimental pulmonary-fibrosis studies suggest that SCFA-related pathways may influence fibroblast activation and collagen deposition.
But there is a crucial clinical limitation:
Evidence that SCFAs influence fibrotic biology is not equivalent to evidence that taking butyrate supplements treats pulmonary fibrosis.
At present, butyrate should be considered an important research pathway, not an established antifibrotic treatment. (pubmed.ncbi.nlm.nih.gov)
4. Tryptophan Metabolism and the Lung
Tryptophan provides another example of how the gut microbiome may communicate with distant organs.
Intestinal microorganisms transform dietary tryptophan into multiple bioactive compounds.
Some microbial tryptophan metabolites interact with the aryl hydrocarbon receptor (AhR), an important regulator of mucosal immunity and epithelial homeostasis.
Tryptophan metabolism can influence:
immune tolerance
epithelial integrity
inflammatory signaling
oxidative stress
immune-cell behavior
Emerging research suggests that disruption of these pathways may be relevant to chronic lung inflammation and potentially pulmonary fibrosis.
However, this remains predominantly a mechanistic and experimental field rather than a validated therapeutic strategy.
5. Bile Acids and Microbial Signaling
Bile acids are often thought of simply as substances required for fat digestion.
Biologically, they are much more than that.
Gut bacteria transform primary bile acids into secondary bile acids, creating signaling molecules capable of interacting with metabolic and immune receptors.
Altered bile-acid metabolism may influence:
inflammatory pathways
oxidative stress
immune regulation
epithelial function
Recent pulmonary-fibrosis literature identifies altered bile-acid metabolites as another possible connection between gut dysbiosis and fibrotic signaling.
This remains an emerging area of investigation. (pmc.ncbi.nlm.nih.gov)
6. Autophagy, Cellular Stress and Fibrosis
Autophagy is the cellular recycling system responsible for removing damaged proteins and organelles and maintaining cellular homeostasis.
Impaired autophagy has been implicated in pulmonary fibrosis.
Microbial metabolites may influence signaling pathways involved in autophagy, including pathways related to PI3K/AKT/mTOR.
This provides another possible mechanistic bridge between microbial metabolism and fibrotic cellular behavior.
Again, the science is biologically compelling, but translation into human treatment remains incomplete. (pmc.ncbi.nlm.nih.gov)
7. Alveolar Epithelial Injury and Fibroblast Activation
Modern understanding of IPF places repeated alveolar epithelial injury and abnormal repair near the center of disease pathogenesis.
When alveolar epithelial cells are injured, multiple signals can activate fibroblasts.
Fibroblasts can differentiate into myofibroblasts, producing collagen and other extracellular-matrix components.
The gut microbiome is unlikely to be the sole driver of this process.
Instead, current models suggest that microbial signals could potentially modify the biological environment surrounding fibrosis by influencing:
inflammation
immune activation
oxidative stress
epithelial integrity
autophagy
profibrotic signaling
This distinction is important.
Pulmonary fibrosis should not be reduced to a “gut disease.”
The gut–lung axis is better viewed as one potential modifier within a complex fibrotic network.
The Gut–Lung Axis May Be Particularly Important in Autoimmune ILD
One of the most clinically interesting areas of gut–lung research involves connective-tissue-disease-associated interstitial lung disease (CTD-ILD).
This includes ILD associated with:
systemic sclerosis
rheumatoid arthritis
inflammatory myopathies
Sjögren’s disease
mixed connective tissue disease
antisynthetase syndrome
Why might the gut be particularly relevant here?
Because the microbiome is already implicated in the regulation of systemic immunity and autoimmunity.
The question therefore becomes whether intestinal dysbiosis could contribute simultaneously to systemic immune dysregulation and pulmonary manifestations.
We do not yet know the complete answer, but systemic sclerosis provides particularly compelling emerging evidence.
Systemic Sclerosis–Associated ILD: Important New Evidence
Systemic sclerosis is especially relevant to the gut–lung axis because gastrointestinal involvement is extremely common.
Patients may experience:
esophageal dysmotility
gastroesophageal reflux
altered intestinal motility
small intestinal bacterial overgrowth (SIBO)
intestinal dysbiosis
At the same time, ILD is one of the most important pulmonary complications of systemic sclerosis.
A major international study recently examined stool microbiota in 285 patients with systemic sclerosis across seven centers on five continents.
Approximately 62.5% had ILD.
Patients with SSc-ILD demonstrated a distinct intestinal microbial signature compared with patients without ILD. Importantly, specific bacterial species and microbial functional pathways were associated with the radiologic extent of ILD.
This represents an important step beyond purely experimental evidence.
It suggests that the intestinal microbiome may potentially relate not only to systemic sclerosis but specifically to its pulmonary phenotype.
Nevertheless, intervention trials are still needed before microbiome manipulation can be recommended as treatment for SSc-ILD. (pubmed.ncbi.nlm.nih.gov)
What About the Lung Microbiome?
The gut microbiome should not be considered in isolation.
The lungs themselves contain microbial communities.
Research in IPF has identified changes in pulmonary bacterial burden and composition, and the lung microbiome may interact directly with local pulmonary immunity.
There may therefore be several interconnected microbial axes:
Gut → immune system → lung
Oral cavity → microaspiration → lung
Lung microbiome → local immunity → epithelial injury
The emerging model is therefore not simply a gut–lung axis but a complex gut–oral–lung microbial network.
Current ILD literature recognizes these interactions but also emphasizes that the gut and oral components require considerably more research. (pubmed.ncbi.nlm.nih.gov)
GERD, Microaspiration and the Gut–Lung Connection
Gastroesophageal reflux disease is common in patients with pulmonary fibrosis, particularly IPF and systemic sclerosis.
Reflux may potentially influence the lungs through a different mechanism from the classical gut–lung axis: microaspiration.
Small amounts of gastric or esophageal contents may reach the respiratory tract, exposing the lung to acid, bile acids, digestive enzymes, microorganisms, and other substances.
This creates an important distinction:
Gut–lung axis: systemic communication through immunity, microbial metabolites and barrier signaling.
Reflux–lung/oral–lung pathways: more direct exposure through aspiration into the respiratory tract.
Both may be relevant, but they should not be confused.
Can Diet Influence the Gut–Lung Axis?
Potentially, yes.
Diet is one of the strongest environmental influences on the intestinal microbiome.
A diet rich in diverse plant fibers can provide substrates for microbial fermentation and SCFA production.
From an integrative-medicine perspective, nutritional assessment may therefore be relevant in patients with chronic lung disease—not because a particular diet has been proven to reverse fibrosis, but because nutrition affects:
microbiome composition
metabolic health
muscle mass
immune function
gastrointestinal symptoms
body weight
overall resilience during chronic disease
An individualized nutritional strategy may include adequate protein, diverse whole foods where tolerated, fiber appropriate to gastrointestinal tolerance, healthy fats, and correction of documented nutritional deficiencies.
However, patients with advanced ILD, significant weight loss, SIBO, severe reflux, dysmotility, or systemic sclerosis may require individualized dietary modification.
Simply telling every patient to “eat more fiber” is not appropriate.
Do Probiotics Treat Pulmonary Fibrosis?
Currently, no clinical evidence establishes probiotics as a treatment for pulmonary fibrosis.
This is an important distinction because experimental microbiome research can easily be overinterpreted.
Probiotics, prebiotics, dietary modification and fecal microbiota transplantation have produced interesting results in experimental models and other disease contexts.
But we do not yet have sufficient human randomized clinical trials demonstrating that these interventions slow FVC decline, improve survival, prevent progression, or reverse established pulmonary fibrosis.
Therefore, they should not replace:
antifibrotic therapy when indicated
immunomodulatory therapy for appropriate autoimmune ILD
oxygen therapy when required
pulmonary rehabilitation
vaccination
reflux management when clinically indicated
lung-transplant evaluation when appropriate
established multidisciplinary ILD care
What About Fecal Microbiota Transplantation?
FMT is another intriguing area of research.
It can dramatically alter the intestinal microbial ecosystem and is an established treatment in selected settings such as recurrent Clostridioides difficile infection.
Its role in pulmonary fibrosis, however, remains experimental.
Animal studies and mechanistic research have generated interest in whether microbiome restoration could alter inflammatory or fibrotic signaling.
That does not mean FMT should currently be performed to treat pulmonary fibrosis.
Important unanswered questions include:
Which patients might benefit?
Which microbial signatures are actually harmful?
Which organisms or metabolites are protective?
What is the appropriate donor profile?
How durable are microbiome changes?
Could microbiome manipulation cause unintended immune or infectious consequences?
Until these questions are addressed in controlled human studies, FMT for pulmonary fibrosis remains investigational. (pubmed.ncbi.nlm.nih.gov)
A Functional and Integrative Medicine Approach to Pulmonary Fibrosis
Functional and integrative medicine can contribute to pulmonary-fibrosis care when it is used to expand comprehensive patient assessment—not replace evidence-based pulmonary medicine.
An integrative evaluation may consider several domains.
1. The pulmonary diagnosis
The first priority remains determining the correct ILD phenotype and cause.
IPF, hypersensitivity pneumonitis, systemic sclerosis-associated ILD, rheumatoid arthritis-associated ILD, myositis-associated ILD and other fibrotic lung diseases are biologically different diseases.
They should not be treated as one entity simply because fibrosis is present.
2. Gastrointestinal health
Depending on symptoms and underlying disease, assessment may include:
reflux
dysphagia
esophageal dysmotility
constipation or diarrhea
bloating
SIBO risk
medication effects
nutritional intake
3. Nutrition and metabolic health
Evaluation should consider:
unintended weight loss
obesity
muscle loss
protein intake
micronutrient deficiencies
metabolic disease
dietary quality
4. Environmental exposures
A careful history may identify clinically relevant exposures such as:
mold and damp environments
birds
occupational dusts
silica
metal or wood dust
farming exposures
medications
smoking
Importantly, these exposures must be evaluated using established pulmonary frameworks rather than automatically attributing disease to nonspecific “toxins.”
5. Lifestyle and physiological reserve
Physical activity, pulmonary rehabilitation, sleep, psychological stress, skeletal-muscle preservation, vaccination and smoking cessation can all influence overall health and resilience.
6. Microbiome-related factors
The gut microbiome is an emerging area worth considering scientifically, particularly in patients with significant gastrointestinal disease or autoimmune ILD.
But current commercial stool microbiome testing should not be interpreted as if it can identify the cause of pulmonary fibrosis or dictate an established antifibrotic treatment.
That level of evidence does not yet exist.
What We Know, What We Don’t Know, and What This Means Clinically
What We Know
The gut and lungs communicate through immune, metabolic and microbial pathways.
Patients with pulmonary fibrosis can exhibit alterations in gut and lung microbial communities.
Recent human IPF data demonstrate associations between gut microbial characteristics, disease severity and transplant-free survival. (pubmed.ncbi.nlm.nih.gov)
A large multinational SSc study has also identified intestinal microbial signatures associated with the presence and radiologic severity of SSc-ILD. (pubmed.ncbi.nlm.nih.gov)
SCFAs, tryptophan metabolites, bile acids, LPS and other microbial products provide biologically plausible mechanisms through which the gut microbiome could influence systemic and pulmonary biology. (pmc.ncbi.nlm.nih.gov)
What We Don’t Know
We do not yet know whether gut dysbiosis is a cause, consequence, disease modifier—or some combination of these in pulmonary fibrosis.
We do not have a validated “pulmonary fibrosis microbiome signature” that can currently be used routinely in clinical practice.
We do not have evidence that probiotics, prebiotics, butyrate, FMT or other microbiome-targeted therapies can reverse established pulmonary fibrosis.
And we do not yet know which patients, if any, are most likely to benefit from microbiome-directed treatment.
What This Means Clinically
The gut–lung axis represents an important emerging dimension of pulmonary-fibrosis research.
It should neither be dismissed nor overpromoted.
For patients, the practical message is that optimizing gastrointestinal health, nutritional status, metabolic health and lifestyle can form part of comprehensive care—but these strategies should complement rather than replace established ILD treatment.
For clinicians and researchers, the gut microbiome represents a potentially important source of biomarkers, mechanistic insights and future therapeutic targets.
The Future: Precision Medicine for the Gut–Lung Axis
The future of this field will probably extend far beyond asking whether a patient has “good” or “bad” bacteria.
Research is moving toward integrated multi-omics approaches combining:
metagenomics
metabolomics
transcriptomics
immune profiling
host genetics
clinical phenotyping
The clinically important question may ultimately be not:
“Which bacteria are present?”
but rather:
“What are these microorganisms doing, which metabolites are they producing, how is the host responding, and does that biological pathway modify the patient’s specific form of ILD?”
That is a much more sophisticated model of personalized medicine.
Recent reviews emphasize the need for longitudinal cohorts, mechanistic validation, multi-omics studies and carefully designed human intervention trials before gut-targeted treatments can become part of routine pulmonary-fibrosis management. (pubmed.ncbi.nlm.nih.gov)
Conclusion: Can Gut Health Affect Pulmonary Fibrosis?
The emerging answer is:
Possibly—but the relationship is complex, and the science is still developing.
The intestine and lungs communicate through immune pathways, microbial metabolites, systemic circulation and epithelial barriers. Gut dysbiosis has now been documented in patients with pulmonary fibrosis, while newer human studies demonstrate associations between gut microbiome characteristics and clinically important features of IPF and systemic sclerosis-associated ILD.
SCFAs such as butyrate, tryptophan metabolites, bile acids, LPS and other microbial products provide plausible biological mechanisms connecting intestinal ecology with pulmonary immunity and fibrotic signaling.
About Dr. Samar Shadly
Dr. Samar Shadly is a Consultant Pulmonologist and certified functional medicine practitioner with advanced subspecialty training in interstitial lung disease, pulmonary fibrosis, pulmonary hypertension, and lung transplantation, together with expertise in functional and integrative medicine.
Her approach combines evidence-based pulmonary medicine with a broader assessment of factors that may influence a patient’s overall health, including nutrition, gastrointestinal health, the gut microbiome, metabolic health, lifestyle, and relevant environmental exposures.
A particular focus of her work is the emerging field of Integrative and Functional Pulmonology, especially in pulmonary fibrosis and autoimmune-associated interstitial lung disease. Her goal is to bridge conventional respiratory medicine with scientifically grounded integrative strategies, while clearly distinguishing established clinical evidence from promising but still experimental research.
Living with Pulmonary Fibrosis or Interstitial Lung Disease?
If you are looking for a more comprehensive assessment that combines specialist pulmonary expertise with a functional and integrative perspective, you can explore whether this approach may be appropriate for your individual condition.
To learn more about consultation options or request an assessment, contact us through the consultation page or WhatsApp.
Integrative care is intended to complement—not replace—evidence-based pulmonary treatment and should always be individualized according to the diagnosis and clinical situation.