Huang HJ, Liu PP, Dong DF. Research progress on comorbidity between gastrointestinal and pulmonary diseases from the perspective of the gut-lung axis. World J Gastroenterol 2026; 32(11): 115846 [DOI: 10.3748/wjg.v32.i11.115846]
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05755618
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March 27, 2026, 05:33
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Reader Comments:
The gut–muscle axis shares its conceptual underpinnings with the gut–lung axis, encompassing bidirectional crosstalk driven by gut dysbiosis, microbial translocation, immune dysregulation, and epigenetic modification. Short-chain fatty acids (SCFAs) — most notably butyrate — serve as the principal metabolic intermediary, promoting skeletal muscle protein synthesis and mitochondrial integrity through FFAR2/FFAR3 receptor signaling, AMPK–PGC-1α pathway activation, and PI3K/Akt/mTOR-mediated anabolism, while simultaneously exerting epigenetic regulation via histone deacetylase (HDAC) inhibition.
A mechanistically distinctive feature of the gut–muscle axis is robust retrograde signaling from muscle to gut. Exercise-derived lactate directly fuels SCFA-producing bacteria, and muscle-secreted myokines actively modulate microbial diversity — thereby constituting an actionable, bidirectional feedback loop with no clear counterpart in the gut–lung axis. Furthermore, gut microbiota-derived secondary bile acids activate farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) in skeletal muscle, representing a pathway of particular relevance to gut–muscle biology.
Clinically, dysbiosis-driven SCFA depletion accelerates sarcopenia in aging populations, whereas patients with inflammatory bowel disease (IBD) face compounded muscle wasting attributable to chronic inflammation and nutrient malabsorption. Therapeutic strategies — encompassing probiotics, fecal microbiota transplantation (FMT), and butyrate supplementation — mirror those proposed for the gut–lung axis, with multi-omics integration and AI-driven analytics defining the shared frontier of precision medicine.
In summary, the gut–muscle axis both extends and substantively complements the gut–lung axis paradigm. Crucially, physical activity emerges as a uniquely potent bidirectional therapeutic modality, making it particularly suited for addressing muscle wasting in IBD and aging populations.