First Exploration of the Altered Microbial Gut-Lung Axis in the Pathogenesis of Human Refractory Chronic Cough.

Mario D'Ambrosio, Alessio Fabbrizzi, Giovanni Fontana, Claudia Mannini, Federico Lavorini, Simone Baldi, Leandro Di Gloria, Marco Pallecchi, Gianluca Bartolucci, Giulia Nannini, Cristina Luceri, Amedeo Amedei, Matteo Ramazzotti

Journal: Lung 2024;202(2):107-118

PMID: 38526572

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Abstract

PURPOSE

Cough represents a natural mechanism that plays an important defensive role in the respiratory tract, but in some conditions, it may become persistent, nonproductive, and harmful. In general, refractory chronic cough (RCC) occurs in about 20% of individuals; hence, we aimed to assess the presence of altered gut-lung communication in RCC patients through a compositional and functional characterization of both gut (GM) and oral microbiota (OM).

METHODS

16S rRNA sequencing was used to characterize both GM and OM composition of RCC patients and healthy controls (HC). PICRUST2 assessed functional changes in microbial communities while gas chromatography was used to evaluate fecal short-chain fatty acid levels and serum-free fatty acid (FFA) abundances.

RESULTS

In comparison with HC, RCC patients reported increased saliva alpha-diversity and statistically significant beta-diversity in both GM and OM. Also, a, respectively, significant increased or reduced Firmicutes/Bacteroidota ratio in stool and saliva samples of RCC patients has been shown, in addition to a modification of the abundances of several taxa in both GM and OM. Moreover, a potential fecal over-expression of lipopolysaccharide biosynthesis and lipoic acid metabolism pathways and several differences in serum FFA levels have been reported in RCC patients than in HC.

CONCLUSION

Since differences in both GM and OM of RCC patients have been documented, these findings could provide new information about RCC pathogenesis and also pave the way for the development of novel nutritional or pharmacological interventions for the management of RCC through the restoration of eubiotic gut-lung communication.

Address: Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Florence, Italy.; Department of Respiratory Physiopathology, Palagi Hospital, 50122, Florence, Italy.; Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", University of Florence, 50134, Florence, Italy.; Department of Neuroscience, Psychology, Drug Research and Child Health NEUROFARBA, University of Florence, 50139, Florence, Italy.; Department of Neuroscience, Psychology, Drug Research and Child Health NEUROFARBA, University of Florence, 50139, Florence, Italy.; Enteric Neuroscience Program, Department of Medicine, Section of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 55905, USA.; Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Florence, Italy. [email protected].; Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Florence, Italy. [email protected].; SOD of Interdisciplinary Internal Medicine, Azienda Ospedaliera Universitaria Careggi (AOUC), 50134, Florence, Italy. [email protected].

DOI: 10.1007/s00408-024-00681-7