The presence of Rothia mucilaginosa in the lower respiratory tract potentially inhibits inflammation, which, in turn, could impact the severity and progression of chronic respiratory disorders, according to research published in the European Respiratory Journal.

For the study, researchers in Belgium examined the immunomodulatory effects of several members of the lung microbiota, often reported as being detected in the lower respiratory tracts of patients with cystic fibrosis (CF).The researchers theorized that the lung microbiota contains bacteria with immunomodulatory activity, which regulate net levels of immune activation by such key respiratory pathogens as Pseudomonas aeruginosa. The immunomodulatory effects of certain components of the lung microbiota were assessed, including such recognized pathogens as Staphylococcus  aureus, such less frequently recovered pathogens as Achromobacter xylosoxidans and Streptococcus anginosus, and such upper respiratory tract commensals as R mucilaginosa and Gemella haemolysans. Findings showed that R mucilaginosa exhibits anti-inflammatory activity in vitro, which was subsequently validated in an animal model of lung inflammation, as well as in a cohort of patients with neutrophilic airway disease.

R mucilaginosa, which is also a common resident of the oral cavity, has an inhibitory effect on pathogen- and lipopolysaccharide (LPS)-induced pro-inflammatory responses, both in vitro (per a 3-dimensional [3-D] cell culture model) and in vivo (per a mouse model). Additionally, in a cohort of adult patients with bronchiectasis, the profusion of Rothia species was negatively associated with pro-inflammatory markers, such as interleukin (IL)-8 and IL-1β, as well as with matrix metalloproteinases (MMPs), including MMP-1, MMP-8, and MMP-9, in sputum.


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Further, mechanistic studies have shown that R mucilaginosa inhibits activation of the nuclear factor kappa B (NF-κB) pathway by decreasing phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor-alpha (IκB-α) and thus expression of NF-κB target genes.

Results of the study showed that R mucilaginosa inhibits production of pro-inflammatory cytokines by lung epithelial cells in vitro. Additionally, R mucilaginosa lowers the LPS-generated pro-inflammatory response in an in vivo mouse model. Overall, Rothia species were shown to inhibit NF-κB pathway activation in epithelial cells. R mucilaginosa supernatant inhibits the production of IL-8 and NF-κB pathway activation in response to pro-inflammatory stimuli in 3-D lung epithelial cells. In patients with neutrophilic airway disease, an inverse relationship was demonstrated between airway inflammation and Rothia species. 

Thus, common members of the lung microbiota in the Rothia species exert anti-inflammatory properties in vitro, with this effect also apparent in vivo in R mucilaginosa. In fact, R mucilaginosa is frequently considered to be part of the salivary contamination of samples obtained from the lower airways.

“The discovery of Rothia as an anti-inflammatory genus in the lung microbiota raises the question whether other non-pathogenic commensals in the respiratory tract, in particular originating from the oral cavity, may have immunomodulatory properties,” the study authors wrote.

Prospective studies designed to evaluate the clinical utility of R mucilaginosa as a marker of airway inflammation and the extent to which this species may provide a basis for the development of novel therapeutics are now warranted.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Rigauts C, Aizawa J, Taylor S, et al. Rothia mucilaginosa is an anti-inflammatory bacterium in the respiratory tract of patients with chronic lung disease. Eur Respir J. Published online September 29, 2021. doi:10.1183/13993003.01293-2021