Rothia mucilaginosa is an anti-inflammatory bacterium in the respiratory tract of patients with chronic lung disease

Abstract

Chronic airway inflammation is the main driver of pathogenesis in respiratory diseases, such as severe asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and bronchiectasis. While the role of common pathogens in airway inflammation is widely recognized, the influence of other microbiota members is still poorly understood. Here, we show that Rothia mucilaginosa, a common resident of the oral cavity that is also often detectable in the lower airways in chronic disease, has an inhibitory effect on pathogen- and LPS-induced pro-inflammatory responses, both in vitro (3-D cell culture model) and in vivo (mouse model). Furthermore, in a cohort of adults with bronchiectasis, the abundance of Rothia spp. was negatively correlated with pro-inflammatory markers (IL-8, IL-1β) and matrix metalloproteinases (MMP-1, MMP-8 and MMP-9) in sputum. Mechanistic studies revealed that R. mucilaginosa inhibits NF-κB pathway activation by reducing the phosphorylation of IκB-α and consequently the expression of NF-κB target genes. These findings indicate that the presence of R. mucilaginosa in the lower airways potentially mitigates inflammation, which could in turn influence severity and progression of chronic respiratory disorders.

Commensal Bacteria in the Cystic Fibrosis Airway Microbiome Reduce P. aeruginosa Induced Inflammation

“…It is known that airway epithelial cells have innate sensor functions and may detect microbial signals (Weitnauer et al, 2016). It was shown in a recent report that Rothia mucilaginosa could inhibit host NF-kB pathway activation in a human lung epithelial cell line (Rigauts et al, 2021), and another commensal Prevotella histicola was reported to be able to induce alternative NF-kB activation in CF bronchial epithelial cells (Bertelsen et al, 2020). Earlier work from us has shown that airway epithelial cells adjust their expression pattern of innate immune receptors with less TLR2 and CD36 being expressed, resulting in low reactivity towards microbes that preferentially activate through TLR1/2 or TLR2/6.…”

The Gut Microbiome of Preterm Infants Treated With Aminophylline Is Closely Related to the Occurrence of Feeding Intolerance and the Weight Gain

“…Rothia , a butyrate-producing bacterium, has been found to colonize the human oral cavity and is also part of the characteristic microbiome carried in the gut of vaginally delivered neonates ( 30 ). A cohort study reported that it is one of the most characteristic symbiotic bacteria associated with breast milk and the infant's gut ( 31 ); research in another cohort also showed that this genus may mediate a protective effect against asthma through the metabolite butyrate ( 32 ), reducing chronic airway inflammation ( 33 ). While breastfeeding was an effective method to reduce the incidence of FI ( 34 – 36 ), it was speculated that a low relative abundance of Rothia may be a disadvantage during feeding in the aminophylline-treated preterm infant population.…”

Bronchiectasis enters the inflammation era

“…were negatively correlated with pro-inflammatory mediators, demonstrating that the presence of this organism in the lower airways may reduce inflammation. 6 These studies add to evidence that the interactions between bacteria are important in determining patient outcomes 7 and demonstrate that modulation of the microbiome may be a powerful tool in reducing inflammation. How to modulate the microbiome remains a challenging question.…”

“…While much research has focused on the roles of conventional pathogens such as P. aeruginosa, which are consistently associated with poor clinical outcomes, recent research using next-generation sequencing has given us a more nuanced view of the role of bacteria in BE. 6,7 The concept of 'good bacteria' in the microbiome is well accepted in the gut but poorly defined in the airways. Commensals such as Rothia may have a beneficial effect on inflammation, as demonstrated in a recent study by Rigauts et al Using murine models, Rothia mucilaginosa was shown to have an inhibitory effect on pathogen and LPS-induced proinflammatory responses through inhibiting nuclear factor kappa B (NF-kB) pathway activation.…”

“…While much research has focused on the roles of conventional pathogens such as P . aeruginosa , which are consistently associated with poor clinical outcomes, recent research using next‐generation sequencing has given us a more nuanced view of the role of bacteria in BE 6,7 …”