Alterations of lung microbial communities in obese allergic asthma and metabolic potential

Abstract

In recent years, there has been a rapid increase in microbiome studies to explore microbial alterations causing disease status and unveil disease pathogenesis derived from microbiome environmental modifications. Convincing evidence of lung microbial changes involving asthma has been collected; however, whether lung microbial changes under obesity leads to severe asthma in a state of allergen exposure has not been studied sufficiently. Here, we measured bacterial alterations in the lung of an allergen mouse model induced by a high fat diet (HFD) by using 16S rRNA gene sequencing. A total of 33 pathogen‑free 3‑week‑old male C57BL/6 mice were used, and they divided randomly into two groups. The Chow diet (n = 16) and high fat diet (n = 17) was administrated for 70 days. Mice were sensitized with PBS or Dermatophagoides pteronyssinus extract (Der.p), and concentration levels of total IgE and Der.p-IgE in the blood were measured to quantify immune responses. Although there were no meaningful differences in bacterial species richness in the HFD mouse group, momentous changes of bacterial diversity in the HFD mouse group were identified after the mouse group was exposed to allergens. At a genus level, the fluctuations of taxonomic relative abundances in several bacteria such as Ralstonia, Lactobacillus, Bradyrhizobium, Gaiella, PAC001932_g, Pseudolabrys, and Staphylococcus were conspicuously observed in the HFD mouse group exposed to allergens. Also, we predicted metabolic signatures occurring under microbial alterations in the Chow group versus the Chow group exposed to allergens, as well as in the HFD mouse group versus the HFD group exposed to allergens. We then compared their similarities and differences. Metabolic functions associated with macrophages such as propanoate metabolism, butanoate metabolism, and glycine-serine-threonine metabolism were identified in the HFD group versus the Chow group. These results provide new insights into the understanding of a microbiome community of obese allergic asthma, and shed light on the functional roles of lung microbiota inducing the pathogenesis of severe asthma.

Airway immune response in the mouse models of obesity-related asthma

“…Other immune cells were identified in the male model. Increases in M1 and decreases in M2 and AMs were found in obesity-related asthma, possibly consistent with an obese state ( Lee et al, 2021 ). NKT and CD69 + NKT cells increased in the HFD/OVA-induced model.…”

“…The abundance of a specific lung microbiome differed between lean and obese mice exposed to Der. p , which revealed metabolic signatures related to an obese asthma phenotype ( Lee et al, 2021 ). Traditional Chinese medicine is effective in treating obese asthma, such as celastrol, which can suppress AHR through Th17 inhibition ( Zeng et al, 2018 ).…”

Gut‐lung axis and asthma: A historical review on mechanism and future perspective

“…In fact, different types of gut microbiota affect asthma via the gut‐lung axis with different pathological changes. For example, the decreased abundances of gut microbiota such as lachnospira , veillonella , faecalibacterium and rothia increase the risk of asthma 109,110 . Moraxella catarrhalis can cause lung neutrophil infiltration, IL‐6 and TNF‐α elevated and moderate levels of CD4T cell‐derived IFN‐γ and lung IL‐17 69 .…”

“…For example, the decreased abundances of gut microbiota such as lachnospira , veillonella , faecalibacterium and rothia increase the risk of asthma. 109 , 110 Moraxella catarrhalis can cause lung neutrophil infiltration, IL‐6 and TNF‐α elevated and moderate levels of CD4T cell‐derived IFN‐γ and lung IL‐17. 69 By contrast, high doses of ICS treatment in patients with neutrophilic asthma can lead to the transformation of steroid‐sensitive diseases into steroid‐resistant diseases, manifested by relative enrichment of Haemophilus .…”

“…In fact, different types of gut microbiota affect asthma via the gutlung axis with different pathological changes. For example, the decreased abundances of gut microbiota such as lachnospira, veillonella, faecalibacterium and rothia increase the risk of asthma 109,110. SONG ET AL.…”