- Title
- Characterisation of the immune cell-microbiome interaction within the gut-lung axis in cigarette smoke induced experimental COPD
- Creator
- Alemao, Charlotte
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2023
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- COPD is a prevalent, progressive disease with a significant socioeconomic burden. The gut-lung axis has been implicated in COPD pathogenesis, partly due to immune regulation by the gastrointestinal microbiome on responses in the lung. Although the mechanisms of this relationship are unclear, the gut microbiome is vital in regulating the differentiation and recruitment of immune cells in multiple body sites. This thesis reports on the understanding and characterising of the microbiome-immune cell interplay within the gut-lung axis in cigarette smoke induced experimental COPD model. Our study demonstrated that recolonisation of mice with faeces from cigarette smoke-exposed mice alone reduced immune cells in the gut and spleen but increased immune cells in the lung, which suggests a divergent effect of the cigarette smoke microbiome on different organs within the gut-lung axis. Moreover, cigarette smoke suppresses mature resident macrophages in the gut, leading to vulnerability to pathogenic microbiome members. Long-lived macrophages rely on a healthy microbiome and were significantly affected after faecal microbiota transplantation from cigarette smoke-exposed mice. Maintaining a healthy microbiome is crucial for gut health. Nonetheless, the underlying mechanisms behind how gut microbiota dysbiosis affects the immune cell profile in the lung are not fully understood. One hypothesis is that macrophages may be redirected to the lung, which could explain the decreased numbers observed in both the spleen and gut. We then showed that antibiotics did not have an effect initially but is showed to have a prolonged effect on immune cell profiles and population numbers in the gut-lung axis, likely via the bone marrow. Antibiotics in the short-term model caused a collagen build up and alveolar destruction in the lungs, that suggests that antibiotics administered through oral gavage to the gut can affect systemic organs and may even create a pro-inflammatory environment in the lungs, possibly via the bone marrow. The effects are short-term in a ten-week model, but alveolar destruction persists and may increase disease susceptibility, particularly in cigarette smoke induced COPD. Recolonisation with FMT from air-exposed mice was beneficial in alleviating the consequences of antibiotic-induced dysbiosis. Our study found that recolonizing mice with air microbiome after antibiotics helps maintain immune cell levels similar to control groups. This effect was observed in the colon, lungs, and histology. Recolonization 9 with air microbiome is an effective way to restore a healthy gut ecosystem after antibiotics and provides protection to the gut. Lastly, we demonstrated that human Beta defensin 2, a cysteine-rich cationic low molecular weight antimicrobial peptide decreases immune cell numbers in the gut and lung upon cigarette smoke exposure, supporting the probability of having protective and anti-inflammatory functions against cigarette smoke-caused inflammation. In conclusion, this project aimed to understand the effects caused by gut microbiome modifications and their immunological impact on the gut-lung axis in the presence of cigarette smoke. Gut dysbiosis caused by antibiotics significantly altered the immune cell populations and was made worse by cigarette smoke exposure, whereas gut microbiome modification by antimicrobial peptide-hBD2 acted as a protective effect against long-term cigarette smoke in the gut-lung axis.
- Subject
- COPD; hBD2; gut-Lung axis; gut microbiome; cigarette smoke; faecal recolonisation
- Identifier
- http://hdl.handle.net/1959.13/1479285
- Identifier
- uon:50285
- Rights
- Copyright 2023 Charlotte Alemao
- Language
- eng
- Full Text
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 9 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 307 KB | Adobe Acrobat PDF | View Details Download |