15 Nov 2022

Obesity-related gut damage may worsen asthma symptoms

Changes in gut function caused by weight gain are associated with an increase in asthma severity, according to research to be presented at the Society for Endocrinology annual conference in Harrogate. The study reports a significant association of increasing body weight with higher levels of inflammation, signs of gut permeability, and poorer control of asthma. These findings not only suggest that losing weight could improve symptoms for patients with severe asthma but also highlights the gut as a potential, alternative therapeutic target for improving asthma control in patients with obesity.

Weight gain has previously been shown to alter the composition of gut bacteria, which can lead to increased gut permeability. Having a ‘leaky gut’ can allow harmful bacteria to enter the bloodstream, triggering inflammatory responses throughout the body. Asthma is a chronic inflammatory condition known to be exacerbated in patients with obesity. Although it is common, if poorly controlled it can lead to serious complications including fatigue, lung infections and an increased risk of severe asthma attacks, which can be life threatening. How increased gut permeability may affect asthma control has not previously been investigated.

Cristina Parenti and colleagues at Nottingham Trent University examined the relationship between body weight and gut permeability with the symptoms of 98 patients with severe asthma. Patients with lean to obese body mass index (BMI) reported their symptoms using the Asthma Control Questionnaire-6. Blood tests were taken to measure levels of gut permeability markers (lipopolysaccharide binding protein (LPB)) and calprotectin), as well as markers of asthma-related inflammation (granzyme-A, IL-5, IL-6, CCL-4). Patients with poorly controlled asthma had significantly higher levels of LBP and levels of LBP increased with increasing body weight. Increasing concentrations of LBP also correlated with higher levels of asthma-related inflammatory markers.

Lead investigator, Cristina Parenti, comments, “We have found a significant link between gut permeability, being overweight and poor asthma control, particularly in people with obesity. This suggests that dietary interventions to improve gut barrier function may be an effective, alternative treatment target for asthma patients who are overweight or have obesity.”

The current study included only a small number of patients with severe, uncontrolled asthma. The team now plan to recruit more patients to the study and to investigate the effects in participants with well-controlled asthma, over a range of BMIs, as well as examining whether targeting the gut can improve asthma control in affected patients.

Cristina Parenti concludes, “Our initial findings show that increased gut permeability is likely to be a factor in worsening asthma symptoms in patients with obesity, so it will be interesting to look at whether dietary interventions can improve symptoms for these patients.”

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Abstract: P211

Investigating the effect of obesity on gut damage, systemic inflammation, enhanced asthma severity due to gut derived bacteria, endotoxin

Cristina Parenti¹, Alice M. Murphy², Nikita Lad¹, Philip G. McTernan³, Carl P. Nelson⁴, Graham R. Sharpe³, Claire Barber^5,6, Rana Abadalkareem^5,6, Adnan Azim^5,6, Ramesh J. Kurukulaaratchy^5,6, Hans M. Haitchi^5,6, Neil C. Williams¹

¹Nottingham Trent University, Nottingham, United Kingdom. ²Nottinham Trent University, Nottingham, United Kingdom. ³Nottingham Trent University, Nottingham, United Kingdom. ⁴Nottigham Trent University, Nottingham, United Kingdom. ⁵University of Southampton, Southampton, United Kingdom. ⁶University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom

Background: Obesity exacerbates a number of chronic inflammatory diseases including asthma, with increasing adiposity observed to worsen asthma severity and disease control. This exacerbation may arise as gut-derived bacterial fragments (endotoxin) and associated markers of endotoxin (lipopolysaccharide binding protein (LPB)), enter the circulation through a damaged gut barrier, provoking systemic inflammation. This study investigated the role of body weight on gut permeability and systemic inflammation, to influence asthma control and asthma status.  

Methods: Fasted blood was collected from Caucasian men (age:52.72±16.08yrs; BMI: 29.16±5.69Kg/m2; n=29) and women (age: 46.42±14.60yrs; BMI: 32.34±7.48Kg/m2; n=69) with severe asthma, with and without obesity. Gut permeability marker Calprotectin, LBP and inflammatory markers (granzyme-A,IL-5,IL-6,CCL-4) were assessed in serum and plasma by ELISA. Anthropometric data and Asthma Control Questionnaire-6 (ACQ-6) data were collected.

Results: Our findings highlighted that BMI significantly correlated with self-reported impaired asthma control (ACQ-6score≥1.5;p<0.05). Significant positive correlations were identified between BMI and pro-inflammatory biomarkers (granzyme A,p<0.001;IL-6, CCL-4, IL-5, all p<0.0001). In addition, analysis of circulating LBP showed that patients with poorly controlled asthma (ACQ-6 score≥1.5) had increased LBP levels compared with well controlled patients with asthma (LBP:15.10±7.88µg/mL Vs 10.95±4.5 µg/mL; p=0.0279). Furthermore, irrespective of asthma control, LBP was increased in patients with obesity (LBP:17.06±8.35µg/mL) compared with patients who were overweight (LPB:11.83±6.6µg/mL; p=0.0003) or lean (LBP:11.36±4.27µg/mL; p=0.0004). LBP levels were also significantly positively correlated with BMI (p<0.0001), permeability marker (p<0.0001) and inflammatory biomarkers (p<0.05).

Conclusion: In summary, patients with asthma and obesity were observed to experience impaired asthma control, with increased gut permeability and raised inflammatory mediators and markers. These data therefore suggest that reducing body weight, or therapeutically targeting the gut to reduce gut permeability, may offer people with obesity and severe asthma some improvement in their chronic inflammation conditions and disease management