DEMAND v1.0
Research type
Research Study
Full title
Defining mechanisms underpinning antibiotic mediated disruption of pulmonary immune responses
IRAS ID
354874
Contact name
Tim Felton
Contact email
Sponsor organisation
The University of Manchester
ISRCTN Number
ISRCTN15326567
Clinicaltrials.gov Identifier
G80788, Manchester University NHS FT Research and Innovation reference
Duration of Study in the UK
2 years, 1 months, 31 days
Research summary
The widespread use of antibiotics, often inappropriately prescribed for viral infections, may be linked to rising asthma rates. There are existing concerns about antibiotic use promoting antimicrobial resistance, however less attention has been given to how changing the body’s normal resident bacteria (the “microbiome”), especially in the gut (which contains the majority of the microbiome), can affect immune function.
Asthma involves what is called “type-2 immunity”. Pilot data from mice, and observational studies in human asthma patients, demonstrate that gut bacteria may help regulate these type-2 responses, but we have not found the actual mechanism of how the immune profile changes when the microbiome is changed. Our study will demonstrate if this relationship, called the “gut-lung axis”, can be replicated in humans and try to define the mechanism that this axis works through.
Recent research also shows that the lungs also have their own microbiome, with a less well-defined relationship with immunity and we will explore this too.
We will explore how antibiotics influence gut and lung bacteria, and the downstream effect on lung and systemic immune profiles. 34 healthy volunteers and 34 with mild asthma, as two separate cohorts, will be randomised to either amoxicillin or a placebo for 7 days. Most healthy adults aged from 18 to 80 years will be eligible to take part, but some conditions that increase the risk of bronchoscopy or that we know independently affect the gut microbiome will be excluded. We will collect lung fluid samples by bronchoscopy before and after treatment, alongside paired nasal swab, fraction of exhaled nitric oxide (FeNO), and blood samples. Over a year, the blood, FeNO, and stool samples will be repeated at intervals to demonstrate how long any observed changes persist.
REC name
London - Bloomsbury Research Ethics Committee
REC reference
25/LO/0649
Date of REC Opinion
24 Sep 2025
REC opinion
Further Information Favourable Opinion