Host gut resistome in Gulf War chronic multisymptom illness correlates with persistent inflammation
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Dipro Bose1, Somdatta Chatterjee1, Ethan Older2
1Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA.
Abstract:
Chronic multisymptom illness (CMI) affects a subsection of elderly and war Veterans and is associated with systemic inflammation. Here, using a mouse model of CMI and a group of Gulf War (GW) Veterans' with CMI we show the presence of an altered host resistome. Results show that antibiotic resistance genes (ARGs) are significantly altered in the CMI group in both mice and GW Veterans when compared to control. Fecal samples from GW Veterans with persistent CMI show a significant increase of resistance to a wide class of antibiotics and exhibited an array of mobile genetic elements (MGEs) distinct from normal healthy controls. The altered resistome and gene signature is correlated with mouse serum IL-6 levels. Altered resistome in mice also is correlated strongly with intestinal inflammation, decreased synaptic plasticity, reversible with fecal microbiota transplant (FMT). The results reported might help in understanding the risks to treating hospital acquired infections in this population.
Insights
Chronic multisymptom illness (CMI) in veterans is linked to an altered host resistome, with increased antibiotic resistance genes. Fecal microbiota transplant reversed some CMI symptoms in a mouse model.
Area of Science:
- Microbiology
- Immunology
- Veterans' Health
Background:
- Chronic multisymptom illness (CMI) affects veterans and is linked to systemic inflammation.
- The host resistome, including antibiotic resistance genes (ARGs), plays a role in CMI.
Purpose of the Study:
- To investigate the host resistome in a mouse model of CMI and in Gulf War (GW) Veterans with CMI.
- To explore the correlation between the altered resistome, inflammation, and neurological function.
Main Methods:
- Comparative analysis of ARGs and mobile genetic elements (MGEs) in fecal samples from CMI patients and controls.
- Correlation analysis between resistome alterations, serum IL-6 levels, and intestinal inflammation in a mouse model.
- Assessment of synaptic plasticity and the effects of fecal microbiota transplant (FMT) in the mouse model.
Main Results:
- Significantly altered ARGs were observed in both the mouse model and GW Veterans with CMI compared to controls.
- GW Veterans with CMI showed increased antibiotic resistance and distinct MGEs.
- Altered resistome in mice correlated with increased IL-6, intestinal inflammation, and decreased synaptic plasticity, which was reversible with FMT.
Conclusions:
- CMI is associated with a distinct and altered host resistome in both animal models and human veterans.
- The findings suggest a potential link between the gut microbiome, antibiotic resistance, and CMI pathogenesis.
- Understanding the altered resistome may inform strategies for treating hospital-acquired infections in veterans with CMI.
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