Examining the association between the gastrointestinal microbiota and Gulf War illness: A prospective cohort study

Ashley KatesJulie KeatingKelsey BaubieNathan Putman-BuehlerLauren WatsonJared GodfreyCourtney L DebloisGarret SuenDane B CookDavid RabagoRonald GangnonNasia Safdar
PMID: 35901037
PMCID: PMC9333223

Abstract

Gulf War Illness (GWI) affects 25-35% of the 1991 Gulf War Veteran (GWV) population. Patients with GWI experience pain, fatigue, cognitive impairments, gastrointestinal dysfunction, skin disorders, and respiratory issues. In longitudinal studies, many patients with GWI have shown little to no improvement in symptoms since diagnosis. The gut microbiome and diet play an important role in human health and disease, and preliminary studies suggest it may play a role in GWI. To examine the relationship between the gut microbiota, diet, and GWI, we conducted an eight-week prospective cohort study collecting stool samples, medications, health history, and dietary data. Sixty-nine participants were enrolled into the study, 36 of which met the case definition for GWI. The gut microbiota of participants, determined by 16S rRNA sequencing of stool samples, was stable over the duration of the study and showed no within person (alpha diversity) differences. Between group analyses (beta diversity) identified statistically significant different between those with and without GWI. Several taxonomic lineages were identified as differentially abundant between those with and without GWI (n = 9) including a greater abundance of Lachnospiraceae and Ruminococcaceae in those without GWI. Additionally, there were taxonomic differences between those with high and low healthy eating index (HEI) scores including a greater abundance of Ruminococcaceae in those with higher HEI scores. This longitudinal cohort study of GWVs found that participants with GWI had significantly different microbiomes from those without GWI. Further studies are needed to determine the role these differences may play in the development and treatment of GWI.

Figures

Fig 1. Flowchart of study enrollment. 

Note: The database providing contact information for the 1100 Veterans provided mailing addresses for all Veterans aged 43–75 deployed to the Persian Gulf as part of Operation Desert Storm/Desert Shield between 1990 and 1991 who lived in our catchmant area. This was not a clean dataset with many Veterans having multiple addresses listed, addresses that were not current, addresses for Veterans who no longer live in our catchment area, and addresses that were innacurately recorded. This lead to needing to mail a large number of letters to reach a small number of Veterans.

Fig 2. Relative abundance bar plot of the top 8 phyla by aggregated by week and GWI status.

Fig 3. Linear mixed-effects modeling of alpha diversity by week. 

Red line is those with GWI and blue line is the controls. Lighter bands represent the 95% confidence interval of the regression line.

Fig 4. Alpha diversity by week and GWI status stratified by the presence of moderate/severe gastrointestinal symptoms (Yes/No).

Fig 5. NMDS plot of the Bray-Curtis dissimilarity matrix by week and GWI status.