Gulf War Illness Is Associated with Host Gut Microbiome Dysbiosis and Is Linked to Altered Species Abundance in Veterans from the BBRAIN Cohort

Gulf War Illness (GWI) is a debilitating condition marked by chronic fatigue, cognitive problems, pain, and gastrointestinal (GI) complaints in veterans who were deployed to the 1990-1991 Gulf War. Fatigue, GI complaints, and other chronic symptoms continue to persist more than 30 years post-deployment. Several potential mechanisms for the persistent illness have been identified and our prior pilot study linked an altered gut microbiome with the disorder. This study further validates and builds on our prior preliminary findings of host gut microbiome dysbiosis in veterans with GWI. Using stool samples and Multidimensional Fatigue Inventory (MFI) data from 89 GW veteran participants (63 GWI cases and 26 controls) from the Boston biorepository, recruitment, and integrative network (BBRAIN) for Gulf War Illness, we found that the host gut bacterial signature of veterans with GWI showed significantly different Bray-Curtis beta diversity than control veterans. Specifically, a higher <i>Firmicutes</i> to <i>Bacteroidetes</i> ratio, decrease in <i>Akkermansia</i> sp., <i>Bacteroides thetaiotamicron</i>, <i>Bacteroides fragilis</i>, and <i>Lachnospiraceae</i> genera and increase in <i>Blautia</i>, <i>Streptococcus</i>, <i>Klebsiella</i>, and <i>Clostridium</i> genera, that are associated with gut, immune, and brain health, were shown. Further, using MaAsLin and Boruta algorithms, <i>Coprococcus</i> and <i>Eisenbergiella</i> were identified as important predictors of GWI with an area under the curve ROC predictive value of 74.8%. Higher self-reported MFI scores in veterans with GWI were also significantly associated with an altered gut bacterial diversity and species abundance of <i>Lachnospiraceae</i> and <i>Blautia</i>. These results suggest potential therapeutic targets for veterans with GWI that target the gut microbiome and specific symptoms of the illness.