Abstract
The microbiota’s influence on host (patho) physiology has gained interest in the context of Gulf War Illness (GWI), a chronic disorder featuring dysregulation of the gut–brain–immune axis. This study examined short- and long-term effects of GWI-related chemicals on gut health and fecal microbiota and the potential benefits of Lacto-N-fucopentaose-III (LNFPIII) treatment in a GWI model. Male C57BL/6J mice were administered pyridostigmine bromide (PB; 0.7 mg/kg) and permethrin (PM; 200 mg/kg) for 10 days with concurrent LNFPIII treatment (35 μg/mouse) in a short-term study (12 days total) and delayed LNFPIII treatment (2×/week) beginning 4 months after 10 days of PB/PM exposure in a long-term study (9 months total). Fecal 16S rRNA sequencing was performed on all samples post-LNFPIII treatment to assess microbiota effects of GWI chemicals and acute/delayed LNFPIII administration. Although PB/PM did not affect species composition on a global scale, it affected specific taxa in both short- and long-term settings. PB/PM elicited more prominent long-term effects, notably, on the abundances of bacteria belonging to Lachnospiraceae and Ruminococcaceae families and the genus Allobaculum. LNFPIII improved a marker of gut health (i.e., decreased lipocalin-2) independent of GWI and, importantly, increased butyrate producers (e.g., Butyricoccus, Ruminococcous) in PB/PM-treated mice, indicating a positive selection pressure for these bacteria. Multiple operational taxonomic units correlated with aberrant behavior and lipocalin-2 in PB/PM samples; LNFPIII was modulatory. Overall, significant and lasting GWI effects occurred on specific microbiota and LNFPIII treatment was beneficial.
Highlights
Gulf War Illness (GWI), which afflicts one-third of the veterans from the 1990–1991 Gulf War (GW), is a chronic disorder presenting with a myriad of debilitating symptoms, including neurological, musculoskeletal, immunological and gastrointestinal disturbances that appeared shortly after veterans returned from deployment and have persisted or worsened throughout the last 30 years [1]
Composition of the microbiota on a global scale, this study found that both pyridostigmine bromide (PB)/PM and Lacto-N-fucopentaose III (LNFPIII) resulted in the enrichment/depletion of specific bacterial taxa, and that some bacterial OTUs were significantly correlated with GWIphysiological endpoints of interest
This study provides additional evidence to support previous work showing that GWI-related chemical exposure induces significant perturbations of select bacterial taxa of the mouse GI microbiota
Summary
Gulf War Illness (GWI), which afflicts one-third of the veterans from the 1990–1991 Gulf War (GW), is a chronic disorder presenting with a myriad of debilitating symptoms, including neurological, musculoskeletal, immunological and gastrointestinal disturbances that appeared shortly after veterans returned from deployment and have persisted or worsened throughout the last 30 years [1].Epidemiological evidence suggests that co-exposure to numerous toxicants, including neuro-prophylactics (pyridostigmine bromide: PB), pesticides (permethrin: PM and N,N-Diethyl-methylbenzamide: DEET), and chemical nerve agents (sarin) during the GW may be linked to GWI etiopathogenesis [1]. Gulf War Illness (GWI), which afflicts one-third of the veterans from the 1990–1991 Gulf War (GW), is a chronic disorder presenting with a myriad of debilitating symptoms, including neurological, musculoskeletal, immunological and gastrointestinal disturbances that appeared shortly after veterans returned from deployment and have persisted or worsened throughout the last 30 years [1]. Previous work suggests GW-related exposures accelerate age-related chronic conditions, such as high blood pressure, increased heart attack and stroke risk, diabetes, and arthritis [2]; many of the persisting symptoms. GWI veterans experience (i.e., cognitive, memory and motor impairments) could be exacerbated by accelerated aging [1,2]. GI disturbances precede PD motor dysfunction, and a recent study suggests that aberrant gut–brain–immune axis plays a role in the neurobehavioral deficits in this disease [7]
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