Full title: Altered gut microbiome in a mouse model of Gulf War Illness causes neuroinflammation and intestinal injury via leaky gut and TLR4 activation Authors: Alhasson F1, Das S1, Seth R1, Dattaroy D1, Chandrashekaran V1, Ryan CN2, Chan LS2, Testerman T3, Burch J4, Hofseth LJ5, Horner R6, Nagarkatti M3, Nagarkatti P3, Lasley SM7, Chatterjee S1. Abstract: Many of the symptoms of Gulf War Illness (GWI) that include neurological abnormalities, neuroinflammation, chronic fatigue and gastrointestinal disturbances have been traced to Gulf War chemical exposure. Though the association and subsequent evidences are strong, the mechanisms that connect exposure to intestinal and neurological abnormalities remain unclear. Using an established rodent model of Gulf War Illness, we show that chemical exposure caused significant dysbiosis in the gut that included increased abundance of phylum Firmicutes and Tenericutes, and decreased abundance of Bacteroidetes. Several gram negative bacterial genera were enriched in the GWI-model that included Allobaculum sp. Altered microbiome caused significant decrease in tight junction protein Occludin with a concomitant increase in Claudin-2, a signature of a leaky gut. Resultant leaching of gut caused portal endotoxemia that led to upregulation of toll like receptor 4 (TLR4) activation in the small intestine and the brain. TLR4 knock out mice and mice that had gut decontamination showed significant decrease in tyrosine nitration and inflammatory mediators IL1β and MCP-1 in both the small intestine and frontal cortex. These events signified that gut dysbiosis with simultaneous leaky gut and systemic endotoxemia-induced TLR4 activation contributes to GW chemical-induced neuroinflammation and gastrointestinal disturbances. Link: https://www.ncbi.nlm.nih.gov/pubmed/28328972 (PLoS One. 2017 Mar 22;12(3)) I found this paper interesting because it raises a hypothesis for a systemic, multi-system illness in terminology we're hearing a lot in ME/CFS discourse currently. The gut-brain axis, leaky gut, dysbiosis, endotoxins, IL1β and TLR4. I imagine a future hypothesis for ME/CFS will look much the same: an extended, multi-systemic series of causes and effects culminating in our patterns of illness.