Assessing the Beneficial Effects of the Immunomodulatory Glycan LNFPIII on Gut Microbiota and Health in a Mouse Model of Gulf War Illness

Ryan S. Mote, Jessica M. Carpenter, Rachel L. Dockman, Andrew J. Steinberger, Garret Suen, Thomas Norberg, Donald A. Harn, John J. Wagner and Nikolay M. Filipov
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Ryan S. Mote: Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA
Jessica M. Carpenter: Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA
Rachel L. Dockman: Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA
Andrew J. Steinberger: Department of Bacteriology, University of Wisconsin—Madison, Madison, WI 53706, USA
Garret Suen: Department of Bacteriology, University of Wisconsin—Madison, Madison, WI 53706, USA
Thomas Norberg: Department of Chemistry-BMC, University of Uppsala, 75123 Uppsala, Sweden
Donald A. Harn: Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA
John J. Wagner: Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA
Nikolay M. Filipov: Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA

IJERPH, 2020, vol. 17, issue 19, 1-18

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.

Keywords: Gulf War Illness; gut inflammation and health; gut microbiome; lacto-N-fucopentaose-III (LNFPIII); permethrin; pyridostigmine bromide (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2020
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