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

Author

Listed:
  • Ryan S. Mote

    (Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA
    Authors contributed equally.)

  • Jessica M. Carpenter

    (Department of Physiology and Pharmacology, University of Georgia, Athens, GA 30602, USA
    Authors contributed equally.)

  • 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
    Center for Tropical and Emerging 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)

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.

Suggested Citation

  • Ryan S. Mote & Jessica M. Carpenter & Rachel L. Dockman & Andrew J. Steinberger & Garret Suen & Thomas Norberg & Donald A. Harn & John J. Wagner & Nikolay M. Filipov, 2020. "Assessing the Beneficial Effects of the Immunomodulatory Glycan LNFPIII on Gut Microbiota and Health in a Mouse Model of Gulf War Illness," IJERPH, MDPI, vol. 17(19), pages 1-18, September.
  • Handle: RePEc:gam:jijerp:v:17:y:2020:i:19:p:7081-:d:420608
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    References listed on IDEAS

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    1. Patricia A. Janulewicz & Ratanesh K. Seth & Jeffrey M. Carlson & Joy Ajama & Emily Quinn & Timothy Heeren & Nancy Klimas & Steven M. Lasley & Ronnie D. Horner & Kimberly Sullivan & Saurabh Chatterjee, 2019. "The Gut-Microbiome in Gulf War Veterans: A Preliminary Report," IJERPH, MDPI, vol. 16(19), pages 1-14, October.
    2. Clara G. Zundel & Maxine H. Krengel & Timothy Heeren & Megan K. Yee & Claudia M. Grasso & Patricia A. Janulewicz Lloyd & Steven S. Coughlin & Kimberly Sullivan, 2019. "Rates of Chronic Medical Conditions in 1991 Gulf War Veterans Compared to the General Population," IJERPH, MDPI, vol. 16(6), pages 1-16, March.
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