Increased butyrate priming in the gut stalls microbiome associated-gastrointestinal inflammation and hepatic metabolic reprogramming in a mouse model of Gulf War Illness

Toxicology and Applied Pharmacology
Ratanesh Kumar SethSaurabh Chatterjee

Abstract

Most of the associated pathologies in Gulf War Illness (GWI) have been ascribed to chemical and pharmaceutical exposures during the war. Since an increased number of veterans complain of gastrointestinal (GI), neuroinflammatory and metabolic complications as they age and there are limited options for a cure, the present study was focused to assess the role of butyrate, a short chain fatty acid for attenuating GWI-associated GI and metabolic complications. Results in a GWI-mouse model of permethrin and pyridostigmine bromide (PB) exposure showed that oral butyrate restored gut homeostasis and increased GPR109A receptor copies in the small intestine (SI). Claudin-2, a protein shown to be upregulated in conditions of leaky gut was significantly decreased following butyrate administration. Butyrate decreased TLR4 and TLR5 expressions in the liver concomitant to a decrease in TLR4 activation. GW-chemical exposure showed no clinical signs of liver disease but a significant alteration of metabolic markers such as SREBP1c, PPAR-α, and PFK was evident. Liver markers for lipogenesis and carbohydrate metabolism that were significantly upregulated following GW chemical exposure were attenuated by butyrate priming in vivo and in human prima...Continue Reading

Citations

Oct 9, 2019·International Journal of Environmental Research and Public Health·Patricia A JanulewiczSaurabh Chatterjee
Oct 1, 2020·International Journal of Environmental Research and Public Health·Ryan S MoteNikolay M Filipov
Jun 14, 2020·Scientific Reports·Mariana Angoa-PérezDonald M Kuhn
Dec 7, 2018·Current Opinion in Allergy and Clinical Immunology·Peggy S Lai, David C Christiani
Jan 24, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Liwei WuChuanyong Guo
Nov 10, 2020·Pharmacology & Therapeutics·Brandon DickeyAshok K Shetty
Jun 18, 2021·Life Sciences·Saurabh ChatterjeeRatanesh Seth
Jun 26, 2021·Pharmacology & Therapeutics·Ana C R Ribeiro, Laxmikant S Deshpande
Sep 7, 2021·Journal of Occupational and Environmental Medicine·Erin K DursaAaron I Schneiderman

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