Administration of Hookworm Excretory/Secretory Proteins Improves Glucose Tolerance in a Mouse Model of Type 2 Diabetes

Khudhair, Zainab, Alhallaf, Rafid, Eichenberger, Ramon M., Field, Matt, Krause, Lutz, Sotíllo, Javier, and Loukas, Alex (2022) Administration of Hookworm Excretory/Secretory Proteins Improves Glucose Tolerance in a Mouse Model of Type 2 Diabetes. Biomolecules, 12 (5). 637.

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Abstract

Diabetes is recognised as the world's fastest growing chronic condition globally. Helminth infections have been shown to be associated with a lower prevalence of type 2 diabetes (T2D), in part due to their ability to induce a type 2 immune response. Therefore, to understand the molecular mechanisms that underlie the development of T2D-induced insulin resistance, we treated mice fed on normal or diabetes-promoting diets with excretory/secretory products (ES) from the gastrointestinal helminth Nippostrongylus brasiliensis. We demonstrated that treatment with crude ES products from adult worms (AES) or infective third-stage larvae (L3ES) from N. brasiliensis improved glucose tolerance and attenuated body weight gain in mice fed on a high glycaemic index diet. N. brasiliensis ES administration to mice was associated with a type 2 immune response measured by increased eosinophils and IL-5 in peripheral tissues but not IL-4, and with a decrease in the level of IL-6 in adipose tissue and corresponding increase in IL-6 levels in the liver. Moreover, treatment with AES or L3ES was associated with significant changes in the community composition of the gut microbiota at the phylum and order levels. These data highlight a role for N. brasiliensis ES in modulating the immune response associated with T2D, and suggest that N. brasiliensis ES contain molecules with therapeutic potential for treating metabolic syndrome and T2D.

Item ID: 74499
Item Type: Article (Research - C1)
ISSN: 2218-273X
Keywords: Diabetes, Eosinophils, Excretory/secretory products, Helminth, M2 macrophage, Nippostrongylus, T helper 2
Copyright Information: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Funders: National Health and Medical Research Council (NHMRC), Australian Research Council (ARC)
Projects and Grants: NHMRC program grant (1132975), ARC strategic research initiative award (SRI40200003)
Date Deposited: 14 Jun 2022 04:29
FoR Codes: 31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310206 Sequence analysis @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320701 Medical bacteriology @ 50%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 100%
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