Impact of Parabacteroides distasonis colonization on host microbiome, metabolome, immunity, and diabetes onset

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F25%3A00638839" target="_blank" >RIV/61388971:_____/25:00638839 - isvavai.cz</a>

Result on the web

<a href="https://jme.bioscientifica.com/view/journals/jme/75/2/JME-25-0025.xml" target="_blank" >https://jme.bioscientifica.com/view/journals/jme/75/2/JME-25-0025.xml</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1530/JME-25-0025" target="_blank" >10.1530/JME-25-0025</a>

Result language

angličtina

Original language name

Impact of Parabacteroides distasonis colonization on host microbiome, metabolome, immunity, and diabetes onset

Original language description

Type 1 diabetes (T1D) is caused by autoimmune destruction of pancreatic β-cells. The insulin B-chain 9-23 (insB9-23) peptide is a critical epitope in triggering T1D. In our previous study, we showed that Parabacteroides distasonis, a human gut commensal, contains an insB9-23 mimic in its hprt protein (residues 4-18). This mimic (hprt4-18) peptide activates insB9-23-specific T cells, and P. distasonis colonization enhanced diabetes in NOD mice. However, the impact of the P. distasonis colonization on inflammation, gut microbiome, intestinal immune cells, gut permeability, cytokine, and serum metabolome profiles remained unknown. Here, we investigated these effects using specific pathogen-free (SPF) and germ-free (GF) female NOD mice. P. distasonis colonization minimally impacted gut microbiome composition, altering only 28 ASVs. In P. distasonis-colonized mice, there was a reduction in T-helper, T-effector, and B-cell populations in the intraepithelial lymphocytes, indicating a potential decrease in immune activation. Furthermore, P. distasonis colonization did not alter serum metabolome and circulating cytokine profiles (except for a decrease in IL-15) and gut permeability gene expressions. P. distasonis colonization in GF NOD mice induced severe insulitis without affecting gut permeability. Interestingly, mice gavaged with heat-inactivated (HI) P. distasonis did not affect insulitis scores or immune cell composition. These findings support our hypothesis that P. distasonis functions as a gut commensal, exerting no effect on the gut microbiome, metabolome, gut permeability, intestinal immune cell composition, or nonspecific immune activation. Instead, P. distasonis appears to trigger an insB9-23-specific immune response, potentially accelerating T1D onset in NOD mice through molecular mimicry.

Czech name

—

Czech description

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Type

J_SC - Article in a specialist periodical, which is included in the SCOPUS database

CEP classification

—

OECD FORD branch

30202 - Endocrinology and metabolism (including diabetes, hormones)

Project

<a href="/en/project/EH22_008%2F0004597" target="_blank" >EH22_008/0004597: Talking microbes - understanding microbial interactions within One Health framework</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Molecular Endocrinology

ISSN

0952-5041

e-ISSN

1479-6813

Volume of the periodical

75

Issue of the periodical within the volume

2

Country of publishing house

GB - UNITED KINGDOM

Number of pages

16

Pages from-to

e250025

UT code for WoS article

001567555400007

EID of the result in the Scopus database

2-s2.0-105014374991