The ROS-generating enzyme NADPH oxidase 1 modulates the colonic microbiota but offers minor protection against dextran sulfate sodium-induced low-grade colon inflammation in mice.

Autor: Herfindal AM; Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, P. O. Box 5003, N-1432, Ås, Norway. Electronic address: anne.mari.herfindal@nmbu.no., Rocha SDC; Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, P. O. Box 5003, N-1432, Ås, Norway; Faculty of Biosciences, Norwegian University of Life Sciences, P. O. Box 5003, N-1432, Ås, Norway. Electronic address: sergio.rocha@nmbu.no., Papoutsis D; Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, P. O. Box 5003, N-1432, Ås, Norway. Electronic address: dimitrios.papoutsis@nmbu.no., Bøhn SK; Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, P. O. Box 5003, N-1432, Ås, Norway. Electronic address: siv.kjolsrud.bohn@nmbu.no., Carlsen H; Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, P. O. Box 5003, N-1432, Ås, Norway. Electronic address: harald.carlsen@nmbu.no.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2022 Aug 01; Vol. 188, pp. 298-311. Date of Electronic Publication: 2022 Jun 23.
DOI: 10.1016/j.freeradbiomed.2022.06.234
Abstrakt: The enzyme NADPH oxidase 1 (NOX1) is a major producer of superoxide which together with other reactive oxygen and nitrogen species (ROS/RNS) are implicated in maintaining a healthy epithelial barrier in the gut. While previous studies have indicated NOX1's involvement in microbial modulation in the small intestine, less is known about the effects of NOX1-dependent ROS/RNS formation in the colon. We investigated the role of NOX1 in the colon of NOX1 knockout (KO) and wild type (WT) mice, under mild and subclinical low-grade colon inflammation induced by 1% dextran sulfate sodium (DSS). Ex vivo imaging of ROS/RNS in the colon revealed that absence of NOX1 strongly decreased ROS/RNS production, particularly during DSS treatment. Furthermore, while absence of NOX1 did not affect disease activity, some markers of inflammation (mRNA: Tnfa, Il6, Ptgs2; protein: lipocalin 2) in the colonic mucosa tended to be higher in NOX1 KO than in WT mice following DSS treatment. Lack of NOX1 also extensively modulated the bacterial community in the colon (16S rRNA gene sequencing), where NOX1 KO mice were characterized mainly by lower α-diversity (richness and evenness), higher abundance of Firmicutes, Akkermansia, and Oscillibacter, and lower abundance of Bacteroidetes and Alistipes. Together, our data suggest that NOX1 is pivotal for colonic ROS/RNS production in mice both during steady-state (i.e., no DSS treatment) and during 1% DSS-induced low-grade inflammation and for modulation of the colonic microbiota, with potential beneficial consequences for intestinal health.
(Copyright © 2022. Published by Elsevier Inc.)
Databáze: MEDLINE
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