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\begin{document}

\title{Alkaline phosphatase relieves colitis in obese mice subjected to forced
exercise via its antiinflammatory and intestinal microbiota-shaping
properties}



\author[1]{Dagmara Wojcik}%
\author[1]{Zbigniew Sliwowski}%
\author[1]{Slawomir Kwiecien}%
\author[2]{Grzegorz Ginter}%
\author[2]{Marcin Surmiak}%
\author[2]{Magdalena Hubalewska-Mazgaj}%
\author[1]{Anna Chmura}%
\author[1]{Adrianna Wojcik}%
\author[1]{Tomasz Kosciolek}%
\author[1]{Aleksandra Danielak}%
\author[1]{Aneta Targosz}%
\author[1]{Malgorzata Strzalka}%
\author[1]{Urszula Szczyrk}%
\author[1]{Agata Ptak-Belowska}%
\author[1]{Marcin Magierowski}%
\author[1]{Thomas Brzozowski}%
\affil[1]{Jagiellonian University in Kraków Medical College}%
\affil[2]{Jagiellonian University in Kraków Faculty of Medicine}%


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  \date{June 18, 2024}


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\begin{abstract}
Background and Purpose Intestinal alkaline phosphatase (IAP) is an
important apical brush border enzyme that dephosphorylates
lipopolysaccharide released from bacteria. Considering its protective
effect, we determined the effect of intragastric administration of IAP
on the course of experimental colitis in mice exercising on a forced
treadmill with diet-induced obesity. Experimental approach C57BL/6 mice
with TNBS colitis fed a high-fat diet (HFD) were subjected to forced
treadmill exercise with or without intragastric treatment with IAP. Grip
muscle strength and disease activity index (DAI) were monitored, pro-
and anti-inflammatory cytokines and markers of oxidative stress were
measured by Luminex and ELISA, respectively. The mRNA expression of the
barrier proteins ZO-1, MUC2 and claudins was assessed by RT-PCR, and the
fecal composition of the intestinal microbiota was assessed by the NGS.
Key results Significant increases in DAI, MDA+4-HNE in the colonic
mucosa, and plasma leptin, MCP, TNF-\selectlanguage{greek}α, \selectlanguage{english}IL-6, and IL-17a were observed in
obese mice with colitis on a treadmill, and these effects have been
significantly reduced by IAP treatment. IAP increased ZO-1, claudins and
Muc2 mRNAs expression in the colonic mucosa. NGS revealed the relative
proportion of Firmicutes in favor of higher Verrucomicbiota content and
reducing the incidence of pathogenic Clostridia and Odoribacter.
Conclusions and Implications IAP treatment ameliorates the worsening
effect of forced exercise on murine colitis due to attenuation of
oxidative stress, downregulation of pro-inflammatory biomarkers in the
colonic mucosa, and beneficial changes in the gut microbiota. IAP
deserves attention as promising candidate in future clinical trials of
ulcerative colitis.%
\end{abstract}%



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