The Combination of Intestinal Alkaline Phosphatase Treatment with Moderate Physical Activity Alleviates the Severity of Experimental Colitis in Obese Mice via Modulation of Gut Microbiota, Attenuation of Proinflammatory Cytokines, Oxidative Stress Biomarkers and DNA Oxidative Damage in Colonic Mucosa

Abstract

Inflammatory bowel diseases (IBD) are commonly considered as Crohn’s disease and ulcerative colitis, but the possibility that the alterations in gut microbiota and oxidative stress may affect the course of experimental colitis in obese physically exercising mice treated with the intestinal alkaline phosphatase (IAP) has been little elucidated. Mice fed a high-fat-diet (HFD) or normal diet (ND) for 14 weeks were randomly assigned to exercise on spinning wheels (SW) for 7 weeks and treated with IAP followed by intrarectal administration of TNBS. The disease activity index (DAI), grip muscle strength test, oxidative stress biomarkers (MDA, SOD, GSH), DNA damage (8-OHdG), the plasma levels of cytokines IL-2, IL-6, IL-10, IL-12p70, IL-17a, TNF-α, MCP-1 and leptin were assessed, and the stool composition of the intestinal microbiota was determined by next generation sequencing (NGS). The TNBS-induced colitis was worsened in obese sedentary mice as manifested by severe colonic damage, an increase in DAI, oxidative stress biomarkers, DNA damage and decreased muscle strength. The longer running distance and weight loss was observed in mice given IAP or subjected to IAP + SW compared to sedentary ones. Less heterogeneous microbial composition was noticed in sedentary obese colitis mice and this effect disappeared in IAP + SW mice. Absence of Alistipes, lower proportion of Turicibacter, Proteobacteria and Faecalibacterium, an increase in Firmicutes and Clostridium, a decrease in oxidative stress biomarkers, 8-OHdG content and proinflammatory cytokines were observed in IAP + SW mice. IAP supplementation in combination with moderate physical activity attenuates the severity of murine colitis complicated by obesity through a mechanism involving the downregulation of the intestinal cytokine/chemokine network and oxidative stress, the modulation of the gut microbiota and an improvement of muscle strength.

Exploration of the Gut Microbiome in Thai Patients with Major Depressive Disorder Shows a Specific Bacterial Profile with Depletion of the Ruminococcus Genus as a Putative Biomarker

“…In addition, species of this genus display cellulolytic activity and may degrade LPS. Furthermore, different Ruminococcus species produce alkaline phosphatase [34], which improves gut barrier functions and detoxifies LPS, thereby preventing activation of NINONS pathways [49,50]. One could, therefore, hypothesize that depletion of this genus may have contributed to lowered LPS breakdown and thus increased translocation of LPS in MDD particularly when deficits in tight junctions are present [13][14][15][16].…”

Natural flavones from edible and medicinal plants exhibit enormous potential to treat ulcerative colitis

“…Oxidant stress exerts a crucial action in pathophysiology of UC ( Wojcik-Grzybek et al, 2022 ). Studies have revealed that increased production of ROS destroys the cellular macromolecules (DNA, lipids and proteins) and breaks epithelia cell integrality ( Juan et al, 2021 ).…”

Protective Properties of Intestinal Alkaline Phosphatase Supplementation on the Intestinal Barrier: Interactions and Effects

“…165 IAP can alleviate myocardial ischemia and reperfusion injury by inhibiting inflammatory response and reducing oxidative stress. 166 IAP can reduce the risk of cardiac events by regulating intestinal barrier function and reducing the entry of gut-derived endotoxins. 9 Additionally, IAP can also affect lipid levels by regulating cholesterol metabolism and lipid absorption, thus influencing cardiovascular development.…”

“…Recent studies found a clear correlation between IAP deficiency and IHD . IAP can alleviate myocardial ischemia and reperfusion injury by inhibiting inflammatory response and reducing oxidative stress . IAP can reduce the risk of cardiac events by regulating intestinal barrier function and reducing the entry of gut-derived endotoxins .…”