TDAG51 deficiency attenuates dextran sulfate sodium-induced colitis in mice

Abstract

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a group of chronic inflammatory diseases of the gastrointestinal tract. Although the multifactorial etiology of IBD pathogenesis is relatively well documented, the regulatory factors that confer a risk of IBD pathogenesis remain less explored. In this study, we report that T-cell death-associated gene 51 (TDAG51/PHLDA1) is a novel regulator of the development of dextran sulfate sodium (DSS)-induced colitis in mice. TDAG51 expression was elevated in the colon tissues of DSS-induced experimental colitis mice. TDAG51 deficiency protected mice against acute DSS-induced lethality and body weight changes and disease severity. DSS-induced structural damage and mucus secretion in colon tissues were significantly reduced in TDAG51-deficient mice compared with wild-type mice. We observed similar results in a DSS-induced chronic colitis mouse model. Finally, we showed that the production of inflammatory mediators, including proinflammatory enzymes, molecules and cytokines, was decreased in DSS-treated TDAG51-deficient mice compared with DSS-treated wild-type mice. Thus, we demonstrated that TDAG51 deficiency plays a protective role against DSS-induced colitis by decreasing the production of inflammatory mediators in mice. These findings suggest that TDAG51 is a novel regulator of the development of DSS-induced colitis and is a potential therapeutic target for IBD.

Orange juice containing Pediococcus acidilactici CE51 modulates the intestinal microbiota and reduces induced inflammation in a murine model of colitis

“…Kwon et al 34 show that DSS-induced colitis is associated with adipose tissue dysfunction and disrupted hepatic lipid metabolism leading to hepatosteatosis and dyslipidemia in mice. However, in the present study there were no histopathological differences in both organs and tissues 35 .…”

Interactions between toll‐like receptors signaling pathway and gut microbiota in host homeostasis

“…Accumulating evidence suggests that the interaction between TLR4 and gut microbiota serves as the forefront link connecting innate immune responses to chronic inflammation in related diseases. Studies have reported an increase in TLR4 expression in animals with acute colitis as well as chronic conditions such as diabetes and nonalcoholic steatohepatitis 39–41 Notably, knockout or downregulation of TLR4 has been shown to protect animals from obesity‐induced insulin resistance. Additionally, TLR4 expression has been found to be positively correlated with LPS‐producing bacteria and negatively correlated with prebiotics in numerous metabolic disease models 42,43 .…”

Melatonin as a promising factor in correction of the intestinal microbiome in inflammatory bowel diseases

“…В результате нарушения иммунологической толерантности и формирования дисбиоза в стенке кишки накапливаются клетки воспалительного ответа и усугубляются реакции, связанные с цитокинами, такими как фактор некроза опухоли (TNF-α), интерлейкин (IL)-1β, IL-17, интерферон (IFN)-γ и др., которые приводят к активации лейкоцитов, разрушению стенки кишечника [Lee et al, 2021;Marié et al, 2021;Vakadaris et al, 2023]. При ВЗК хорошо изучены изменения количественного и качественного состава микробиома кишечника, видовое разнообразие варьирует в зависимости от варианта ВЗК: у пациентов с ЯК на фоне уменьшения Bacteroidota (Bacteroidetes) и Bacillota (Firmicutes) возрастает количество грамотрицательных Enterobacteriaceae (Klebsiella pneumoniae, Escherichia coli, Clostridium difficile), в то время как при БК сокращается представительство Clostridium spp., а повышение Escherichia coli выражено в большей степени, чем при ЯК [Jeon et al, 2022]. Bacteroidota (Bacteroidetes) составляют около 30% всех кишечных бактерий и могут рассматриваться как одна из основных биот грамотрицательных бактерий в кишечнике [Ortiz et al, 2023].…”