High-Throughput Screen Identifies Host and Microbiota Regulators of Intestinal Barrier Function

Grosheva, Inna; Zheng, Danping; Levy, Maayan; Polansky, Omer; Lichtenstein, Alexandra; Golani, Ofra; Dori-Bachash, Mally; Moresi, Claudia; Shapiro, Hagit; Mare-Roumani, Sara Del; Valdés-Mas, Rafael; He, Yiming; Karbi, Hodaya; Chen, Minhu; Harmelin, Alon; Straussman, Ravid; Yissachar, Nissan; Elinav, Eran; Geiger, Benjamin

doi:10.1053/j.gastro.2020.07.003

Cited by 130 publications

(85 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results showed that mRNA expressions of M1 macrophage-associated factors including Il-1β , and Inos were significantly decreased while the levels of M2 macrophage-associated markers including Arg1 , Chil3 , and Cd206 were markedly increased with tiliroside (25.0, 50.0 mg/kg) treatments ( Figure 3B ). We then further investigated the effect of tiliroside on the epithelial barrier function and the proportion of CD4 + T cells, CD8 + T cell and CD19 + B cells, which have been demonstrated to play an important role in the occurrence and development of colitis ( 24 – 26 ). Tiliroside (12.5, 25.0, and 50.0 mg/kg) exerted little effect on the mRNA expressions of Cdh1 , Cldn7 , and marginally increased the expression of Ocln only at the dosage of 50.0 mg/kg ( Figure 3C ).…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, we 3B). We then further investigated the effect of tiliroside on the epithelial barrier function and the proportion of CD4 + T cells, CD8 + T cell and CD19 + B cells, which have been demonstrated to play an important role in the occurrence and development of colitis (24)(25)(26). Tiliroside (12.5, 25.0, and 50.0 mg/kg) exerted little effect on the mRNA expressions of Cdh1, Cldn7, and marginally increased the expression of Ocln only at the dosage of 50.0 mg/kg (Figure 3C).…”

Section: Tiliroside Modulates the Balance Between M1 And M2 Macrophagmentioning

confidence: 99%

See 1 more Smart Citation

Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway

Zhuang

Zhong

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Macrophages polarized to different phenotypes critically contribute to colitis development by coordinating inflammatory and anti-inflammatory processes. Herein, targeting the balance between the pro-inflammatory M1 and the anti-inflammatory M2 macrophage phenotypes can be a novel therapeutic approach for colitis. In the present study, we firstly demonstrated that tiliroside possessed the ability to alleviate the clinical symptoms of colitis as evidenced by decreased disease activity index (DAI) scores, longer colon length, reduced myeloperoxidase (MPO) activity, and improvement of colonic pathological damage in vivo. Furthermore, we showed that tiliroside modulated the balance between M1 and M2 macrophages toward a more anti-inflammatory status in colonic lamina propria but has little effect on the T cell population and epithelial barrier function in colitis mice. The macrophage depletion study further showed the protective effect of tiliroside was macrophage dependent in vivo. Mechanistically, our study demonstrated that tiliroside regulated cellular metabolism by inhibiting aerobic glycolysis in LPS and IFNγ stimulated macrophages. At the molecular level, tiliroside facilitated the proteasomal degradation of HIF-1α and downregulated mRNA expressions of HIF-1α dependent glycolytic enzymes in macrophages. Collectively, our data highlight the aberrant M1/M2 macrophage polarization in the initiation and development of ulcerative colitis and put forth the stage for considering tiliroside as a metabolic regulator in reprogramming macrophage polarization, which may serve as a promising therapeutic approach for treatment of inflammation-associated and metabolic disorders.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Tiliroside Modulates the Balance Between M1 And M2 Macrophagmentioning

confidence: 99%

Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway

Zhuang

Zhong

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…As mentioned above, commensal‐derived metabolites (including taurine, histamine and spermine) modulate the gut epithelial NLRP6 inflammasome and IL‐18 secretion, and subsequently impact the expression of downstream antimicrobial peptide (AMP) genes in the gut, thus shaping the host–microbiome interface and determining susceptibility to DSS‐induced colitis 29 . A mechanism for this modulation may involve metabolite‐induced morphological alterations of IEC intercellular connections and cellular morphology 41 . In addition to commensal‐associated modulators, NLRP6 can directly bind and be activated by LTA derived from Gram‐positive bacteria, that is Listeria monocytogenes 27 .…”

Section: Nlrp6 Inflammasome Assembly Regulation and Effector Functionmentioning

confidence: 99%

The NLRP6 inflammasome

2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Intestinal barrier integrity plays a fundamental role in healthy gut function. The intestinal barrier disruptions that facilitate the uptake of harmful agents are often associated with the alterations of gut microbiome (Grosheva et al, 2020). In current study, histological and ultrastructural abnormalities were detected in the colon of mice treated with ceftriaxone, which were reversed by CB RH2 intervention (Figure 3).…”

Section: Discussionmentioning

confidence: 48%

The Anti-Inflammatory Effect and Mucosal Barrier Protection of Clostridium butyricum RH2 in Ceftriaxone-Induced Intestinal Dysbacteriosis

Liu

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

This study aimed at determining the beneficial effect of Clostridium butyricum (CB) RH2 on ceftriaxone-induced dysbacteriosis. To this purpose, BALB/c mice were exposed to ceftriaxone (400 mg/ml) or not (control) for 7 days, and administered a daily oral gavage of low-, and high-dose CB RH2 (108 and 1010 CFU/ml, respectively) for 2 weeks. CB RH2 altered the diversity of gut microbiota, changed the composition of gut microbiota in phylum and genus level, decreased the F/B ratio, and decreased the pro-inflammatory bacteria (Deferribacteres, Oscillibacter, Desulfovibrio, Mucispirillum and Parabacteroides) in ceftriaxone-treated mice. Additionally, CB RH2 improved colonic architecture and intestinal integrity by improving the mucous layer and the tight junction barrier. Furthermore, CB RH2 also mitigated intestinal inflammation through decreasing proinflammatory factors (TNF-α and COX-2) and increasing anti-inflammatory factors (IL-10). CB RH2 had direct effects on the expansion of CD4+ T cells in Peyer’s patches (PPs) in vitro, which in turn affected their immune response upon challenge with ceftriaxone. All these data suggested that CB RH2 possessed the ability to modulate the intestinal mucosal and systemic immune system in limiting intestinal alterations to relieve ceftriaxone-induced dysbacteriosis.

show abstract

High-Throughput Screen Identifies Host and Microbiota Regulators of Intestinal Barrier Function

Cited by 130 publications

References 47 publications

Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway

Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway

The NLRP6 inflammasome

The Anti-Inflammatory Effect and Mucosal Barrier Protection of Clostridium butyricum RH2 in Ceftriaxone-Induced Intestinal Dysbacteriosis

Contact Info

Product

Resources

About