<i>Fusobacterium nucleatum</i> exacerbates colitis by damaging epithelial barriers and inducing aberrant inflammation

Liu, Hua; Xiang, Hong; Sun, Tian; Huang, Xiao Wen; Wang, Jilin; Xiong, Hua

doi:10.1111/1751-2980.12909

Cited by 105 publications

(81 citation statements)

References 45 publications

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“…The redistribution of TJ proteins could lead to disruption of intestinal barrier and increased epithelial permeability. 101,102 In contrast, pretreatment with C-L resulted in a strong and continuous marginal distribution of occludin in the villi and crypt of the intestinal epithelium. The presence of TJs between gut epithelial cells was confirmed by TEM, further supporting the defensive effect of C-L against LPS-stimulated damage and defective function of the mucosal barrier.…”

Section: Discussionmentioning

confidence: 97%

“…The appropriate localization of occludin at the intestinal epithelium boundaries corresponds to intact TJs, whereas the abnormal redistribution of occludin corresponds to functional TJ deficiencies in the intestine. 101,102 In control mouse, occludin was strongly expressed in the margin of the villi and the crypt showing the characteristic epithelial surface staining. In LPS injury mouse, however, occludin was diffusely expressed within villi and crypt rather than along the epithelial cell boundaries.…”

Section: Discussionmentioning

confidence: 99%

“…In LPS injury mouse, however, occludin was diffusely expressed within villi and crypt rather than along the epithelial cell boundaries. The redistribution of TJ proteins could lead to disruption of intestinal barrier and increased epithelial permeability 101,102 . In contrast, pretreatment with C‐L resulted in a strong and continuous marginal distribution of occludin in the villi and crypt of the intestinal epithelium.…”

Section: Discussionmentioning

confidence: 99%

“…However, in C‐L‐pretreated mice, the average TEER value increased to a level within the normal range. The appropriate localization of occludin at the intestinal epithelium boundaries corresponds to intact TJs, whereas the abnormal redistribution of occludin corresponds to functional TJ deficiencies in the intestine 101,102 . In control mouse, occludin was strongly expressed in the margin of the villi and the crypt showing the characteristic epithelial surface staining.…”

Section: Discussionmentioning

confidence: 99%

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A highly efficient hybrid peptide ameliorates intestinal inflammation and mucosal barrier damage by neutralizing lipopolysaccharides and antagonizing the lipopolysaccharide‐receptor interaction

Xin

Zhang

et al. 2020

FASEB j.

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Intestinal inflammatory disorders, such as inflammatory bowel disease, are major contributors to mortality and morbidity in humans and animals worldwide. While some native peptides have great potential as therapeutic agents against intestinal inflammation, potential cytotoxicity, anti-inciting action, and suppression of antiinflammatory activity may limit their development as anti-inflammatory agents. Peptide hybridization is an effective approach for the design and engineering of novel functional peptides because hybrid peptides combine the advantages and benefits of various native peptides. In the present study, a novel hybrid anti-inflammatory peptide that combines the active center of Cecropin A (C) and the core functional region of LL-37 (L) was designed [C-L peptide; C (1-8)-L (17-30)] through in silico analysis to reduce cytotoxicity and improve the anti-inflammatory activity of the parental peptides. The resulting C-L peptide exhibited lower cytotoxicity than either C or L peptides alone. C-L also exerted a protective effect against lipopolysaccharide (LPS)induced inflammatory responses in RAW264.7 macrophages and in the intestines of a mouse model. The hybrid peptide exhibited increased anti-inflammatory activity compared to the parental peptides. C-L plays a role in protecting intestinal tissue from damage, LPS-induced weight loss, and leukocyte infiltration. In addition, C-L reduces the expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 2 | WEI Et al.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

A highly efficient hybrid peptide ameliorates intestinal inflammation and mucosal barrier damage by neutralizing lipopolysaccharides and antagonizing the lipopolysaccharide‐receptor interaction

Xin

Zhang

et al. 2020

FASEB j.

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“…Each group contained 7 mice. The model of acute colitis was established by the administration of 3% (wt/vol) DSS in the drinking water for 7 days, with or without the daily gavage of 10 9 CFU bacteria ( F. nucleatum or/and L. rhamnosus ) solution in phosphate-buffered saline (PBS) for 7 days prior to DSS administration as previously described ( 22 , 23 ). In the control and DSS groups, the same volume of PBS was administered by gavage as the vehicle control.…”

Section: Methodsmentioning

confidence: 99%

Lactobacillus rhamnosus attenuates intestinal inflammation induced by Fusobacterium nucleatum infection by restoring the autophagic flux

et al. 2020

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Autophagy plays a dual role in the responses to the gut microflora. The present study aimed to examine the effects of Lactobacillus rhamnosus ( L. rhamnosus ) on Fusobacterium nucleatum ( F. nucleatum )-induced intestinal dysfunction and to elucidate the underlying mechanisms, with particular focus on autophagy. Inflammatory models were established by treatment with L. rhamnosus following F. nucleatum intervention using cells or a mouse model of dextran sulfate sodium (DSS)-induced acute colitis. Autophagosomes were visualized by confocal microscopy following transfection with a tandem GFP-mCherry-LC3 construct and also by transmission electron microscopy. Autophagy-associated protein levels were examined by western blot analysis and immunohistochemistry. It was observed that F. nucleatum induced the production of pro-inflammatory cytokines in Caco-2 cells and aggravated DSS-induced acute colitis. The autophagic flux was impaired following infection with F. nucleatum . L. rhamnosus treatment attenuated the inflammation induced by F. nucleatum infection and effectively recovered the impaired autophagic flux. In addition, the production of pro-inflammatory cytokines induced by F. nucleatum was enhanced with autophagy inhibitors or the RNA interference of autophagy-related gene 16 like 1 (Atg16L1) in Caco-2 cells. Notably, this inhibition of autophagy weakened the effects of L. rhamnosus . Finally, the PI3K/AKT/mTOR pathway was found to be involved in this process. On the whole, the present study demonstrates that the mediation of autophagy by L. rhamnosus may be involved in the protective effects against F. nucleatum -related intestinal inflammation. Thus, L. rhamnosus treatment may prove to be a novel therapeutic strategy for F. nucleatum -realated gut disorders.

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Platelet Membrane Fragment Self‐Assembled Oral Hydrogel Microspheres for Restoring Intestinal Microvascular Injury

Liu

Cai

Wang

et al. 2023

Adv Funct Materials

Self Cite

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Non‐invasive management of intestinal microvascular injury with hemorrhage under constant biochemical‐mechanical encroachment of luminal contents is a major clinical challenge. Herein, an oral hydrogel microsphere is designed, encapsulating the platelet membrane fragment self‐assembled nanohydrogel fabricated by double‐crosslinking of methacrylated hyaluronic acid and Rebamipide‐loaded dendrimer (Rng@PMS), for self‐localization of hemorrhagic focus and intensive management of intestinal microvascular injury via suppression of inflammation‐mediated tissue injury and reintegration of the damaged mucosal barrier. The results indicate that Rng@PMS effectively adheres to exposed collagen on injured microvasculature and attaches to over 90% of activated macrophages within 10 min, endowing Rng@PMS with a significantly prolonged enteral dwell time (over 24 hours). Importantly, Rng@PMS generated from alginate is designed for oral colon‐targeted delivery to avoid the erosion of gastrointestinal contaminants. In vivo study reveals oral administration of microspheres in murine hematochezia model upregulates the intestinal barrier proteins zonula occludens‐1, Occludin, and muc2, and inhibits infiltration of neutrophils, dendritic cells, and macrophages in hemorrhagic foci, thereby reducing the hematochezia score from 4 to 0.8, and the pathology score from 5.3 to 0.5. Oral microspheres for in situ management of intestinal microvascular injury may be applicable more broadly to noninvasively treat diseases with symptoms of mucosal hemorrhage.

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Fusobacterium nucleatum exacerbates colitis by damaging epithelial barriers and inducing aberrant inflammation

Cited by 105 publications

References 45 publications

A highly efficient hybrid peptide ameliorates intestinal inflammation and mucosal barrier damage by neutralizing lipopolysaccharides and antagonizing the lipopolysaccharide‐receptor interaction

A highly efficient hybrid peptide ameliorates intestinal inflammation and mucosal barrier damage by neutralizing lipopolysaccharides and antagonizing the lipopolysaccharide‐receptor interaction

Lactobacillus rhamnosus attenuates intestinal inflammation induced by Fusobacterium nucleatum infection by restoring the autophagic flux

Platelet Membrane Fragment Self‐Assembled Oral Hydrogel Microspheres for Restoring Intestinal Microvascular Injury

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