SCID/NOD mice model for 5-FU induced intestinal mucositis: Safety and effects of probiotics as therapy

Huang, Lawrence; Chiau, Jen-Shiu Chiang; Cheng, Mei-Lien; Chan, Wai-Tao; Jiang, Chuen-Bin; Chang, Szu-Wen; Yeung, Chun‐Yan; Lee, Hung‐Chang

doi:10.1016/j.pedneo.2018.07.007

Cited by 29 publications

(31 citation statements)

References 41 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our previous study, we demonstrated that those mice in the 5-FU-induced intestinal mucositis group had significantly higher levels of circulating pro-inflammatory cytokines which decreased significantly after probiotic administration ( 26 ). We found similar results in using SCID/NOD mice as animal model, suggesting that innate immunity plays a role in the pathogenesis of intestinal mucositis ( 40 ). It seems that VD also exerts similar anti-inflammatory effects through the inhibition of pro-inflammatory cytokine expressions according to the results of this mouse model study.…”

Section: Discussionsupporting

confidence: 72%

Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background and Aims: Vitamin D (VD) plays an important role not only in mineral balance and skeletal maintenance but also in immune modulation. VD status was found correlated with the pathophysiology and severity of inflammatory bowel diseases and other autoimmune disorders. Epithelial barrier function is primarily regulated by the tight-junction (TJ) proteins. In this study, we try to establish an animal model by raising mice fed VD-deficient diet and to investigate the effects of VD-deficient diet on gut integrity and zonulin expression.Methods: Male C57BL/6 mice were administered either VD-deficient [VDD group, 25(OH)2D3 0 IU/per mouse] or VD-sufficient [VDS group, 25(OH)2D3 37.8 IU/per mouse] special diets for 7 weeks. Body weight and diet intake were recorded weekly. Serum VD levels were detected. After sacrifice, jejunum and colon specimens were collected. The villus length and crypt depth of the jejunum as well as mucosa thickness of the colon were measured. Various serum pro-inflammatory cytokines and intestinal TJ proteins were assessed. The serum level of zonulin and the mRNA expression of jejunum zonulin were also investigated.Results: We found that mice fed a VDD diet had a lower serum level of VD after 7 weeks (p < 0.001). VDD mice gained significant less weight (p = 0.022) and took a similar amount of diet (p = 0.398) when compared to mice raised on a VDS diet. Significantly decreased colon mucosa thickness was found in VDD mice compared with the VDS group (p = 0.022). A marked increase in serum pro-inflammatory cytokine levels was demonstrated in VDD mice. All relative levels of claudin (CLD)-1 (p = 0.007), CLD-3 (p < 0.001), CLD-7 (p < 0.001), and zonulin-1 (ZO-1, p = 0.038) protein expressions were significantly decreased in the VDD group when compared to the VDS group. A significant upregulation of mRNA expression of jejunum zonulin (p = 0.043) and elevated serum zonulin (p = 0.001) were found in the VDD group.Conclusions: We successfully demonstrated that VDD could lead to impaired barrier properties. We assume that sufficient VD could maintain intestinal epithelial integrity and prevent mucosal barrier dysfunction. VD supplementation may serve as part of a therapeutic strategy for human autoimmune and infectious diseases with intestinal barrier dysfunction (leaky gut) in the future. To our knowledge, this is the first study to demonstrate that VDD could lead to a significant upregulation in mRNA expression of the jejunum zonulin level and also a marked elevation of serum zonulin in a mouse model.

show abstract

Section: Discussionsupporting

confidence: 72%

Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our previous research successfully demonstrated that Lactobacillus were associated with the maintenance of the tight junction integrity and appearance . These results shed light on the potential of probiotics to restore the dysbiosis of 5‐FU‐induced intestinal mucositis both in BALB/c and SCID/NOD mice models: repairing the jejunum, ameliorating diarrhea, and halting bodyweight loss . The exact mechanisms by which probiotics exert their beneficial effects remain unclear.…”

Section: Discussionmentioning

confidence: 74%

“…However, there were obvious bacterial translocations found in mesentery lymph node, and small amount bacterial number was found in liver. In our previous study, we found no evidence of strains in blood, liver, and spleen samples of BALB mice and SCID/NOD mice…”

Section: Discussionmentioning

confidence: 74%

“…In a study including 150 colorectal cancer patients treated with 5‐FU, Lactobacillus rhamnosus supplementation could decrease the incidence of severe diarrhea and the need for chemotherapy dose reduction as compared with placebo . Besides, in our previous mouse model studies, we successfully demonstrated that oral administration of probiotics Lactobacillus casei variety rhamnosus and Lactobacillus acidophilus and Bifidobacterium bifidum could ameliorate the chemotherapy‐induced intestinal mucositis …”

Section: Discussionmentioning

confidence: 90%

“…Recent studies had shown probiotics could modulate intestinal barrier function and improve chemotherapy‐induced mucositis in the animal model . Our previous researches demonstrated the effects of probiotic supplementation in ameliorating 5‐FU‐induced intestinal mucositis in an experimental mouse model . A better understanding of the pathogenesis of chemotherapy‐induced mucositis is mandatory to develop optimal preventive and curative measures for patient care.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Modulations of probiotics on gut microbiota in a 5‐fluorouracil‐induced mouse model of mucositis

Yeung

Chiau

Cheng

et al. 2019

J of Gastro and Hepatol

View full text Add to dashboard Cite

Background and Aim:Intestinal mucositis remained one of the most deleterious complications in cancer patients undergoing chemotherapy. 5-FU treatment was reported to affect the abundance of gut microbiota and cause mucositis, which might be ameliorated by probiotics. We investigate the potential changes of 5-FU treatment and the modulations of probiotics on gut microbiota in a mouse model. Methods: Male BALB/c mice received either 5-FU or saline (S). They were separated and fed saline, Lactobacillus casei variety rhamnosus (Lcr) and Lactobacillus reuteri DSM 17938 (BG). Lcr and BG were simultaneously administered with 5-FU for 5 days. Stool specimens were collected for DNA extraction and pyrosequenced for bioinformatic analysis. Results: Fecal microbial communities were obviously diverse. Bacteroides and Bacteroidaceae were the most abundant microbiota in FU.BG group while S24_7 was the most in S.S group. At phylum and class levels, abundances of Betaproteobacteria, Erysipelotrichi, Gammaproteobacteria, and Verrucomicrobia were significantly increased in the FU groups. Probiotics supplementation did increase the abundances of Enterobacteriales and Turicibacterales. We demonstrated that probiotics did modulate the abundance and diversity of gut microbiota. Bacterial motility proteins were found enriched and upregulated in the S.BG group. No mortality was noted. No bacterial translocation was found in spleen and blood among the six groups. Conclusion: Gut microbiota of mice undergoing chemotherapy exhibited a distinct disruption in bacterial composition. Probiotic did modulate the abundance and diversity of gut microbiota. This is the first study to analyze the effects and safety of Lactobacillus strains on 5-FU-induced mucositis systematically and assess changes in the intestinal microbiota after probiotic intervention.Additional supporting information may be found online in the Supporting Information section at the end of the article. Data S1. Supporting information.

show abstract

Ganoderma immunomodulatory proteins: mushrooming functional FIPs

Lin

Chen

Bai

et al. 2022

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

SCID/NOD mice model for 5-FU induced intestinal mucositis: Safety and effects of probiotics as therapy

Cited by 29 publications

References 41 publications

Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model

Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model

Modulations of probiotics on gut microbiota in a 5‐fluorouracil‐induced mouse model of mucositis

Ganoderma immunomodulatory proteins: mushrooming functional FIPs

Contact Info

Product

Resources

About