Wei Niu,Yuelin Dong,Ziwei Fu,Jiajie Lv,Ligui Wang,Zhenhai Zhang,Jiege Huo,Jianming Ju
This study investigated the therapeutic effects and mechanisms of chitosans (CSs) with different molecular weights on ulcerative colitis (UC). Three size classes of CSs (Mw ≤ 3, 50, and 200 kDa) were used in this study. The effect of large CSs (Mw ≤ 200 kDa) on UC was the best, followed by that of medium CSs (Mw ≤ 50 kDa), and that of small CSs (Mw ≤ 3 kDa) was the least in the LPS-induced Raw 264.7 cell model and DSS-induced UC mice model. The therapeutic mechanisms of three CSs are related to anti-oxidation, anti-inflammation, and regulation of immunoglobulin and intestinal flora by attenuating body weight loss, decreasing the disease activity index (DAI) and MPO activity, suppressing proinflammatory cytokines and IgG levels, down-regulating the level of oxidative stress, increasing anti-inflammatory cytokines, SOD activity and Prevotellaceae_UCG-001 levels, and reducing the abundance of Proteobacteria, Actinobacteria, and Escherichia-Shigella . In general, the molecular weight of CSs influences their efficacy against UC. CSs with an optimal molecular weight demonstrate good development prospects for ameliorating UC.
Lulu An,Jimusi Wuri,Zhitong Zheng,Wenqui Li,Tao Yan
Chemotherapy has several adverse effects to patients, some of which are life-threatening. We hypothesized that Doxorubicin induced microbiome imbalance and intestinal damage may contribute to Doxorubicin induced cardiac dysfunction. Male adult (2–3 months) C57BL/6 mice were administered 3 mg/kg, 5 mg/kg, 7.5 mg/kg,15 mg/kg, 20 mg/kg doses of Doxorubicin. Echocardiography was performed at 7 and 14 days after Doxorubicin administration. 16S rRNA amplicon sequencing was used to characterize microbiome changes. Fecal microbiota transplantation (FMT) was performed to evaluate the role of the microbiota on Doxorubicin induced cardiac dysfunction. Doxorubicin dose dependently increases mortality rate and induces cardiac dysfunction. 5 mg/kg-Doxorubicin significantly induces decreased left ventricular ejection fraction (LVEF) and fraction shortening (FS) as well as increased cardiac fibrosis , inflammation and oxidative stress respond without increasing mortality. 5 mg/kg-Doxorubicin induces significant decreased colorectum length, increased loss of goblet cells, numbers of ulcers and infiltration of lymphocyte clusters and decreased tight junction protein ZO-1, as well as increased plasma endotoxin level measured by ELISA assay. 16S rRNA microbiota analysis shows that Doxorubicin-induced microbiota dysbiosis with decreased community richness compared with normal control mice. FMT to Doxorubicin-5 mg treated mice significantly improved cardiac function by increasing LVEF and FS as well as decreased perivascular and interstitial fibrosis ; increased colorectum length, decreased the loss of goblet cells,infiltration of lymphocyte clusters,the number of ulcers and plasma endotoxin level; improved microbiota composition, function and diversity with increased abundance of Alloprevotella, Prevotellaceae_UCG−001 and Rikenellaceae_RC9_gut_group. We find that normal fecal transplantation improves cardiac function, decreases gut damage and alter microbiota composition induced by Doxorubicin. The microbiota appears to contribute to heart-gut interaction.
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