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Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota.
Pharmacol Res. 2019 12; 150:104489.PR

Abstract

Phloretin, extracted from the pericarp and velamen of apples or pears, is a dihydrochalcone flavonoid with anti-bacterial and anti-inflammatory activities. It has been reported that phloretin has anti-inflammatory effects in ulcerative colitis (UC) mice. However, the role of the gut microbiota in the phloretin anti-UC process remains unclear. In this study, we observed that the anti-UC effect of phloretin was affected by co-housing, probably because of the transmissible nature of the gut micobiota. Through fecal micobiota transplantation (FMT), the effects of the gut microbiota on the anti-UC of phloretin were further confirmed. UC was induced in mice by administrating 3% dextran sulfate sodium (DSS) in drinking water for 7 days. Phloretin (60 mg/kg) was administered by gavage every day during the experiment. Fecal microbes (109 CFU/mL) from phloretin-treated UC mice were administered by gavage to non-phloretin-treated UC mice for 7 days. The results showed that FMT, like phloretin, ameliorated UC by improving disease symptoms and colon inflammation, balancing inflammatory cytokines, maintaining intestinal barrier integrity, restoring systemic immune function, inhibiting NF-κB and NLRP3 inflammasome activation and ameliorating the oxidant stress. Both FMT and phloretin treatment increased the levels of Bacteroidetes, Alistipes and Lactobacillus and decreased those of Firmicutes, Oscillibacter and Ruminiclostridium_6. Correlation analysis between gut microbes and micro-environmental factors revealed that Alistipes abundance was negatively correlated with DAI, pathological score, and TNF-α, IL-6 and IL-1β levels, and Alistipes was more abundant in phloretin or FMT treated UC mice. Oscillibacter abundance was significantly positively correlated with IL-6 and IL-1β levels and pathological score, and Oscillibacter was increased in UC mice. Furthermore, network analysis of the dominant genera revealed that Alistipes abundance was negatively related to Oscillibacter abundance. In conclusion, this study suggests that the anti-UC effects of phloretin are achieved through regulation of the gut microbiota and phloretin has the potential to be developed as a promising agent for the treatment of UC.

Authors+Show Affiliations

School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, Henan, China. Electronic address: minnawu@xxmu.edu.cn.School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, Henan, China.School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, Henan, China.School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, Henan, China.School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, Henan, China.The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 453003, Henan, China.School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, Henan, China.School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, Henan, China.Henan Key Laboratory of Immunology and Targeted Therapy, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan, China.Henan Key Laboratory of Immunology and Targeted Therapy, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan, China. Electronic address: zhonggs@xxmu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31689519

Citation

Wu, Minna, et al. "Phloretin Ameliorates Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice By Regulating the Gut Microbiota." Pharmacological Research, vol. 150, 2019, p. 104489.
Wu M, Li P, An Y, et al. Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota. Pharmacol Res. 2019;150:104489.
Wu, M., Li, P., An, Y., Ren, J., Yan, D., Cui, J., Li, D., Li, M., Wang, M., & Zhong, G. (2019). Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota. Pharmacological Research, 150, 104489. https://doi.org/10.1016/j.phrs.2019.104489
Wu M, et al. Phloretin Ameliorates Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice By Regulating the Gut Microbiota. Pharmacol Res. 2019;150:104489. PubMed PMID: 31689519.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota. AU - Wu,Minna, AU - Li,Puze, AU - An,Yunying, AU - Ren,Jie, AU - Yan,Dong, AU - Cui,Jiazeng, AU - Li,Duan, AU - Li,Min, AU - Wang,Mingyong, AU - Zhong,Genshen, Y1 - 2019/11/02/ PY - 2019/07/06/received PY - 2019/10/04/revised PY - 2019/10/10/accepted PY - 2019/11/7/pubmed PY - 2020/8/25/medline PY - 2019/11/6/entrez KW - Gut microbiota KW - Immune function KW - Intestinal barrier KW - Phloretin KW - Ulcerative colitis SP - 104489 EP - 104489 JF - Pharmacological research JO - Pharmacol. Res. VL - 150 N2 - Phloretin, extracted from the pericarp and velamen of apples or pears, is a dihydrochalcone flavonoid with anti-bacterial and anti-inflammatory activities. It has been reported that phloretin has anti-inflammatory effects in ulcerative colitis (UC) mice. However, the role of the gut microbiota in the phloretin anti-UC process remains unclear. In this study, we observed that the anti-UC effect of phloretin was affected by co-housing, probably because of the transmissible nature of the gut micobiota. Through fecal micobiota transplantation (FMT), the effects of the gut microbiota on the anti-UC of phloretin were further confirmed. UC was induced in mice by administrating 3% dextran sulfate sodium (DSS) in drinking water for 7 days. Phloretin (60 mg/kg) was administered by gavage every day during the experiment. Fecal microbes (109 CFU/mL) from phloretin-treated UC mice were administered by gavage to non-phloretin-treated UC mice for 7 days. The results showed that FMT, like phloretin, ameliorated UC by improving disease symptoms and colon inflammation, balancing inflammatory cytokines, maintaining intestinal barrier integrity, restoring systemic immune function, inhibiting NF-κB and NLRP3 inflammasome activation and ameliorating the oxidant stress. Both FMT and phloretin treatment increased the levels of Bacteroidetes, Alistipes and Lactobacillus and decreased those of Firmicutes, Oscillibacter and Ruminiclostridium_6. Correlation analysis between gut microbes and micro-environmental factors revealed that Alistipes abundance was negatively correlated with DAI, pathological score, and TNF-α, IL-6 and IL-1β levels, and Alistipes was more abundant in phloretin or FMT treated UC mice. Oscillibacter abundance was significantly positively correlated with IL-6 and IL-1β levels and pathological score, and Oscillibacter was increased in UC mice. Furthermore, network analysis of the dominant genera revealed that Alistipes abundance was negatively related to Oscillibacter abundance. In conclusion, this study suggests that the anti-UC effects of phloretin are achieved through regulation of the gut microbiota and phloretin has the potential to be developed as a promising agent for the treatment of UC. SN - 1096-1186 UR - https://www.unboundmedicine.com/medline/citation/31689519/Phloretin_ameliorates_dextran_sulfate_sodium_induced_ulcerative_colitis_in_mice_by_regulating_the_gut_microbiota_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-6618(19)31296-4 DB - PRIME DP - Unbound Medicine ER -