본문 바로가기
KERD
논문KCI 등재

Interplay between the Gut Microbiome and Metabolism in Ulcerative Colitis Mice Treated with the Dietary Ingredient Phloretin

1

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류생물학

초록

A growing number of healthy dietary ingredients in fruits and vegetables have been shown to exhibit diverse biological activities. Phloretin, a dihydrochalcone flavonoid that is abundant in apples and pears, has anti-inflammatory effects on ulcerative colitis (UC) mice. The gut microbiota and metabolism are closely related to each other due to the existence of the food-gut axis in the human colon. To investigate the interplay of faecal metabolites and the microbiota in UC mice after phloretin treatment, phloretin (60 mg/kg) was administered by gavage to ameliorate dextran sulfate sodium (DSS)-induced UC in mice. Gut microbes and faecal metabolite profiles were detected by high-throughput sequencing and liquid chromatography mass spectrometry (LC-MS) analysis, respectively. The correlations between gut microbes and their metabolites were evaluated by Spearman correlation coefficients. The results indicated that phloretin reshaped the disturbed faecal metabolite profile in UC mice and improved the metabolic pathways by balancing the composition of faecal metabolites such as norepinephrine, mesalazine, tyrosine, 5-acetyl-2,4- dimethyloxazole, and 6-acetyl-2,3-dihydro-2-(hydroxymethyl)-4(1H)-pyridinone. Correlation analysis identified the relations between the gut microbes and their metabolites. Proteus was negatively related to many faecal metabolites, such as norepinephrine, L-tyrosine, laccarin, dopamine glucuronide, and 5-acetyl-2,4-dimethyloxazole. The abundance of unidentified Bacteriodales_S24-7_group was positively related to ecgonine, 15-KETE and 6-acetyl-2,3-dihydro-2- (hydroxymethyl)-4(1H)-pyridinone. The abundance of Christensenellaceae_R-7_group was negatively related to the levels of 15-KETE and netilmicin. Stenotrophomonas and 15-KETE were negatively related, while Intestinimonas and alanyl-serine were positively related. In conclusion, phloretin treatment had positive impacts on faecal metabolites in UC mice, and the changes in faecal metabolites were closely related to the gut microbiota.

Abstract

A growing number of healthy dietary ingredients in fruits and vegetables have been shown to exhibit diverse biological activities. Phloretin, a dihydrochalcone flavonoid that is abundant in apples and pears, has anti-inflammatory effects on ulcerative colitis (UC) mice. The gut microbiota and metabolism are closely related to each other due to the existence of the food-gut axis in the human colon. To investigate the interplay of faecal metabolites and the microbiota in UC mice after phloretin treatment, phloretin (60 mg/kg) was administered by gavage to ameliorate dextran sulfate sodium (DSS)-induced UC in mice. Gut microbes and faecal metabolite profiles were detected by high-throughput sequencing and liquid chromatography mass spectrometry (LC-MS) analysis, respectively. The correlations between gut microbes and their metabolites were evaluated by Spearman correlation coefficients. The results indicated that phloretin reshaped the disturbed faecal metabolite profile in UC mice and improved the metabolic pathways by balancing the composition of faecal metabolites such as norepinephrine, mesalazine, tyrosine, 5-acetyl-2,4- dimethyloxazole, and 6-acetyl-2,3-dihydro-2-(hydroxymethyl)-4(1H)-pyridinone. Correlation analysis identified the relations between the gut microbes and their metabolites. Proteus was negatively related to many faecal metabolites, such as norepinephrine, L-tyrosine, laccarin, dopamine glucuronide, and 5-acetyl-2,4-dimethyloxazole. The abundance of unidentified Bacteriodales_S24-7_group was positively related to ecgonine, 15-KETE and 6-acetyl-2,3-dihydro-2- (hydroxymethyl)-4(1H)-pyridinone. The abundance of Christensenellaceae_R-7_group was negatively related to the levels of 15-KETE and netilmicin. Stenotrophomonas and 15-KETE were negatively related, while Intestinimonas and alanyl-serine were positively related. In conclusion, phloretin treatment had positive impacts on faecal metabolites in UC mice, and the changes in faecal metabolites were closely related to the gut microbiota.

참고문헌 (45)

  1. Rezk BM, "The antioxidant activity of phloretin : the disclosure of a new antioxidant pharmacophore in flavonoids", Biochem. Biophys. Res. Commun, 295, pp.9~13 (2002)
  2. Lin SC, "Phloretin inhibits Zika virus infection by interfering with cellular glucose utilisation", Int. J. Antimicrob. Agents, 54, pp.80~84 (2019)
  3. Matsuoka K, "Evidence-based clinical practice guidelines for inflammatory bowel disease", J. Gastroenterol, 53, pp.305~353 (2018)
  4. Ananthakrishnan AN, "Epidemiology and risk factors for IBD", Nat. Rev. Gastroenterol. Hepatol, 12, pp.205~217 (2015)
  5. Rangan P, "Fasting-mimicking diet modulates microbiota and promotes intestinal regeneration to reduce inflammatory bowel disease pathology", Cell Rep, 26, pp.2704~2719 (2019)
  6. Desai MS, "A Dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility", Cell, 167, pp.1339~1353.e21 (2016)
  7. Zhang D, "High glucose intake exacerbates autoimmunity through reactive-oxygenspecies-mediated TGF-β cytokine activation", Immunity, 51, pp.671~681.e5 (2019)
  8. Miranda PM, "High salt diet exacerbates colitis in mice by decreasing Lactobacillus levels and butyrate production", Microbiome, 6, pp.57~ (2018)
  9. Sender R, "Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans", Cell, 164, pp.337~340 (2016)
  10. Valdes AM, "Role of the gut microbiota in nutrition and health", BMJ, 361, pp.k2179~ (2018)
  11. Rooks MG, "Gut microbiota, metabolites and host immunity", Nat. Rev. Immunol, 16, pp.341~352 (2016)
  12. Kim MH, "Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice", Gastroenterology, 145, pp.396~406 (2013)
  13. Agus A, "Gut microbiota regulation of tryptophan metabolism in health and disease", Cell Host Microbe, 23, pp.716~724 (2018)
  14. De Angelis M, "The food-gut human axis : the effects of diet on gut microbiota and metabolome", Curr. Med. Chem, 26, pp.3567~3583 (2019)
  15. Visconti A, "Interplay between the human gut microbiome and host metabolism", Nat. Commun, 10, pp.4505~ (2019)
  16. Dorrestein PC, "Finding the missing links among metabolites, microbes, and the host", Immunity, 40, pp.824~832 (2014)
  17. Turnbaugh PJ, "An obesity-associated gut microbiome with increased capacity for energy harvest", Nature, 444, pp.1027~1031 (2006)
  18. Liao X, "Alteration of gut microbiota induced by DPP-4i treatment improves glucose homeostasis", EBioMedicine, 44, pp.665~674 (2019)
  19. Torres-Fuentes C, "The microbiota-gut-brain axis in obesity", Lancet Gastroenterol. Hepatol, 2, pp.747~756 (2017)
  20. Dabke K, "The gut microbiome and metabolic syndrome", J. Clin. Invest, 129, pp.4050~4057 (2019)
  21. Franzosa EA, "Gut microbiome structure and metabolic activity in inflammatory bowel disease", Nat. Microbiol, 4, pp.293~305 (2019)
  22. Yu M, "Variations in gut microbiota and fecal metabolic phenotype associated with depression by 16S rRNA gene sequencing and LC", MS-based metabolomics, 2017, pp.138, 231~239
  23. Wu M, "Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota", Pharmacol. Res, 150, pp.104489~ (2019)
  24. Alsanea S, "Phloretin prevents high-fat diet-induced obesity and improves metabolic homeostasis", AAPS J, 19, pp.797~805 (2017)
  25. Okayasu I, "A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice", Gastroenterology, 98, pp.694~702 (1990)
  26. Murthy SN, "Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin", Dig. Dis. Sci, 38, pp.1722~1734 (1993)
  27. Dennis PG, "Spatial uniformity of microbial diversity in a continuous bioelectrochemical system", Bioresour. Technol, 129, pp.599~605 (2013)
  28. Wang G, "Phloretin reduces cell injury and inflammation mediated by Staphylococcus aureus via targeting sortase B and the molecular mechanism", Appl. Microbiol. Biotechnol, 102, pp.10665~10674 (2018)
  29. 윤정한, "Induction of Apoptosis in HT-29 Colon Cancer Cells by Phloretin", Journal of Medicinal Food, 10(4), pp.581~586 (2007), 한국식품영양과학회
  30. Fraga CG, "The effects of polyphenols and other bioactives on human health", Food Funct, 10, pp.514~528 (2019)
  31. Wang Q, "Administration of Bifidobacterium bifidum CGMCC 15068 modulates gut microbiota and metabolome in azoxymethane(AOM)", dextran sulphate sodium(DSS)-induced colitis-associated colon cancer(CAC)in mice, 2020, pp.104, 5915~5928
  32. Del Chierico F, "Gut microbiota profiling of pediatric nonalcoholic fatty liver disease and obese patients unveiled by an integrated meta-omics-based approach", Hepatology, 65, pp.451~464 (2017)
  33. Nagpal R, "Modified Mediterranean-ketogenic diet modulates gut microbiome and shortchain fatty acids in association with Alzheimer's disease markers in subjects with mild cognitive impairment", EBioMedicine, 47, pp.529~542 (2019)
  34. Okumura R, "Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia", Nature, 532, pp.117~121 (2016)
  35. Garrett WS, "Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis", Cell Host Microbe, 8, pp.292~300 (2010)
  36. Willemze RA, "Loss of intestinal sympathetic innervation elicits an innate immune driven colitis", Mol. Med, 25, pp.1~ (2019)[DOI]
  37. Ağaç D, "The β2-adrenergic receptor controls inflammation by driving rapid IL-10secretion", Brain Behav. Immun, 74, pp.176~185 (2018)
  38. Sehgal P, "Systematic review : safety of mesalazine in ulcerative colitis", Aliment Pharmacol. Ther, 47, pp.1597~1609 (2018)
  39. Baker DE, "The short-and long-term safety of 5-aminosalicylate products in the treatment of ulcerative colitis", Rev. Gastroenterol. Disord, 4, pp.86~91 (2004)
  40. Podolsky DK, "Inflammatory bowel disease", N. Engl. J. Med, 347, pp.417~429 (2002)
  41. Dahl JU, "The anti-inflammatory drug mesalamine targets bacterial polyphosphate accumulation", Nat. Microbiol, 2, pp.16267~ (2017)
  42. Lin HM, "Metabolomic analysis identifies inflammatory and noninflammatory metabolic effects of genetic modification in a mouse model of Crohn's disease", J. Proteome Res, 9, pp.1965~1975 (2010)
  43. Hase A, "Behavioral and cognitive effects of tyrosine intake in healthy human adults", Pharmacol. Biochem. Behav, 133, pp.1~6 (2015)
  44. Capuron L, "Chronic low-grade inflammation in elderly persons is associated with altered tryptophan and tyrosine metabolism : role in neuropsychiatric symptoms", Biol. Psychiatry, 70, pp.175~182 (2011)
  45. Hill CJ, "Evolution of gut microbiota composition from birth to 24 weeks in the INFANTMET Cohort", Microbiome, 5, pp.4~ (2017)

관련 논문AI추천

Synbiotic of Pediococcus acidilactici and Inulin Ameliorates Dextran Sulfate Sodium-Induced Acute Ulcerative Colitis in MiceCui Chengdu, Cui Lianhua, Jin Xin, Jin Yuanming, Piao Huiyan, Wang Mingzhu, Yan Chunri, Zhang Longzhou한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2024 · 제34권 제3호Protective Potential of Limosilactobacillus fermentum Strains and Their Mixture on Inflammatory Bowel Disease via Regulating Gut Microbiota in MiceChoi Kayoung, Joung Jae Yeon, Lee Ju-Hoon, Oh Nam Su한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2025 · 제35권 The Combination of Bacillus natto JLCC513 and Ginseng Soluble Dietary Fiber Attenuates Ulcerative Colitis by Modulating the LPS/TLR4/NF-κB Pathway and Gut MicrobiotaHe Yuguang, Hua Mei, Li Da, Li Yueqiao, Ma Mingyue, Miao Xinyu, Niu Honghong, Sun Mubai, Su Ying, Wang Jinghui, Zhang Hua한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2024 · 제34권 제6호The Ameliorative Effect of Rubi Fructus on DSS-induced Colitis in Mice명노일한국자원식물학회 · 한국자원식물학회지2021 · 제34권 제3호Modulation of the Gut Microbiome and Metabolomes by Fermentation Using a Probiotic Complex in a Dysbiosis-Associated Fecal ModelBang Won Yeong, Jeong Hye Min, Jeon Hyeon Ji, Jung Young Hoon, Kim Hayoung, Kwon Hyeji, Lee Han Bin, Lee Jongkyun, Lee Kyu-Shik, Moon Jin Seok, Yang Jungwoo한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2025 · 제35권 Astragalin Inhibits Nuclear Factor-κB Signaling in Human Colonic Epithelial Cells and Attenuates Experimental Colitis in Mice김주성, 한유민, Im Jong Pil, Kim Jee Hyun, Koh Jaemoon, Lee Jooyoung거트앤리버 소화기연관학회협의회 · Gut and Liver2021 · 제15권 제1호

이 간행물의 다른 논문 (6건)