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Immunomodulatory effects of intestinal flora on glucose and lipid metabolism disorders in high⁃fat diet induced obese mice
Received date: 2023-11-24
Online published: 2024-06-13
Objective To explore the effect of mixed antibiotics on the intestinal flora of mice to affect the immune regulation of the body， explore the role of intestinal flora in the development of obesity， and provide new ideas and ways for the prevention and treatment of obesity. Methods Seventy-two 10-week-old male C57BL/6 mice were randomly divided into blank control （Ctrl） group， high-fat diet （HF） group， antibiotic （ABX） group， and combined （COMB） group （n = 18）. At the first 2 weeks （lavage intervention weeks）， Ctrl and HF group were given normal saline gavage； ABX and COMB group were given mixed antibiotics gavage， and the gavage volume was 0.2 mL/ animal/day. For the following 8 weeks （feeding weeks）， Ctrl and ABX group were fed with ordinary diet， HF and COMB group were fed with high-fat diet. Body weight was measured weekly， and fasting blood glucose was measured before and after gavage， and at the 4th and 8th week of feeding. Oral glucose tolerance test was performed at the end of the experiment. The organ coefficient was measured and the cell morphology of white and brown adipose tissue was observed. Serum was collected for the determination of free fatty acid， high-density lipoprotein， low-density lipoprotein， triglyceride， and total cholesterol. Serum TNF-α， IL-10， IL-4， IL-13， IL-33 and MCP-1 was detected by ELISA. The stool of mice was collected for second generation sequencing. Results High-fat diet increased body weight， serum total cholesterol， low-density lipoprotein， IL-13， IL-33， TNF-α， MCP-1 content， and decreased glucose tolerance and organ coefficient in mice （P < 0.05）. From the first feeding week to the end of the experiment， body weight in COMB group was significantly lower than that in HF group（P < 0.05）. The level of glucose tolerance， serum total cholesterol， low density lipoprotein， IL-13， IL-33， TNF-α and MCP-1 in COMB group was lower than those in HF group （P < 0.05）. The α diversity of intestinal flora in ABX group was lower than that in Ctrl group （P < 0.05）. Congestion and bleeding in WAT were obvious in HF group， but not in COMB group. The microbial community composition of ABX and HF group was similar to that of Ctrl and COMB group， respectively. Conclusion High-fat diet induces obesity， disorder of glucose and lipid metabolism and inflammation in mice. Short-term mixed antibiotic use can regulate the intestinal flora of mice， mediate increased expression of related anti-inflammatory factors， up-regulate host immunity， and improve glucose and lipid metabolism in mice.
Key words： intestinal flora; high-fat diet; antibiotic; glucose and lipid metabolism; immune
Xinwen BI , Yuanjie CUI , Qiuxian LU , Jia CUI , Fan BU , Fang HE , Hua YANG , Ming. LI . Immunomodulatory effects of intestinal flora on glucose and lipid metabolism disorders in high⁃fat diet induced obese mice[J]. The Journal of Practical Medicine, 2024 , 40(11) : 1505 -1512 . DOI: 10.3969/j.issn.1006-5725.2024.11.007
| 1 | PICHé M E， TCHERNOF A， DESPRéS J P. Obesity phenotypes，diabetes，and cardiovascular diseases［J］. Circ Res，2020，126（11）：1477-1500. doi:10.1161/circresaha.120.316101 |
| 2 | DIAF M， BENCHIKH H， BENNOUR I，et al. The relationship between body mass index， blood pressure， and atherosclerosis risk factors in type 1 and 2 diabetic patients from northwestern Algeria［J］. Endocr Regul，2022，56（3）：190-200. doi:10.2478/enr-2022-0020 |
| 3 | LI G， XIE C， LU S，et al.Intermittent fasting promotes white adipose browning and decreases obesity by shaping the gut microbiota［J］. Cell Metab，2017，26（4）：671-685. doi:10.1016/j.cmet.2017.08.019 |
| 4 | CHEVALIER C，STOJANOVI?O， COLIN D J，et al. Gut microbiota orchestrates energy homeostasis during cold［J］.Cell，2015，163（6）：1360-1374. doi:10.1016/j.cell.2015.11.004 |
| 5 | GOU W， LING C W， HE Y，et al. Interpretable machine learning framework reveals robust gut microbiome features associated with type 2 diabetes［J］. Diabetes Care，2021，44（2）：358-366. doi:10.2337/dc20-1536 |
| 6 | STANFORD K I， MIDDELBEEK R J， TOWNSEND K L，et al.Brown adipose tissue regulates glucose homeostasis and insulin sensitivity［J］. J Clin Invest，2013，123（1）：215-223. doi:10.1172/jci62308 |
| 7 | BETZ M J， ENERBACK S. Targeting thermogenesis in brown fat and muscle to treat obesity and metabolic disease［J］. Nat Rev Endocrinol，2018，14：77-87. doi:10.1038/nrendo.2017.132 |
| 8 | MORENO-NAVARRETE J M， FERNANDEZ-REA J M. The gut microbiota modulates both browning of white adipose tissue and the activity of brown adipose tissue［J］. Rev Endocr Metab disord，2019，20（4）：387-397. doi:10.1007/s11154-019-09523-x |
| 9 | 张雪晴，吴斌. 间歇性禁食对肥胖个体代谢与免疫的影响及作用机制研究进展［J］. 实用医学杂志，2021，37（2）：272-276. doi:10.3969/j.issn.1006-5725.2021.02.028 |
| 10 | LE CHATELIER E， NIELSEN T， QIN J，et al. Richness of human gut microbiome correlates with metabolic markers［J］. Nature，2013；500（7464）：541-546. |
| 11 | ZHANG X， JIN C， LIU H，et al. Polysaccharide extract from Rosa laevigata fruit attenuates inflammatory obesity by targeting redox balance and gut interface in high-fat diet-fed rats［J］. Food Science and Human Wellness，2023，12（2）： 442-453. doi:10.1016/j.fshw.2022.07.046 |
| 12 | KAWANO Y， EDWARDS M， HUANG Y，et al. Microbiota imbalance induced by dietary sugar disrupts immune-mediated protection from metabolic syndrome［J］. Cell， 2022，185（19）：3501-3519.e20. doi:10.1016/j.cell.2022.08.005 |
| 13 | WAN Y， WANG F， YUAN J，et al. Effects of dietary fat on gut microbiota and faecal metabolites， and their relationship with cardiometabolic risk factors： a 6-month randomised controlled-feeding trial［J］. Gut， 2019，68（8）：1417-1429. doi:10.1136/gutjnl-2018-317609 |
| 14 | SO S Y， WU Q， LEUNG K S，et al. Yeast beta-glucan reduces obesity-associated Bilophila abundance and modulates bile acid metabolism in healthy and high-fat diet mouse models［J］. Am J Physiol Gastrointest Liver Physiol， 2021，321（6）：G639-G655. doi:10.1152/ajpgi.00226.2021 |
| 15 | LUO S， ZHANG H， JIANG X，et al. Antibiotics ad ministration alleviates the high fat diet-induced obesity through altering the lipid metabolism in young mice［J］. Lipids， 2023；58（1）：19-32. doi:10.1002/lipd.12361 |
| 16 | MURUGESAN S， NIRMALKAR K， HOYOVADILLO C，et al. Gut microbiome Production of short-chain fatty acids and obesity in children［J］. Eur J Clin Microbiol Infect Dis， 2018，37（4）：621. doi:10.1007/s10096-017-3143-0 |
| 17 | ASHRAFIAN F， KESHAVARZ AZIZI RAFTAR S， LARI A，et al.Extracellular vesicles and pasteurized cells derived from Akkermansia muciniphila protect against high-fat induced obesity in mice［J］. Microb Cell Fact， 2021，20（1）：219. doi:10.1186/s12934-021-01709-w |
| 18 | OUYANG J， LIN J， ISNARD S，et al. The Bacterium Akkermansia muciniphila： A Sentinel for Gut Permeability and Its Relevance to HIV-Related Inflammation［J］. Front Immunol， 2020，11：645. doi:10.3389/fimmu.2020.00645 |
| 19 | GU Z， PEI W， SHEN Y，et al.Akkermansia muciniphila and its outer protein Amuc_1100 regulates tryptophan metabolism in colitis［J］. Food Funct， 2021，12（20）：10184-10195. doi:10.1039/d1fo02172a |
| 20 | SHI Z， LEI H， CHEN G，et al. Impaired intestinal Akkermansia muciniphila and aryl hydrocarbon receptor ligands contribute to nonalcoholic fatty liver disease in mice［J］. mSystems， 2021，6（1）：e00985-20. doi:10.1128/msystems.00985-20 |
| 21 | VILLARROYA F， CEREIJO R， VILLARROYA J，et al. Toward an Understanding of How Immune Cells Control Brown and Beige Adipobiology［J］. Cell Metab， 2018，27（5）：954-961. doi:10.1016/j.cmet.2018.04.006 |
| 22 | SUáREZ-ZAMORANO N， FABBIANO S， CHEVALIER C，et al.Microbiota depletion Promotes browning of white adipose tissue and reduces obesity［J］. Nat Med， 2015，21（12）：1497-1501. doi:10.1038/nm.3994 |
| 23 | NGUYEN K D， QIU Y， CUI X，et al. Alternatively activated macrophages Produce catechola mines to sustain adaptive thermogenesis［J］. Nature， 2011，480（7375）：104-108. doi:10.1038/nature10653 |
| 24 | RAO R R， LONG J Z， WHITE J P，et al. Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis［J］. Cell， 2014，157（6）：1279-1291. doi:10.1016/j.cell.2014.03.065 |
| 25 | FABBIANO S， SUAREZ-ZAMORANO N， RIGO D，et al. Caloric Restriction Leads to Browning of White Adipose Tissue through Type 2 Immune Signaling［J］. Cell Metab， 2016，24（3），434-446. doi:10.1016/j.cmet.2016.07.023 |
| 26 | GARCIA M C， PAZOS P， LIMA L，et al. Regulation of energy expenditure and brown/beige thermogenic activity by interleukins： New roles for old actors［J］. Int J Mol Sci， 2018，19（9）：2569. doi:10.3390/ijms19092569 |
| 27 | 商佳琪，郭宇帆，张梦洁，等. 抗生素处理对高脂饲料诱导肥胖SD大鼠肠道菌群与血清炎性因子的影响［J］. 营养学报， 2021，43（5）：498-503. doi:10.3969/j.issn.0512-7955.2021.05.014 |
| 28 | KWON H， LAURENT S， TANG Y，et al. Adipocyte-Specific IKKbeta Signaling Suppresses Adipose Tissue Inflammation through an IL-13-Dependent Paracrine Feedback Pathway［J］. Cell Rep，2014，9（5）：1574-1583. doi:10.1016/j.celrep.2014.10.068 |
| 29 | CAYROL C， GIRARD J P. Interleukin-33（IL-33）： A nuclear cytokine from the IL-1 family［J］. Immunol Rev， 2018，281（1）：154-168. doi:10.1111/imr.12619 |
| 30 | TAKENAGA K， AKIMOTO M， KOSHIKAWA N，et al. Cancer cell-derived interleukin-33 decoy receptor sST2 enhances orthotopic tumor growth in a murine pancreatic cancer model［J］. PLoS One， 2020，15（4）：e0232230. doi:10.1371/journal.pone.0232230 |
| 31 | ZEYDA M， WERNLY B， DEMYANETS S，et al. Severe obesity increases adipose tissue expression of interleukin-33 and its receptor ST2， both Predo minantly detectable in endothelial cells of human adipose tissue［J］. Int J Obes （Lond）， 2013，37（5）：658-665. doi:10.1038/ijo.2012.118 |
| 32 | KAI Y， GAO J， LIU H，et al. Effects of IL-33 on 3T3-L1 cells and obese mice models induced by a high-fat diet［J］. Int Immunopharmacol， 2021，101（Pt A）：108209. doi:10.1016/j.intimp.2021.108209 |
| 33 | TANG H， LIU N， FENG X，et al. Circulating levels of IL-33 are elevated by obesity and positively correlated with metabolic disorders in Chinese adults［J］. J Transl Med， 2021，19（1）：52. doi:10.1186/s12967-021-02711-x |
| 34 | SYARIF， RASYID H， AMAN M，et al. High-fat diet increases the level of circulating Monocyte Chemoattractant Protein-1 in Wistar rats， independent of obesity［J］. Ann Med Surg （Lond）， 2021，65：102266. doi:10.1016/j.amsu.2021.102266 |
| 35 | AHMED B， SULTANA R， GREENE M W. Adipose tissue and insulin resistance in obese［J］. Biomed Pharmacother， 2021，137：111315. doi:10.1016/j.biopha.2021.111315 |
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