肠道菌群对高脂饮食诱导肥胖小鼠糖脂代谢紊乱的免疫调节作用

doi:10.3969/j.issn.1006-5725.2024.11.007

Abstract

Abstract:

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

CLC Number:

R392.6

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.

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References 35

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物种	Ctrl组	HF组	ABX组	COMB组
厚壁菌门（Firmicutes）	50.66 ± 6.67	58.10 ± 6.36	45.70 ± 7.71	47.42 ± 5.99
拟杆菌门（Bacteroidota）	31.54 ± 7.22	19.00 ± 3.63	44.07 ± 8.41	23.50 ± 5.19^b
变形菌门（Proteobacteria）	4.12 ± 1.82	12.22 ± 3.97	1.96 ± 0.66	10.03 ± 2.70^b
疣微菌门（Verrucomicrobiota）	4.22 ± 1.70	1.70 ± 0.69	1.00 ± 0.31	7.37 ± 2.43^ab
脱铁杆菌门（Deferribacterota）	0.03 ± 0.02	0.08 ± 0.04	0.00 ± 0.00	0.03 ± 0.01^b
F/B值	4.46 ± 1.96	6.20 ± 1.50	2.71 ± 1.22	4.55 ± 1.33

物种	Ctrl组	HF组	ABX组	COMB组
另枝菌属（Alistipes）	2.52 ± 0.51	1.17 ± 0.30^a	2.40 ± 0.76	3.62 ± 1.20
粪杆菌属（Faecalibaculum）	1.27 ± 0.37	6.19 ± 2.10^a	2.35 ± 0.55	7.93 ± 2.50^ac
阿克曼菌属（Akkermansia）	4.21 ± 1.70	1.70 ± 0.69	1.00 ± 0.31	7.37 ± 2.43^bc
拟杆菌属（Bacteroides）	0.77 ± 0.21	3.21 ± 0.79^a	1.83 ± 0.43^a	6.83 ± 2.44^a
拟普雷沃氏菌属（Alloprevotella）	1.44 ± 0.52	1.12 ± 0.32	0.91 ± 0.29	1.19 ± 0.05^abc
嗜胆菌属（Bilophila）	0.03 ± 0.01	0.50 ± 0.31^a	0.08 ± 0.02	0.04 ± 0.03^b

分组	IL-10（pg/ mL）	IL-4（pg/ mL）	IL-13（pg/ mL）	IL-33（pg/ mL）	MCP-1（pg/ mL）	TNF-α（pg/ mL）
Ctrl组	268.18 ± 10.17	114.01 ± 3.77	22.11 ± 1.06	50.47 ± 3.58	7.56 ± 0.68	278.91 ± 15.00
HF组	178.02 ± 7.78^a	74.85 ± 4.08^a	36.48 ± 1.22^a	96.22 ± 3.66^a	14.70 ± 0.67^a	452.43 ± 16.00^a
ABX组	267.28 ± 7.26	106.23 ± 2.98^a	25.57 ± 1.03^a	56.72 ± 2.79^a	8.81 ± 0.48^a	292.01 ± 11.63^a
COMB组	238.56 ± 6.19^bc	95.23 ± 2.77^bc	28.06 ± 1.05^bc	67.21 ± 2.56^bc	11.06 ± 0.40^bc	346.82 ± 9.66^bc

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Immunomodulatory effects of intestinal flora on glucose and lipid metabolism disorders in high⁃fat diet induced obese mice

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