本文選題：斷食 + 腸道菌群��； 參考：《南方醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:1.研究間歇性斷食對(duì)老年前期肥胖大鼠代謝及腸道菌群的影響。2.研究不同斷食形式對(duì)人體腸道菌群的影響。3.研究飲水?dāng)嗍硨?duì)人體代謝的影響。方法:1.雌性Wistar大鼠經(jīng)42w高脂高糖飼料飼養(yǎng)造模,根據(jù)體質(zhì)量(x±SD)選取模型鼠進(jìn)行間歇性斷食干預(yù)。干預(yù)方法為每2w斷食72h,總干預(yù)時(shí)間18w。干預(yù)后進(jìn)行口服葡萄糖耐量試驗(yàn)、血脂四項(xiàng)檢測(cè)。收集糞便,通過Illumina高通量測(cè)序檢測(cè)16S rRNA基因V4可變區(qū),運(yùn)用BIPES、QIIME及LEfSe分析腸道菌群。2.招募健康志愿者進(jìn)行持續(xù)7日的斷食實(shí)驗(yàn),分為飲水?dāng)嗍辰M和果汁斷食組。收集斷食前兩周至斷食后四周的糞便樣本,通過Illumina高通量測(cè)序檢測(cè)16S rRNA基因V4可變區(qū),運(yùn)用BIPES、QIIME及LEfSe分析腸道菌群。3.收集飲水?dāng)嗍辰M志愿者在斷食前后的血液標(biāo)本,進(jìn)行生理生化指標(biāo)檢測(cè)以及預(yù)處理后進(jìn)行核磁共振分析樣本中的代謝產(chǎn)物。使用MestReNova對(duì)1H CPMG譜進(jìn)行分析,Simca-P進(jìn)行多元統(tǒng)計(jì)分析。根據(jù)人類代謝產(chǎn)物數(shù)據(jù)庫對(duì)斷食前后有統(tǒng)計(jì)差異的代謝產(chǎn)物成分進(jìn)行鑒定。結(jié)果:1.大鼠實(shí)驗(yàn)中間歇性斷食組體質(zhì)量相對(duì)于模型對(duì)照組顯著下降(P0.01);高密度脂蛋白膽固醇和低密度脂蛋白膽固醇均顯著下降(P0.05);空腹血糖顯著上升(P0.01);葡萄糖耐量測(cè)試曲線下面積顯著高于模型對(duì)照組,糖耐量減退(P0.05);HE染色顯示間歇性斷食輕度減少肝臟脂肪變性。腸道菌群結(jié)果顯示,斷食組腸道菌群得到顯著改善,具體表現(xiàn)為YS2、RF32、Helicobacteraceae(螺桿菌科)增加,Lactobacillus(乳桿菌屬)、Roseburia(羅氏菌屬)、Erysipelotrichaceae(韋榮球菌科)、Ralstonia(青枯菌屬)、Bradyrhizobiaceae(慢生根瘤菌科)和RF39減少。Spearman相關(guān)性分析發(fā)現(xiàn)Bradyrhizobiaceae與總膽固醇、高密度脂蛋白膽固醇呈正相關(guān);RF39與大鼠體質(zhì)量呈正相關(guān)。2.飲水?dāng)嗍潮裙瓟嗍硨?duì)人腸道菌群的影響更為強(qiáng)烈,且效果在宿主恢復(fù)飲食后能長久維持。但飲水?dāng)嗍车男Ч哂袀�(gè)體差異,總的來看飲水?dāng)嗍衬苁鼓c道菌群變成以Prevotella(普雷沃氏菌屬)、Bacteroides(擬桿菌屬)、Faecalibacterium(柔嫩菌屬)和Succinivibrio(琥拍酸弧菌屬)為主。3.飲水?dāng)嗍城昂蟮拇x產(chǎn)物水平存在明顯差異,斷食期間3-羥基丁酸酯和乙酰乙酸的表達(dá)上升(P0.05),而丙氨酸、谷氨酸鹽、組氨酸、氧化三甲胺、β-葡萄糖、α-葡萄糖的表達(dá)顯著下降(P0.05)。斷食期間,機(jī)體的血糖、胰島素、甘油三酯下降,酮體、總膽固醇、低密度脂蛋白膽固醇、血肌酐、血尿酸、皮質(zhì)醇升高,提示機(jī)體可能通過促進(jìn)代謝脂肪酸、肌肉、核酸等物質(zhì)產(chǎn)生能量。機(jī)體代謝改變可能與脂肪酸合成、鳥氨酸循環(huán)、氨基酸代謝、丙氨酸循環(huán)、轉(zhuǎn)錄翻譯、酮體代謝、三羧酸循環(huán)、糖異生、糖酵解等多個(gè)通路相關(guān)。在恢復(fù)飲食3天后代謝產(chǎn)物水平恢復(fù)至與斷食前相似。結(jié)論:1.間歇性斷食能改善腸道菌群,降低老年前期肥胖大鼠體質(zhì)量和血脂水平,但對(duì)糖代謝可能有不良影響。2.無卡路里攝入比限制卡路里攝入的斷食方式對(duì)腸道菌群影響更大。3.飲水?dāng)嗍衬馨褦M桿菌為主的腸道菌群變?yōu)橐云绽孜质暇鸀橹?而對(duì)普雷沃氏菌為主的腸道菌群結(jié)構(gòu)影響不大。4.機(jī)體在飲水?dāng)嗍称陂g可能通過調(diào)節(jié)能量相關(guān)的代謝通路,消耗脂肪酸、肌肉、核酸維持機(jī)體活動(dòng)所需的能量消耗。5.飲水?dāng)嗍澈蠡謴?fù)飲食第3天,機(jī)體的代謝產(chǎn)物都恢復(fù)到正常水平,但腸道菌群仍沒有恢復(fù),說明機(jī)體代謝調(diào)節(jié)比腸道菌群對(duì)飲食的改變更加敏感�？傮w而言,斷食對(duì)腸道菌群的影響個(gè)體差異性較為顯著,用于臨床疾病預(yù)防和治療仍需深入研究,但能為肥胖患者提供新的視角。
[Abstract]:Objective: 1. study the effect of intermittent feeding on metabolism and intestinal microflora in obese rats.2. study the influence of different forms of food break on human intestinal flora.3. study on the effect of drinking water break on human metabolism. Methods: 1. female Wistar rats were fed with 42W high fat and high sugar diet, and the model rats were selected according to body mass (x + SD). Intermittent fasting intervention. The intervention method was 72h per 2W, oral glucose tolerance test and four blood lipid tests. Feces were collected, V4 variable region of 16S rRNA gene was detected by Illumina sequencing, and BIPES, QIIME and LEfSe analysis of intestinal flora.2. were used for 7 day continuous feeding. The experiment was divided into the drinking water feeding group and the fruit juice group. The faecal samples were collected from two weeks to the four weeks after the disconnection. The 16S rRNA gene V4 variable region was detected by Illumina high throughput sequencing, and BIPES, QIIME and LEfSe were used to analyze the intestinal microflora.3. to collect the blood specimens before and after the broken food in the drinking water group, and the physiological and biochemical indexes were examined. The metabolites in the nuclear magnetic resonance analysis samples were measured and pretreated. The 1H CPMG spectrum was analyzed with MestReNova, and the Simca-P was analyzed by multivariate statistical analysis. According to the human metabolite database, the metabolites of the statistical differences before and after the disconnection were identified. Results: the mass of the intermittent feeding group in the 1. rats was relative. In model control group (P0.01), high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (HDL) were significantly decreased (P0.05), fasting blood glucose increased significantly (P0.01), and the area under glucose tolerance test curve was significantly higher than that of model control group, impaired glucose tolerance (P0.05), and HE staining showed intermittent intermittent feeding reduced liver steatosis slightly. The intestinal flora showed that the intestinal microflora of the diet group improved significantly, including YS2, RF32, Helicobacteraceae (helicobacteraceae), Lactobacillus (Lactobacillus), Roseburia (Roche), Erysipelotrichaceae (Wei Rong family), Ralstonia (Rhizoctonia), Bradyrhizobiaceae (slow Rhizobiaceae) and RF39 reduced.Spearman Correlation analysis found that Bradyrhizobiaceae was positively correlated with total cholesterol and high density lipoprotein cholesterol; RF39 was positively related to the body mass of rats;.2. was more strongly influenced by the drinking water break than the fruit juice feeding on the human intestinal flora, and the effect could be maintained for a long time after the host was restored to the diet. Drinking water break can make intestinal flora become Prevotella (Poulet Was bacteria), Bacteroides (bacteriobacterium), Faecalibacterium (tenella) and Succinivibrio (Vibrio succinate), the metabolic products of.3. before and after drinking water are significantly different, and the expression of 3- hydroxybutyrate and acetoacetic acid increases during the period of feeding (P0.05). The expression of alanine, glutamate, histidine, trimethylamine, beta glucose, and alpha glucose decreased significantly (P0.05). During the diet, the body's blood sugar, insulin, triglyceride, ketone body, total cholesterol, low density lipoprotein cholesterol, serum creatinine, blood uric acid, cortisol increased, suggesting that the body may promote the metabolism of fatty acids and muscles. Meat, nucleic acid and other substances produce energy. Metabolic changes may be related to fatty acid synthesis, ornithine cycle, amino acid metabolism, alanine cycle, transcription translation, ketone metabolism, three carboxylic acid cycle, sugar isogenesis, glycolysis, etc. after 3 days of recovery, the level of metabolite recovery is similar to that before eating. Conclusion: 1. intermittent feeding It can improve the intestinal flora and reduce the body mass and blood lipid level of the obese rats, but it may have adverse effects on the glucose metabolism. The effect of.2. without calorie intake on intestinal microflora is greater than that of the limit calorie intake..3. drinking water break can turn the bacilli mainly intestinal flora into Poulet Was bacteria, and to pervo. The structure of intestinal microflora with the main bacteria was not much affected by.4.. The body could consume the energy related metabolic pathway during drinking water feeding, consumption of fatty acid, muscle, and nucleic acid to maintain the energy consumption of the body.5.. After drinking water for third days after drinking water, the metabolic products of the body recovered to the normal level, but the intestinal flora was still not. It shows that the metabolic regulation of the body is more sensitive than the intestinal flora on the change of diet. In general, the effect of feeding on the intestinal microflora is more distinct, and the prevention and treatment of clinical diseases still need to be further studied, but it can provide a new perspective for the obese patients.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R589.2

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