中国食品学报

肠道菌群介导支链氨基酸升高与肥胖相关认知障碍的关系

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刘锐 ¹ , 郭洋 ¹ , 孙乐妍 ¹ , 刘奕彤 ¹

中国食品学报 | 营养与功能 2026,26(1): 121-131

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中国食品学报 | 营养与功能 2026, 26(1): 121-131

肠道菌群介导支链氨基酸升高与肥胖相关认知障碍的关系

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刘锐¹, 郭洋¹, 孙乐妍¹, 刘奕彤¹

作者信息

^1.江汉大学医学部认知与情感障碍湖北省重点实验室湖北省医学实验教学示范中心武汉 430056

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刘锐: 刘锐，女，博士，讲师

The Relationship between Gut Microbiota-Mediated Elevation of Branched-Chain Amino Acids and Obesity-Associated Cognitive Decline

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出版时间: 2026-01-31 doi: 10.16429/j.1009-7848.2026.01.011

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目的:高脂饮食是认知功能障碍的危险因素，然而其潜在的生物学机制尚未明晰。方法:将24只雄性3月龄C57BL/6J小鼠随机分为对照组和高脂组，对照组给予正常饲料，高脂组给予高脂饲料(脂肪供能比46%)。喂养12周，采用葡萄糖耐量试验(GTT)评价小鼠胰岛素敏感性，Morris水迷宫评估小鼠的认知功能。实验结束后处死小鼠，收集血清、结肠内容物和脑组织。检测血清胰岛素、葡萄糖浓度，计算胰岛素抵抗指数。观察海马齿状回神经元核抗原(NeuN)蛋白表达，检测血清3种支链氨基酸(BCAAs)水平，分析小鼠肠道菌群变化，并将差异细菌与血清BCAAs进行关联分析。结果:喂养12周，与对照组小鼠相比，高脂组小鼠体质量(31.6 g vs 37.5 g，P<0.001)、体脂率(3.2% vs 5.8%，P<0.001)、GTT血糖曲线下面积显著增加(1 440 mmol/L·min vs 1 841 mmol/L·min，P<0.05)，血清异亮氨酸(高脂组为对照组的1.27倍，P<0.05)及总BCAAs(高脂组为对照组的1.16倍，P<0.05)水平显著升高；高脂组小鼠海马齿状回NeuN阳性反应区荧光强度显著降低(27 vs 12，P<0.01)；高脂组小鼠Morris水迷宫空间探索实验中，穿越平台和目标象限次数显著降低，并且与血清异亮氨酸和总BCAAs水平呈负相关。此外，高脂组小鼠肠道菌群组成与对照组显著不同；小鼠肠道菌群代谢功能预测分析显示，与对照组相比，高脂组BCAAs生物降解相关微生物通路显著增加。Spearman相关分析表明，微小杆菌属与异亮氨酸水平呈负相关(P=0.01)，布劳特氏菌属和厌氧杆状菌属与异亮氨酸水平呈正相关(P值分别为0.00和0.03)。结论:高脂饮食诱导认知功能障碍，可能与其介导肠道菌群紊乱引起BCAAs水平升高有关。

关键词

肠道菌群 / 支链氨基酸 / 肥胖 / 认知功能障碍 / 高脂饮食

Abstract

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Objective: A high-fat diet is a risk factor for cognitive impairment， but its underlying biological mechanisms have not been elucidated. Methods: twenty-four male 3-month-old C57BL/6J mice were randomly divided into two groups， and fed with normal chow diet (ND) and high-fat diet (HFD) for 12 weeks. At the end of the experiment， the glucose tolerance test (GTT) was performed. Cognitive function was evaluated with the Morris Water Maze (MWM) test. After overnight fast， the mice were sacrificed and serum and colon contents were collected. Serum insulin levels were detected by ELISA， serum glucose levels were determined by colorimetric method and HOMA-IR was calculated. Liquid chromatography tandem mass spectrometry was used to detect serum BCAA levels. 16S rDNA amplicon sequencing was used to detect gut microbiota alterations， and their correlation with serum BCAAs was performed by Spearman correlation. Results: After 12 weeks feeding， compared with the control mice， the HFD-fed mice showed significant increases in body weight (31.6 g vs 37.5 g， P<0.001)， body fat rate (3.2% vs 5.8%， P<0.001)， area under curve (AUC) of GTT (1 440 mmol/L·min vs 1 841 mmol/L·min， P<0.05)， and fasting serum levels of isoleucine (1.27-fold of the control group， P<0.05) and total BCAAs (1.16-fold of the control group， P<0.05). Additionally， the fluorescence intensity of NeuN-positive immunoreactive regions in the dentate gyrus of the hippocampus was significantly decreased in the HFD group (27 vs 12， P<0.01). HFD-fed mice displayed a decrease in the number of platform and the target quadrant entries during the probe trial compared with the control group， and these indicators were negatively correlated with serum isoleucine and total BCAA levels. In addition， the composition of gut microbiota in HFD group was significantly different from that in the control group. At the genus level， Romboutsia and Blautia are the dominant microbiota in the colon of HFD-fed mice. Bacterial functionality prediction indicated that gut microbiota genes involved in BCAA degradation were significantly reduced in HFD group compared with the control group. The Parvibacter genus is negatively correlated with isoleucine levels (P=0.01)， while the Blautia and Anaerotruncuus genus are positively correlated with isoleucine levels (the P-value were 0.00 and 0.03， respectively). Conclusion: Gut microbiota may be the link between elevated serum BCAA levels and HFD-induced cognitive impairment.

Key words

gut microbiota / branched-chain amino acids / obesity / cognitive impairment / high-fat diet

引用本文

刘锐, 郭洋, 孙乐妍, 刘奕彤. 肠道菌群介导支链氨基酸升高与肥胖相关认知障碍的关系. 中国食品学报, 2026 , 26 (1) : 121 -131 . DOI: 10.16429/j.1009-7848.2026.01.011

. The Relationship between Gut Microbiota-Mediated Elevation of Branched-Chain Amino Acids and Obesity-Associated Cognitive Decline[J]. Journal of Chinese Institute of Food Science and Technology, 2026 , 26 (1) : 121 -131 . DOI: 10.16429/j.1009-7848.2026.01.011

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国家自然科学基金青年基金项目

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OTTOSSON F, BRUNKWALL L, ERICSON U, et al.Connection between BMI-related plasma metabolite profile and gut microbiota[J].J Clin Endocrinol Metab, 2018, 103(4): 1491-1501.

BRUCE-KELLER A J, SALBAUM J M, LUO M, et al.Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity[J].Biological Psychiatry, 2015, 77(7): 607-615.

FELIG P, MARLISS E, CAHILL JR G F.Plasma amino acid levels and insulin secretion in obesity[J].N Engl J Med, 1969, 281(15): 811-816.

SIDDIK M A B, MULLINS C A, KRAMER A, et al.Branched-chain amino acids are linked with Alzheimer's disease-related pathology and cognitive deficits[J].Cells, 2022, 11(21): 3523.

JACHTHUBER TRUB C, BALIKCIOGLU M, FREEMARK M, et al.Impact of lifestyle Intervention on branched-chain amino acid catabolism and insulin sensitivity in adolescents with obesity[J].Endocrinol Diabetes Metab, 2021, 4(3): e00250.

GOJDA J, CAHOVA M.Gut microbiota as the link between elevated BCAA serum levels and insulin resistance[J].Biomolecules, 2021, 11(10): 1414.

CHEN Y M, JIANG S J, WANG H L, et al.The probiotic parabacteroides johnsonii ameliorates metabolic disorders through promoting BCAAs to BSCFAs conversion[J].Adv Sci, 2025, 12(38): e02624.

TANG X Y, ZHAO W, LU M, et al.Relationship between central obesity and the incidence of cognitive impairment and dementia from cohort studies involving 5,060,687 participants[J].Neuroscience and Biobehavioral Reviews, 2021, 130: 301-313.

WANG Y L, RONG X, GUAN H, et al.The potential effects of isoleucine restricted diet on cognitive impairment in high-fat-induced obese mice via gut microbiota-brain axis[J].Mol Nutr Food Res, 2023, 67(20): e2200767.

YOO H S, SHANMUGALINGAM U, SMITH P D.Potential roles of branched-chain amino acids in neurodegeneration[J].Nutrition, 2022, 103-104: 111762.

BOCARSLY M E, FASOLINO M, KANE G A, et al.Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function[J].Proceedings of the national Academy of Sciences of the United states of America, 2015, 112(51): 15731-15736.

ARANY Z, NEINAST M.Branched chain amino acids in metabolic disease[J].Curr Diab Rep, 2018, 18(10): 76.

WANG D N, WANG L Y, HAN L Y, et al.Leucine-restricted diet ameliorates obesity-linked cognitive deficits: Involvement of the microbiota-gut-brain axis[J].J Agric Food Chem, 2023, 71(24): 9404-9418.

WU H C, ZHANG W X, HUANG M Y, et al.Prolonged high-fat diet consumption throughout adulthood in mice induced neurobehavioral deterioration via gut-brain axis[J].Nutrients, 2023, 15(2): 392.

JAMARAL A U, LEIPNITZ G, FERNANDES C G, et al.Alpha-ketoisocaproic acid and leucine provoke mitochondrial bioenergetic dysfunction in rat brain[J].Brain Res, 2010, 1324: 75-84.

JOUVET P, RUSTIN P, TAYLOR D L, et al.Branched chain amino acids induce apoptosis in neural cells without mitochondrial membrane depolarization or cytochrome c release: Implications for neurological impairment associated with maple syrup urine disease[J].Mol Biol Cell, 2000, 11(5): 1919-1932.

ZHANG L, YUE Y S, SHI M X, et al.Dietary Luffa cylindrica (L.) roem promotes branched-chain amino acid catabolism in the circulation system via gut microbiota in diet-induced obese mice[J].Food Chem, 2020, 320: 126648.

NEIS E P, DEJONG C H, RENSEN S S.The role of microbial amino acid metabolism in host metabolism[J].Nutrients, 2015, 7(4): 2930-2946.

CHOI M S, REHMAN S U, KIM I S, et al.Development of a mixed-mode chromatography with tandem mass spectrometry method for the quantitative analysis of 23 underivatized amino acids in human serum[J].J Pharm Biomed Anal, 2017, 145: 52-58.

WURTZ P, SOININEN P, KANGAS A J, et al.Branched-chain and aromatic amino acids are predictors of insulin resistance in young adults[J].Diabetes care, 2013, 36(3): 648-655.

ZHANG Y, HE X Q, QIAN Y W, et al.Plasma branched-chain and aromatic amino acids correlate with the gut microbiota and severity of Parkinson's disease[J].NPJ Parkinsons Dis, 2022, 8(1): 48.

VALLIANOU N, STRATIGOU T, CHRISTODOU-LATOS G S, et al.Understanding the role of the gut microbiome and microbial metabolites in obesity and obesity-associated metabolic disorders: Current evidence and perspectives[J].Current Obesity Reports, 2019, 8(3): 317-332.

O'BRIEN P D, HINDER L M, CALLAGHAN B C, et al.Neurological consequences of obesity[J].The Lancet Neurology, 2017, 16(6): 465-477.

PEDERSEN H K, GUDMUNDSDOTTIR V, NIELSEN H B, et al.Human gut microbes impact host serum metabolome and insulin sensitivity[J].Nature, 2016, 535(7612): 376-381.

ORG E, BLUM Y, KASELA S, et al.Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort[J].Genome Biol, 2017, 18(1): 70.

MCCORMACK S E, SHAHAM O, MCCARTHY M A, et al.Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents[J].Pediatr Obes, 2013, 8(1): 52-61.

LIU R X, HONG J, XU X Q, et al.Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention[J].Nat Med, 2017, 23(7): 859-868.

2026年第26卷第1期

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doi: 10.16429/j.1009-7848.2026.01.011

接收时间：2024-12-10
首发时间：2026-05-27
出版时间：2026-01-31

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收稿日期：2024-12-10

基金

国家自然科学基金青年基金项目

作者信息

^1.江汉大学医学部认知与情感障碍湖北省重点实验室湖北省医学实验教学示范中心武汉 430056

通讯作者:

刘锐: 刘锐，女，博士，讲师

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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