Gut microbiome and metabolome in a non-human primate model of chronic excessive alcohol drinking.
Gut microbiome and metabolome in a non-human primate model of chronic excessive alcohol drinking.
复制标题
DOI：
10.1038/s41398-021-01728-6
复制
发表时间：
2021-12-01
影响因子：
6.8
通讯作者：
Leggio L
中科院分区：
文献类型：
--
作者：
Piacentino D;Grant-Beurmann S;Vizioli C;Li X;Moore CF;Ruiz-Rodado V;Lee MR;Joseph PV;Fraser CM;Weerts EM;Leggio L
肠道微生物组与酒精使用障碍之间的关联已被提出。过度饮酒会使啮齿动物和人类的粪便微生物组和代谢组发生变化。然而，这些变化仅在研究人群的一个亚组中可被观察到，并且在戒酒之后并不总是会逆转。我们旨在分析一种在转化上相关的狒狒慢性重度饮酒模型（该模型也符合酗酒标准，即多年来每天在2小时内饮酒约1克/千克且血液酒精浓度≥0.08克/分升）中的粪便微生物组成和功能。我们比较了三组雄性狒狒（东非狒狒）：L = 长期饮酒组（12.1年）；S = 短期饮酒组（2.7年）；C = 对照组，饮用无酒精强化剂（Tang®）（8.2年）。在饮酒3天（D）期间收集粪便，随后是短暂的戒酒3天（A）。L组与S组和C组相比，粪便微生物的α -多样性和β -多样性显著更低（p值<0.05）。共生菌毛螺菌科和普雷沃氏菌科的成员相对减少，而机会致病菌链球菌属在L组与S组和C组相比相对增加（p值<0.05）。与微生物群相关的芳香族氨基酸、三羧酸循环和戊糖的代谢物在L组与S组和C组相比增加（错误发现率校正p <0.01），后两者表明肠道腔内因酒精作用出现高能量代谢和糖酵解增强。与长期酒精暴露一致，黏膜损伤和氧化应激标志物（N -乙酰化氨基酸、2 -羟基丁酸以及甲硫氨酸循环的代谢物）在L组与S组和C组相比增加（错误发现率校正p <0.01）。总体而言，S组与C组相比差异很少，可能是因为改变正常肠道微生物群需要长期、慢性的酒精暴露。在这三组中，条件D和A之间的粪便微生物组几乎没有差异，而代谢组在从条件D到A的转变过程中发生了变化。总之，在长期大量饮酒后粪便微生物组和代谢组会发生变化，并且仅部分受到急性强制戒酒的影响。这些结果在受控的实验环境中以及使用独特的慢性过度饮酒的非人灵长类动物模型，为粪便微生物组和代谢组之间的关系提供了新的信息。
A relationship between the gut microbiome and alcohol use disorder has been suggested. Excessive alcohol use produces changes in the fecal microbiome and metabolome in both rodents and humans. Yet, these changes can be observed only in a subgroup of the studied populations, and reversal does not always occur after abstinence. We aimed to analyze fecal microbial composition and function in a translationally relevant baboon model of chronic heavy drinking that also meets binge criteria (drinking too much, too fast, and too often), i.e., alcohol ~1 g/kg and blood alcohol levels (BALs) ≥ 0.08 g/dL in a 2-hour period, daily, for years. We compared three groups of male baboons (Papio anubis): L = Long-term alcohol drinking group (12.1 years); S = Short-term alcohol drinking group (2.7 years); and C = Control group, drinking a non-alcoholic reinforcer (Tang®) (8.2 years). Fecal collection took place during 3 days of Drinking (D), followed by a short period (3 days) of Abstinence (A). Fecal microbial alpha- and beta-diversity were significantly lower in L vs. S and C (p’s < 0.05). Members of the commensal families Lachnospiraceae and Prevotellaceae showed a relative decrease, whereas the opportunistic pathogen Streptococcus genus showed a relative increase in L vs. S and C (p’s < 0.05). Microbiota-related metabolites of aromatic amino acids, tricarboxylic acid cycle, and pentose increased in L vs. S and C (FDR-corrected p < 0.01), with the latter two suggesting high energy metabolism and enhanced glycolysis in the gut lumen in response to alcohol. Consistent with the long-term alcohol exposure, mucosal damage and oxidative stress markers (N-acetylated amino acids, 2-hydroxybutyrate, and metabolites of the methionine cycle) increased in L vs. S and C (FDR-corrected p < 0.01). Overall, S showed few differences vs. C, possibly due to the long-term, chronic alcohol exposure needed to alter the normal gut microbiota. In the three groups, the fecal microbiome barely differed between conditions D and A, whereas the metabolome shifted in the transition from condition D to A. In conclusion, changes in the fecal microbiome and metabolome occur after significant long-term excessive drinking and are only partially affected by acute forced abstinence from alcohol. These results provide novel information on the relationship between the fecal microbiome and metabolome in a controlled experimental setting and using a unique non-human primate model of chronic excessive alcohol drinking.
登录
查看更多内容
影响因子：
29.4
作者：
Chen P;Torralba M;Tan J;Embree M;Zengler K;Stärkel P;van Pijkeren JP;DePew J;Loomba R;Ho SB;Bajaj JS;Mutlu EA;Keshavarzian A;Tsukamoto H;Nelson KE;Fouts DE;Schnabl B
通讯作者：
Schnabl B
在狒狒的会话设计中，巴氯芬对酒精寻求、自我管理和寻求反应消退的影响。
影响因子：
3.4
作者：
Duke AN;Kaminski BJ;Weerts EM
通讯作者：
Weerts EM
DOI：
10.1111/acer.12732
发表时间：
2015-06
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Cresci GA
通讯作者：
Cresci GA
影响因子：
15.5
作者：
Fadrosh DW;Ma B;Gajer P;Sengamalay N;Ott S;Brotman RM;Ravel J
通讯作者：
Ravel J
影响因子：
3.7
作者：
Couch RD;Dailey A;Zaidi F;Navarro K;Forsyth CB;Mutlu E;Engen PA;Keshavarzian A
通讯作者：
Keshavarzian A