Normandie University, UNIROUEN, INSERM UMR 1073 "Nutrition, Inflammation and Gut-brain Axis", Rouen, France; Institute for Research and Innovation in Biomedicine (IRIB), UNIROUEN, Rouen, France.
Normandie University, UNIROUEN, INSERM UMR 1073 "Nutrition, Inflammation and Gut-brain Axis", Rouen, France; Institute for Research and Innovation in Biomedicine (IRIB), UNIROUEN, Rouen, France; Department of Nutrition, CHU Rouen, Rouen, France.
Clin Nutr. 2021 May;40(5):2734-2744. doi: 10.1016/j.clnu.2021.04.014. Epub 2021 Apr 20.
BACKGROUND & AIMS: In the last decade, the role of the microbiota-gut-brain axis in eating behavior and anxiety-depressive disorders has gained increasing attention. Although a gut microbiota dysbiosis has been reported in anorectic patients, its pathophysiological role remains poorly understood. Thus, we aimed to characterize the potential role of gut microbiota by evaluating the effects of its depletion in the Activity-Based Anorexia (ABA) mouse model both in male and female mice.
Male and female C57Bl/6 mice were submitted (ABA group) or not (CT group) to the ABA protocol, which combines access to a running wheel with a progressive limited food access. Gut microbiota was previously depleted or not by a cocktail of antibiotics (ATB) delivered by oral gavages. We monitored body composition, anxiety-like behavior, leptin and adiponectin plasma levels, hypothalamic and hippocampal neuropeptides mRNA levels, as well as dopamine (DRD) and serotonin (5HT1 and 4) receptors mRNA expression.
In response to the ABA model, the body weight loss was less pronounced in ATB-treated ABA compared to untreated ABA, while food intake remained unaffected by ATB treatment. ATB-treated ABA exhibited increased fat mass and decreased lean mass compared to untreated ABA both in male and female mice, whereas but plasma adipokine concentrations were affected in a sex-dependent manner. Only male ABA mice showed a reduced anticipatory physical activity in response to ATB treatment. Similarly, anxiety-like behavior was mainly affected in ATB-treated ABA male mice compared to ATB-treated ABA female mice, which was associated with male-specific alterations of hypothalamic CRH mRNA and hippocampal DRD and 5-HT1A mRNA levels.
Our study provides evidence that ATB-induced gut microbiota depletion triggers alterations of nutritional and behavioral responses to the activity-based anorexia model in a sex-dependent manner.
在过去的十年中，微生物群-肠道-大脑轴在饮食行为和焦虑抑郁障碍中的作用引起了越来越多的关注。虽然厌食症患者的肠道微生物群失调已经得到报道，但它的病理生理作用仍知之甚少。因此，我们旨在通过评估其在雄性和雌性 ABA 小鼠模型中的耗竭对其的潜在作用来描述肠道微生物群的潜在作用。
雄性和雌性 C57Bl/6 小鼠分别进行（ABA 组）或不进行（CT 组）ABA 方案，该方案将使用跑步轮与渐进性食物限制相结合。肠道微生物群通过口服灌胃预先用抗生素鸡尾酒（ATB）耗竭或不耗竭。我们监测了身体成分、焦虑样行为、瘦素和脂联素的血浆水平、下丘脑和海马神经肽的 mRNA 水平，以及多巴胺（DRD）和 5-羟色胺（5HT1 和 4）受体的 mRNA 表达。
在 ABA 模型的作用下，与未处理的 ABA 相比，经 ATB 处理的 ABA 模型中的体重减轻程度不那么明显，而 ATB 处理对食物摄入没有影响。与未处理的 ABA 相比，经 ATB 处理的 ABA 雄性和雌性小鼠的脂肪量增加，瘦体量减少，而血浆 adipokine 浓度则以性别依赖的方式受到影响。只有雄性 ABA 小鼠对 ATB 处理表现出预期的体力活动减少。同样，焦虑样行为主要影响 ATB 处理的 ABA 雄性小鼠，而不是 ATB 处理的 ABA 雌性小鼠，这与雄性特定的下丘脑 CRH mRNA 和海马 DRD 和 5-HT1A mRNA 水平的改变有关。
我们的研究提供了证据，表明 ATB 诱导的肠道微生物群耗竭以性别依赖的方式触发了对基于活动的厌食症模型的营养和行为反应的改变。
