Melatonin influences intestinal microbiota and the pathogenesis of various diseases. This study was conducted to explore whether melatonin alleviates weanling stress through intestinal microbiota in a weanling mouse model. Melatonin supplementation in weanling mice (provided in the drinking water at a dosage of 0.2 mg/mL for 2 weeks) significantly improved body weight gain (1.4 ± 0.03 g/day in melatonin group vs 1.2 ± 0.06 g/day in control group) and intestinal morphology (ie, villus length, crypt depth, and villus to crypt ratio), but had little effect on the proliferation or apoptosis of intestinal cells, the numbers of Paneth cells and goblet cells, as well as the expression of makers related to enterocytes (sucrase) and endocrine cells (chromogranin A and peptide YY) in the ileum. Melatonin supplementation had little effect on serum levels of amino acids or stress‐related parameters (eg, SOD, TNF‐α, and angiotensin I). 16S rRNA sequencing suggested that melatonin supplementation increased the richness indices of intestinal microbiota (observed species, Chao 1, and ACE) and shaped the composition of intestinal microbiota (eg, increase in the abundance of Lactobacillus [19 ± 3% in melatonin group vs 6 ± 2% in control group]), which was demonstrated using an ex vivo proliferation assay and colonic loop proliferation assay. Melatonin supplementation also significantly influenced the metabolism of intestinal microbiota, such as amino acid metabolism and drug metabolism. More importantly, in antibiotic‐treated weanling mice and germ‐free weanling mice, melatonin failed to affect body weight gain or intestinal morphology. Melatonin significantly reduced (by about 60%) the bacterial load in enterotoxigenic Escherichia coli (ETEC)‐infected weanling mice, but had little effect on ETEC load in antibiotic‐pretreated animals. In conclusion, melatonin affects body weight gain, intestinal morphology, and intestinal ETEC infection through intestinal microbiota in weanling mice. The findings highlight the importance of intestinal microbiota in mediating the various physiological functions of melatonin in the host.

中文翻译：

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褪黑素减轻小鼠的断奶压力：肠道菌群的参与

褪黑素影响肠道菌群和各种疾病的发病机理。进行这项研究以探讨褪黑激素是否能通过断奶小鼠模型中的肠道菌群缓解断奶压力。在断奶小鼠中补充褪黑激素（在饮用水中以0.2 mg / mL的剂量提供2周）可显着改善体重增加（褪黑激素组为1.4±0.03 g /天，对照组为1.2±0.06 g /天），并且肠道形态（即绒毛长度，隐窝深度和绒毛与隐窝比率），但对肠道细胞的增殖或凋亡，Paneth细胞和杯状细胞的数量以及与肠上皮细胞相关的造物主的表达影响很小回肠中的（蔗糖酶）和内分泌细胞（嗜铬粒蛋白A和YY肽）。补充褪黑激素对血清氨基酸水平或与压力相关的参数（例如SOD，TNF-α和血管紧张素I）影响很小。16S rRNA测序表明补充褪黑激素可增加肠道菌群的丰富指数（观察到的物种，Chao 1和ACE），并影响肠道菌群的组成（例如，增加肠道菌群的丰度）。乳杆菌（褪黑素组为19±3％，对照组为6±2％）），已通过离体增殖测定和结肠环增殖测定证实。补充褪黑激素还显着影响肠道微生物群的代谢，例如氨基酸代谢和药物代谢。更重要的是，在用抗生素治疗的断奶小鼠和无菌的断奶小鼠中，褪黑激素未能影响体重增加或肠道形态。褪黑激素可显着降低（约降低60％）肠毒素性大肠杆菌中的细菌负荷（ETEC）感染的断奶小鼠，但对抗生素预处理的动物的ETEC负荷影响很小。总之，褪黑激素通过断奶小鼠的肠道菌群影响体重增加，肠道形态和肠道ETEC感染。这些发现突出了肠道菌群在介导褪黑激素在宿主中的各种生理功能中的重要性。