猪肠道微生物对黏膜5-羟色胺表达和转运的调节机制

Gut is the key site for nutrient metabolism and digestion in pigs. Serotonin is known as an important neurotransmitter regulating intestinal transmit, nutrient digestion and neural activities. The applicant has found that an alteration in the composition of large intestine microbiota is accompanied with the alteration of serotonin concentration in pigs. However, key microbes responsible for regulating serotonin production, the major gut site and the underlying mechanism remain unclear. Employing an in vivo pig experiment, the present project will study the effects of selective microbiota intervention on the microbial composition and serotonin production, combining high-throughput sequencing and immunohistochemistry techniques. Furthermore, the key microbes that may mediate serotonin expression will be isolated, which will be subsequently used for in vitro culture of epithelial cell lineages.The effects of gut isolates on serotonin synthesis and transporter expression will be analyzed. Meanwhile, the possible role of toll-like receptors in mediating microbial function will be investigated. The project aims to identify the regulatory mechanism of large intestine microbiota on serotonin expression. The proposed results will gain deep insights into the relationship between specific gut microbes and serotonin in pigs, which further provides new ideas on targeting gut microbiota to regulate intestinal transmit and nutrient metabolism.

猪肠道是营养代谢和消化吸收的关键场所，而5-羟色胺是调节肠道运动、营养吸收和神经活动的重要神经递质。申请者前期研究发现，猪大肠微生物区系的变化伴随体内5-羟色胺浓度的变化，然而，猪肠道内参与5-羟色胺调节的微生物种类、关键肠道位点及其调节机制还不清楚。本研究通过猪在体试验，结合高通量测序和免疫组化等技术，研究干预大肠微生物后猪肠道微生物区系和5-羟色胺表达的变化；在此基础上，分离、筛选大肠中与5-羟色胺表达密切相关的关键细菌，通过肠上皮细胞系培养试验，分析肠道细菌对5-羟色胺合成和转运体表达的影响，并研究Toll受体是否参与微生物介导的调节，进而揭示大肠微生物对5-羟色胺表达的调节机制。预期结果有助于从菌株水平揭示肠道微生物与5-羟色胺表达的关系，为通过菌群靶向干预调节猪肠道蠕动和营养代谢提供新思路。

猪肠道是营养代谢和消化吸收的关键场所，而5-羟色胺是调节肠道运动、营养吸收和神经活动的重要神经递质。申请者前期研究发现，猪大肠微生物区系的变化伴随体内5-羟色胺浓度的变化，然而，猪肠道内参与5-羟色胺调节的微生物种类、关键肠道位点及其调节机制还不清楚。本研究通过猪在体试验，结合高通量测序和免疫组化等技术，研究干预大肠微生物后，猪结肠微生物区系和5-羟色胺发生变化，表明猪肠道微生物参与调节肠道5-羟色胺途径；在此基础上，分离、筛选大肠中与5-羟色胺表达密切相关的3株关键细菌，通过细胞培养试验，表明链球菌Streptococcus alactolyticus具有调节5-羟色胺合成和转运体表达的能力，可能主要通过代谢物乙酸进行调节。本研究有助于从菌株水平揭示肠道微生物与5-羟色胺表达的关系，为通过菌群靶向干预调节猪肠道蠕动和营养代谢提供新思路。