Mishra Sidharth P, Karunakar Prashantha, Taraphder Subhash, Yadav Hariom
Department of Internal Medicine, Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.
Department of Animal Genetics and Breeding, West Bengal University of Animal and Fishery Science, Kolkata, West-Bengal 700037, India.
Biomedicines. 2020 Jun 8;8(6):154. doi: 10.3390/biomedicines8060154.
The role of the gut microbiome in human health is becoming apparent. The major functional impact of the gut microbiome is transmitted through the microbial metabolites that are produced in the gut and interact with host cells either in the local gut environment or are absorbed into circulation to impact distant cells/organs. Short-chain fatty acids (SCFAs) are the major microbial metabolites that are produced in the gut through the fermentation of non-digestible fibers. SCFAs are known to function through various mechanisms, however, their signaling through free fatty acid receptors 2 and 3 (FFAR2/3; type of G-coupled protein receptors) is a new therapeutic approach. FFAR2/3 are widely expressed in diverse cell types in human and mice, and function as sensors of SCFAs to change several physiological and cellular functions. FFAR2/3 modulate neurological signaling, energy metabolism, intestinal cellular homeostasis, immune response, and hormone synthesis. FFAR2/3 function through Gi and/or Gq signaling, that is mediated through specific structural features of SCFAs-FFAR2/3 bindings and modulating specific signaling pathway. In this review, we discuss the wide-spread expression and structural homologies between human and mice FFAR2/3, and their role in different human health conditions. This information can unlock opportunities to weigh the potential of FFAR2/3 as a drug target to prevent human diseases.
肠道微生物群在人类健康中的作用正日益显现。肠道微生物群的主要功能影响是通过在肠道中产生的微生物代谢产物传递的，这些代谢产物在局部肠道环境中与宿主细胞相互作用，或被吸收进入循环系统以影响远处的细胞/器官。短链脂肪酸（SCFAs）是通过不可消化纤维的发酵在肠道中产生的主要微生物代谢产物。已知SCFAs通过多种机制发挥作用，然而，它们通过游离脂肪酸受体2和3（FFAR2/3；G蛋白偶联受体类型）发出信号是一种新的治疗方法。FFAR2/3在人和小鼠的多种细胞类型中广泛表达，并作为SCFAs的传感器来改变多种生理和细胞功能。FFAR2/3调节神经信号传导、能量代谢、肠道细胞内稳态、免疫反应和激素合成。FFAR2/通过Gi和/或Gq信号传导发挥作用，这是由SCFAs-FFAR2/3结合的特定结构特征介导的，并调节特定的信号通路。在这篇综述中，我们讨论了人和小鼠FFAR2/3之间广泛的表达和结构同源性，以及它们在不同人类健康状况中的作用。这些信息可以为评估FFAR2/3作为预防人类疾病的药物靶点的潜力提供机会。
