Microbial metabolites have emerged as key players in the interplay between diet, the gut microbiome, and host health. Two major classes, short-chain fatty acids (SCFAs) and tryptophan (Trp) metabolites, are recognized to regulate inflammatory, immune, and metabolic responses within the host. Given that many human diseases are associated with dysbiosis of the gut microbiome and consequent reductions in microbial metabolite production, the administration of these metabolites represents a direct, multi-targeted treatment. While a multitude of preclinical studies showcase the therapeutic potential of both SCFAs and Trp metabolites, they often rely on high doses and frequent dosing regimens to achieve systemic effects, thereby constraining their clinical applicability. To address these limitations, a variety of pharmaceutical formulations approaches that enable targeted, delayed, and/or sustained microbial metabolite delivery have been developed. These approaches, including enteric encapsulations, esterification to dietary fiber, prodrugs, and nanoformulations, pave the way for the next generation of microbial metabolite-based therapeutics.

中文翻译：

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通过先进的制药方法利用和提供微生物代谢物作为治疗剂

微生物代谢物已成为饮食、肠道微生物组和宿主健康之间相互作用的关键因素。短链脂肪酸 (SCFA) 和色氨酸 (Trp) 代谢物这两大类被认为可以调节宿主体内的炎症、免疫和代谢反应。鉴于许多人类疾病与肠道微生物群失调以及随之而来的微生物代谢物产生的减少有关，这些代谢物的施用代表了一种直接的、多靶点的治疗。虽然大量临床前研究展示了 SCFA 和色氨酸代谢物的治疗潜力，但它们通常依赖高剂量和频繁的给药方案来实现全身效应，从而限制了它们的临床适用性。为了解决这些限制，已经开发了多种能够靶向、延迟和/或持续微生物代谢物递送的药物制剂方法。这些方法，包括肠溶胶囊、膳食纤维酯化、前药和纳米制剂，为下一代基于微生物代谢物的疗法铺平了道路。