Sorbitol, a poorly absorbable sweetener, is catabolized by gut microbiota, mainly Clostridia. Lee et al. now elucidate the pathophysiology of sorbitol intolerance and highlight a role for Clostridia and butyrate, a short-chain fatty acid metabolite.

Stable engraftment of Escherichia coli strain Nissle 1917, a probiotic that catabolizes sorbitol, restored caecal SDH activity in mice and protected them from diarrhoea. Inocculation of Anaerostipes caccae, an abundant component of the human gut microbiome that belongs to Clostridia and uses sorbitol as a carbon source, also protected against sorbitol intolerance, even despite transient gut colonization. The protective effect of A. caccae involved both endogenous sorbitol catabolism early after inoculation and butyrate-dependent promotion of gut re-colonization by diverse Clostridia species, which took over sorbitol catabolism upon A. caccae clearance. A. caccae-derived or exogenous butyrate activated the transcription factor PPARγ in host intestinal epithelium. PPARγ activation restored the hypoxic microenvironment that is required by the anaerobic Clostridia and that is perturbed by a high-fat diet. Prophylactic administration of the PPARγ agonist 5-ASA protected mice from prolonged sorbitol intolerance. “While current guidelines for the diagnosis and treatment of intolerance to sugar alcohols or other FODMAPs emphasize on eliminating the causative dietary ingredients, our study provides an entirely new starting point for strategies to diagnose, prevent, and manage sorbitol intolerance,” notes Lee. Further research by the group will “examine how the consumption of artificial sweeteners, such as sorbitol, may exacerbate intestinal inflammation in the context of dysbiosis,” adds Lee.

山梨醇是一种难以吸收的甜味剂，由肠道微生物群（主要是梭状芽胞杆菌）分解代谢。李等人。现在阐明山梨醇不耐受的病理生理学，并强调梭菌和丁酸盐（一种短链脂肪酸代谢物）的作用。

大肠杆菌菌株 Nissle 1917（一种分解代谢山梨醇的益生菌）的稳定植入，可恢复小鼠盲肠 SDH 活性并保护它们免受腹泻。Anaerostipes caccae是人类肠道微生物组的丰富成分，属于梭状芽胞杆菌，使用山梨醇作为碳源，即使在肠道短暂定植，也能防止山梨醇不耐受。A. caccae的保护作用涉及接种后早期的内源性山梨醇分解代谢，以及丁酸盐依赖性促进不同梭状芽孢杆菌物种的肠道重新定植，这些梭菌在A. caccae清除后接管了山梨醇分解代谢。A. caccae来源的或外源性丁酸盐激活宿主肠上皮中的转录因子 PPARγ。 PPARγ 激活恢复了厌氧梭状芽胞杆菌所需且受到高脂肪饮食干扰的缺氧微环境。预防性给予 PPARγ 激动剂 5-ASA 可保护小鼠免受长期山梨醇不耐受的影响。 “虽然目前糖醇或其他 FODMAP 不耐受的诊断和治疗指南强调消除致病膳食成分，但我们的研究为诊断、预防和管理山梨醇不耐受的策略提供了一个全新的起点，”Lee 指出。 Lee补充道，该小组的进一步研究将“研究山梨糖醇等人工甜味剂的消耗如何在生态失调的情况下加剧肠道炎症”。