La Sala Lucia, Carlini Valentina, Macas-Granizo Maria Belen, Trabucchi Emilio, Pontiroli Antonio E, Berra Cesare, Naselli Angelo, D'Anzeo Marco, Porta Andrea, Martin Delgado Jimmy, Vianello Elena, Dozio Elena, Corsi Romanelli Massimiliano, Drago Lorenzo
IRCCS MultiMedica, Via Fantoli 16/15, 20138 Milan, Italy; University of Milan, Dept. of Biomedical Sciences for Health, Via Mangiagalli 31, 20133 Milan, Italy.
IRCCS MultiMedica, Via Fantoli 16/15, 20138 Milan, Italy.
J Adv Res. 2025 Sep 14. doi: 10.1016/j.jare.2025.09.021.
The prevalence of dysbiosis in type 2 diabetes (T2D) is increasing globally as a consequence of an imbalance in the distribution of gut microbial populations. Dysmotility of the gastrointestinal tract has emerged as a contributor to pathophysiology of T2D, where impaired motility may exacerbate dysbiosis and metabolic dysfunction. Current management of T2D, such as Metformin (Metf), demonstrate efficacy in improving metabolic parameters but are linked to gastrointestinal side effects, the mechanisms of which remain poorly understood. Novel promising therapeutic agents, based on the modulation of the gut microbiota has emerged for the treatment of metabolic disorders, particularly for T2D, in which Fecal microbiota transplant (FMT) assumes the major weight as strategy to improves insulin sensitivity and glucose tolerance, and potentially ameliorating gut motility. Although FMT represents a potential therapeutic alternative, its comparative effectiveness and safety profile relative to Metf in this specific setting remain to be established.
This review aims to evaluate and compare these two potent modulators of microbial landscape, Metf and FMT, in addressing insulin resistance (IR) and gastrointestinal dysmotility in T2D. The study seeks to systematically delineate the mechanisms underlying their effects and assess their therapeutic potential, safety, and clinical efficacy.
The physiological roles of the gut microbiota and their metabolites are explored, highlighting their contribution to the onset and progression of metabolic disorders, particularly T2D. We examined the mechanisms through which Metf and FMT influence gut microbiota, insulin sensitivity, and glucose tolerance. Novel therapeutic approaches, including the combined use of Metf and FMT, are discussed in terms of molecular mechanisms, clinical outcomes, and safety profiles. Finally, the potential integration of these strategies into T2D management and their impact on gastrointestinal dysfunction are considered as areas for further research.
由于肠道微生物群分布失衡，全球2型糖尿病（T2D）中生态失调的患病率正在上升。胃肠道运动功能障碍已成为T2D病理生理学的一个促成因素，其中运动功能受损可能会加剧生态失调和代谢功能障碍。目前T2D的治疗方法，如二甲双胍（Metf），在改善代谢参数方面显示出疗效，但与胃肠道副作用有关，其机制仍知之甚少。基于调节肠道微生物群的新型有前景的治疗药物已出现用于治疗代谢紊乱，特别是对于T2D，其中粪便微生物群移植（FMT）作为改善胰岛素敏感性和葡萄糖耐量以及潜在改善肠道运动的策略占据主要地位。尽管FMT代表了一种潜在的治疗选择，但其在这种特定情况下相对于Metf的相对有效性和安全性仍有待确定。
本综述旨在评估和比较这两种微生物景观的强效调节剂Metf和FMT在解决T2D中的胰岛素抵抗（IR）和胃肠道运动功能障碍方面的作用。该研究旨在系统地描述其作用的潜在机制，并评估其治疗潜力、安全性和临床疗效。
探讨了肠道微生物群及其代谢产物的生理作用，强调了它们对代谢紊乱，特别是T2D的发生和发展的贡献。我们研究了Metf和FMT影响肠道微生物群、胰岛素敏感性和葡萄糖耐量的机制。从分子机制、临床结果和安全性方面讨论了包括联合使用Metf和FMT在内的新型治疗方法。最后，这些策略在T2D管理中的潜在整合及其对胃肠功能障碍的影响被视为进一步研究的领域。
