The eternal struggle between titans: Fecal microbiota transplant (FMT) versus metformin in type 2 diabetes (T2D) gut dysmotility

BACKGROUND: 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. AIM OF THE REVIEW: 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. KEY SCIENTIFIC CONCEPTS OF THE REVIEW: 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.