The gut, oxidative stress & T1D
luwatomisono I. Akinrimisi, Kim Maasen, Jean L.J.M. Scheijen, Ina Nemet, Max Nieuwdorp, Casper G. Schalkwijk, Nordin M.J. Hanssen
Does Gut Microbial Methylglyoxal Metabolism Impact Human Physiology? Antioxidants (Basel). 2025 Jun 21;14(7):763.
People with type 1 diabetes (T1D) are exposed to lifelong glycaemic variability, which promotes the formation of methylglyoxal (MGO) — a highly reactive dicarbonyl compound that contributes to oxidative stress, inflammation, and the formation of advanced glycation end products. Elevated MGO levels have been strongly associated with the development of microvascular and macrovascular complications in T1D, even in individuals with apparently good glycaemic control.
At the same time, T1D is associated with alterations in the gut microbiome that may influence immune regulation, intestinal permeability, and host metabolism. While MGO production and detoxification have traditionally been studied in host tissues, emerging evidence suggests that gut microbes may directly and indirectly regulate MGO stress, potentially modifying long-term complication risk in T1D.
This review synthesizes experimental and clinical evidence on methylglyoxal biology, with a specific focus on microbiome-mediated mechanisms relevant to cardiometabolic and diabetic complications. The authors discuss endogenous MGO production driven by glucose metabolism, microbial pathways involved in MGO synthesis and detoxification, and how gut microbial metabolites may influence oxidative stress, vascular function, and inflammation. The review highlights emerging concepts that are particularly relevant for long-term complication risk in T1D.
Key findings:
- Methylglyoxal levels are elevated in diabetes and are mechanistically linked to microvascular and cardiovascular complications relevant to T1D.
- Gut microbes possess metabolic pathways capable of both producing and detoxifying MGO, potentially influencing systemic MGO exposure.
- MGO exposure can alter gut microbiome composition, while microbial metabolites such as short-chain fatty acids may suppress microbial MGO production.
- Alterations in gut barrier integrity and immune signaling provide plausible pathways by which microbiome-derived MGO could influence vascular inflammation in T1D.
- The contribution of microbially derived MGO to systemic MGO levels in people with T1D has not yet been quantified but represents an important research gap.
The review highlights the gut microbiome as a potential modifier of dicarbonyl stress in T1D, complementing traditional glucose-centred approaches to complication prevention. If microbiome-derived MGO proves biologically relevant, dietary strategies, microbiome-targeted therapies, or metabolic interventions could emerge as adjunctive approaches to reduce long-term vascular risk in T1D. Importantly, this perspective aligns with a broader shift toward precision and systems-based care in diabetes, integrating metabolic, inflammatory, and microbial pathways.
Concluding, the authors state
"While the role of microbially derived MGO in human physiology remains unclear, the tools and methodologies now exist to explore this important frontier in host–microbe interaction" -
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