Gut Microbiome Research & Therapies for T1D
Shanti P. Kok, Max Nieuwdorp and Elena Rampanelli
Translating gut microbiome research into therapies for type 1 diabetes. Experimental Physiology. Exp Physiol. 2026 Sep 10:10.1113/EP093273
Type 1 diabetes (T1D) is an autoimmune disease characterised by the loss of insulin-producing pancreatic beta cells. Although insulin remains essential for treatment, growing evidence suggests that the gut microbiome may influence immune regulation, intestinal health and metabolic processes involved in T1D. This has raised interest in whether targeting the gut microbiome could eventually complement existing therapies.
In this narrative review, the authors summarise current knowledge on changes in the gut microbiome and microbiota-derived metabolites in T1D, with particular attention to short-chain fatty acids (SCFAs), secondary bile acids and tryptophan-derived metabolites. The review also evaluates emerging microbiome-based interventions, including prebiotics, probiotics, postbiotics, synbiotics and faecal microbiota transplantation (FMT), drawing on both preclinical and clinical studies.
Key findings:
- Gut microbial metabolism is altered in T1D: Studies have identified changes in SCFAs, secondary bile acids and tryptophan-derived metabolites, together with differences in the abundance of microbes and microbial genes responsible for producing or metabolising these compounds. These metabolites are particularly relevant because they can affect intestinal barrier integrity, immune regulation and metabolic signalling.
- SCFAs may link diet, the microbiome and immune regulation: Acetate, propionate and butyrate are produced through microbial fermentation of dietary fibre. Several studies have reported lower SCFA concentrations and fewer butyrate-producing bacteria in people with T1D. SCFAs can influence intestinal integrity and immune responses, making these pathways potential therapeutic targets.
- Secondary bile acid and tryptophan metabolism may also be important: Alterations in these microbial metabolic pathways have been observed in T1D and may affect inflammation, intestinal integrity and immune tolerance. However, these pathways are less extensively studied than SCFAs and require further investigation.
- Prebiotic and probiotic interventions show promising, but inconsistent, results: Some clinical studies have reported improvements in glycaemic or inflammatory markers, while others found little or no effect on beta-cell function. Results may depend on factors such as age, disease duration, baseline microbiome composition, the intervention used and treatment duration.
- Postbiotics and combination approaches are emerging therapeutic strategies:
Interventions targeting microbial metabolites have shown immunological effects, but improvements in beta-cell function in people with long-standing T1D remain limited. Combining different approaches could potentially be more effective; for example, preclinical combination therapy with Akkermansia muciniphila and butyrate produced stronger effects than either intervention alone.
- FMT provides further evidence that the microbiome may influence T1D: Early clinical studies suggest that microbiota transplantation can modify gut microbial composition, immune responses and metabolic pathways. Some studies have also reported preservation or stabilisation of residual beta-cell function, although responses appear to depend on factors such as baseline microbiome characteristics and remaining beta-cell function.
Overall, the evidence supports an interaction between the gut microbiome, microbial metabolism and processes relevant to T1D. However, results vary considerably between studies, and most of the strongest therapeutic effects have so far been observed in preclinical models—often when treatment was started before diabetes developed. Clinical evidence, particularly for preservation or restoration of beta-cell function, remains limited.
The authors therefore emphasise the need for larger and more robust clinical trials. Importantly, future studies should investigate microbiome-based interventions at different stages of T1D, including people at increased risk or with islet autoimmunity before clinical diagnosis, people with newly diagnosed T1D and those with long-standing disease.
Concluding, the authors state
“These interventions may represent adjuvant treatments to the current standard of care (insulin therapy) and to upcoming immunotherapies.”
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