{"id":"575e66a9da31","type":"article","url":"https://hartvaat.nl/2026/12/31/darmmicrobioot-afgeleid-ipa-is-lager-bij-t2d-en-gekoppeld-aan-glycemische-variab/","title":"Darmmicrobioot-afgeleid IPA is lager bij T2D en gekoppeld aan glycemische variabiliteit","title_en":"Plasma indole-3-propionic acid is a gut-derived metabolite and is associated with type 2 diabetes and cardiometabolic outcomes: Evidence from a human antibiotic intervention.","category":"cholesterol","category_label":"Cholesterol","professions":["huisarts","internist"],"tags":[],"journal":"Gut microbes","doi":"10.1080/19490976.2026.2736321","source_url":"https://doi.org/10.1080/19490976.2026.2736321","authors":["Florine H M Westerbeke","Moritz V Warmbrunn","Melany Rios-Morales","Xinmin S Li","Melissa Y Tian","Madelyn A Novak","Austin M Williams","Stanley L Hazen","Ilias Attaye","Max Nieuwdorp"],"significance":3,"published":"2026-10-04","source_date":"2026-12-31","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/lpa-meten-wanneer-waarom/","https://hartvaat.nl/kennis/preventie/risicofactoren-cardiovasculair/"],"congress":"","summary_en":"The study investigated the gut microbiota-derived metabolite indole-3-propionic acid (IPA) in patients with type 2 diabetes (T2D) and healthy controls. Seven days of broad-spectrum antibiotics reduced plasma IPA to near-undetectable levels, confirming its microbial origin; lower baseline IPA correlated with T2D, higher BMI, and greater glycemic variability. For clinical practice, this provides mechanistic insight into the microbiome-metabolism link, but there are currently no direct therapeutic or preventive implications.","created":"2026-09-28T00:47:25Z","updated":"2026-09-28T00:47:25Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Onderzocht werd het darmmicrobioot-afgeleide metaboliet indole-3-propionzuur (IPA) bij patiënten met type 2 diabetes (T2D) en gezonde controlepersonen. Zeven dagen breedspectrumantibiotica reduceerden IPA tot bijna onmeetbare niveaus, wat de microbiële oorsprong bevestigt; lager voorafgaand IPA-correlateerde met T2D, een hogere BMI en grotere glycemische variabiliteit. Voor de klinische praktijk biedt dit mechanistisch inzicht in de link tussen darmflora en metabole gezondheid, maar er zijn op dit moment geen directe therapeutische of preventieve implicaties.","abstract_original":"The gut microbiota influences host metabolism through diverse metabolites, many of which have been linked to glucose homeostasis and type 2 diabetes (T2D). Understanding microbial contributions to metabolite biosynthesis is essential for developing dietary and microbiota-targeted T2D prevention and treatment strategies. We performed targeted plasma metabolomics in individuals with T2D and healthy controls, all receiving histidine supplementation, before and after gut microbiota suppression using 7-day broad-spectrum antibiotic treatment. Associations between pre-antibiotic metabolite levels and fecal metagenomics-derived gut microbiota composition were examined using co-abundance network analysis and Random Forest modeling. Indole-3-propionic acid (IPA) was the only gut-derived metabolite differing between groups before antibiotics, with lower levels in T2D and higher levels associated with reduced T2D odds. Antibiotic treatment reduced IPA to near-undetectable levels in both groups, confirming its predominantly microbial origin. Beyond established inverse associations with BMI and glycemic markers, we found a novel inverse correlation between IPA and glycemic variability, consistent with a protective association with T2D. Plasma IPA was associated with gut microbiota beta diversity. IPA-associated species clustered within a single co-abundance module, but did not include known IPA producers, suggesting plasma IPA is influenced by broader microbial community composition rather than IPA-producing capacity of individual taxa alone. This study provides direct human evidence that plasma IPA is virtually exclusively gut microbiota-derived in individuals with T2D, extending prior findings in healthy populations. It highlights IPA's relevance to metabolic health and T2D, and guides future research on dietary and microbiota-targeted strategies to modulate IPA, advancing T2D prevention and treatment."}