Bacterial Metabolites in the Plasma of Type 1 Diabetes Patients: Acetate Levels Are Elevated and Correlate with Glycated Haemoglobin and Para-Cresol Is Associated with Liver Disturbances and Hypertension

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INTRODUCTION: While the exact cause of Type 1 Diabetes (T1D) remains unclear, it is widely believed that both genetic and environmental factors contribute to the development of the disease. Recent research has explored the potential role of gut microbiota and its metabolites in modulating immune responses and influencing the development of autoimmune diseases like T1D. With this purpose, we designed a study: 1. to compare the levels of different bacterial metabolites in plasma samples of T1D patients and healthy controls (HC). 2. to correlate the levels of these metabolites with different demographic, clinical and analytical variables collected from the T1D patients. METHODS: A total of 91 T1D patients were recruited. Plasma samples were collected and analyzed with gas chromatography coupled to mass spectrometry for the detection of the metabolites: short-chain fatty acids (SCFA: acetate [AA], propionate [PA], isobutyrate [IBA], butyrate [BA], isovalerate [IVA], valerate [VA] and methyl valerate [MVA]), medium-chain fatty acids (MCFA: hexanoate [HxA] and heptanoate [HpA]) and para-cresol (p-cresol). We also calculated the ratios between the different SCFA with AA. RESULTS: 1. AA levels were significantly higher in T1D patients than in HC (p=0.0009). PA/AA and IBA/AA ratios were significantly higher in HC (p=0.0004 and p=0.0001, respectively). 2. Glycated haemoglobin (HbA1c) was positively correlated with AA levels (p=0.0001; r=0.406) and a significant negative correlation with a rSpearman< -0.3 was found for PA/AA, IBA/AA and BA/AA ratios. 3. p-cresol correlated with Ferritin levels (p=0.04; r=0.362); besides, p-cresol levels were lower in T1D patients with a normal liver profile (p=0.002) and in T1D patients without hypertension (p=0.005). CONCLUSIONS: Serum levels of bacterial metabolites were significantly different in T1D patients. AA levels were significantly increased in T1D patients and p-cresol was higher in T1D patients with liver disturbances and hypertension. To develop strategies to restore gut microbiota health and immune balance could be essential for the control of T1D.

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