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.

T1D patients showed significantly higher circulating acetate (AA) levels than healthy controls, along with reduced PA/AA and IBA/AA ratios.

• A total of 91 T1D patients and 58 healthy controls (HC) were recruited.
• Plasma samples were analyzed with gas chromatography coupled to mass spectrometry (GC-MS).
• Metabolites measured included SCFAs (acetate, propionate, isobutyrate, butyrate, isovalerate, valerate, and methyl valerate), MCFAs (hexanoate and heptanoate), and para-cresol.
• Reduced PA/AA and IBA/AA ratios indicated an altered SCFA profile in T1D patients.
• Total SCFA levels were increased in T1D mainly due to elevated AA.

SCFA diversity was lower in T1D patients, with reduced detection of butyrate (BA).

• SCFA diversity was assessed across 91 T1D patients and 58 HC.
• Butyrate detection frequency was reduced in T1D patients compared to healthy controls.
• The reduction in SCFA diversity was observed alongside elevated total SCFA levels driven primarily by acetate.

Sex-specific differences in metabolite profiles were observed, with women with T1D showing higher AA levels and lower SCFA ratios, while men with T1D showed higher p-cresol levels than healthy men.

• AA levels were higher and SCFA ratios lower in women with T1D compared with healthy women.
• p-cresol levels were higher in men with T1D than in healthy men.
• These sex-specific differences were identified within the overall T1D cohort of 91 patients.

In T1D patients, acetate levels positively correlated with HbA1c, while PA/AA, IBA/AA, and BA/AA ratios showed negative correlations with HbA1c, particularly in women.

• AA levels positively correlated with HbA1c in T1D patients.
• PA/AA, IBA/AA, and BA/AA ratios showed negative correlations with HbA1c.
• These correlations were particularly pronounced in women with T1D.
• MV/AA and non-AA/AA ratios were inversely associated with glucose levels, again mainly in women.

p-cresol levels correlated positively with age and ferritin, and were higher in T1D patients with liver dysfunction or hypertension.

• p-cresol levels showed a positive correlation with age in T1D patients.
• p-cresol levels showed a positive correlation with ferritin in T1D patients.
• p-cresol levels were significantly higher in T1D patients with liver dysfunction compared to those without.
• p-cresol levels were significantly higher in T1D patients with hypertension compared to those without.