THU075 Sex And Age Specificity Of Correlations Among IGF-1, GH, And Duodenal Microbial Diversity Predicting TMA Biosynthesis

Abstract

Abstract Disclosure: N. Tal: None. G. Leite: None. G. Barlow: None. W. Morales: None. R. de Souza Santos: None. M. Pimentel: None. R. Mathur: None. Varied gut microbial profiles and functional potentials may increase or decrease cardiovascular (CVD) disease risk. Trimethylamine (TMA), a known bacterial metabolite associated with red meat ingestion, is linked to increased CVD risk and morbidity through its liver-transformed form trimethylamine N-oxide (TMAO). As the somatotroph axis is also linked both to the microbiome and CVD morbidity, we explored the relationships between the duodenal microbiome, microbial pathways, IGF-1 and GH levels. Methods: Female (F) and male (M) subjects undergoing upper endoscopy without colon prep were enrolled and completed a medical history including CV conditions and risk factors such as exercise and diet. Whole blood was collected and duodenal aspirates obtained using a double lumen sterile catheter. Microbial DNA was extracted and 16S sequenced. Analyses were performed with CLC Microbial Module. Predicted pathways were identified using MetaCyc Database. Fasting circulating GH, IGF-1 (Luminex FLEXMAP) and cholesterol fractions (Cobas 400) were measured. Results: 177 subjects were grouped by age (sex and BMI, P=NS): 18-35yrs (N=21, F=11), 36-50yrs (N=29, F=15), 51-65yrs (N=69, F=38) and 66-80yrs (N=58, F=28). IGF-1 levels gradually decreased in older subjects (P<0.0001). In older M (66-80yrs), GH correlated positively with IGF-1 (R=0.371, P=0.044) and negatively with duodenal microbial diversity (R=-0.517, P=0.003). M and F had similar CVD risks (hypertension, smoking, exercise habits, obesity, LDL levels and weekly red meat consumption [P=NS for all]). In M only: 1) GH levels correlated with overall number of CV conditions (R=0.339, P=0.001), 2) Red meat consumption correlated with GH (R=0.353, P=0.002) and predicted microbial TMA biosynthesis from L-carnitine (R=0.272, P=0.009), and 3) Higher IGF-1 correlated with predicted microbial TMA production from L-carnitine (R=0.208, P=0.05) and predicted microbial conversion of TMA to TMAO (R=0.257, P=0.018). Duodenal relative abundance (RA) of Prevotellaceae (which positively impacts duodenal microbial diversity) inversely correlated with both GH (R=-0.174, P=0.019) and predicted TMA production (R=-0.174, P=0.019). Positive associations among Prevotellaceae and duodenal diversity (R=0.570, P<0.0001) and inverse associations with TMA production (R=-0.354, P=0.029) were stronger in older M (66-80yrs). In M, Prevotellaceae RA decreased gradually with age (P=0.023). Conclusion: IGF-1 and GH levels exhibit differential relationships with the duodenal microbiome and cardiovascular risk. In males, IGF-1 levels strongly associate with duodenal microbial pathways linked to TMA production and conversion to TMAO. Red meat consumption is linked to GH levels and to predicted TMA biosynthesis pathways. The microbial family Prevotellaceae appears to mitigate predicted TMA production and its relative abundance is lower in older men. Presentation: Thursday, June 15, 2023