THU076 GH, IGF-1 And Inflammatory Marker Interactions With Small Bowel Microbial Diversity Are Age And Sex Dependent
Authors: Leite Gabriela , Tal Noa , Barlow Gillian , Morales Walter , de Souza Santos Roberta , Rashid Mohamad , Hosseini Ava , Pimentel Mark , Mathur Ruchi 
Published: October 2023

Disclosure: G. Leite: None. N. Tal: None. G. Barlow: None. W. Morales: None. R. de Souza Santos: None. M. Rashid: None. A. Hosseini: None. M. Pimentel: None. R. Mathur: None.

Attenuated somatotroph axis function correlates inversely with age-related comorbidities in both animal and human studies. Mechanisms by which GH and IGF-1 may promote aging include increasing inflammation, DNA damage and cell senescence. Bidirectional interactions between GH, IGF-1 and stool microbial diversity occur with malnutrition, inflammatory bowel disease, colon cancer and acromegaly. Given the importance of the small bowel in sustaining immune system homeostasis, we assessed the relationship of the duodenal microbiome, GH, IGF-1 and inflammatory markers in human subjects of different age groups. Methods: Female (F) and male (M) subjects (18-80 years) undergoing upper endoscopy without colon preparation were recruited. Subjects answered a comprehensive medical history, and whole blood was collected. Duodenal luminal samples were obtained using a double lumen sterile catheter. Microbial DNA was extracted and 16S sequenced. Analyses were performed using CLC Genomics Microbial Module. Circulating GH, IGF-1, IGFBP3 and cytokine (GM-CSF, IFNγ, IL10, IL12P70, IL13, IL1B, IL2, IL4, IL5, IL6, IL8 and TNFα) levels were measured (Luminex FLEXMAP 3D). 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). While IGFBP3 levels were similar (P=0.22), IGF-1 levels gradually decreased in older subjects (18-35yrs: 41.8-173.8 ng/mL; 36-50yrs: 12-160 ng/mL; 51-65yrs: 2-156.8 ng/mL; 66-80yrs: 2-142.6 ng/mL, P&lt;0.0001). Overall GH did not change among groups (P=0.58). In both M and F systemic GH inversely correlated with duodenal microbial diversity [Spearman r (R)=-0.234, P=0.001], and this was most pronounced in older M (66-80yrs, R=-0.517, P=0.003). GH and IGF-1 correlated positively with systemic inflammatory markers: GMCSF (GH: R=0.159, P=0.032; IGF-1: P=NS); IFNγ (GH: R=0.178, P=0.016; IGF-1: R=0.154, P=0.041); IL1B (GH: P=NS; IGF-1: R=0.210, P=0.005); IL6 (GH: R=0.160, P=0.031; IGF-1: P=NS) and IL8 (GH: R=0.219, P=0.003; IGF-1: P=NS). IL8 was negatively linked to duodenal microbial diversity (R=-0.213, P=0.001), and higher in older M and F subjects (P=0.008). All associations seen were stronger in M. In addition, systemic TNFα (P=0.024) and IL5 (P=0.011) levels were also higher in M vs. F.In M only, GH was also associated with TNFα (R=0.226, P=0.034) and IL5 (R=0.279, P=0.008). Conclusion: IGF-1 and GH are associated with circulating inflammatory biomarkers in both a sex-and age- dependent manner. We show that systemic levels of GH and the specific inflammatory marker IL-8 are associated with diminished duodenal microbial diversity. This association is most profound in older males. Considering that IL8 is an important senescence marker, the mutual regulation of the small bowel microbiome and the somatotroph axis suggest a novel mechanism promoting inflammation and aging.

Presentation: Thursday, June 15, 2023