Biomarkers of intestinal permeability are associated with inflammation in metabolically healthy obesity but not normal-weight obesity

Systemic inflammation is reported in normal-weight obesity (NWO) and metabolically healthy obesity (MHO), which may be linked to their increased cardiovascular disease (CVD) risk. Yet, drivers of this inflammation remain unclear. We characterized factors known to influence inflammatory status (i.e., intestinal permeability, adipose tissue, diet quality, microbiota), and their relationships with measured inflammation, in NWO and MHO, healthy control subjects (CON), and metabolically unhealthy obesity (MUO; N = 80; n = 20/group). Serum indicators of intestinal permeability and inflammation were assessed by ELISA and/or multiplex. Total, visceral, and percent body fat were measured with dual-energy X-ray absorptiometry (DXA). Fecal microbiota composition was assessed via 16S rRNA sequencing (n = 9-10/group). For C-reactive protein (CRP), MUO > NWO > CON (P < 0.0001). In MHO, CRP was intermediate and similar to both MUO and NWO. Lipopolysaccharide binding protein (LBP) and the ratio of LBP to soluble CD14 (sCD14) were higher in MHO and MUO vs. CON/NWO (P < 0.0001). Across correlation and regression analyses, LBP consistently displayed the strongest relationships with CRP in the entire sample (r = 0.78; beta = 0.57; P < 0.0001) and in MHO (r = 0.74; P < 0.01) but not NWO (r = 0.37; P = 0.11). Shannon index was higher in CON compared with MUO (P < 0.05) and inversely correlated with CRP in the full sample (r = -0.37; P < 0.05). These data are consistent with the notion that intestinal permeability is associated with low-grade inflammation in MHO, which could be implicated in this population's reported CVD risk. NEW & NOTEWORTHY This is the first study to our knowledge to examine biomarkers of intestinal permeability in normal-weight obesity and one of few assessing microbiota compositions in this population. Additionally, we report that individuals with metabolically healthy obesity and metabolically unhealthy obesity displayed similar evidence of intestinal permeability, which was more strongly associated with systemic inflammation than total and visceral adipose tissue mass.