Intestinal Permeability Biomarker Zonulin is Elevated in Healthy Aging

Abstract

Introduction Increased gut permeability (“leaky gut”) has been proposed as a potential contributor to age-related inflammation and gut dysbiosis. However, information on the relationship between a leaky gut and inflammation and physical frailty during aging are limited. Objective To investigate the hypothesis that an aging-associated leaky gut is linked to the age-related inflammation and frailty. Methods Two cohorts of healthy adults were studied: young (18–30-years-old, n=19) and older (≥70-years-old, n=18). Serum concentrations of the TNF-α and IL6, zonulin (a marker for leaky gut) and high-mobility group box protein (HMGB1, a nuclear protein triggering inflammation) were measured. Correlations of serum levels of zonulin and HMGB1 with strength of plantar flexor muscles and number of steps taken per day were analyzed. Results Serum concentration of zonulin and HMGB1 were 22% (p = 0.005) and 16% (p = 0.010) higher in the older vs young adults. Serum zonulin was positively associated with the concentrations of the TNF-α (r=0.357, p=0.032) and IL6 (r=0.345, p=0.043). Importantly, both zonulin and HMGB1 were negatively correlated with skeletal muscle strength (zonulin: r=−0.332, p=0.048; HMGB1: r=−0.383, p=0.023) and habitual physical activity (zonulin: r=−0.410, p=0.016; HMGB1: r=−0.483, p=0.004). Conclusions Serum zonulin was associated with both systemic inflammation and two key indices of physical frailty. These data suggest that a leaky gut may play a critical role in the development of age-related inflammation and frailty.

Therapeutic Delivery of Ang(1–7) via Genetically Modified Probiotic: A Dosing Study

“…Moreover, gut dysbiosis is tightly linked with the development of cognitive impairment (21, 22), physical frailty (23,24), and Alzheimer's disease (25). In support of this concept, we recently demonstrated that serum zonulin, a key physiologic regulator of intestinal permeability (26,27) is elevated among healthy older adults compared to young adults (28). Zonulin concentrations were also positively correlated with indices of inflammation and negatively correlated to strength and physical activity.…”

Risk factors associated with intestinal permeability in an adult population: A systematic review

“…Ten studies reported a statistically significant association between 12 anthropometric measurements and IP . The correlation between BMI and IP ranged from a weak to moderate positive correlation, of which most were reported to have a weak positive correlation (Table ).…”

“…Twenty‐four studies reported on 29 statistically significant biomarkers and association with altered IP . Two studies reported that fasting glucose had a weak positive correlation with IP (Table ).…”

“…This review also suggests a synergistic effect is possible when more than one risk factor is experienced. In particular, BMI, age, alcohol consumption and inflammation were all identified as having some degree of synergistic effect; although, inflammation appears to be the driving factor in many of the risk factors…”

“…Ten studies reported a statistically significant association between 12 anthropometric measurements and IP. 10,23,42,51,[53][54][55][56][57][58] The correlation between BMI and IP ranged from a weak to moderate positive correlation, of which most were reported to have a weak positive correlation 23,44,51,55,56,59 (Table 5). Two studies report BMI as an independent risk factor for altered IP as measured by zonulin levels (β = 0.26; ±0.10; P < 0.05, β = 1.507; 0.34 SEM; P < 0.01) 51,54 ( 31.65; P = 0.047), respectively as measured by zonulin (>64 ng/mL) 23 ( Table 3).…”