Biomarkers of leaky gut are related to inflammation and reduced physical function in older adults with cardiometabolic disease and mobility limitations

Abstract

Intestinal barrier dysfunction is hypothesized to be a contributing determinant of two prominent characteristics of aging: inflammation and decline in physical function. A relationship between microbial translocation (MT), or their biomarkers (lipopolysaccharide binding protein-1 [LBP-1], soluble cluster of differentiation [sCD]-14), and physical function has been reported in healthy older adults, rats, and invertebrates. However, it is not known whether the existence of comorbidities, or clinical interventions intended to reduce comorbidities through weight loss or exercise, alters this connection. We measured inflammation, MT, and physical function in 288 overweight/obese older patients with cardiometabolic disease and self-reported mobility limitations who were enrolled in a weight loss and lifestyle intervention study. At baseline, inflammatory cytokines and LBP-1 were positively correlated after adjustment for age, gender, and body mass index. A higher LBP-1 was significantly associated with poorer physical functional after covariate adjustment. Further, even when IL-6 levels were included in the models, 400-m walk time (p = 0.003), short physical performance battery (p = 0.07), and IL-8 (p < 0.001) remained positively associated with LBP-1. Lifestyle interventions improved body mass and some functional measures; however, MT and inflammation were unchanged. MT is reliably related to inflammation, and to poorer physical function in older adults with comorbid conditions. Intestinal barrier function did not appear to improve as a result of intervention assignment, suggesting alternative strategies are needed to target this pro-inflammatory pathway in aging.

A human-origin probiotic cocktail ameliorates aging-related leaky gut and inflammation via modulating the microbiota/taurine/tight junction axis

“…Increased inflammation in older adults is often associated with increased leaky gut indicated by system markers such as LPS binding protein (LBP) and soluble CD14 (sCD14) in circulation/blood that are linked with poor health outcomes (3,5). Interestingly, we found that the feeding of our human-origin probiotic cocktail significantly reduced LBP levels in the serum of older mice compared with their controls ( Figure 3I).…”

“…Increased low-grade inflammation is a major risk factor for morbidity and mortality in older adults (3,4) and a hallmark of aging-related comorbidities. Although the precise etiology of increased inflammation in older adults is not known, emerging evidence suggests that abnormally higher intestinal epithelial permeability ("leaky gut") is associated with increased inflammation in older adults (3,5,6). Higher gut permeability leads to influx of antigens, endotoxins, pathogens, and other proinflammatory substances from gut into the blood and lymphatic circulation, leading to systemic inflammation.…”

“…Therefore, the link between leaky gut and inflammation is bidirectional and remains correlative. Leaky gut and inflammation are commonly associated with poor health of older adults, specifically in individuals with obesity, diabetes, or reduced physical function (5). Abnormal (dysbiotic) gut microbiota could account for leaky gut and inflammation in older adults (3,9), since dysbiotic microbiota can produce metabolites that interact with the host's intestinal epithelial cells to reduce epithelial barrier proteins like zonulin-1 (Zo1), occludin (Ocln), and claudins, resulting in disrupted cell-to-cell connections, which compromises Inflammation is a major risk factor of morbidity and mortality in older adults.…”

Specificity Influences in (1→3)-β-d-Glucan-Supported Diagnosis of Invasive Fungal Disease

“…The past two decades have seen an explosion in data regarding intestinal barrier permeability, its myriad causes, and its relationship to inflammation-related pathophysiology [ 73 , 74 , 75 ]. Multiple biomarkers such as zonulin and various claudins have been identified as useful markers in characterizing the nature of barrier injury [ 76 , 77 ]. Data regarding elevated circulating BDG, its correlation with other markers of microbial translocation and inflammation, and orthogonal testing with enteral polysaccharides such as fluorescein labeled dextran demonstrate that it is also a translocated entity [ 78 , 79 , 80 ].…”

Introduction to host microbiome symbiosis in health and disease

“…39,40 Importantly, intestinal barrier dysfunction is commonly observed in aging vertebrates and invertebrates. [41][42][43][44][45] A current hypothesis is that decreasing intestinal barrier function with aging can cause increased microbial translocation into the systemic blood circulation, that subsequently causes systemic inflammation (inflammaging) and significant clinical outcomes (e.g., metabolic syndrome, decreased physical function, and mortality).…”