The intestinal immune system and gut barrier function in obesity and ageing

Abstract

Obesity and ageing predispose to numerous, yet overlapping chronic diseases. For example, metabolic abnormalities, including insulin resistance (IR) and type 2 diabetes (T2D) are important causes of morbidity and mortality. Low‐grade chronic inflammation of tissues, such as the liver, visceral adipose tissue and neurological tissues, is considered a significant contributor to these chronic diseases. Thus, it is becoming increasingly important to understand what drives this inflammation in affected tissues. Recent evidence, especially in the context of obesity, suggests that the intestine plays an important role as the gatekeeper of inflammatory stimuli that ultimately fuels low‐grade chronic tissue inflammation. In addition to metabolic diseases, abnormalities in the intestinal mucosal barrier have been linked to a range of other chronic inflammatory conditions, such as neurodegeneration and ageing. The flow of inflammatory stimuli from the gut is in part controlled by local immunological inputs impacting the intestinal barrier. Here, we will review the impact of obesity and ageing on the intestinal immune system and its downstream consequences on gut barrier function, which is strongly implicated in the pathogenesis of obesity and age‐related diseases. In particular, we will discuss the effects of age‐related intestinal dysfunction on neurodegenerative diseases.

Analysis of correlations between gut microbiota, stool short chain fatty acids, calprotectin and cardiometabolic risk factors in postmenopausal women with obesity: a cross-sectional study

“…Gut barrier dysfunction is increasingly recognized as a key factor in the pathogenesis of obesity, diabetes and metabolic disorders [ 30 ]. Calprotectin has the potential to be used as an indirect marker of gut permeability [ 31 ].…”

Differentially Expressed Genes and Molecular Susceptibility to Human Age-Related Diseases

“…First, we used the PubMed database [ 75 ] and characterized each of the 39 novel PAG-related DEGs of the tame and aggressive rats ( Table 2 ) by answering the question as to how under- or overexpression of their human orthologs can aggravate or alleviate ARDs [ 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , ...…”

A mechanism by which gut microbiota elevates permeability and inflammation in obese/diabetic mice and human gut

“…3 Indeed, elevated gut permeability allows the nonspecific transfer of proinflammatory antigens, metabolites and microbes from the gut lumen to intestinal mucosa and the bloodstream, which, in turn, stimulates an inflammatory response through local and systemic immune cells. [4][5][6][7] However, we do not fully understand the mechanistic origins of elevated gut permeability, and thus prevention and treatments are lacking. In the last two decades, a mounting body of evidence suggests that the gut of the obese patients can harbour significantly different microbiota than are found in non-obese individuals.…”