Fig. 1

The continuum of gastrointestinal abnormalities in treated and untreated HIV disease. In HIV-negative individuals, a highly diversified microbiota resides in the gut lumen and is shielded from the lamina propria, thus preventing the translocation of bacteria and microbial products to the peripheral blood. Microbial translocation is blocked thanks to the structural integrity of the epithelial barrier and function of gut-resident immune cells, e.g. IL-17- and IL-22- producing cells. In the acute phase of HIV disease, no significant alterations of luminal bacteria and epithelial barrier have been reported. Indeed, markers of microbial translocation (LPS, peptidoglycan, EndoCAb, sCD14, 16S rDNA) and enterocyte damage (I-FABP, sST2) were not detected in plasma samples of acutely-infected individuals and both mucosal and peripheral Th17 cells were only slightly decreased in the earliest phases of HIV infection. Following 6 months from infection (early HIV infection), however, a rise in parameters of microbial translocation and gut impairment was measured in peripheral blood, suggesting initial disruption of mucosal integrity. In the chronic stages of untreated HIV disease, new research studies have demonstrated profound alterations of the intestinal epithelium, with marked impairment of proteins forming the gut junctional complex (JC; cadherin, claudins, zonula occludens 1) which can be found in the peripheral blood. These anatomical alterations are accompanied by changes in the composition and function of the gut microbiota as well as the reduction of IL-17- and IL-22-secreting cell numbers, allowing for the translocation of pathogenic bacteria. Combination antiretroviral therapy (cART) is able to correct gut abnormalities only in part. Persistent defects in JC protein expression, microbial composition and immune function have in fact been described in aviremic individuals. Importantly, these defects appear to be differentially expressed according to the degree of CD4+ T-cell recovery on cART