Gut barrier structure, mucosal immunity and intestinal microbiota in the pathogenesis and treatment of HIV infection

Abstract

Over the past 10 years, extensive work has been carried out in the field of microbial translocation in HIV infection, ranging from studies on its clinical significance to investigations on its pathogenic features. In the present work, we review the most recent findings on this phenomenon, focusing on the predictive role of microbial translocation in HIV-related morbidity and mortality, the mechanisms by which it arises and potential therapeutic approaches. From a clinical perspective, current work has shown that markers of microbial translocation may be useful in predicting clinical events in untreated HIV infection, while conflicting data exist on their role in cART-experienced subjects, possibly due to the inclusion of extremely varied patient populations in cohort studies. Results from studies addressing the pathogenesis of microbial translocation have improved our knowledge of the damage of the gastrointestinal epithelial barrier occurring in HIV infection. However, the extent to which mucosal impairment translates directly to increased gastrointestinal permeability remains an open issue. In this respect, novel work has established a role for IL-17 and IL-22-secreting T cell populations in limiting microbial translocation and systemic T-cell activation/inflammation, thus representing a possible target of immune-therapeutic interventions shown to be promising in the animal model. Further, recent reports have not only confirmed the presence of a dysbiotic intestinal community in the course of HIV infection but have also shown that it may be linked to mucosal damage, microbial translocation and peripheral immune activation. Importantly, technical advances have also shed light on the metabolic activity of gut microbes, highlighting the need for novel therapeutic approaches to correct the function, as well as the composition, of the gastrointestinal microbiota.

Helminths and intestinal barrier function

“…1,2 The mobilization of mucosal immunity in the context of enteric helminth infection is multi-faceted, complex and intriguing but a comprehensive discussion of such is beyond the scope of this commentary: the reader is referred to excellent recent reviews of this topic. [3][4][5][6][7][8] For the purposes of this review we will use 'epithelial permeability' to denote studies that address the physical properties of the epithelial layer and 'barrier function' is used as a more encompassing term that refers to the many extrinsic (e.g.…”

Biomarkers of aging in HIV: inflammation and the microbiome

“…At the very beginning of the epidemic HIV-related enteropathy with malabsorption and steathorrea in untreated individuals was described in literature and featured both jejunal (partial villus atrophy with crypt hyperplasia) and colonic abnormalities (focal cell degeneration near the crypt base) [46].…”

“…Another important alteration that occurs in the gastrointestinal tract which may fuel microbial translocation is the impairment of mucosal immunity: early studies highlighted the massive depletion of CD4+ T-cell at mucosal sites in all phases of HIV infection and their partial reconstitution in the course of treatment [46]. More recently, studies have focused on cell populations which safeguard mucosal surfaces, namely IL-17-producing subsets: indeed, IL-17 is a crucial cytokine for protection against infectious microbes [53] and epithelial maintenance occurs through wound repair [54][55][56].…”

Microbiome and Probiotics inHealth and HIV Infection

“…Delayed gastric emptying may also contribute to the increased bacterial colonization of upper digestive tract in Acquired Immune Deficiency Syndrome (AIDS) patients, playing a key role in chronic diarrhea and weight loss, frequently observed in HIV infected subjects. In HIV, malabsorption and GI infections are common conditions that are further impaired as HIV disease progresses [41,42].…”