Treating From the Inside Out: Relevance of Fecal Microbiota Transplantation to Counteract Gut Damage in GVHD and HIV Infection

Abstract

The gastrointestinal (GI) tract is a complex and well-balanced milieu of anatomic and immunological barriers. The epithelial surface of the GI tract is colonized by trillions of microorganisms, known as the gut microbiota, which is considered an "organ" with distinctive endocrine and immunoregulatory functions. Dysregulation of the gut microbiota composition, termed dysbiosis, has been associated with epithelial damage and translocation of microbial products into the circulating blood. Dysbiosis, increased gut permeability and chronic inflammation play a major role on the clinical outcome of inflammatory bowel diseases, graft-vs.-host disease (GVHD) and HIV infection. In this review, we focus on GVHD and HIV infection, conditions sharing gut immune damage leading to dysbiosis. The degree of dysbiosis and level of epithelial gut damage predict poor clinical outcome in both conditions. Emerging interventions are therefore warranted to promote gut microbiota homeostasis and improve intestinal barrier function. Interventions such as anti-inflammatory medications, and probiotics have toxicity and/or limited transitory effects, justifying innovative approaches. Fecal microbiota transplantation (FMT) is one such approach where fecal microorganisms are transferred from healthy donors into the GI tract of the recipient to restore microbiota composition in patients with Clostridium difficile-induced colitis or inflammatory bowel diseases. Preliminary findings point toward a beneficial effect of FMT to improve GVHD and HIV-related outcomes through the engraftment of beneficial donor bacteria, notably Ouyang et al. FMT for GVHD and HIV those producing anti-inflammatory metabolites. Herein, we critically review the potential for FMT in alleviating dysbiosis and gut damage in patients with GVHD or HIV-infection. Understanding the underlying mechanism by which FMT restores gut function will pave the way toward novel scalable and targeted interventions.

Differences in HIV burden in the inflamed and non-inflamed colon from a person living with HIV and ulcerative colitis

“… 13 There is solid evidence that HIV infection breaches the gut barrier in a way similar to UC. 6 , 7 , 18 …”

“…Novel therapies that restore gut barrier integrity may reduce inflammation and HIV reservoir size in the gut of ART-treated PLWH. 18 …”

Gut Leakage of Fungal‐Related Products: Turning Up the Heat for HIV Infection

“…Specific strategies have not been developed to prevent microbial translocation of fungal products in ART-treated PLWH. Fecal microbiota transplantation (FMT) could influence the mass of the mycobiome and allow improvement of gut epithelium integrity, reducing fungal translocation ( 68 ). Although several pilot trials of FMT have been initiated in PLWH, few have studied fungal translocation before and after treatment.…”

Utilizing Probiotics for the Prevention and Treatment of Gastrointestinal Diseases

“…Diarrhea in HIV/AIDS affected individuals can be caused by a variety of opportunistic infections or noninfectious causes linked to treatment regimens ( Dikman et al, 2015 ). Current treatment for patients suffering from AIDS-AD involve antisecretory agents and/or fecal microbiota transplantation therapy ( Dikman et al, 2015 ; Ouyang, 2020 ). Several promising studies have provided insight into utilizing probiotics as an affordable and accessible option to combat diarrhea in patients with HIV/AIDS induced diarrhea.…”