Evaluation of Six Weekly Oral Fecal Microbiota Transplants in People with HIV

Abstract

Background: Reduced microbiota diversity (dysbiosis) in people with HIV (PWH) likely contributes to inflammation, a driver of morbidity and mortality. We aimed to evaluate the safety and tolerability of 6 weekly oral fecal microbiota transplants (FMT) administered to reverse this dysbiosis.Methods: Six PWH on suppressive antiretroviral therapy (ART) received 6 weekly doses of lyophilized fecal microbiota product from healthy donors. Shotgun sequencing on stool before, after last FMT, and 20 weeks thereafter was performed. Inflammation and gut permeability biomarkers were measured.Results: Median age at week 0 was 39 years, CD4+ T cell count 496 cells/mm3, HIV RNA levels <20 copies/mL. FMT was safe and well-tolerated. Alpha diversity increased in 4 participants from weeks 0 to 6, including the 3 with the lowest alpha diversity at week 0. At week 26, alpha diversity more closely resembled week 0 than week 6 in these 4 participants. Metagenomic analysis showed no consistent changes across all participants. One participant had high gut permeability and inflammation biomarker levels and low alpha diversity that improved between weeks 0 and 6 with a shift in distribution.Conclusions: Weekly FMT was safe and well-tolerated. Alpha diversity increased in participants with the lowest baseline alpha diversity during the treatment period. Future randomized, controlled trials of FMT should consider evaluating PWH with greater inflammation, gut damage, or dysbiosis as this population may be most likely to show a significant response.ClinicalTrials.gov Identifier: NCT03329560

Fecal Microbiota Transplantation in Human Immunodeficiency Virus-Infected Patient Population: A Systematic Review and Meta-Analysis

“…Multiple doses of oral FMT also showed improvement in symptoms during 48 weeks of follow-up, compared to previous supplements [ 25 ]. Utay et al [ 24 ] also reported the safety and tolerability of repeated doses of oral FMT. However, they did not explain the required dose or duration.…”

“…However, they did not explain the required dose or duration. The small number of study participants limits the dependence on the results [ 24 ]. The study by Garcia-Garcia-de-Paredes et al reported the resolution of diarrhea in 87% of patients with Clostridium difficile infection.…”

The Role of Gut Dysbiosis in the Loss of Intestinal Immune Cell Functions and Viral Pathogenesis

“…Another smaller study, which involved weekly FMT in six people living with HIV, demonstrated increased gut microbial diversity over a 6-week treatment period. One participant in this study also experienced an improvement in biomarkers of gut permeability and inflammation [ 152 ]. Moreover, FMT in chickens improved resistance against the avian influenza virus [ 118 ].…”

The microbiota as a modulator of mucosal inflammation and HIV/HPV pathogenesis: From association to causation

“…Current evidence supports investigating therapeutic strategies for immune modulation in HIV. However, so far, no intervention targeting the microbiota of PLWH either by using prebiotics ( 16 , 16 , 60 ), probiotics ( 61 – 63 ), synbiotics ( 64 ), rifaximin ( 65 , 66 ), or even fecal microbiota transplants ( 67 , 68 ) have convincingly proved to effectively temper inflammation or enhance boost immune recovery following ART initiation. In general, there was lack of standardization in the outcomes assessed (ranging from studies designed to assess T cell changes ( 60 , 64 ) to exploratory studies evaluating multiple markers of T cell activation ( 69 ) or soluble markers of inflammation or bacterial translocation), the duration of the intervention (from weeks ( 16 , 61 , 62 , 69 ) up to one year), the disease status (from ART naive patients followed without ART ( 60 ) or patients presenting at advanced stages of the disease ( 64 ) starting ART to patients under ART-mediated HIV RNA suppression ( 61 – 63 ), and even the dosage and components of the prebiotic or probiotic mixtures ( 16 , 62 – 64 , 69 ).…”