Fecal microbiota transplantation in HIV: A pilot placebo-controlled study

Serrano‐Villar, Sergio; Talavera-Rodríguez, Alba; Gosalbes, María José; Madrid, Nadia; Pérez‐Molina, José A.; Elliott, Ryan J.; Navia, Beatriz; Lanza, Val F.; Vallejo, Alejandro; Osman, Majdi; Dronda, Fernando; Budree, Shrish; Zamora, Javier; Gutiérrez, Carolina; Manzano, Mónica; Vivancos, María Jesús; Ron, Raquel; Martínez-Sanz, Javier; Herrera, Sabina; Ansa, Uxua; Moya, Andrés; Moreno, Santiago

doi:10.1038/s41467-021-21472-1

Cited by 67 publications

(60 citation statements)

References 48 publications

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“…In addition, Serrano-Villar et al reported that repeated oral FMT capsules caused long-lasting effects in the recipients' microbiome, specifically in several members of the Lachnospiraceae family. A significant amelioration of the gut damage biomarker I-FABP was also observed in the FMT group (188).…”

Section: Therapeutic Strategies To Improve the Intestinal Barriermentioning

confidence: 67%

Alcohol Use and Abuse Conspires With HIV Infection to Aggravate Intestinal Dysbiosis and Increase Microbial Translocation in People Living With HIV: A Review

et al. 2021

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The intestinal microbiome is an essential so-called human “organ”, vital for the induction of innate immunity, for metabolizing nutrients, and for maintenance of the structural integrity of the intestinal barrier. HIV infection adversely influences the richness and diversity of the intestinal microbiome, resulting in structural and functional impairment of the intestinal barrier and an increased intestinal permeability. Pathogens and metabolites may thus cross the “leaky” intestinal barrier and enter the systemic circulation, which is a significant factor accounting for the persistent underlying chronic inflammatory state present in people living with HIV (PLWH). Additionally, alcohol use and abuse has been found to be prevalent in PLWH and has been strongly associated with the incidence and progression of HIV/AIDS. Recently, converging evidence has indicated that the mechanism underlying this phenomenon is related to intestinal microbiome and barrier function through numerous pathways. Alcohol acts as a “partner” with HIV in disrupting microbiome ecology, and thus impairing of the intestinal barrier. Optimizing the microbiome and restoring the integrity of the intestinal barrier is likely to be an effective adjunctive therapeutic strategy for PLWH. We herein critically review the interplay among HIV, alcohol, and the gut barrier, thus setting the scene with regards to development of effective strategies to counteract the dysregulated gut microbiome and the reduction of microbial translocation and inflammation in PLWH.

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Section: Therapeutic Strategies To Improve the Intestinal Barriermentioning

confidence: 67%

Alcohol Use and Abuse Conspires With HIV Infection to Aggravate Intestinal Dysbiosis and Increase Microbial Translocation in People Living With HIV: A Review

et al. 2021

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“…However, less invasive therapy would be required. Successful fecal microbiota transplantation (FMT) is reported in patients with HIV (Serrano-Villar et al, 2021) and the mouse model of Behcet's disease (Ye et al, 2018), while there is no evidence of FMT in patients with IEIs including HA20. Further study is required to clarify the mechanism of dysbiosis in patients with HA20 and IEIs, to determine the biomarker of the disease, and to discover if FMT works or not.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of the Intestinal Microbiome in Patients With Haploinsufficiency of A20

Toyofuku

Takeshita

Ohnishi

et al. 2022

Front. Cell. Infect. Microbiol.

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IntroductionHaploinsufficiency of A20 (HA20) is a form of inborn errors of immunity (IEI). IEIs are genetically occurring diseases, some of which cause intestinal dysbiosis. Due to the dysregulation of regulatory T cells (Tregs) observed in patients with HA20, gut dysbiosis was associated with Tregs in intestinal lamina propria.MethodsStool samples were obtained from 16 patients with HA20 and 15 of their family members. Infant samples and/or samples with recent antibiotics use were excluded; hence, 26 samples from 13 patients and 13 family members were analyzed. The 16S sequencing process was conducted to assess the microbial composition of samples. Combined with clinical information, the relationship between the microbiome and the disease activity was statistically analyzed.ResultsThe composition of gut microbiota in patients with HA20 was disturbed compared with that in healthy family members. Age, disease severity, and use of immunosuppressants corresponded to dysbiosis. However, other explanatory factors, such as abdominal symptoms and probiotic treatment, were not associated. The overall composition at the phylum level was stable, but some genera were significantly increased or decreased. Furthermore, among the seven operational taxonomic units (OTUs) that increased, two OTUs, Streptococcus mutans and Lactobacillus salivarius, considerably increased in patients with autoantibodies than those without autoantibodies.DiscussionDetailed interaction on intestinal epithelium remains unknown; the relationship between the disease and stool composition change helps us understand the mechanism of an immunological reaction to microorganisms.

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“…There are several approaches proposed for managements of chronic inflammation and immune activation in PLHIV. However, results from clinical trials on the use of conventional and unconventional anti-inflammatory agents as well as probiotics [ 25 , 26 ], are promising but remain unsatisfactory [ 27 – 30 ]. In this study, we observed that relationship between markers of inflammation varied with treatment status.…”

Section: Discussionmentioning

confidence: 99%

Advanced baseline immunosuppression is associated with elevated levels of plasma markers of fungal translocation and inflammation in long-term treated HIV-infected Tanzanians

et al. 2021

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Background For over a decade, antiretroviral therapy (ART) in resource-limited countries was only recommended for patients with advanced HIV disease. We investigated this group of patients in order to determine any relationship between degree of immunosuppression during treatment initiation and the subsequent levels of inflammatory biomarkers, reservoir size and plasma marker of fungal translocation after achieving long-term virological control. Methods We analyzed 115 virally suppressed (female 83.5%) and 40 untreated (female 70%) subjects from Dar es Salaam, Tanzania. The size of HIV latent reservoir (proviral DNA copy) was determined using quantitative PCR. Inflammatory biomarkers; IL-6, IL-10, and soluble CD14 (sCD14), were measured using multiplex cytometric beads array. Antibody titers for Cytomegalovirus (CMV) and Epstein Barr virus (EBV), plasma level of 1-3-beta-d-Glucan (BDG) was measured using ELISA. High-sensitivity C-reactive protein (hsCRP) was measured using nephelometric method. Results The median age was 36 (IQR 32-44) and 47 (IQR 43–54) years in untreated and virally suppressed patients respectively. Median duration of treatment for virally suppressed patients was 9 years (IQR 7–12) and median baseline CD4 count was 147 cells/mm3 (IQR 65–217). Virally suppressed patients were associated with significantly lower plasma levels of IL-10, sCD14 and BDG (P < 0.05) when compared to untreated patients. However, plasma level of IL-6 was similar between the groups. Baseline advanced level of immunosuppression (CD4 < 100cells/cm3) was associated with significantly higher plasma level of IL-6 (P = 0.02), hsCRP (P = 0.036) and BDG (P = 0.0107). This relationship was not seen in plasma levels of other tested markers. Degree of baseline immunosuppression was not associated with the subsequent proviral DNA copy. In addition, plasma levels of inflammatory marker were not associated with sex, CMV or EBV antibody titers, treatment duration or regimen. Conclusions Our data suggest that advanced immunosuppression at ART initiation is associated with severity of inflammation and elevated fungal translocation marker despite long term virological control. Further studies are needed to evaluate the potential increased burden of non-AIDS comorbidities that are linked to elevated inflammatory and fungal translocation markers as a result of the policy of HIV treatment at CD4 count < 200 cells/cm3 implemented for over a decade in Tanzania.

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Fecal microbiota transplantation in HIV: A pilot placebo-controlled study

Cited by 67 publications

References 48 publications

Alcohol Use and Abuse Conspires With HIV Infection to Aggravate Intestinal Dysbiosis and Increase Microbial Translocation in People Living With HIV: A Review

Alcohol Use and Abuse Conspires With HIV Infection to Aggravate Intestinal Dysbiosis and Increase Microbial Translocation in People Living With HIV: A Review

Dysregulation of the Intestinal Microbiome in Patients With Haploinsufficiency of A20

Advanced baseline immunosuppression is associated with elevated levels of plasma markers of fungal translocation and inflammation in long-term treated HIV-infected Tanzanians

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