Safety and efficacy of fecal microbiota transplantation for treatment of systemic lupus erythematosus: An EXPLORER trial

Huang, Cancan; Yi, Ping; Zhu, Minghui; Zhou, Wenhui; Zhang, Bo; Yi, Xiaoqing; Long, Hai; Zhang, Guiying; Wu, Haijing; Tsokos, George C.; Zhao, Ming; Lu, Qianjin

doi:10.1016/j.jaut.2022.102844

Cited by 71 publications

(51 citation statements)

References 55 publications

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“…EPEC implemented by OpenBiome [ 51 ]), broader assessment of conditions (e.g. anti-nuclear antibody test for autoimmune diseases [ 52 ]), and mandatory donation of feces in a dedicated supervised bathroom (resulting in higher logistic, facility and employee expenses). By reporting the average costs associated with our donor screening program we provide an estimate for clinicians thinking of establishing a pool of healthy stool donors for FMT research.…”

Section: Discussionmentioning

confidence: 99%

Challenges and costs of donor screening for fecal microbiota transplantations

Bénard

Bruijn²,

Fenneman³

et al. 2022

PLoS ONE

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Background The increasing interest to perform and investigate the efficacy of fecal microbiota transplantation (FMT) has generated an urge for feasible donor screening. We report our experience with stool donor recruitment, screening, follow-up, and associated costs in the context of clinical FMT trials. Methods Potential stool donors, aged between 18−65 years, underwent a stepwise screening process starting with an extensive questionnaire followed by feces and blood investigations. When eligible, donors were rescreened for MDROs and SARS-CoV-2 every 60-days, and full rescreening every 4−6 months. The costs to find and retain a stool donor were calculated. Results From January 2018 to August 2021, 393 potential donors underwent prescreening, of which 202 (51.4%) did not proceed primarily due to loss to follow-up, medication use, or logistic reasons (e.g. COVID-19 measures). 191 potential donors filled in the questionnaire, of which 43 (22.5%) were excluded. The remaining 148 candidates underwent parasitology screening: 91 (61.5%) were excluded, mostly due to Dientamoeba fragilis and/or high amounts of Blastocystis spp. After additional feces investigations 18/57 (31.6%) potential donors were excluded (mainly for presence of Helicobacter Pylori and ESBL-producing organisms). One donor failed serum testing. Overall, 38 out of 393 (10%) potential donors were enrolled. The median participation time of active stool donors was 13 months. To recruit 38 stool donors, €64.112 was spent. Conclusion Recruitment of stool donors for FMT is challenging. In our Dutch cohort, failed eligibility of potential donors was often caused by the presence of the protozoa Dientamoeba fragilis and Blastocystis spp.. The exclusion of potential donors that carry these protozoa, especially Blastocystis spp., is questionable and deserves reconsideration. High-quality donor screening is associated with substantial costs.

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Section: Discussionmentioning

confidence: 99%

Challenges and costs of donor screening for fecal microbiota transplantations

Bénard

Bruijn²,

Fenneman³

et al. 2022

PLoS ONE

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“…After FMT, the alpha diversity of the gut microbiota of the patients was increased, with significant enrichment of short-chain fatty acid production-related genera, while inflammationrelated bacterial taxa decreased, and short-chain fatty acid production in the gut increased. The ratio of CD4+ memory T cells/naive T cells in the peripheral blood of patients and serum IL-6 concentration of SRI-4 responders was significantly decreased (147). This clinical trial confirmed for the first time that FMT, a new medical technology, is safe and effective in the treatment of SLE, providing a new option for the treatment of SLE patients and laying an important foundation for the subsequent promotion and application of larger-scale FMT in the treatment of SLE.…”

Section: Fecal Microbiota Transplantation For Other Diseasesmentioning

confidence: 94%

“…Several studies have shown that gut microbiota can regulate a variety of inflammatory factors (142)(143)(144), and clinical trials have found abnormal concentrations of anti-inflammatory or pro-inflammatory cytokines in the peripheral blood of SLE patients (145,146). A non-RCT recruited 20 patients with active SLE who still had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 despite standard care (147). They found that the SLEDAI-2K score, urine protein/urine creatinine ratio, and serum anti-dsDNA antibody levels decreased significantly after FMT treatment (147).…”

Section: Fecal Microbiota Transplantation For Other Diseasesmentioning

confidence: 99%

“…A non-RCT recruited 20 patients with active SLE who still had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 despite standard care (147). They found that the SLEDAI-2K score, urine protein/urine creatinine ratio, and serum anti-dsDNA antibody levels decreased significantly after FMT treatment (147). After FMT, the alpha diversity of the gut microbiota of the patients was increased, with significant enrichment of short-chain fatty acid production-related genera, while inflammationrelated bacterial taxa decreased, and short-chain fatty acid production in the gut increased.…”

Section: Fecal Microbiota Transplantation For Other Diseasesmentioning

confidence: 99%

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Safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases: A systematic review and meta-analysis

et al. 2022

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ObjectiveTo evaluate the safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases.MethodsRelevant literature was retrieved from the PubMed database, Embase database, Cochrane Library database, etc. The search period is from the establishment of the database to January 2022. The outcomes include clinical symptoms, improvement in biochemistry, improvement in intestinal microbiota, improvement in the immune system, and adverse events. Literature screening and data extraction were independently carried out by two researchers according to the inclusion and exclusion criteria, and RevMan 5.3 software was used for statistics and analysis.ResultsOverall, a total of 14 randomized controlled trials (RCTs) involving six types of autoimmune diseases were included. The results showed the following. 1) Type 1 diabetes mellitus (T1DM): compared with the autologous fecal microbiota transplantation (FMT) group (control group), the fasting plasma C peptide in the allogenic FMT group at 12 months was lower. 2) Systemic sclerosis: at week 4, compared with one of two placebo controls, three patients in the experimental group reported a major improvement in fecal incontinence. 3) Ulcerative colitis, pediatric ulcerative colitis, and Crohn’s disease: FMT may increase clinical remission, clinical response, and endoscopic remission for patients with ulcerative colitis and increase clinical remission for patients with Crohn’s disease. 4) Psoriatic arthritis: there was no difference in the ratio of ACR20 between the two groups.ConclusionBased on current evidence, the application of FMT in the treatment of autoimmune diseases is effective and relatively safe, and it is expected to be used as a method to induce remission of active autoimmune diseases.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235055, identifier CRD42021235055.

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“…Although fecal transplantation is never been tested in patients with lupus, the fecal microbiota transplantation (FMT) of feces from patients with lupus into germ-free mice induces some lupus-like characteristics, including increased autoantibodies, cytokines, altered immune cell distribution (in mucosa and blood), and upregulated SLE-related genes [ 149 ]. Due to a possible causal role of aberrant gut microbiota in lupus pathogenesis, FMT of feces from healthy individuals might be beneficial in patients with lupus and a clinical trial of FMT in patients with active SLE effectively modified the gut microbiota [ 150 ]. More studies on this topic are ongoing [ 151 , 152 , 153 , 154 ].…”

Section: Therapeutics Targeting Gut Leakage In Lupusmentioning

confidence: 99%

Gut Barrier Damage and Gut Translocation of Pathogen Molecules in Lupus, an Impact of Innate Immunity (Macrophages and Neutrophils) in Autoimmune Disease

Charoensappakit

Sae-khow

Leelahavanichkul

2022

IJMS

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The gut barrier is a single cell layer that separates gut micro-organisms from the host, and gut permeability defects result in the translocation of microbial molecules from the gut into the blood. Despite the silent clinical manifestation, gut translocation of microbial molecules can induce systemic inflammation that might be an endogenous exacerbating factor of systemic lupus erythematosus. In contrast, circulatory immune-complex deposition and the effect of medications on the gut, an organ with an extremely large surface area, of patients with active lupus might cause gut translocation of microbial molecules, which worsens lupus severity. Likewise, the imbalance of gut microbiota may initiate lupus and/or interfere with gut integrity which results in microbial translocation and lupus exacerbation. Moreover, immune hyper-responsiveness of innate immune cells (macrophages and neutrophils) is demonstrated in a lupus model from the loss of inhibitory Fc gamma receptor IIb (FcgRIIb), which induces prominent responses through the cross-link between activating-FcgRs and innate immune receptors. The immune hyper-responsiveness can cause cell death, especially apoptosis and neutrophil extracellular traps (NETosis), which possibly exacerbates lupus, partly through the enhanced exposure of the self-antigens. Leaky gut monitoring and treatments (such as probiotics) might be beneficial in lupus. Here, we discuss the current information on leaky gut in lupus.

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Safety and efficacy of fecal microbiota transplantation for treatment of systemic lupus erythematosus: An EXPLORER trial

Cited by 71 publications

References 55 publications

Challenges and costs of donor screening for fecal microbiota transplantations

Challenges and costs of donor screening for fecal microbiota transplantations

Safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases: A systematic review and meta-analysis

Gut Barrier Damage and Gut Translocation of Pathogen Molecules in Lupus, an Impact of Innate Immunity (Macrophages and Neutrophils) in Autoimmune Disease

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