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Conference paperKing OG, Yip AY, Horrocks V, et al., 2024,
Sa1927 ANTIBIOTIC TREATMENT PROMOTES THE INTESTINAL COLONISATION OF VANCOMYCIN-RESISTANT ENTEROCOCCUS BY KILLING MEMBERS OF THE GUT MICROBIOTA AND DECREASING NUTRIENT COMPETITION
, Publisher: Elsevier BV, Pages: S-584, ISSN: 0016-5085 -
Conference paperRadhakrishnan ST, Alexander JL, Mullish BH, et al., 2024,
Sa1871 THE COMPOSITION AND FUNCTION OF THE GUT MICROBIOTA IN A TREATMENT NAIVE INCEPTION COHORT OF INFLAMMATORY BOWEL DISEASE (IBD) CAN ACCURATELY DIFFERENTIATE IBD PHENOTYPE.
, Publisher: Elsevier BV, Pages: S-559, ISSN: 0016-5085 -
Journal articlePitashny M, Kao D, Ianiro G, et al., 2024,
Lyophilized fecal microbiome transfer for primary Clostridioides difficile infection: a multicenter randomized controlled trial (DONATE Study)
, Open Research Europe, Vol: 4, Pages: 61-61<ns4:p>Background Primary Clostridioides difficile infection (pCDI) carries high recurrence and mortality rates and is globally spread. pCDI is often a consequence of exposure to antibiotics, disrupting the healthy intestinal microbiota composition. Not surprisingly, in this antibiotic-associated infection, failure of the standard antibiotic treatment is high. Frozen fecal microbiota transplantation (FMT), the introduction of the microbial community from a healthy donor, has been shown to be safe and highly effective in cases of recurrent CDI, reaching >90% cumulative success rate. Importantly, FMT has shown potential for intestinal decolonization of multidrug-resistant organisms (MDRO), and/or mitigation of their ability to cause invasive infection. The use of FMT for pCDI, has been tested in small studies, showing promising results. The use of frozen FMT graft is often administered via colonoscopy or enteral (naso-jejunal) tubes, which are invasive procedures, placing significant burden on these often frail patients and the institutions providing the services. Moreover, frozen FMT is hampered by storage needs which limit accessibility and spread. Methods We have developed a lyophilized FMT product (Lyo-FMT - a dry compound that does not need freezing) that retains viability, prolongs the shelf time of the product and improves patient acceptance. In a randomized controlled multicenter trial, we aim to assess the efficacy of Lyo-FMT for pCDI in comparison to standard antibiotic therapy. Expected results This easy-to-administer product will restore the microbial community, fight the infective agent and reduce the overall antibiotic-resistant gene burden. This, in turn, will lower the recurrence rate and decrease carriage of other MDRO, coupled with a reduction in antibiotic use. Data on microbial shifts during treatment will shed light on our understanding of the pathophysiology of the disease. Clinicaltrials.gov registration <ns4:bold>NCT05709184
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Conference paperGhani R, Mullish B, Ghazy A, et al., 2024,
P3438 – Intestinal microbiota transplantation for patients colonised with multidrug-resistant organisms have an improvement in clinical outcomes associated with a significant increase in alpha-diversity metrics of the gastrointestinal microbiota
, ESCMID Global, Publisher: Elsevier -
Journal articleMullish BH, Bak A, Merrick B, et al., 2024,
Overview of the second edition of the joint British Society of Gastroenterology and Healthcare Infection Society faecal microbiota transplant guidelines, 2024
, Journal of Hospital Infection, ISSN: 0195-6701 -
Journal articleRouty B, Lenehan JG, Miller Jr WH, et al., 2024,
Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial (vol 29, pg 2121, 2023 )
, NATURE MEDICINE, Vol: 30, Pages: 604-604, ISSN: 1078-8956 -
Journal articleKragsnaes MS, Jensen JRB, Nilsson AC, et al., 2024,
Dynamics of inflammation-associated plasma proteins following faecal microbiota transplantation in patients with psoriatic arthritis and healthy controls: exploratory findings from the FLORA trial.
, RMD Open, Vol: 10OBJECTIVES: The gut microbiota can mediate both pro and anti-inflammatory responses. In patients with psoriatic arthritis (PsA), we investigated the impact of faecal microbiota transplantation (FMT), relative to sham transplantation, on 92 inflammation-associated plasma proteins. METHODS: This study relates to the FLORA trial cohort, where 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate treatment, were included in a 26-week, double-blind, randomised, sham-controlled trial. Participants were allocated to receive either one gastroscopic-guided healthy donor FMT (n=15) or sham (n=16). Patient plasma samples were collected at baseline, week 4, 12 and 26 while samples from 31 age-matched and sex-matched healthy controls (HC) were collected at baseline. Samples were analysed using proximity extension assay technology (Olink Target-96 Inflammation panel). RESULTS: Levels of 26 proteins differed significantly between PsA and HC pre-FMT (adjusted p<0.05), of which 10 proteins were elevated in PsA: IL-6, CCL20, CCL19, CDCP1, FGF-21, HGF, interferon-γ (IFN-γ), IL-18R1, monocyte chemotactic protein 3, and IL-2. In the FMT group, levels of 12 proteins changed significantly across all timepoints (tumour necrosis factor (TNF), CDCP1, IFN-γ, TWEAK, signalling lymphocytic activation molecule (SLAMF1), CD8A, CD5, Flt3L, CCL25, FGF-23, CD6, caspase-8). Significant differences in protein levels between FMT and sham-treated patients were observed for TNF (p=0.002), IFN-γ (p=0.011), stem cell factor (p=0.024), matrix metalloproteinase-1 (p=0.038), and SLAMF1 (p=0.042). FMT had the largest positive effect on IFN-γ, Axin-1 and CCL25 and the largest negative effect on CCL19 and IL-6. CONCLUSIONS: Patients with active PsA have a distinct immunological plasma protein signature compared with HC pre-FMT. FMT affects several of these disease markers, including sustained elevation of IFN-γ. TRIAL R
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Journal articleForlano R, Martinez-Gili L, Takis P, et al., 2024,
Disruption of gut barrier integrity and host-microbiome interactions underlie MASLD severity in patients with type-2 diabetes mellitus.
, Gut Microbes, Vol: 16Aberration of the "gut-liver axis" contributes to the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we use multi-omics to analyze the gut microbiota composition and metabolic profile of patients with type-2 diabetes mellitus (T2DM). T2DM patients were screened for liver disease by blood tests, ultrasound, and liver stiffness measurements. Stool microbiota was analyzed by 16S rRNA gene sequencing; metabolomic profiling by Nuclear Magnetic Resonance spectroscopy and Ultra-High Performance-Mass Spectrometry. Microbiome and metabolic signatures were analyzed in the whole cohort and in matched subsets to identify signatures specific for steatosis (MASLD±) or fibrosis (Fibrosis±). Gut permeability was assessed in-vitro using monolayers of MDCK cells and trans-epithelial electric resistance (TEER). Cytokine profile was assessed in serum and stools.Overall, 285 patients were enrolled: 255 serum, 252 urine and 97 stool samples were analyzed. Anaeroplasma and Escherichia/Shigella ASVs were higher, while Butyricicoccus ASVs were lower in those with normal liver. In MASLD±, Butyricicoccus ASV was significantly higher in those with steatosis. In the Fibrosis±, Butyricicoccus ASV was significantly lower in those with fibrosis. Glycochenodeoxycholic acid-3-sulfate (G-UDCA-3S) appeared to be higher in MASLD with fibrosis. Fecal water from patients with MASLD and fibrosis caused the greatest drop in the TEER vs those with normal liver; this was reversed with protease inhibitors. Finally, fecal IL-13 was lower in MASLD with fibrosis. We identified microbiome signatures which were specific for steatosis and fibrosis and independent of other metabolic risk factors. Moreover, we conclude that protease-related gut permeability plays a role in those MASLD patients with fibrosis, and that disease progression is linked to a gut-liver axis which is at least partially independent of T2DM.
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Journal articleBibbò S, Porcari S, Del Vecchio LE, et al., 2023,
Gut microbiota and immunotherapy of renal cell carcinoma
, Human Vaccines & Immunotherapeutics, Vol: 19, ISSN: 2164-5515 -
Journal articleMullish BH, Tohumcu E, Porcari S, et al., 2023,
The role of faecal microbiota transplantation in chronic noncommunicable disorders
, Journal of Autoimmunity, Vol: 141, Pages: 103034-103034, ISSN: 0896-8411
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