Publications by authors named "Julian Marchesi"

Background: Large-scale multicentre studies are needed to understand complex relationships between the gut microbiota, health and disease. Interrogating the mucosal microbiota may identify important biology not captured by stool analysis. Gold standard tissue cryopreservation ('flash freezing') limits large-scale study feasibility.

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Lactobacillus species dominance of the vaginal microbiome is a hallmark of vaginal health. Pathogen displacement of vaginal lactobacilli drives innate immune activation and mucosal barrier disruption, increasing the risks of STI acquisition and, in pregnancy, of preterm birth. We describe differential TLR mediated activation of the proinflammatory transcription factor NF-κB by vaginal pathogens and commensals.

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Background: We conducted a single-arm interventional study, to explore mucosal changes associated with clinical remission under oral vancomycin (OV) treatment, in primary sclerosing cholangitis associated inflammatory bowel disease (PSC-IBD); NCT05376228.

Method: Fifteen patients with PSC and active colitis (median faecal calprotectin 459µg/g; median total Mayo score 5) were treated with OV (125mg QID) for 4 weeks and followed-up for a further 4 weeks of treatment withdrawal (8 weeks, end-of-study). Colonic biopsies were obtained at baseline and week 4.

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Objective: To evaluate South Asian (SA) and White (WH) inflammatory bowel disease (IBD) phenotypes, and to explore treatment approach variations between these cohorts in the UK using the IBD BioResource database.

Design: Differences between WH and SA IBD patients were analysed using demographic, phenotypic and outcome data. Drug utilisation patterns and surgical outcomes were assessed in propensity score-matched (PSM) cohorts with multivariable logistic regression, Cox regression and Kaplan-Meier analysis.

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There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value.

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  • * An analysis of 302 pregnant women revealed that non-secretors with certain types of bacterial diversity had shorter gestational periods, particularly in those with depleted bacterial types early in pregnancy.
  • * The findings suggest that secretor status and the expression of blood-group antigens play a crucial role in the interaction between vaginal microbiota and pregnancy outcomes, especially regarding preterm birth risks.
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Faecal/intestinal microbiota transplant (FMT/IMT) is an efficacious treatment option for recurrent infection, which has prompted substantial interest in FMT's potential role in the management of a much broader range of diseases associated with the gut microbiome. Despite its promise, the success rates of FMT in these other settings have been variable. This review critically evaluates the current evidence on the impact of clinical, biological, and procedural factors upon the therapeutic efficacy of FMT, and identifies areas that remain nebulous.

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  • Human microbiomes play a crucial role in health by impacting metabolism, immune functions, and neurological processes, but their complete complexity is still not fully understood.
  • The definition of a "healthy" microbiome is controversial due to variations in microbial communities and the difficulty in establishing a standard definition for health across different individuals and conditions.
  • The article highlights progress in microbiome research and identifies gaps in knowledge, proposing a roadmap that utilizes epidemiological methods to better understand the relationship between microbiomes and health.
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Metabolomics aims to study the downstream effects of variables like diet, environment, or disease on a given biological system. However, inconsistencies in sample preparation, data acquisition/processing protocols lead to reproducibility and accuracy concerns. A systematic study was conducted to assess how sample preparation methods and data analysis platforms affect metabolite susceptibility.

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  • * The study found that a decrease in serum zonulin levels (a marker of intestinal permeability) was correlated with both weight loss and a reduction in liver fat, indicating improved metabolic health.
  • * While initial changes in gut microbiota and short-chain fatty acids (SCFAs) occurred at 12 weeks, these effects did not persist at 24 weeks, suggesting that longer-term benefits in MASH may not be linked to sustained changes in the gut microbiome.
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Chronic urinary infection may have implications for disease because of reactivation of toxins in the urine or damage to bladder defences. Exploration of these possibilities requires a scrupulous scientific approach.

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Investigating the gut microbiome and metabolome frequently requires faecal samples, which can be difficult to obtain. Previous studies have shown that rectal swabs are comparable to faecal samples for analysing gut microbiota composition and key metabolites. In this study, 3D printed rectal swabs were compared with conventional flocked swabs and faecal samples, due to the potential advantages 3D printing as a technique offers for swab production and development.

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Background: Endometrial cancer is a multifactorial disease with inflammatory, metabolic and potentially microbial cues involved in disease pathogenesis. The endometrial cancer microbiome has been poorly characterised so far and studies have often overestimated bacterial biomass due to lack of integration of appropriate contamination controls. There is also a scarcity of evidence on the functionality of microbial microenvironments in endometrial cancer.

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Chronic lung disease (CLD) of prematurity, a common cause of morbidity and mortality in preterm-born infants, has a multifactorial aetiology. This review summarizes the current evidence for the effect of the gut and airway microbiota on the development of CLD, highlighting the differences in the early colonisation patterns in preterm-born infants compared to term-born infants. Stool samples from preterm-born infants who develop CLD have less diversity than those who do not develop CLD.

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  • The human ileum has a lot of L-cells that produce hormones like GLP-1 and PYY, which help suppress appetite when we eat.
  • A study explored how different diets (high-fiber vs. low-fiber) affect the release of these hormones and their connection to food structure and ileal metabolites.
  • Results showed that high-fiber diets significantly boosted PYY release compared to low-fiber, and the study found changes in the ileum's molecular environment after eating, linking it to appetite regulation.
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  • A study was conducted to determine if the macrolide antibiotic azithromycin can improve survival rates without chronic lung disease in preterm infants born before 30 weeks of gestation.
  • The AZTEC trial involved 799 preterm infants across 28 UK neonatal units and randomly assigned them to receive either azithromycin or a placebo.
  • The primary outcome measured was the survival of infants without developing significant lung disease by 36 weeks postmenstrual age.
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Introduction: Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient's quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%.

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Objective: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis.

Design: Performance of Yaq-001 was evaluated .

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  • - The study investigated the safety and effectiveness of combining transarterial chemoembolization (TACE) with pembrolizumab in patients with liver-confined hepatocellular carcinoma (HCC), aiming to enhance immunotherapy results and boost adaptive immunity.
  • - Among 15 patients, most experienced treatment-related side effects like skin rash and fatigue, but there were no significant toxicity issues from combining therapies; notable results included a 53% objective response rate and a median overall survival of 33.5 months following treatment.
  • - The research findings suggest that the combination of TACE and pembrolizumab is tolerable and may have a synergistic effect in treating HCC, warranting further exploration of immunotherapy in conjunction with TACE
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  • This study explored the impact of fecal microbiota transplantation (FMT) on inflammation-related proteins in patients with psoriatic arthritis (PsA), who had not responded to traditional treatment.
  • In a randomized, double-blind trial involving 31 PsA patients, FMT was compared to a sham procedure, with blood samples taken at multiple points throughout the study.
  • The results showed significant differences in inflammatory protein levels between PsA patients and healthy controls, with FMT leading to notable changes in several proteins, suggesting a potential therapeutic effect on inflammation in PsA.
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Immune checkpoint inhibitors (CPIs) are a relatively newly licenced cancer treatment, which make a once previously untreatable disease now amenable to a potential cure. Combination regimens of anti-CTLA4 and anti-PD-1 show enhanced efficacy but are prone to off-target immune-mediated tissue injury, particularly at the barrier surfaces. To probe the impact of immune checkpoints on intestinal homoeostasis, mice are challenged with anti-CTLA4 and anti-PD-1 immunotherapy and manipulation of the intestinal microbiota.

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Objective: We investigated intestinal permeability and fecal, plasma, and urine metabolomic profiles in methotrexate-treated active psoriatic arthritis (PsA) and how this related to clinical response following one sham or fecal microbiota transplantation (FMT).

Methods: This exploratory study is based on the FLORA trial cohort, in which 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, 1:1 randomized, sham-controlled trial. Participants were randomly allocated to receive either one healthy donor FMT (n = 15) or sham (n = 16) via gastroscopy.

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Stool sampling is a useful tool for diagnosing gastrointestinal disease in veterinary medicine. The sub-clinical disease burden of spp. in cattle can become significant for farmers.

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