Julian Marchesi

Cardiff University | CU · School of Biosciences

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...

Introduction Lower diversity of the gut microbiome prior to allogeneic haematopoietic cell transplantation (HCT) correlates with reduced survival after the intervention. Most patients undergoing HCT for a haematological malignancy have previously received intensive chemotherapy, resulting in prolonged neutropenic episodes requiring broad-spectrum a...

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; media...

Antibiotic treatment significantly disrupts the gut microbiome and promotes vancomycin-resistant Enterococcus (VRE) intestinal colonisation. These disruptions lead to the intestine acting as a reservoir for VRE that seed difficult-to-treat infections. Patients would benefit from new treatments that prevent or treat VRE intestinal colonisation. Howe...

Mutations in the FUT2 gene that result in a lack of expression of histo-blood group antigens on secreted glycoproteins may shape the vaginal microbiota with consequences for birth outcome. To test this, we analysed the relationship between secretor status, vaginal microbiota and gestational length in an ethnically diverse cohort of 302 pregnant wom...

Faecal/intestinal microbiota transplant (FMT/IMT) is an efficacious treatment option for recurrent Clostridioides difficile 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...

Background and significance: Reduced gut microbiome diversity pre-allogeneic hematopoietic cell transplantation (HCT) strongly correlates with poorer survival after the procedure. Most hematologic malignancy patients undergoing HCT have previously received intensive chemotherapy, resulting in prolonged neutropenic episodes and opportunistic infecti...

Human microbiomes are essential to health throughout the lifespan and are increasingly recognized and studied for their roles in metabolic, immunological and neurological processes. Although the full complexity of these microbial communities is not fully understood, their clinical and industrial exploitation is well advanced and expanding, needing...

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 anal...

Weight loss improves metabolic dysfunction-associated steatohepatitis (MASH). We investigated whether there were associated changes in intestinal permeability, short-chain fatty acids (SCFAs), and gut microbiota, which are implicated in the pathophysiology of MASH. Sixteen adults with MASH, moderate fibrosis, and obesity received a low-energy total...

Background Environmental enteropathy (EE) is a highly prevalent subclinical inflammatory intestinal disorder associated with growth failure, impaired neurocognitive development, poor response to oral vaccines, and micronutrient deficiencies. However, EE research and clinical trials are hampered by the lack of non-invasive tools for measuring intest...

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 fa...

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...

Introduction Large multicentre studies are key to understanding complex relationships between the gut microbiome and outcomes in IBD. Interrogating the mucosal microbiome may identify biological signals not captured by stool, which mostly reflects distal colon. Gold standard tissue cryopreservation by ‘flash freezing’ is likely to limit large study...

Introduction Thiopurines (THIO) are frequently used in IBD, as monotherapy and in combination with biologics. Due to a slow onset of action, clinical response to THIO can be delayed. Thiopurine S-methyltransferase (TPMT) enzyme activity can inform on THIO metabolism rates, but it does not predict THIO hypermethylation. We sought to investigate chan...

Introduction Current literature indicates differences in phenotype and severity of UC between South Asian (SA) and White (WH) populations, however, these studies are limited by small sample sizes. In this multi-centre cohort study, the UK IBD BioResource (IBD-BR) dataset was utilised to examine these variations, and to explore differences in diseas...

The human ileum contains a high density of enteroendocrine L-cells, which release the appetite-suppressing hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) in response to food intake. Recent evidence highlighted the potential role of food structures in PYY release, but the link between food structures, ileal metabolites,...

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 c...

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...

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...

Purpose Transarterial chemoembolization (TACE) may prime adaptive immunity and enhance immunotherapy efficacy. PETAL evaluated safety, preliminary activity of TACE plus pembrolizumab and explored mechanisms of efficacy. Patients and Methods Patients with liver-confined hepatocellular carcinoma (HCC) were planned to receive up to two rounds of TACE...

Objectives 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 patien...

Background A previous exploratory study demonstrated the ability of the Lab4 probiotic to alleviate the symptoms of IBS, and post hoc data analysis indicated greatest improvements in the female subgroup. The aim of this study is to confirm the impact of this multistrain probiotic on IBS symptom severity in females. Methods An 8‐week, single‐center...

Background The current evidence suggests ethnic distinctions in IBD phenotype, and differences in the provision of treatment have been reported. This multi-centre cohort study utilised the UK IBD BioResource dataset to evaluate phenotypic differences between South Asian (SA) and White (WH) IBD, and to explore if these were associated with differenc...

Background Mesalazine (5-ASA) is a key initial treatment of ulcerative colitis (UC); recent studies have highlighted the role of the gut microbiota in 5-ASA metabolism. There is no established means of predicting treatment outcome. We sought to investigate changes in the gut microbiota and metabolome with 5-ASA treatment, and whether such changes m...

Aberration 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...

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...

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...

Stool sampling is a useful tool for diagnosing gastrointestinal disease in veterinary medicine. The sub-clinical disease burden of Salmonella spp. in cattle can become significant for farmers. However, current methods of faecal sampling in a rural setting for diagnosis are not consistently sufficient for the preservation of Salmonella spp. in faece...

The intestine is the primary colonisation site for carbapenem-resistant Enterobacteriaceae (CRE) and serves as a reservoir of CRE that cause invasive infections (e.g. bloodstream infections). Broad-spectrum antibiotics disrupt colonisation resistance mediated by the gut microbiota, promoting the expansion of CRE within the intestine. Here, we show...

Background Macrolides, including azithromycin, are increasingly used in preterm-born infants to treat Ureaplasma infections. The baseline carriage of macrolide resistance genes in the preterm stool microbiota is unknown. Objectives Identify carriage of azithromycin resistant bacteria and the incidence of macrolide resistant genes. Methods Azithro...

Fecal microbiota transplantation (FMT) represents a potential strategy to overcome resistance to immune checkpoint inhibitors in patients with refractory melanoma; however, the role of FMT in first-line treatment settings has not been evaluated. We conducted a multicenter phase I trial combining healthy donor FMT with the PD-1 inhibitors nivolumab...

Patients with cirrhosis have reduced gut-bacterial diversity and microbiota enriched with pathobionts. This enrichment, coupled with increased gut permeability and bacterial translocation, increases susceptibility to infection and death. Faecal microbiota transplant [FMT] previously restored gut diversity and improved hepatic encephalopathy (HE) in...

Introduction The microbiota shapes host immune responses at mucosal barrier surfaces and the oral microbiota have been associated with COVID-19 outcomes. We explored the hypothesis that the salivary microbiota are associated with attenuated humoral response to SARS-CoV-2 vaccination in immunocompromised individuals, including inflammatory bowel dis...

4129 Background: Liver resection (LR) is a potentially curative option for early-stage hepatocellular carcinoma (HCC), and immune checkpoint inhibitors (ICI) are being investigated in the perioperatory setting to improve long-term relapse rates and survival outcomes. Methods: PRIME‐HCC is a phase Ib study testing nivolumab (3 mg/kg, day 1 and day 2...

The intestinal microbiota has been proposed to influence human mental health and cognition through the gut-brain axis. Individuals experiencing recurrent Clostridioides difficile infection (rCDI) frequently report depressive symptoms, which are improved after fecal microbiota transplantation (FMT); however, mechanisms underlying this association ar...

Background Metabolite profiling of biofluids has an emergent role in exploring the contribution of host-microbiome interactions to the treatment response of immune-mediated arthritis.[1] Objectives As part of the FLORA trial (exploring the impact of gut microbiome manipulation upon response to methotrexate [MTX]),[2] we investigated plasma metabol...

Background: Rescue of mitochondrial function is a promising neuroprotective strategy for Parkinson's disease (PD). Ursodeoxycholic acid (UDCA) has shown considerable promise as a mitochondrial rescue agent across a range of preclinical in vitro and in vivo models of PD. Objectives: To investigate the safety and tolerability of high-dose UDCA in...

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with ursodeoxycholic acid (UDCA) as first-line treatment. Poor response to UDCA is associated with a higher risk of progressing to cirrhosis, but the underlying mechanisms are unclear. UDCA modulates the composition of primary and bacterial-derived bile acids (BAs). We charact...

An altered gut microbiota is a possible contributing pathogenic factor in myasthenia gravis (MG), an autoimmune neuromuscular disease. However, the significance of the fungal microbiome is an understudied and neglected part of the intestinal microbiome in MG. We performed a sub-analysis of the MYBIOM study including faecal samples from patients wit...

Background Menstrual cups (MCs) are increasingly used to collect cervicovaginal secretions to characterise vaginal mucosal immunology, in conjunction with high vaginal swabs (HVS) for metataxonomics, particularly in HIV transmission studies. We hypothesised that both methods of collecting bacterial biomass are equivalent for 16S rRNA gene sequencin...

Background and aims The gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of the tumoral microbiota on oncological outcomes. Methods A multicentre, prospective observational study was conducted of CRC patients undergoing primary surgical r...

Conventional tissue culture models often lack physiological relevance. In this exploratory study, dynamic flow conditions were applied to 21-day cultured Caco-2 intestinal epithelial cells and their response compared with statically cultured counterparts. Host:microbiome interactions were also explored through co-incubation with Gram positive bacte...

Background Diabetes has reached epidemic proportions in recent years with serious health ramifications. The aim of this study was to evaluate the strength and validity of associations between diabetes and anti-diabetic interventions and the risk of any type of gynaecological or obstetric conditions. Methods Design: Umbrella review of systematic re...

There is a growing awareness that supplementation with probiotic bacteria can impart beneficial effects during gastrointestinal disease, but less is known about the impact of probiotics on healthy subjects. Here, we report the outcomes of a post hoc analysis of recorded daily gastrointestinal events and bowel habits completed by healthy adults part...

Introduction: Fluoropyrimidines are drugs currently used as a first-line treatment for colorectal cancer (CRC)1. The impact of gut bacteria on 5-Fluorouracil (5FU) activity remains relatively unknown. The objective of this analysis was to delineate potential bacteria-drug interactions that modify 5FU. Methods: Tumor and tumor-adjacent healthy tissu...