Publications by authors named "Julian R Marchesi"

163 Publications

The association of weight loss with changes in the gut microbiota diversity, composition, and intestinal permeability: a systematic review and meta-analysis.

Gut Microbes 2022 Jan-Dec;14(1):2020068

Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.

The gut microbiome may be a mediator between obesity and health outcomes. However, it is unclear how intentional weight loss changes the gut microbiota and intestinal permeability. We aimed to systematically review and quantify this association. We searched Medline, Embase, CINAHL, Cochrane databases, and trial registries until June 2020 (PROSPERO: CRD42020205292). We included trials of weight loss interventions (energy-restricted diets, pharmacotherapy, bariatric surgery) reporting on the microbiome. Two reviewers independently completed screening, extraction, and risk assessment with the ROBINS-I tool. Pooled standardized mean differences (SMDs) were obtained from random-effects meta-analyses. Forty-seven trials with 1,916 participants (81% female) and a median follow-up of 6 months (range: 2-24) were included. Based on imprecise evidence but with fairly consistent direction of effect, weight loss was associated with a statistically significant increase in α-diversity [SMD: 0.4 (95% CI: 0.2, 0.6], < .0001, I = 70%, n = 30 studies) and a statistically significant reduction in intestinal permeability [SMD: -0.7 (95% CI: -0.9, -0.4), < .0001, I = 83%, n = 17 studies]. Each kg of weight loss was associated with a 0.012 (95% CI: 0.0003, 0.024, = .045) increase in α-diversity and a -0.017 (95% CI: -0.034, -0.001, = .038) reduction in intestinal permeability. There was clear evidence of increases in the relative abundance of , but no clear evidence of changes in individual phyla, species, or fecal short-chain fatty acids. Restricting the analyses to the studies with lower risk of bias did not materially alter the estimates. Increasing weight loss is positively associated with increases in gut microbiota α-diversity and reductions in intestinal permeability.
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http://dx.doi.org/10.1080/19490976.2021.2020068DOI Listing
January 2022

Vaginal Microbiota, Genital Inflammation and Extracellular Matrix Remodelling Collagenase: MMP-9 in Pregnant Women With HIV, a Potential Preterm Birth Mechanism Warranting Further Exploration.

Front Cell Infect Microbiol 2021 29;11:750103. Epub 2021 Nov 29.

Section of Virology, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom.

Background: Pregnant women living with HIV infection (PWLWH) have elevated rates of preterm birth (PTB) in which HIV and cART are implicated. PWLWH also have a high prevalence of adverse vaginal microbiota, which associate with genital tract inflammation. The mechanism underlying PTB in PWLWH is unknown. We present the first data in PWLWH on genital-tract matrix-metalloproteinase-9(MMP-9), an important collagenase implicated in labour onset, and tissue inhibitor of metalloproteinases-1(TIMP-1) and explore correlations with local inflammation and vaginal bacteria.

Material And Methods: Cervical vaginal fluid (CVF) collected by a soft cup and high vaginal swabs (HVS) were obtained from PWLWH and HIV uninfected pregnant women (HUPW) at three antenatal time points. Maternal characteristics, combination antiretroviral therapy (cART) exposure, and pregnancy outcome were recorded. Concentrations of MMP-9, TIMP-1 and ten cytokines were measured by immunoassays. Vaginal microbiota composition was determined through 16S rRNA amplicon sequencing. MMP-9, TIMP-1 and cytokine concentrations were compared by HIV status, cART, and prematurity and in PWLWH correlations with polymorphonuclear leucocytes, cytokines and bacterial genera were explored.

Results: CVF was available for 50 PWLWH (108 samples) and 12 HUPW (20 samples) between gestation weeks 14-38. Thirty-six PWLWH conceived on cART and 14 initiated post-conception. There were five and one PTB outcomes in PWLWH and HUPW respectively. PWLWH had higher mean CVF concentrations of MMP-9 (p<0.001) and TIMP-1 (p=0.035) in the second trimester compared with HUPW with a similar trend in the third trimester. PWLWH also had higher CVF values of cytokines: IL-1β, IL-8, IL-12 and TNF-α in both trimesters compared to HUPW (p ≤ 0.003). In PWLWH, MMP-9 positively correlated with TIMP-1 (r=0.31, p=0.002) and CVF polymorphonuclear leucocytes (r=0.57, p=0.02). Correlations were observed between MMP-9 and three cytokines: IL-1β (r=0.61), IL-8 (r=0.57) and TNF-α (r=0.64), p<0.001, similarly for TIMP-1. Abundance of anaerobic pathobionts correlated with MMP-9: (r=0.44, p<0.001), (r=0.33, p=0.005), and genera (r=0.39, p<0.001). Conversely proportion of genera negatively correlated with MMP-9 (rho=-0.46, p<0.001). MMP-9/TIMP-1 ratio increased with gestational age at sampling in PWLWH, but this was no longer significant after adjusting for confounders and no difference by prematurity was observed in this sub-study.

Conclusions: Here we show strong correlations of MMP-9 to genital tract inflammation and sub-optimal bacterial genera in PWLWH indicating the ascending genital tract infection pathway may be a contributory mechanism to the high risk of PTB.
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http://dx.doi.org/10.3389/fcimb.2021.750103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667959PMC
November 2021

The Impact of Lab4 Probiotic Supplementation in a 90-Day Study in Wistar Rats.

Front Nutr 2021 25;8:778289. Epub 2021 Nov 25.

Cultech Limited, Port Talbot, United Kingdom.

The anti-inflammatory and cholesterol lowering capabilities of probiotic bacteria highlight them as potential prophylactics against chronic inflammatory diseases, particularly cardiovascular disease. Previous studies , and suggest that the Lab4 probiotic consortium may harbour such capabilities and in the current study, we assessed plasma levels of cytokines/chemokines, short chain fatty acids and lipids and faecal levels of bile acids in a subpopulation of healthy Wistar rats included in 90-day repeat dose oral toxicity study. In the rats receiving Lab4, circulating levels of pro-inflammatory interleukin-6, tumour necrosis factor-α and keratinocyte chemoattractant/growth regulated oncogene were significantly lower compared to the control group demonstrating a systemic anti-inflammatory effect. These changes occurred alongside significant reductions in plasma low density lipoprotein cholesterol and increases in faecal bile acid excretion implying the ability to lower circulating cholesterol the deconjugation of intestinal bile acids. Correlative analysis identified significant associations between plasma tumour necrosis factor-α and the plasma total cholesterol:high density lipoprotein cholesterol ratio and faecal levels of bifidobacteria in the Lab4 rats. Together, these data highlight Lab4 supplementation as a holistic approach to CVD prevention and encourages further studies in humans.
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http://dx.doi.org/10.3389/fnut.2021.778289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8656110PMC
November 2021

Evidence for infection in intervertebral disc degeneration: a systematic review.

Eur Spine J 2021 Dec 4. Epub 2021 Dec 4.

Department of Twin Research and Genetic Epidemiology, King's College London, 3rd and 4th Floor, Block D, South Wing, St. Thomas' Hospital, Westminster Bridge Rd., London, SE1 7EH, UK.

Purpose: Back pain is a major problem worldwide and is linked to intervertebral disc degeneration and Modic change. Several studies report growth of bacteria following extraction of degenerate discs at spine surgery. A pathophysiological role for infection in back pain has been proposed.

Method: We conducted a PRISMA systematic review. MEDLINE, PubMed, Scopus and Web of Science were searched with the terms Modic change, intervertebral dis*, bacteria, microb*, and infect*. Date limits of 2001-2021 were set. Human studies investigating the role of bacteria in disc degeneration or Modic change in vertebrae were included.

Results: Thirty-six articles from 34 research investigations relating to bacteria in human degenerate discs were found. Cutibacterium acnes was identified in pathological disc material. A 'candidate bacterium' approach has been repeatedly adopted which may have biased results to find species a priori, with disc microbial evidence heavily weighted to find C. acnes.

Conclusion: Evidence to date implicates C. acnes identified through culture, microscopy and sequencing, with some suggestion of diverse bacterial colonisation in the disc. This review found studies which used culture methods and conventional PCR for bacterial detection. Further agnostic investigation using newer methods should be undertaken.
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http://dx.doi.org/10.1007/s00586-021-07062-1DOI Listing
December 2021

A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Infection.

Cells 2021 11 19;10(11). Epub 2021 Nov 19.

Shenzhen Digital Life Institute, Shenzhen 518016, China.

Fecal microbiota transplantation (FMT) is highly effective in recurrent infection (CDI); increasing evidence supports FMT in severe or fulminant infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies.
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http://dx.doi.org/10.3390/cells10113234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624539PMC
November 2021

How to adapt an intestinal microbiota transplantation programme to reduce the risk of invasive multidrug-resistant infection.

Clin Microbiol Infect 2021 Nov 23. Epub 2021 Nov 23.

Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.

Background: Vulnerable patients with intestinal colonization of multidrug-resistant organisms (MDROs) are recognized to be at increased risk of invasive MDRO-driven infection. Intestinal microbiota transplantation (IMT, also called faecal microbiota transplant) is the transfer of healthy screened donor stool to an affected recipient, and recent interest has focused on its impact on the reduction of invasive MDRO infection.

Objectives: To describe how to establish a clinical IMT pathway for patients at risk of MDRO invasive infection, with special considerations for optimizing administration and assessment of endpoints.

Sources: Expert guidelines and peer-reviewed clinical studies are encompassed and discussed.

Content: IMT is offered to patients with MDROs detected on rectal or stool screening and either at risk of MDRO invasive infection due to altered immune status or those with recurrent MDRO-mediated invasive disease and considered at risk of further disease. Donor screening should include pathogens with theoretical or demonstrated risk of transmission (including MDROs themselves and SARS-CoV-2) and take into consideration the relative immunosuppressed state of potential recipients. Delivery of IMT is timed for when the patient is free from active infection, but no additional antibiotics are indicated. If administered when future immunosuppression is to take place, IMT is aligned at least 2 weeks beforehand to ensure sufficient time for engraftment. Patients are followed up in terms of adverse effects from IMT and clinicians are advised to discuss with the IMT multidisciplinary team on choice of antibiotics if needed to take into consideration the impact upon the intestinal microbiome. Prevention of invasive disease is the primary measure of success, rather than using intestinal decolonization as a binary outcome. Repeat IMT is considered case by case.

Implications: Future research areas should include randomized studies that consider clinical outcomes and cost-effectiveness, and better understanding of mechanisms to identify markers of treatment success and functional microbiome components that could be used therapeutically.
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http://dx.doi.org/10.1016/j.cmi.2021.11.006DOI Listing
November 2021

Systematic review: the association between the gut microbiota and medical therapies in inflammatory bowel disease.

Aliment Pharmacol Ther 2022 Jan 9;55(1):26-48. Epub 2021 Nov 9.

Departments of Gastroenterology and Hepatology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.

Background: The gut microbiota has been implicated in the pathogenesis of inflammatory bowel disease (IBD), with Faecalibacterium prausnitizii associated with protection, and certain genera (including Shigella and Escherichia) associated with adverse features. The variability of patient response to medical therapies in IBD is incompletely understood. Given the recognised contribution of the microbiota to treatment efficacy in other conditions, there may be interplay between the gut microbiota, IBD medical therapy and IBD phenotype.

Aims: To evaluate the bidirectional relationship between IBD medical therapies and the gut microbiota.

Methods: We conducted a systematic search of MEDLINE and EMBASE. All original studies analysing interactions between the gut microbiota and established IBD medical therapies were included.

Results: We screened 1296 records; 19 studies were eligible. There was heterogeneity in terms of sample analysis, treatment protocols, and outcome reporting. Increased baseline α-diversity was observed in responders versus non-responders treated with exclusive enteral nutrition (EEN), infliximab, ustekinumab or vedolizumab. Higher baseline Faecalibacterium predicted response to infliximab and ustekinumab. A post-treatment increase in Faecalibacterium prausnitzii was noted in responders to aminosalicylates, anti-TNF medications and ustekinumab; conversely, this species decreased in responders to EEN. Escherichia was a consistent marker of unfavourable drug response, and its presence in the gut mucosa correlated with inflammation in aminosalicylate-treated patients.

Conclusions: Both gut microbiota diversity and specific taxonomic features (including high abundance of Faecalibacterium) are associated with the efficacy of a range of IBD therapies. These findings hold promise for a potential role for the gut microbiota in explaining the heterogeneity of patient response to IBD treatments.
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http://dx.doi.org/10.1111/apt.16656DOI Listing
January 2022

The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia.

Genome Med 2021 11 4;13(1):176. Epub 2021 Nov 4.

Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction - Surgery and Cancer, Imperial College London, London, W12 0NN, UK.

Background: Vaginal microbiota (VMB) composition is altered in women with cervical intra-epithelial neoplasia (CIN) compared to healthy controls and is associated with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This observational study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines.

Methods: We sampled 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also sampled. We used metataxonomics to group vaginal swab samples into community state types (CSTs) and ELISA to quantify cytokine and AMP levels in matched vaginal secretions. Analyses were performed to compare the bacterial composition and immune analyte levels before and after CIN excision and in healthy controls.

Results: Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV 21/103, 20% vs 1/39, 3%, p = 0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV 19/103, 20% vs 1/39, 3%, p = 0.0142). Prevotella bivia and Sneathia amnii were significantly higher in samples before treatment compared to untreated controls, and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1β and IL-8 remained significantly elevated pre- (p < 0.0001 and p = 0.0014, respectively) and post-treatment (p < 0.0001 and p = 0.0035, respectively) compared to untreated controls. Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision (p < 0.0001); however, their levels remained lower than controls post-treatment.

Conclusions: Women with CIN have an increased prevalence of Lactobacillus sp. depletion, high-diversity VMB composition, and higher levels of proinflammatory cytokines and AMPs compared to normal controls. Surgical excision of the disease reduces levels of vaginal AMPs but does not alter VMB composition or cytokine levels. These findings suggest that women with CIN have an inherent predisposition to a high-diversity proinflammatory environment that is not corrected by disease excision. The failure to re-establish a Lactobacillus-enriched CST may explain why women remain at high risk of pre-invasive and invasive disease recurrence.
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http://dx.doi.org/10.1186/s13073-021-00977-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567681PMC
November 2021

The potential of fecal microbiota transplantation in oncology.

Trends Microbiol 2022 Jan 26;30(1):10-12. Epub 2021 Oct 26.

Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK.

Immune checkpoint inhibitors (ICPIs) are efficacious treatments for several cancers. However, most patients fail to demonstrate durable complete responses. The gut microbiome composition influences the ICPI response. Two recent proof-of-concept studies have demonstrated the utility of fecal microbiota transplantation to transform ICPI responsiveness in refractory patients, providing intriguing evidence for the future of microbiota modulation within oncology.
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http://dx.doi.org/10.1016/j.tim.2021.10.003DOI Listing
January 2022

Fecal Microbiota Transplant Mitigates Adverse Outcomes Seen in Patients Colonized With Multidrug-Resistant Organisms Undergoing Allogeneic Hematopoietic Cell Transplantation.

Front Cell Infect Microbiol 2021 27;11:684659. Epub 2021 Aug 27.

Centre for Haematology, Imperial College London at Hammersmith Hospital, London, United Kingdom.

The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT). This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. We performed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy for MDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDRO group), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival was significantly higher in the FMT-MDRO group (70% 36% = 0.044). Post-HCT, fewer FMT-MDRO patients required intensive care (0% 46%, = 0.045) or experienced fever (0.29 0.11 days, = 0.027). Intestinal MDRO decolonization occurred in 25% of FMT-MDRO patients 11% non-FMT MDRO patients. Despite the significant differences and statistically comparable patient/transplant characteristics, as the sample size was small, a matched-pair analysis between both groups to non-MDRO colonized control cohorts (2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4% 61.9% respectively, =0.012), and higher non relapse mortality (NRM; 60.2% 16.7% respectively, =0.009) than their paired non-MDRO-colonized cohort. Conversely, there was no difference in survival (70% 43.4%, =0.14) or NRM (12.5% 31.2% respectively, =0.24) between the FMT-MDRO group and their paired non-MDRO cohort. Collectively, these data suggest that negative clinical outcomes, including mortality associated with MDRO colonization, may be ameliorated by pre-HCT FMT, even in the absence of intestinal MDRO decolonization. Further work is needed to explore this observed benefit.
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http://dx.doi.org/10.3389/fcimb.2021.684659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430254PMC
October 2021

Gut bacterial microbiota in patients with myasthenia gravis: results from the MYBIOM study.

Ther Adv Neurol Disord 2021 11;14:17562864211035657. Epub 2021 Aug 11.

Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Background: Myasthenia gravis (MG) is an autoimmune neuromuscular disease, with gut microbiota considered to be a pathogenetic factor. Previous pilot studies have found differences in the gut microbiota of patients with MG and healthy individuals. To determine whether gut microbiota has a pathogenetic role in MG, we compared the gut microbiota of patients with MG with that of patients with non-inflammatory and inflammatory neurological disorders of the peripheral nervous system (primary endpoint) and healthy volunteers (secondary endpoint).

Methods: Faecal samples were collected from patients with MG ( = 41), non-inflammatory neurological disorder (NIND,  = 18), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP,  = 6) and healthy volunteers ( = 12). DNA was isolated from these samples, and the variable regions of the gene were sequenced and statistically analysed.

Results: No differences were found in alpha- and beta-diversity indices computed between the MG, NIND and CIDP groups, indicating an unaltered bacterial diversity and structure of the microbial community. However, the alpha-diversity indices, namely Shannon, Chao 1 and abundance-based coverage estimators, were significantly reduced between the MG group and healthy volunteers. Deltaproteobacteria and were abundant within the faecal microbiota of patients with MG compared with controls with non-inflammatory diseases.

Conclusion: Although the overall diversity and structure of the gut microbiota did not differ between the MG, NIND and CIDP groups, the significant difference in the abundance of Deltaproteobacteria and supports the possible role of gut microbiota as a contributor to pathogenesis of MG. Further studies are needed to confirm these findings and to develop possible treatment strategies.
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http://dx.doi.org/10.1177/17562864211035657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361534PMC
August 2021

Multiomics Profiling Reveals Signatures of Dysmetabolism in Urban Populations in Central India.

Microorganisms 2021 Jul 12;9(7). Epub 2021 Jul 12.

Biochemistry Research Laboratory, Dr. G.M. Taori Central India Institute of Medical Sciences, Nagpur 440010, India.

Background: Non-communicable diseases (NCDs) have become a major cause of morbidity and mortality in India. Perturbation of host-microbiome interactions may be a key mechanism by which lifestyle-related risk factors such as tobacco use, alcohol consumption, and physical inactivity may influence metabolic health. There is an urgent need to identify relevant dysmetabolic traits for predicting risk of metabolic disorders, such as diabetes, among susceptible Asian Indians where NCDs are a growing epidemic.

Methods: Here, we report the first in-depth phenotypic study in which we prospectively enrolled 218 adults from urban and rural areas of Central India and used multiomic profiling to identify relationships between microbial taxa and circulating biomarkers of cardiometabolic risk. Assays included fecal microbiota analysis by 16S ribosomal RNA gene amplicon sequencing, quantification of serum short chain fatty acids by gas chromatography-mass spectrometry, and multiplex assaying of serum diabetic proteins, cytokines, chemokines, and multi-isotype antibodies. Sera was also analysed for -glycans and immunoglobulin G Fc -glycopeptides.

Results: Multiple hallmarks of dysmetabolism were identified in urbanites and young overweight adults, the majority of whom did not have a known diagnosis of diabetes. Association analyses revealed several host-microbe and metabolic associations.

Conclusions: Host-microbe and metabolic interactions are differentially shaped by body weight and geographic status in Central Indians. Further exploration of these links may help create a molecular-level map for estimating risk of developing metabolic disorders and designing early interventions.
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http://dx.doi.org/10.3390/microorganisms9071485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307859PMC
July 2021

Roux-en-Y gastric bypass-induced bacterial perturbation contributes to altered host-bacterial co-metabolic phenotype.

Microbiome 2021 06 14;9(1):139. Epub 2021 Jun 14.

Division of Digestive Disease, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, SW7 2AZ, UK.

Background: Bariatric surgery, used to achieve effective weight loss in individuals with severe obesity, modifies the gut microbiota and systemic metabolism in both humans and animal models. The aim of the current study was to understand better the metabolic functions of the altered gut microbiome by conducting deep phenotyping of bariatric surgery patients and bacterial culturing to investigate causality of the metabolic observations.

Methods: Three bariatric cohorts (n = 84, n = 14 and n = 9) with patients who had undergone Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG) or laparoscopic gastric banding (LGB), respectively, were enrolled. Metabolic and 16S rRNA bacterial profiles were compared between pre- and post-surgery. Faeces from RYGB patients and bacterial isolates were cultured to experimentally associate the observed metabolic changes in biofluids with the altered gut microbiome.

Results: Compared to SG and LGB, RYGB induced the greatest weight loss and most profound metabolic and bacterial changes. RYGB patients showed increased aromatic amino acids-based host-bacterial co-metabolism, resulting in increased urinary excretion of 4-hydroxyphenylacetate, phenylacetylglutamine, 4-cresyl sulphate and indoxyl sulphate, and increased faecal excretion of tyramine and phenylacetate. Bacterial degradation of choline was increased as evidenced by altered urinary trimethylamine-N-oxide and dimethylamine excretion and faecal concentrations of dimethylamine. RYGB patients' bacteria had a greater capacity to produce tyramine from tyrosine, phenylalanine to phenylacetate and tryptophan to indole and tryptamine, compared to the microbiota from non-surgery, normal weight individuals. 3-Hydroxydicarboxylic acid metabolism and urinary excretion of primary bile acids, serum BCAAs and dimethyl sulfone were also perturbed following bariatric surgery.

Conclusion: Altered bacterial composition and metabolism contribute to metabolic observations in biofluids of patients following RYGB surgery. The impact of these changes on the functional clinical outcomes requires further investigation. Video abstract.
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http://dx.doi.org/10.1186/s40168-021-01086-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201742PMC
June 2021

The association between obesity and weight loss after bariatric surgery on the vaginal microbiota.

Microbiome 2021 05 28;9(1):124. Epub 2021 May 28.

IRDB, Department of Metabolism, Digestion and Reproduction - Surgery and Cancer, Hammersmith Campus, Imperial College London, W12 0NN, London, UK.

Background: Obesity and vaginal microbiome (VMB) dysbiosis are each risk factors for adverse reproductive and oncological health outcomes in women. Here, we investigated the relationship between obesity, vaginal bacterial composition, local inflammation and bariatric surgery.

Methods: Vaginal bacterial composition assessed by high-throughput sequencing of bacterial 16S rRNA genes and local cytokine levels measured using a multiplexed Magnetic Luminex Screening Assay were compared between 67 obese and 42 non-obese women. We further assessed temporal changes in the microbiota and cytokines in a subset of 27 women who underwent bariatric surgery.

Results: The bacterial component of the vaginal microbiota in obese women was characterised by a lower prevalence of a Lactobacillus-dominant VMB and higher prevalence of a high diversity (Lactobacillus spp., and Gardnerella- spp. depleted) VMB, compared with non-obese subjects (p<0.001). Obese women had higher relative abundance of Dialister species (p<0.001), Anaerococcus vaginalis (p=0.021), and Prevotella timonensis (p=0.020) and decreased relative abundance of Lactobacillus crispatus (p=0.014). Local vaginal IL-1β, IL-4, IL-6, IL-8, IFNγ, MIP-1α and TNFα levels were all higher among obese women, however, only IL-1β and IL-8 correlated with VMB species diversity. In a subset of obese women undergoing bariatric surgery, there were no significant overall differences in VMB following surgery; however, 75% of these women remained obese at 6 months. Prior to surgery, there was no relationship between body mass index (BMI) and VMB structure; however, post-surgery women with a Lactobacillus-dominant VMB had a significantly lower BMI than those with a high diversity VMB.

Conclusions: Obese women have a significantly different vaginal microbiota composition with increased levels of local inflammation compared to non-obese women. Bariatric surgery does not change the VMB; however, those with the greatest weight loss 6-month post-surgery are most likely to have a Lactobacillus-dominant VMB. Video abstract.
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http://dx.doi.org/10.1186/s40168-021-01011-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164250PMC
May 2021

An inter-laboratory study to investigate the impact of the bioinformatics component on microbiome analysis using mock communities.

Sci Rep 2021 05 19;11(1):10590. Epub 2021 May 19.

Molecular Biology, National Measurement Laboratory, LGC, Queens Road, Teddington, TW11 0LY, Middlesex, UK.

Despite the advent of whole genome metagenomics, targeted approaches (such as 16S rRNA gene amplicon sequencing) continue to be valuable for determining the microbial composition of samples. Amplicon microbiome sequencing can be performed on clinical samples from a normally sterile site to determine the aetiology of an infection (usually single pathogen identification) or samples from more complex niches such as human mucosa or environmental samples where multiple microorganisms need to be identified. The methodologies are frequently applied to determine both presence of micro-organisms and their quantity or relative abundance. There are a number of technical steps required to perform microbial community profiling, many of which may have appreciable precision and bias that impacts final results. In order for these methods to be applied with the greatest accuracy, comparative studies across different laboratories are warranted. In this study we explored the impact of the bioinformatic approaches taken in different laboratories on microbiome assessment using 16S rRNA gene amplicon sequencing results. Data were generated from two mock microbial community samples which were amplified using primer sets spanning five different variable regions of 16S rRNA genes. The PCR-sequencing analysis included three technical repeats of the process to determine the repeatability of their methods. Thirteen laboratories participated in the study, and each analysed the same FASTQ files using their choice of pipeline. This study captured the methods used and the resulting sequence annotation and relative abundance output from bioinformatic analyses. Results were compared to digital PCR assessment of the absolute abundance of each target representing each organism in the mock microbial community samples and also to analyses of shotgun metagenome sequence data. This ring trial demonstrates that the choice of bioinformatic analysis pipeline alone can result in different estimations of the composition of the microbiome when using 16S rRNA gene amplicon sequencing data. The study observed differences in terms of both presence and abundance of organisms and provides a resource for ensuring reproducible pipeline development and application. The observed differences were especially prevalent when using custom databases and applying high stringency operational taxonomic unit (OTU) cut-off limits. In order to apply sequencing approaches with greater accuracy, the impact of different analytical steps needs to be clearly delineated and solutions devised to harmonise microbiome analysis results.
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http://dx.doi.org/10.1038/s41598-021-89881-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134577PMC
May 2021

Probiotics reduce self-reported symptoms of upper respiratory tract infection in overweight and obese adults: should we be considering probiotics during viral pandemics?

Gut Microbes 2021 Jan-Dec;13(1):1-9

Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.

Gut microbiome manipulation to alter the gut-lung axis may potentially protect humans against respiratory infections, and clinical trials of probiotics show promise in this regard in healthy adults and children. However, comparable studies are lacking in overweight/obese people, who have increased risks in particular of viral upper respiratory tract infections (URTI). This further analyses our recent placebo-controlled trial of probiotics in overweight/obese people (focused initially on weight loss) to investigate the impact of probiotics upon the occurrence of URTI symptoms. As well as undergoing loss of weight and improvement in certain metabolic parameters, study participants taking probiotics experienced a 27% reduction in URTI symptoms control, with those ≥45 years or BMI ≥30 kg/m experiencing greater reductions. This symptom reduction is apparent within 2 weeks of probiotic use. Gut microbiome diversity remained stable throughout the study in probiotic-treated participants. Our data provide support for further trials to assess the potential role of probiotics in preventing viral URTI (and possibly also COVID-19), particularly in overweight/obese people.
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http://dx.doi.org/10.1080/19490976.2021.1900997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007143PMC
April 2021

-Depleted Vaginal Microbiota in Pregnant Women Living With HIV-1 Infection Are Associated With Increased Local Inflammation and Preterm Birth.

Front Cell Infect Microbiol 2020 11;10:596917. Epub 2021 Feb 11.

Department of Metabolism, Digestion, and Reproduction, March of Dimes Prematurity Research Centre, Division of the Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, London, United Kingdom.

Background: Pregnant women living with HIV-1 infection (PWLWH) have an elevated risk of preterm birth (PTB) of unknown aetiology, which remains after successful suppression of HIV. Women at high risk for HIV have a common bacterial profile which has been associated with poor birth outcomes. We set out to explore factors associated with gestational age at delivery of PWLWH in a UK population.

Methods: Prospective study of PWLWH (n = 53) in whom the vaginal microbiota and cervicovaginal cytokine were assessed using metataxonomics and multiplexed immunoassays, respectively. Cross-sectional characterisation of vaginal microbiota in PWLWH were compared with 22 HIV uninfected pregnant women (HUPW) at a similar second trimester timepoint. Within PWLWH the relationships between bacterial composition, inflammatory response, and gestational age at delivery were explored.

Findings: There was a high rate of PTB among PWLWH (12%). In the second trimester the vaginal microbiota was more diverse in PWLWH than in HUPW (Inverse Simpson Index, p = 0.0004 and Species Observed, p = 0.009). PWLWH had a lower prevalence of dominant vaginal microbiota group (VMB I, 15 vs 54%) than HUPW and higher prevalence of dominant (VMB III, 36 vs 9% and VMB IIIB, 15 vs 5%) and mixed anaerobes (VMB IV, 21 vs 0%). Across the second and third trimesters in PWLWH, VMB III/IIIB and IV were associated with PTB and with increased local inflammation [cervicovaginal fluid (CVF) cytokine concentrations in upper quartile]. High bacterial diversity and anaerobic bacterial abundance were also associated with CVF pro-inflammatory cytokines, most notably IL-1β.

Interpretation: There is an association between local inflammation, vaginal dysbiosis and PTB in PWLWH. Understanding the potential of antiretroviral therapies to influence this cascade will be important to improve birth outcomes in this population.
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http://dx.doi.org/10.3389/fcimb.2020.596917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905210PMC
June 2021

Modulating gut microbiota in a mouse model of Graves' orbitopathy and its impact on induced disease.

Microbiome 2021 02 16;9(1):45. Epub 2021 Feb 16.

Molecular Ophthalmology, Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany.

Background: Graves' disease (GD) is an autoimmune condition in which autoantibodies to the thyrotropin receptor (TSHR) cause hyperthyroidism. About 50% of GD patients also have Graves' orbitopathy (GO), an intractable disease in which expansion of the orbital contents causes diplopia, proptosis and even blindness. Murine models of GD/GO, developed in different centres, demonstrated significant variation in gut microbiota composition which correlated with TSHR-induced disease heterogeneity. To investigate whether correlation indicates causation, we modified the gut microbiota to determine whether it has a role in thyroid autoimmunity. Female BALB/c mice were treated with either vancomycin, probiotic bacteria, human fecal material transfer (hFMT) from patients with severe GO or ddH2O from birth to immunization with TSHR-A subunit or beta-galactosidase (βgal; age ~ 6 weeks). Incidence and severity of GD (TSHR autoantibodies, thyroid histology, thyroxine level) and GO (orbital fat and muscle histology), lymphocyte phenotype, cytokine profile and gut microbiota were analysed at sacrifice (~ 22 weeks).

Results: In ddH2O-TSHR mice, 84% had pathological autoantibodies, 67% elevated thyroxine, 77% hyperplastic thyroids and 70% orbital pathology. Firmicutes were increased, and Bacteroidetes reduced relative to ddH2O-βgal; CCL5 was increased. The random forest algorithm at the genus level predicted vancomycin treatment with 100% accuracy but 74% and 70% for hFMT and probiotic, respectively. Vancomycin significantly reduced gut microbiota richness and diversity compared with all other groups; the incidence and severity of both GD and GO also decreased; reduced orbital pathology correlated positively with Akkermansia spp. whilst IL-4 levels increased. Mice receiving hFMT initially inherited their GO donors' microbiota, and the severity of induced GD increased, as did the orbital brown adipose tissue volume in TSHR mice. Furthermore, genus Bacteroides, which is reduced in GD patients, was significantly increased by vancomycin but reduced in hFMT-treated mice. Probiotic treatment significantly increased CD25 Treg cells in orbital draining lymph nodes but exacerbated induced autoimmune hyperthyroidism and GO.

Conclusions: These results strongly support a role for the gut microbiota in TSHR-induced disease. Whilst changes to the gut microbiota have a profound effect on quantifiable GD endocrine and immune factors, the impact on GO cellular changes is more nuanced. The findings have translational potential for novel, improved treatments. Video abstract.
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http://dx.doi.org/10.1186/s40168-020-00952-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888139PMC
February 2021

Roux-en-Y gastric bypass surgery in Zucker rats induces bacterial and systemic metabolic changes independent of caloric restriction-induced weight loss.

Gut Microbes 2021 Jan-Dec;13(1):1-20

Department of Metabolism Digestion and Reproduction, Faculty of Medicine, Imperial College London London, UK.

Mechanisms of Roux-en-Y gastric bypass (RYGB) surgery are not fully understood. This study aimed to investigate weight loss-independent bacterial and metabolic changes, as well as the absorption of bacterial metabolites and bile acids through the hepatic portal system following RYGB surgery. Three groups of obese Zucker () rats were included: RYGB (n = 11), sham surgery and body weight matched with RYGB (Sham-BWM, n = 5), and sham surgery fed (Sham-obese, n = 5). Urine and feces were collected at multiple time points, with portal vein and peripheral blood obtained at the end of the study. Metabolic phenotyping approaches and 16S rRNA gene sequencing were used to determine the biochemical and bacterial composition of the samples, respectively. RYGB surgery-induced distinct metabolic and bacterial disturbances, which were independent of weight loss through caloric restriction. RYGB resulted in lower absorption of phenylalanine and choline, and higher urinary concentrations of host-bacterial co-metabolites (e.g., phenylacetylglycine, indoxyl sulfate), together with higher fecal trimethylamine, suggesting enhanced bacterial aromatic amino acid and choline metabolism. Short chain fatty acids (SCFAs) were lower in feces and portal vein blood from RYGB group compared to Sham-BWM, accompanied with lower abundances of , and known to contain SCFA producers, indicating reduced bacterial fiber fermentation. Fecal γ-amino butyric acid (GABA) was found in higher concentrations in RYGB than that in Sham groups and could play a role in the metabolic benefits associated with RYGB surgery. While no significant difference in urinary BA excretion, RYGB lowered both portal vein and circulating BA compared to Sham groups. These findings provide a valuable resource for how dynamic, multi-systems changes impact on overall metabolic health, and may provide potential therapeutic targets for developing downstream non-surgical treatment for metabolic disease.
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http://dx.doi.org/10.1080/19490976.2021.1875108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872092PMC
January 2022

Faecal microbiota transplantation for recurrent infection: An updated systematic review and meta-analysis.

EClinicalMedicine 2020 Dec 23;29-30:100642. Epub 2020 Nov 23.

Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 35, DK-8200 Aarhus N, Denmark.

Background: Faecal microbiota transplantation (FMT) is effective for recurrent infection (CDI), but inconsistent effect rates and uncertain evidence levels have warranted caution. To clarify, we aimed to establish the evidence of FMT for recurrent CDI, updated across different delivery methods, treatment regimens, and in comparison with standard antibiotics.

Methods: In this updated systematic review and meta-analysis, we searched PubMed, Scopus, Embase, Web of Science, Clinical Key, and Svemed+ for FMT literature published in English until November 11, 2019. We included observational and clinical trials with or without antibiotic comparators and excluded studies with below 8 weeks follow-up and fewer than 15 patients. The primary outcome was clinical outcome by week 8. We comprehensively extracted patient and procedural data. In a random-effects meta-analysis, we estimated the clinical effect for repeat or single FMT, different delivery methods, and versus antibiotics. We rated the evidence according to the Cochrane and GRADE methods. The PROSPERO preregistration number is CRD42020158112.

Findings: Of 1816 studies assessed, 45 studies were included. The overall clinical effect week 8 following repeat FMT (24 studies, 1855 patients) was 91% (95% CI: 89-94%, =53%) and 84% (80-88%, =86%) following single FMT (43 studies, 2937 patients). Delivery by lower gastrointestinal endoscopy was superior to all other delivery methods, and repeat FMT significantly increased the treatment effect week 8 (<0·001). Compared with vancomycin, the number needed to treat (NNT) for repeat FMT was 1·5 (1·3-1·9, <0·001) and 2.9 (1·5-37·1, =0·03) for single FMT. Repeat FMT had high quality of evidence.

Interpretation: High-quality evidence supports FMT is effective for recurrent CDI, but its effect varies with the delivery method and the number of administrations. The superior NNT for FMT compared with antibiotics suggests that patients may benefit from advancing FMT to all instances of recurrent CDI.

Funding: Innovation Fund Denmark (j.no. 8056-00006B).
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http://dx.doi.org/10.1016/j.eclinm.2020.100642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788438PMC
December 2020

Impact of fecal microbiota transplantation with capsules on the prevention of metabolic syndrome among patients with obesity.

Hormones (Athens) 2021 Mar 9;20(1):209-211. Epub 2021 Jan 9.

Department of Biomedical Sciences, Cornell University, Ithaca, NY, 14853, USA.

Background: Fecal microbiota transplantation (FMT) has been studied for the treatment of metabolic syndrome with varying success. However, the possibility of utilizing FMT to prevent metabolic syndrome is to date unknown.

Methods: Secondary analysis of a previously published double-blind, randomized, placebo-controlled pilot trial of FMT in obese metabolically healthy patients was conducted. Post-prandial glucose and insulin levels were measured (NCT02741518).

Results: A total of 22 patients were enrolled, 11 in each arm. There were no baseline differences in the area under the curve (AUC) of glucose or insulin in the FMT group compared to placebo. There was a significant change in glucose AUC at week 12 compared to baseline, and in the insulin AUC at week 6 compared to baseline in the FMT group vs. placebo (change in glucose AUC (mg/dl × 60 min): 579 vs 1978, p = 0.03) (change in insulin AUC (μU/ml × 60 min): 137 vs 2728, p = 0.01).

Conclusions: These data suggest that FMT may have a potential role in preventing the development of metabolic syndrome in patients with obesity.
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http://dx.doi.org/10.1007/s42000-020-00265-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432937PMC
March 2021

Changes in IgA-targeted microbiota following fecal transplantation for recurrent infection.

Gut Microbes 2021 Jan-Dec;13(1):1-12

Michael Smith Laboratories and the Department of Microbiology and Immunology, University of British Columbia , Vancouver, British Columbia, Canada.

Secretory immunoglobulin A (IgA) interacts with intestinal microbiota and promotes mucosal homeostasis. IgA-bacteria interactions are altered during inflammatory diseases, but how these interactions are shaped by bacterial, host, and environmental factors remains unclear. In this study, we utilized IgA-SEQ to profile IgA-bound fecal bacteria in 48 recurrent patients before and after successful fecal microbiota transplantation (FMT) to gain further insight. Prior to FMT, was the most highly IgA-targeted taxon; following restoration of the microbiota by FMT, highly IgA-targeted taxa included multiple species. Post-FMT IgA-targeting was unaffected by the route of FMT delivery (colonoscopy versus capsule), suggesting that both methods lead to the establishment of healthy immune-bacterial interactions in the gut. Interestingly, IgA-targeting in FMT recipients closely resembled the IgA-targeting patterns of the donors, and fecal donor identity was significantly associated with IgA-targeting of the recipient microbiota. These data support the concept that intrinsic bacterial properties drive IgA recognition across genetically distinct human hosts. Together, this study suggests that IgA-bacterial interactions are reestablished in human FMT recipients to resemble that of the healthy fecal donor.
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http://dx.doi.org/10.1080/19490976.2020.1862027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781654PMC
January 2022

Application of ecological and evolutionary theory to microbiome community dynamics across systems.

Proc Biol Sci 2020 12 23;287(1941):20202886. Epub 2020 Dec 23.

Department of Integrative Biology, University of California, Berkeley, CA 94720, USA.

A fundamental aim of microbiome research is to understand the factors that influence the assembly and stability of host-associated microbiomes, and their impact on host phenotype, ecology and evolution. However, ecological and evolutionary theories applied to predict microbiome community dynamics are largely based on macroorganisms and lack microbiome-centric hypotheses that account for unique features of the microbiome. This special feature sets out to drive advancements in the application of eco-evolutionary theory to microbiome community dynamics through the development of microbiome-specific theoretical and conceptual frameworks across plant, human and non-human animal systems. The feature comprises 11 research and review articles that address: (i) the effects of the microbiome on host phenotype, ecology and evolution; (ii) the application and development of ecological and evolutionary theories to investigate microbiome assembly, diversity and stability across broad taxonomic scales; and (iii) general principles that underlie microbiome diversity and dynamics. This cross-disciplinary synthesis of theoretical, conceptual, methodological and analytical approaches to characterizing host-microbiome ecology and evolution across systems addresses key research gaps in the field of microbiome research and highlights future research priorities.
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http://dx.doi.org/10.1098/rspb.2020.2886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779500PMC
December 2020

Longitudinal profiling of the gut microbiome in patients with psoriatic arthritis and ankylosing spondylitis: a multicentre, prospective, observational study.

BMC Rheumatol 2020 Nov 10;4(1):60. Epub 2020 Nov 10.

NIHR/Wellcome Trust Imperial CRF, Imperial Centre for Translational and Experimental Medicine, Imperial College Healthcare NHS Trust, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK.

Background: Psoriasis is a chronic inflammatory disease of the skin affecting 2-3% of UK population. 30% of people affected by psoriasis will develop a distinct form of arthritis within 10 years of the skin condition onset. Although the pathogenesis of psoriatic arthritis is still unknown, there is a genetic predisposition triggered by environmental factors. Limited but convincing evidence link the gut microbiome to psoriatic arthritis. The Microbiome in Psoriatic ARThritis (Mi-PART) study propose is to characterise the microbiome-metabolic interface in patients affected by psoriatic arthritis to deepen our understanding of the pathogenesis of the disease.

Methods: This is a multicentre, prospective, observational study. Psoriatic arthritis (n = 65) and ankylosing spondylitis (n = 30) patients will be recruited in addition to a control group of healthy volunteers (n = 30). Patients eligibility will be evaluated against the Criteria for Psoriatic Arthritis (CASPAR), the Bath Ankylosing Spondylitis Activity Index (BASDAI) and the healthy volunteers who fulfil study inclusion and exclusion criteria. Information regarding their medical and medication history, demographics, diet and lifestyle will be collected. All the participants in the study will be asked to complete a 7-day food diary, to provide stool samples and to complete quality of life questionnaires. Routine clinical laboratory tests will be performed on blood and urine samples. Patients and healthy volunteers with gastrointestinal symptoms, previous history of cancer, gastrointestinal surgery in the previous 6 months or alcohol abuse will be excluded from the study.

Discussion: The aim of this trial is to characterise the microbiome of psoriatic arthritis patients and to compare it with microbiome of healthy volunteers and of patient with ankylosing spondylitis in order to define if different rheumatologic conditions are associated with characteristic microbiome profiles. Investigating the role of the microbiome in the development of psoriatic arthritis could deepen our understanding of the pathogenesis of the disease and potentially open the way to new therapies.
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http://dx.doi.org/10.1186/s41927-020-00155-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653819PMC
November 2020

The gut microbiome: an under-recognised contributor to the COVID-19 pandemic?

Therap Adv Gastroenterol 2020 24;13:1756284820974914. Epub 2020 Nov 24.

Departments of Gastroenterology and Hepatology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.

The novel coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus has spread rapidly across the globe, culminating in major global morbidity and mortality. As such, there has been a rapid escalation in scientific and clinical activity aimed at increasing our comprehension of this virus. This volume of work has led to early insights into risk factors associated with severity of disease, and mechanisms that underpin the virulence and dynamics involved in viral transmission. These insights ultimately may help guide potential therapeutics to reduce the human, economic and social impact of this pandemic. Importantly, the gastrointestinal (GI) tract has emerged as an important organ influencing propensity to, and potentially severity of, COVID-19 infection. Furthermore, the gut microbiome has been linked to a variety of risk factors for COVID-19 infection, and manipulation of the gut microbiome is an attractive potential therapeutic target for a number of diseases. While data profiling the gut microbiome in COVID-19 infection to date are limited, they support the possibility of several routes of interaction between COVID-19, the gut microbiome, angiotensin converting enzyme 2 (ACE-2) expression in the small bowel and colon and gut inflammation. This article will explore the evidence that implicates the gut microbiome as a contributing factor to the pathogenesis, severity and disease course of COVID-19, and speculate about the gut microbiome's capability as a therapeutic avenue against COVID-19.

Lay Summary: It has been noted that certain baseline gut profiles of COVID-19 patients are associated with a more severe disease course, and the gut microbiome impacts the disease course of several contributory risk factors to the severity of COVID-19. A protein called ACE-2, which is found in the small intestine among other sites, is a key receptor for COVID-19 virus entry; there is evidence that the gut microbiome influences ACE-2 receptor expression, and hence may play a role in influencing COVID-19 infectivity and disease severity. Furthermore, the gut microbiome plays a significant role in immune regulation, and hence may be pivotal in influencing the immune response to COVID-19. In terms of understanding COVID-19 treatments, the gut microbiome is known to interact with several drug classes being used to target COVID-19 and should be factored into our understanding of how patients respond to treatment. Importantly, our understanding of the role of the gut microbiome in COVID-19 infection remains in its infancy, but future research may potentially aid our mechanistic understanding of viral infection, and new ways in which we might approach treating it.
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http://dx.doi.org/10.1177/1756284820974914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692338PMC
November 2020

Inflammatory Bowel Disease Outcomes Following Fecal Microbiota Transplantation for Recurrent C. difficile Infection.

Inflamm Bowel Dis 2021 08;27(9):1371-1378

Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA.

Background: Recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is a clinical challenge. Fecal microbiota transplantation (FMT) has emerged as a recurrent CDI therapy. Anecdotal concerns exist regarding worsening of IBD activity; however, prospective data among IBD patients are limited.

Methods: Secondary analysis from an open-label, prospective, multicenter cohort study among IBD patients with 2 or more CDI episodes was performed. Participants underwent a single FMT by colonoscopy (250 mL, healthy universal donor). Secondary IBD-related outcomes included rate of de novo IBD flares, worsening IBD, and IBD improvement-all based on Mayo or Harvey-Bradshaw index (HBI) scores. Stool samples were collected for microbiome and targeted metabolomic profiling.

Results: Fifty patients enrolled in the study, among which 15 had Crohn's disease (mean HBI, 5.8 ± 3.4) and 35 had ulcerative colitis (mean partial Mayo score, 4.2 ± 2.1). Overall, 49 patients received treatment. Among the Crohn's disease cohort, 73.3% (11 of 15) had IBD improvement, and 4 (26.6%) had no disease activity change. Among the ulcerative colitis cohort, 62% (22 of 34) had IBD improvement, 29.4% (11 of 34) had no change, and 4% (1 of 34) experienced a de novo flare. Alpha diversity significantly increased post-FMT, and ulcerative colitis patients became more similar to the donor than Crohn's disease patients (P = 0.04).

Conclusion: This prospective trial assessing FMT in IBD-CDI patients suggests IBD outcomes are better than reported in retrospective studies.
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http://dx.doi.org/10.1093/ibd/izaa283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376126PMC
August 2021

Intestinal permeability and bacterial translocation in patients with liver disease, focusing on alcoholic aetiology: methods of assessment and therapeutic intervention.

Therap Adv Gastroenterol 2020 16;13:1756284820942616. Epub 2020 Oct 16.

Department of Metabolism, Digestion and Reproduction, St Mary's Hospital Campus, Imperial College London, W2 1NY, UK.

Increased bacterial translocation (BT) across the gut barrier due to greater intestinal permeability (IP) is seen across a range of conditions, including alcohol-related liver disease (ArLD). The phenomenon of BT may contribute to both the pathogenesis and the development of complications in ArLD. There are a number of methods available to assess IP and in this review we look at their various advantages and limitations. The knowledge around BT and IP in ArLD is also reviewed, as well as the therapeutic strategies currently in use and in development.
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http://dx.doi.org/10.1177/1756284820942616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580143PMC
October 2020

Letter: intestinal microbiota transfer-updating the nomenclature to increase acceptability.

Aliment Pharmacol Ther 2020 11;52(10):1622-1623

Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK.

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http://dx.doi.org/10.1111/apt.16109DOI Listing
November 2020
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