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Michael DR, Davies TS, Jack AA, et al., 2021, Daily supplementation with the Lab4P probiotic consortium induces significant weight loss in overweight adults, Scientific Reports, Vol: 11, ISSN: 2045-2322
This 9-month randomised, parallel, double-blind, single-centre, placebo-controlled study (PROBE, ISRCTN18030882) assessed the impact of probiotic supplementation on bodyweight. Seventy overweight Bulgarian participants aged 45-65 years with BMI 25-29.9 kg/m2 received a daily dose of the Lab4P probiotic comprising lactobacilli and bifidobacteria (50 billion cfu/day). Participants maintained their normal diet and lifestyle over the duration of the study. The primary outcome was change from baseline in body weight and secondary outcomes included changes in waist circumference, hip circumference and blood pressure. A significant between group decrease in body weight (3.16 kg, 95% CI 3.94, 2.38, p < 0.0001) was detected favouring the probiotic group. Supplementation also resulted in significant between group decreases in waist circumference (2.58 cm, 95% CI 3.23, 1.94, p < 0.0001) and hip circumference (2.66 cm, 95% CI 3.28, 2.05, p < 0.0001) but no changes in blood pressure were observed. These findings support the outcomes of a previous shorter-term Lab4P intervention study in overweight and obese participants (PROMAGEN, ISRCTN12562026). We conclude that Lab4P has consistent weight modulation capability in free-living overweight adults.
Huus KE, Frankowski M, Pučić-Baković M, et al., 2021, Changes in IgA-targeted microbiota following fecal transplantation for recurrent Clostridioides difficile infection, Gut Microbes, Vol: 13, Pages: 1-12, ISSN: 1949-0976
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 Clostridioides difficile patients before and after successful fecal microbiota transplantation (FMT) to gain further insight. Prior to FMT, Escherichia coli was the most highly IgA-targeted taxon; following restoration of the microbiota by FMT, highly IgA-targeted taxa included multiple Firmicutes 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.
Garaiova I, Paduchova Z, Nagyova Z, et al., 2021, Probiotics with vitamin C for the prevention of upper respiratory tract symptoms in children aged 3-10 years: randomised controlled trial, BENEFICIAL MICROBES, Vol: 12, Pages: 431-440, ISSN: 1876-2883
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McDonald JE, Marchesi JR, Koskella B, 2020, Application of ecological and evolutionary theory to microbiome community dynamics across systems, PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 287, ISSN: 0962-8452
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- Citations: 11
Innes AJ, Ghani R, Mullish BH, et al., 2020, O105. Faecal microbiota transplant (FMT) can reduce the high NRM associated with multi-drug resistant organism (MDRO) colonisation prior to allogeneic HCT., The 46th Annual Meeting of the European Society for Blood and Marrow Transplantation, Publisher: Springer Nature [academic journals on nature.com], Pages: 122-122, ISSN: 0268-3369
Mullish BH, Michael DR, McDonald JAK, et al., 2020, Identifying the factors influencing outcome in probiotic studies in overweight and obese patients – host or microbiome?, Gut, Vol: 70, Pages: 225-226, ISSN: 0017-5749
Lang S, Brandau S, Marchesi JR, et al., 2020, The microbiome in head and neck tumors-initial findings and outlook, HNO, Vol: 68, Pages: 905-910, ISSN: 0017-6192
Baunwall SMD, Lee MM, Eriksen MK, et al., 2020, Faecal microbiota transplantation for recurrent Clostridioides difficile infection: an updated systematic review and meta-analysis, EClinicalMedicine, Vol: 29-30, Pages: 1-12, ISSN: 2589-5370
BackgroundFaecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile 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.MethodsIn 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.FindingsOf 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%, I2=53%) and 84% (80–88%, I2=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 (P<0·001). Compared with vancomycin, the number needed to treat (NNT) for repeat FMT was 1·5 (1·3–1·9, P<0·001) and 2.9 (1·5–37·1, P=0·03) for single FMT. Repeat FMT had high quality of evidence.InterpretationHigh-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 F
Segal JP, Mak JWY, Mullish BH, et al., 2020, The gut microbiome: an under-recognised contributor to the Covid-19 pandemic?, Therapeutic Advances in Gastroenterology, Vol: 13, Pages: 1-14, ISSN: 1756-2848
The novel Coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus, Covid-19 has rapidly spread 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 for propensity to and severity of Covid-19 infection. Furthermore, the gut microbiome has been linked to a variety of diseases and manipulation of the gut microbiome is an attractive potential therapeutic target for a number of diseases. While the 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, ACE2 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.
Miguens Blanco J, Borghese F, McHugh N, et al., 2020, Longitudinal profiling of the gut microbiome in patients with psoriatic arthritis and ankylosing spondylitis: a multicentre, prospective, observational study, BMC Rheumatology, Vol: 4, Pages: 1-10, ISSN: 2520-1026
Background : Psoriasis is a chronic inflammatory disease of the skin affecting 2-3% ofUK population. 30% of people affected by psoriasis will develop a distinct form ofarthritis within 10 years of the skin condition onset. Although the pathogenesis ofpsoriatic arthritis is still unknown, there is a genetic predisposition triggered byenvironmental factors. Limited but convincing evidence link the gut microbiome topsoriatic arthritis. The Microbiome in Psoriatic ARThritis (Mi-PART) study propose is tocharacterise the microbiome-metabolic interface in patients affected by psoriaticarthritis 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 acontrol group of healthy volunteers (n = 30). Patients eligibility will be evaluated againstthe Criteria for Psoriatic Arthritis (CASPAR), the Bath Ankylosing Spondylitis ActivityIndex (BASDAI) and the healthy volunteers who fulfil study inclusion and exclusioncriteria.Information regarding their medical and medication history, demographics, diet andlifestyle 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. Patientsand healthy volunteers with gastrointestinal symptoms, previous history of cancer,gastrointestinal surgery in the previous 6 months or alcohol abuse will be excludedfrom the study.Discussion : The aim of this trial is to characterise the microbiome of psoriatic arthritispatients and to compare it with microbiome of healthy volunteers and of patient withankylosing spondylitis in order to define if different rheumatologic conditions areassociated with characteristic microbiome profiles. Investigating the role of themicrobiome in the develop
Miguens Blanco J, Selvarajah U, Liu Z, et al., 2020, Identification of New Associations Between Psoriatic Arthritis and the Gut Microbiota. the Mi-PART, a Phenomic Study, ACR Convergence 2020, Publisher: Wiley, ISSN: 2326-5205
Allegretti JR, Kelly CR, Grinspan A, et al., 2020, Outcomes of fecal microbiota transplantation in patients with inflammatory bowel diseases and recurrent Clostridioides difficile infection, Gastroenterology, Vol: 159, Pages: 1982-1984, ISSN: 0016-5085
There has been an increase in the burden of Clostridioides difficile infection (CDI),1 especially in high-risk populations such as patients with inflammatory bowel disease (IBD).2 The prevalence of CDI in the IBD population is up to 8-fold higher than comparable controls, with increased rates of recurrence and CDI-associated mortality.3 In addition, CDI may induce an IBD flare, and worsen disease severity and clinical course.4Fecal microbiota transplantation (FMT) is a guideline recommended therapy for recurrent CDI5; however, supportive randomized trials excluded patients with IBD. In retrospective trials of patients with IBD, FMT failure rates had been reported to be approximately 25% to 30%.6 In addition, Khoruts and colleagues reported that patients with IBD and CDI were more likely to fail FMT,7 leading to further uncertainty regarding the safety and efficacy of FMT in IBD patients with concurrent CDI. Accordingly, we conducted the first prospective study examining the efficacy of FMT among patients with IBD and CDI.MethodsWe conducted an open-label, prospective, single-arm, multicenter cohort study at 4 tertiary care FMT referral centers (Brigham and Women’s Hospital, Indiana University, Brown University, and Mount Sinai Hospital; NCT03106844). Patients with a confirmed diagnosis of IBD and 2 or more confirmed CDI episodes within 12 months, including the most recent episode occurring within 3 months, were enrolled. In keeping with CDI clinical guidelines,5 polymerase chain reaction or glutamate dehydrogenase with toxin enzyme immunoassay were permitted for the qualifying CDI episode. Patients with a total or subtotal colectomy, isolated ileal or small bowel Crohn’s disease, those pregnant or breastfeeding, those treated with vancomycin or metronidazole for more than 60 days, or those who had undergone a prior FMT within 12 months were excluded. Baseline IBD and CDI data were collected. All patients underwent a single FMT via colonoscopy. Four robus
Ferreira MR, Sands CJ, Li JV, et al., 2020, Metabolic profiles do not recover to normal after pelvic IMRT for high-risk prostate cancer., Publisher: ELSEVIER IRELAND LTD, Pages: S119-S119, ISSN: 0167-8140
Craven LJ, McIlroy JR, Mullish BH, et al., 2020, Letter: Intestinal microbiota transfer – Updating the nomenclature to increase acceptability, Alimentary Pharmacology and Therapeutics, Vol: 52, Pages: 1622-1623, ISSN: 0269-2813
This article is linked to Lai et al paper. To view this article, visit https://doi.org/10.1111/apt.15116
Petropoulou K, Salt LJ, Edwards CH, et al., 2020, A natural mutation in Pisum sativum L. (pea) alters starch assembly and improves glucose homeostasis in humans, Nature Food
Skinner C, Thompson AJ, Thursz MR, et al., 2020, Intestinal permeability and bacterial translocation in patients with liver disease, focusing on alcoholic aetiology: methods of assessment and therapeutic intervention, Therapeutic Advances in Gastroenterology, Vol: 13, Pages: 1-16, ISSN: 1756-2848
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.
Taylor H, Serrano-Contreras JI, McDonald JAK, et al., 2020, Multiomic features associated with mucosal healing and inflammation in paediatric Crohn's disease, Alimentary Pharmacology and Therapeutics, Vol: 52, Pages: 1491-1502, ISSN: 0269-2813
BACKGROUND: The gastrointestinal microbiota has an important role in mucosal immune homoeostasis and may contribute to maintaining mucosal healing in Crohn's disease (CD). AIM: To identify changes in the microbiota, metabolome and protease activity associated with mucosal healing in established paediatric CD. METHODS: Twenty-five participants aged 3-18 years with CD, disease duration of over 6 months, and maintenance treatment with biological therapy were recruited. They were divided into a low calprotectin group (faecal calprotectin <100 μg/g, "mucosal healing," n = 11), and a high calprotectin group (faecal calprotectin >100 μg/g, "mucosal inflammation," n = 11). 16S gene-based metataxonomics, 1 H-NMR spectroscopy-based metabolic profiling and protease activity assays were performed on stool samples. RESULTS: Relative abundance of Dialister species was six times greater in the low calprotectin group (q = 0.00999). Alpha and beta diversity, total protease activity and inferred metagenomic profiles did not differ between groups. Pentanoate (valerate) and lysine were principal discriminators in a machine-learning model which differentiated high and low calprotectin samples using NMR spectra (R2 0.87, Q2 0.41). Mean relative concentration of pentanoate was 1.35-times greater in the low calprotectin group (95% CI 1.03-1.68, P = 0.036) and was positively correlated with Dialister. Mean relative concentration of lysine was 1.54-times greater in the high calprotectin group (95% CI 1.05-2.03, P = 0.028). CONCLUSIONS: This multiomic study identified an increase in Dialister species and pentanoate, and a decrease in lysine, in patients with "mucosal healing." It supports further investigation of these as potential novel therapeutic targets in CD.
Martinez-Gili L, McDonald JAK, Liu Z, et al., 2020, Understanding the mechanisms of efficacy of fecal microbiota transplant in treating recurrent Clostridioides difficile infection and beyond: the contribution of gut microbial derived metabolites, Gut Microbes, Vol: 12, ISSN: 1949-0976
Fecal microbiota transplant (FMT) is a highly-effective therapy for recurrent Clostridioides difficile infection (rCDI), and shows promise for certain non-CDI indications. However, at present, its mechanisms of efficacy have remained poorly understood. Recent studies by our laboratory have noted the particular key importance of restoration of gut microbe-metabolite interactions in the ability of FMT to treat rCDI, including the impact of FMT upon short chain fatty acid (SCFAs) and bile acid metabolism. This includes a significant impact of these metabolites upon the life cycle of C. difficile directly, along with potential postulated additional benefits, including effects upon host immune response. In this Addendum, we first present an overview of these recent advancements in this field, and then describe additional novel data from our laboratory on the impact of FMT for rCDI upon several gut microbial-derived metabolites which had not previously been implicated as being of relevance.
Segal JP, Mullish BH, Quraishi MN, et al., 2020, Mechanisms underpinning the efficacy of faecal microbiota transplantation in treating gastrointestinal disease, Therapeutic Advances in Gastroenterology, Vol: 13, Pages: 1-14, ISSN: 1756-2848
Faecal Microbiota transplantation is currently a recommended therapy for recurrent/refractory Clostridioides difficile infection. The success of FMT for CDI has led to interest in its therapeutic potential in many other disorders. The mechanisms that underpin the efficacy of FMT are not fully understood. Importantly, FMT remains a crucial treatment in managing CDI and hence understanding the mechanisms that underpin its success will be critical to improve its clinical efficacy, safety and usability. Furthermore, a deeper understanding may allow us to expose FMT’s full potential as a therapeutic tool for other disease states. This review will explore the current understanding of the mechanisms underlying the efficacy of FMT across a variety of diseases.
Pataia V, McIlvride S, Papacleovoulou G, et al., 2020, Obeticholic acid improves fetal bile acid profile in a mouse model of gestational hypercholanemia, AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, Vol: 319, Pages: G197-G211, ISSN: 0193-1857
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Ding NS, McDonald JAK, Perdones-Montero A, et al., 2020, Metabonomics and the Gut Microbiome Associated With Primary Response to Anti-TNF Therapy in Crohn's Disease, JOURNAL OF CROHNS & COLITIS, Vol: 14, Pages: 1090-1102, ISSN: 1873-9946
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- Citations: 51
McIlroy JR, Mullish BH, Goldenberg SD, et al., 2020, Intestinal microbiome transfer, a novel therapeutic strategy for COVID-19 induced hyperinflammation?, Clinical Immunology, ISSN: 1521-6616
Blanco JM, Liu Z, Selvarajah U, et al., 2020, Sa1923 identification of new associations between psoriatic arthritis and the gut microbiota, a phenomic study, Gastroenterology, Vol: 158, Pages: S-481, ISSN: 0016-5085
Ghani R, Mullish BH, McDonald JA, et al., 2020, 1144 FECAL MICROBIOTA TRANSPLANT FOR MULTI-DRUG RESISTANT ORGANISMS: IMPROVED CLINICAL OUTCOMES BEYOND INTESTINAL DECOLONISATION, Publisher: Elsevier BV, ISSN: 0016-5085
Allegretti JR, Kassam Z, Hurtado J, et al., 2020, Tu1909 IMPACT OF FECAL MICROBIOTA TRANSPLANTATION ON PREVENTION OF METABOLIC SYNDROME AMONG PATIENTS WITH OBESITY, Gastroenterology, Vol: 158, ISSN: 0016-5085
Monaghan T, Russell L, Rosati E, et al., 2020, Mo1939 TEMPORAL MODULATION OF TCR REPERTOIRE FOLLOWING SEQUENTIAL FMT TREATMENT IN PATIENTS WITH SEVERE OR FULMINANT CLOSTRIDIOIDES DIFFICILE INFECTION, Gastroenterology, Vol: 158, ISSN: 0016-5085
Allegretti JR, Hurtado J, Carrellas M, et al., 2020, 121 ULCERATIVE COLITIS PATIENTS ACHEIVE MORE ROBUST ENGRAFTMENT COMPARED TO PATIENTS WITH CROHN'S DISEASE AFTER FECAL MICROBIOTA TRANSPLANTATION FOR THE TREATMENT OF RECURRENT C. DIFFICLE INFECTION, Gastroenterology, Vol: 158, Pages: S-22, ISSN: 0016-5085
Martinez-Gili L, McDonald JA, Liu Z, et al., 2020, 644 identification of novel changes in microbially-derived metabolites after fecal microbiota transplant for recurrent clostridioides difficile infection, Publisher: Elsevier BV, Pages: S-138-S-139, ISSN: 0016-5085
Mitra A, MacIntyre D, Ntritsos G, et al., 2020, The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions, Nature Communications, Vol: 11, Pages: 1-13, ISSN: 2041-1723
Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN); however, causal inference remains uncertain. Here, we use bacterial DNA sequencing from serially collected vaginal samples from a cohort of 87 adolescent and young women aged 16–26 years with histologically confirmed, untreated CIN2 lesions to determine whether VMB composition affects rates of regression over 24 months. We show that women with a Lactobacillus-dominant microbiome at baseline are more likely to have regressive disease at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression. These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies.
Allegretti JR, Kassam Z, Mullish BH, et al., 2020, Effects of fecal microbiota transplantation with oral capsules in obese patients, Clinical Gastroenterology and Hepatology, Vol: 18, Pages: 855-863.e2, ISSN: 1542-3565
Background & AimsStudies in mice have shown that the intestinal microbiota can contribute to obesity via the anorexigenic gut hormone glucagon-like peptide 1 (GLP1) and bile acids, which affect lipid metabolism. We performed a randomized, placebo-controlled pilot study of the effects of fecal microbiota transplantation (FMT) in obese, metabolically uncompromised patients.MethodsWe performed a double-blind study of 22 obese patients (body mass index [BMI] ≥ 35kg/m2) without a diagnosis of diabetes, non-alcoholic steatohepatitis, or metabolic syndrome. Participants were randomly assigned (1:1) to groups that received FMT by capsules (induction dose of 30 capsules at week 4 and maintenance dose of 12 capsules at week 8) or placebo capsules. FMT capsules were derived from a single, lean donor (BMI, 17.5 kg/m2). Patients were followed through week 26; the primary outcome was safety. Stool and serum samples were collected from patients at baseline and at weeks 1, 4, 6, 8 and 12 after administration of the first dose of FMT or placebo and analyzed by 16S RNA gene sequencing. Stool and serum samples were analyzed for metabolomics by liquid chromatography-mass spectrometry. Additional outcomes were change in area under the curve for GLP1 at week 12.ResultsWe observed no significant differences in adverse events between patients who received FMT vs placebo. There was no increase in the area under the curve of GLP1 in either group. Patients who received FMT had sustained shifts in microbiomes associated with obesity toward those of the donor (P<.001). Patients who received FMT had a sustained decrease in stool levels of taurocholic acid (P<.05), compared with baseline; bile acid profiles began to more closely resemble those of the donor. We did not observe significant changes in mean BMI at week 12 in either group.ConclusionsIn a placebo-controlled pilot study, we found that FMT capsules (derived from a lean donor) were safe but did not reduce BMI in obese metabol
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