-
1.
A double-blind, randomized, placebo-controlled study assessing the impact of probiotic supplementation on the symptoms of irritable bowel syndrome in females.
Mullish, BH, Michael, DR, Dabcheva, M, Webberley, TS, Coates, N, John, DA, Wang, D, Luo, Y, Plummer, SF, Marchesi, JR
Neurogastroenterology and motility. 2024;(4):e14751
Abstract
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, randomized, double-blinded, placebo-controlled, superiority study in 70 females with Rome IV-diagnosed irritable bowel syndrome (IBS) receiving the Lab4 probiotic (25 billion colony-forming units) daily or a matched placebo. Changes from baseline in the IBS-symptom severity score (IBS-SSS), daily bowel habits, anxiety, depression, IBS-related control, and avoidance behavior, executive function, and the fecal microbiota composition were assessed. The study was prospectively registered: ISRCTN 14866272 (registration date 20/07/22). KEY RESULTS At the end of the study, there were significant between-group reductions in IBS-SSS (-85.0, p < 0.0001), anxiety and depression scores (-1.9, p = 0.0002 and -2.4, p < 0.0001, respectively), and the IBS-related control and avoidance behavior score (-7.5, p = 0.0002), all favoring the probiotic group. A higher proportion of the participants in the probiotic group had normal stool form (p = 0.0106) and/or fewer defecations with loose stool form (p = 0.0311). There was little impact on the overall diversity of the fecal microbiota but there were significant differences in Roseburia, Holdemanella, Blautia, Agathobacter, Ruminococcus, Prevotella, Bacteroides, and Anaerostipes between the probiotic and placebo groups at the end of the study. CONCLUSIONS & INFERENCES Daily supplementation with this probiotic may represent an option to be considered in the management of IBS.
-
2.
Applying Lipidomics to Non-Alcoholic Fatty Liver Disease: A Clinical Perspective.
Huang, J, Sigon, G, Mullish, BH, Wang, D, Sharma, R, Manousou, P, Forlano, R
Nutrients. 2023;(8)
Abstract
The prevalence of Non-alcoholic fatty liver disease (NAFLD) and associated complications, such as hepatocellular carcinoma (HCC), is growing worldwide, due to the epidemics of metabolic risk factors, such as obesity and type II diabetes. Among other factors, an aberrant lipid metabolism represents a crucial step in the pathogenesis of NAFLD and the development of HCC in this population. In this review, we summarize the evidence supporting the application of translational lipidomics in NAFLD patients and NAFLD associated HCC in clinical practice.
-
3.
A Double-Blind, Randomized, Placebo-Controlled Trial of Ursodeoxycholic Acid (UDCA) in Parkinson's Disease.
Payne, T, Appleby, M, Buckley, E, van Gelder, LMA, Mullish, BH, Sassani, M, Dunning, MJ, Hernandez, D, Scholz, SW, McNeill, A, et al
Movement disorders : official journal of the Movement Disorder Society. 2023;(8):1493-1502
-
-
Free full text
-
Abstract
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 PD and determine midbrain target engagement. METHODS The UP (UDCA in PD) study was a phase II, randomized, double-blind, placebo-controlled trial of UDCA (30 mg/kg daily, 2:1 randomization UDCA vs. placebo) in 30 participants with PD for 48 weeks. The primary outcome was safety and tolerability. Secondary outcomes included 31-phosphorus magnetic resonance spectroscopy (31 P-MRS) to explore target engagement of UDCA in PD midbrain and assessment of motor progression, applying both the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) and objective, motion sensor-based quantification of gait impairment. RESULTS UDCA was safe and well tolerated, and only mild transient gastrointestinal adverse events were more frequent in the UDCA treatment group. Midbrain 31 P-MRS demonstrated an increase in both Gibbs free energy and inorganic phosphate levels in the UDCA treatment group compared to placebo, reflecting improved ATP hydrolysis. Sensor-based gait analysis indicated a possible improvement of cadence (steps per minute) and other gait parameters in the UDCA group compared to placebo. In contrast, subjective assessment applying the MDS-UPDRS-III failed to detect a difference between treatment groups. CONCLUSIONS High-dose UDCA is safe and well tolerated in early PD. Larger trials are needed to further evaluate the disease-modifying effect of UDCA in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
-
4.
Systematic review: the association between the gut microbiota and medical therapies in inflammatory bowel disease.
Radhakrishnan, ST, Alexander, JL, Mullish, BH, Gallagher, KI, Powell, N, Hicks, LC, Hart, AL, Li, JV, Marchesi, JR, Williams, HRT
Alimentary pharmacology & therapeutics. 2022;(1):26-48
Abstract
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.
-
5.
Impact of Fecal Microbiota Transplantation on Gut Bacterial Bile Acid Metabolism in Humans.
Bustamante, JM, Dawson, T, Loeffler, C, Marfori, Z, Marchesi, JR, Mullish, BH, Thompson, CC, Crandall, KA, Rahnavard, A, Allegretti, JR, et al
Nutrients. 2022;(24)
Abstract
Fecal microbiota transplantation (FMT) is a promising therapeutic modality for the treatment and prevention of metabolic disease. We previously conducted a double-blind, randomized, placebo-controlled pilot trial of FMT in obese metabolically healthy patients in which we found that FMT enhanced gut bacterial bile acid metabolism and delayed the development of impaired glucose tolerance relative to the placebo control group. Therefore, we conducted a secondary analysis of fecal samples collected from these patients to assess the potential gut microbial species contributing to the effect of FMT to improve metabolic health and increase gut bacterial bile acid metabolism. Fecal samples collected at baseline and after 4 weeks of FMT or placebo treatment underwent shotgun metagenomic analysis. Ultra-high-performance liquid chromatography-mass spectrometry was used to profile fecal bile acids. FMT-enriched bacteria that have been implicated in gut bile acid metabolism included Desulfovibrio fairfieldensis and Clostridium hylemonae. To identify candidate bacteria involved in gut microbial bile acid metabolism, we assessed correlations between bacterial species abundance and bile acid profile, with a focus on bile acid products of gut bacterial metabolism. Bacteroides ovatus and Phocaeicola dorei were positively correlated with unconjugated bile acids. Bifidobacterium adolescentis, Collinsella aerofaciens, and Faecalibacterium prausnitzii were positively correlated with secondary bile acids. Together, these data identify several candidate bacteria that may contribute to the metabolic benefits of FMT and gut bacterial bile acid metabolism that requires further functional validation.
-
6.
The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey.
Baunwall, SMD, Terveer, EM, Dahlerup, JF, Erikstrup, C, Arkkila, P, Vehreschild, MJ, Ianiro, G, Gasbarrini, A, Sokol, H, Kump, PK, et al
The Lancet regional health. Europe. 2021;:100181
Abstract
BACKGROUND Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe. METHODS We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT. FINDINGS In 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10-64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0•3%) unaccounted for. Adjusted to population size, 0•257 per 100,000 population received FMT for CDI and 0•189 per 100,000 population for experimental indications. With estimated 12,400 (6,100-28,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres. INTERPRETATION FMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need. FUNDING NordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056-00006B).
-
7.
Daily supplementation with the Lab4P probiotic consortium induces significant weight loss in overweight adults.
Michael, DR, Davies, TS, Jack, AA, Masetti, G, Marchesi, JR, Wang, D, Mullish, BH, Plummer, SF
Scientific reports. 2021;(1):5
Abstract
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.
-
8.
Probiotics reduce self-reported symptoms of upper respiratory tract infection in overweight and obese adults: should we be considering probiotics during viral pandemics?
Mullish, BH, Marchesi, JR, McDonald, JAK, Pass, DA, Masetti, G, Michael, DR, Plummer, S, Jack, AA, Davies, TS, Hughes, TR, et al
Gut microbes. 2021;(1):1-9
-
-
Free full text
-
Abstract
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 Addendum 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 versus control, with those ≥45 years or BMI ≥30 kg/m2 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.
-
9.
A randomised controlled study shows supplementation of overweight and obese adults with lactobacilli and bifidobacteria reduces bodyweight and improves well-being.
Michael, DR, Jack, AA, Masetti, G, Davies, TS, Loxley, KE, Kerry-Smith, J, Plummer, JF, Marchesi, JR, Mullish, BH, McDonald, JAK, et al
Scientific reports. 2020;(1):4183
Abstract
In an exploratory, block-randomised, parallel, double-blind, single-centre, placebo-controlled superiority study (ISRCTN12562026, funded by Cultech Ltd), 220 Bulgarian participants (30 to 65 years old) with BMI 25-34.9 kg/m2 received Lab4P probiotic (50 billion/day) or a matched placebo for 6 months. Participants maintained their normal diet and lifestyle. Primary outcomes were changes in body weight, BMI, waist circumference (WC), waist-to-height ratio (WtHR), blood pressure and plasma lipids. Secondary outcomes were changes in plasma C-reactive protein (CRP), the diversity of the faecal microbiota, quality of life (QoL) assessments and the incidence of upper respiratory tract infection (URTI). Significant between group decreases in body weight (1.3 kg, p < 0.0001), BMI (0.045 kg/m2, p < 0.0001), WC (0.94 cm, p < 0.0001) and WtHR (0.006, p < 0.0001) were in favour of the probiotic. Stratification identified greater body weight reductions in overweight subjects (1.88%, p < 0.0001) and in females (1.62%, p = 0.0005). Greatest weight losses were among probiotic hypercholesterolaemic participants (-2.5%, p < 0.0001) alongside a significant between group reduction in small dense LDL-cholesterol (0.2 mmol/L, p = 0.0241). Improvements in QoL and the incidence rate ratio of URTI (0.60, p < 0.0001) were recorded for the probiotic group. No adverse events were recorded. Six months supplementation with Lab4P probiotic resulted in significant weight reduction and improved small dense low-density lipoprotein-cholesterol (sdLDL-C) profiles, QoL and URTI incidence outcomes in overweight/obese individuals.
-
10.
International consensus conference on stool banking for faecal microbiota transplantation in clinical practice.
Cammarota, G, Ianiro, G, Kelly, CR, Mullish, BH, Allegretti, JR, Kassam, Z, Putignani, L, Fischer, M, Keller, JJ, Costello, SP, et al
Gut. 2019;(12):2111-2121
-
-
Free full text
-
Abstract
Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.