378 results found
Dos Santos Correia G, Marchesi J, MacIntyre D, 2023, Moving beyond DNA: towards functional analysis of the vaginal microbiome by non-sequencing-based methods, Current Opinion in Microbiology, Vol: 73, Pages: 1-11, ISSN: 1369-5274
Over the last two decades, sequencing-based methods have revolutionised our understanding of niche-specific microbial complexity. In the lower female reproductive tract, these approaches have enabled identification of bacterial compositional structures associated with health and disease. Application of metagenomics and metatranscriptomics strategies have provided insight into the putative function of these communities but it is increasingly clear that direct measures of microbial and host cell function are required to understand the contribution of microbe–host interactions to pathophysiology. Here we explore and discuss current methods and approaches, many of which rely upon mass-spectrometry, being used to capture functional insight into the vaginal mucosal interface. In addition to improving mechanistic understanding, these methods offer innovative solutions for the development of diagnostic and therapeutic strategies designed to improve women’s health.
Alexander J, Posma J, Scott A, et al., 2023, Pathobionts in the tumour microbiota predict survival following resection for colorectal cancer, Microbiome, ISSN: 2049-2618
Alexander J, Powell N, Marchesi J, et al., 2023, Considerations for peripheral blood transport and storage during large-scale multicentre metabolome research, Gut, Pages: 1-4, ISSN: 0017-5749
Semertzidou A, Grout-Smith H, Kalliala I, et al., 2023, Diabetes and anti-diabetic interventions and the risk of gynaecological and obstetric morbidity: an umbrella review of the literature, BMC Medicine, ISSN: 1741-7015
Alexander JL, Mullish BH, Danckert NP, et al., 2023, The gut microbiota and metabolome are associated with diminished COVID-19 vaccine-induced antibody responses in immunosuppressed inflammatory bowel disease patients, EBioMedicine, Vol: 88, ISSN: 2352-3964
Background:Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients.Methods:Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination.Findings:Forty-three infliximab-treated patients with IBD were recruited (30 Crohn's disease, 12 ulcerative colitis, 1 IBD-unclassified; 26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.037). Bilophila abundance was associated with better serological response, while Streptococcus was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R2X 0.25, R2Y 0.26, Q2 0.15; CV-ANOVA p = 0.038). Trimethylamine, isobutyrate and omega-muricholic acid were associated with better response, while succinate, phenylalanine, taurolithoc
Chrysostomou D, Roberts LA, Marchesi JR, et al., 2023, Gut Microbiota Modulation of Efficacy and Toxicity of Cancer Chemotherapy and Immunotherapy., Gastroenterology, Vol: 164, Pages: 198-213
Accumulating evidence supports not only the functional role of the gut microbiome in cancer development and progression but also its role in defining the efficacy and toxicity of chemotherapeutic agents (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and immunotherapeutic compounds (anti-programmed death-ligand 1/anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte-associated antigen 4). This evidence is supported in numerous in vitro, animal, and clinical studies that highlight the importance of microbial mechanisms in defining therapeutic responses. The microbiome therefore shapes oncologic outcomes and is now being leveraged for the development of novel personalized therapeutic approaches in cancer treatment. However, if the microbiome is to be successfully translated into next-generation oncologic treatments, a new multimodal model of the oncomicrobiome must be conceptualized that incorporates gut microbial cometabolism of pharmacologic agents into cancer care. The objective of this review is therefore to outline the current knowledge of oncologic pharmacomicrobiomics and to describe how the multiparametric functions of the gut microbiome influence treatment response across cancer types. The secondary objective is to propose innovative approaches for modulating the gut microbiome in clinical environments that improve therapy efficacy and diminish toxic effects derived from antineoplastic agents for patient benefit.
Biscarini F, Masetti G, Muller I, et al., 2023, Gut microbiome associated with Graves' disease and Graves' orbitopathy: the INDIGO* multi-centre European study., J Clin Endocrinol Metab
CONTEXT: Gut bacteria can influence host immune responses but little is known about their role in tolerance-loss mechanisms in Graves' disease (GD; hyperthyroidism caused by autoantibodies, TRAB, to the thyrotropin receptor, TSHR) and its progression to Graves' orbitopathy (GO). OBJECTIVE: To compare the fecal microbiota in GD patients, with GO of varying severity, and healthy controls (HC). DESIGN, SETTING AND PATIENTS: Patients were recruited from four European countries (105 GD patients, 41 HC) for an observational study with cross-sectional and longitudinal components. RESULTS: At recruitment, when patients were hyperthyroid and TRAB positive, Actinobacteria were significantly increased and Bacteroidetes significantly decreased in GD/GO compared with HC. The Firmicutes to Bacteroidetes (F:B) ratio was significantly higher in GD/GO than in HC. Differential abundance of 15 genera was observed in patients, being most skewed in mild GO. Bacteroides displayed positive and negative correlations with TSH and FT4 respectively and was also significantly associated with smoking in GO, smoking is a risk factor for GO but not GD. Longitudinal analyses revealed that the presence of certain bacteria (Clostridiales) at diagnosis correlated with the persistence of TRAB 200 + days after commencing anti-thyroid drug treatment. CONCLUSIONS: The increased F:B ratio observed in GD/GO mirrors our finding in a murine model comparing TSHR-immunized with control mice. We defined a microbiome signature and identified changes associated with autoimmunity as distinct from those due to hyperthyroidism. Persistence of TRAB is predictive of relapse, identification of these patients at diagnosis, via their microbiome, could improve management with potential to eradicate Clostridiales.
Mullish BH, Michael DR, Webberley TS, et al., 2023, The gastrointestinal status of healthy adults: a post hoc assessment of the impact of three distinct probiotics, Beneficial Microbes, ISSN: 1876-2883
Radhakrishnan ST, Gallagher KI, Mullish BH, et al., 2023, Rectal swabs as a viable alternative to faecal sampling for the analysis of gut microbiota functionality and composition, Scientific Reports, Vol: 13, Pages: 1-9, ISSN: 2045-2322
Faecal or biopsy samples are frequently used to analyse the gut microbiota, but issues remain with the provision and collection of such samples. Rectal swabs are widely-utilised in clinical practice and previous data demonstrate their potential role in microbiota analyses; however, studies to date have been heterogenous, and there are a particular lack of data concerning the utility of swabs for the analysis of the microbiota’s functionality and metabolome. We compared paired stool and rectal swab samples from healthy individuals to investigate whether rectal swabs are a reliable proxy for faecal sampling. There were no significant differences in key alpha and beta diversity measures between swab and faecal samples, and inter-subject variability was preserved. Additionally, no significant differences were demonstrated in abundance of major annotated phyla. Inferred gut functionality using Tax4Fun2 showed excellent correlation between the two sampling techniques (Pearson’s coefficient r = 0.9217, P < 0.0001). Proton nuclear magnetic resonance (1H NMR) spectroscopy enabled the detection of 20 metabolites, with overall excellent correlation identified between rectal swab and faecal samples for levels all metabolites collectively, although more variable degrees of association between swab and stool for levels of individual metabolites. These data support the utility of rectal swabs in both compositional and functional analyses of the gut microbiota.
Koutoukidis DA, Jebb SA, Zimmerman M, et al., 2022, The association of weight loss with changes in the gut microbiota diversity, composition, and intestinal permeability: a systematic review and meta-analysis, GUT MICROBES, Vol: 14, ISSN: 1949-0976
- Author Web Link
- Citations: 12
Bustamante J-M, Dawson T, Loeffler C, et al., 2022, Impact of fecal microbiota transplantation on gut bacterial bile acid metabolism in humans, Nutrients, Vol: 14, ISSN: 2072-6643
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.
Misra R, Sarafian M, Pechlivanis A, et al., 2022, Ethnicity associated microbial and metabonomic profiling in newly diagnosed ulcerative colitis, Clinical and Experimental Gastroenterology, Vol: 15, Pages: 199-212, ISSN: 1178-7023
Introduction:Ulcerative colitis (UC) differs across geography and ethnic groups. Gut microbial diversity plays a pivotal role in disease pathogenesis and differs across ethnic groups. The functional diversity in microbial-driven metabolites may have a pathophysiologic role and offer new therapeutic avenues.Methods:Demographics and clinical data were recorded from newly diagnosed UC patients. Blood, urine and faecal samples were collected at three time points over one year. Bacterial content was analysed by 16S rRNA sequencing. Bile acid profiles and polar molecules in three biofluids were measured using liquid-chromatography mass spectrometry (HILIC) and nuclear magnetic resonance spectroscopy.Results:We studied 42 patients with a new diagnosis of UC (27 South Asians; 15 Caucasians) with 261 biosamples. There were significant differences in relative abundance of bacteria at the phylum, genus and species level. Relative concentrations of urinary metabolites in South Asians were significantly lower for hippurate (positive correlation for Ruminococcus) and 4-cresol sulfate (Clostridia) (p<0.001) with higher concentrations of lactate (negative correlation for Bifidobacteriaceae). Faecal conjugated and primary conjugated bile acids concentrations were significantly higher in South Asians (p=0.02 and p=0.03 respectively). Results were unaffected by diet, phenotype, disease severity and ongoing therapy. Comparison of time points at diagnosis and at 1 year did not reveal changes in microbial and metabolic profile.Conclusion:Ethnic-related microbial metabolite associations were observed in South Asians with UC. This suggests a predisposition to UC may be influenced by environmental factors reflected in a distinct gene-environment interaction. The variations may serve as markers to identify risk factors for UC and modified to enhance therapeutic response.
Mullish BH, Martinez Gili L, Chekmeneva E, et al., 2022, Assessing the clinical value of faecal bile acid profiling to predict recurrence in primary Clostridioides difficile infection, Alimentary Pharmacology and Therapeutics, Vol: 56, Pages: 1556-1569, ISSN: 0269-2813
Background:Factors influencing recurrence risk in primary Clostridioides difficile infection (CDI) are poorly understood, and tools predicting recurrence are lacking. Perturbations in bile acids (BAs) contribute to CDI pathogenesis and may be relevant to primary disease prognosis.Aims:To define stool BA dynamics in patients with primary CDI and explore signatures predicting recurrenceMethodsWeekly stool samples were collected from patients with primary CDI from the last day of anti-CDI therapy until recurrence or, otherwise, through 8 weeks post-completion. Ultra-high performance liquid chromatography-mass spectrometry was used to profile BAs; stool bile salt hydrolase (BSH) activity was measured to determine primary BA bacterial deconjugation capacity. Multivariate and univariate models were used to define differential BA trajectories in patients with recurrence versus those without, and to assess faecal BAs as predictive markers for recurrence.Results:Twenty (36%) of 56 patients (median age: 57, 64% male) had recurrence; 80% of recurrences occurred within the first 9 days post-antibiotic treatment. Principal component analysis of stool BA profiles demonstrated clustering by recurrence status and post-treatment timepoint. Longitudinal faecal BA trajectories showed recovery of secondary BAs and their derivatives only in patients without recurrence. BSH activity increased over time only among non-relapsing patients (β = 0.056; likelihood ratio test p = 0.018). A joint longitudinal-survival model identified five stool BAs with area under the receiver operating characteristic curve >0.73 for predicting recurrence within 9 days post-CDI treatment.Conclusions:Gut BA metabolism dynamics differ in primary CDI patients between those developing recurrence and those who do not. Individual BAs show promise as potential novel biomarkers to predict CDI recurrence.
Creedon AC, Dimidi E, Hung ES, et al., 2022, The impact of almonds and almond processing on gastrointestinal physiology, luminal mand gastrointestinal symptoms: a randomized controlled trial and mastication study., American Journal of Clinical Nutrition, Vol: 116, Pages: 1790-1804, ISSN: 0002-9165
BACKGROUND: Almonds contain lipid, fiber and polyphenols and possess physicochemical properties that impact nutrient bioaccessibility, which are hypothesized to impact gut physiology and microbiota. OBJECTIVES: Investigate the impact of whole almonds and ground almonds (almond flour) on fecal bifidobacteria (primary outcome), gut microbiota composition and transit time. DESIGN: Healthy adults (n = 87) participated in a parallel, 3-arm randomized controlled trial. Participants received whole almonds (56 g/d), ground almonds (56 g/d) or an isocaloric control muffin in place of habitual snacks for 4 weeks. Gut microbiota composition and diversity (16S rRNA gene sequencing), short-chain fatty acids (gas-chromatography), volatile organic compounds (gas-chromatography mass-spectrometry), gut transit time (wireless motility capsule), stool output and gut symptoms (7-day diary) were measured at baseline and endpoint. The impact of almond form on particle size distribution (PSD) and predicted lipid release was measured in a subgroup (n = 31). RESULTS: Modified intention-to-treat analysis was performed on 79 participants. There were no significant differences in abundance of fecal bifidobacteria following consumption of whole almonds (8.7%, SD 7.7%), ground almonds (7.8%, SD 6.9%) or control (13.0%, SD 10.2%; q = 0.613). Consumption of almonds (whole and ground pooled) resulted in higher butyrate (24.1 μmol/g, SD 15.0 μmol/g) in comparison to control (18.2 μmol/g, SD 9.1 μmol/g; p = 0.046). There was no effect of almonds on gut microbiota at the phylum level or diversity, gut transit time, stool consistency or gut symptoms. Almond form (whole versus ground) had no effect on study outcomes. Ground almonds resulted in significantly smaller PSD and higher predicted lipid release (10.4%, SD 1.8%) in comparison to whole almonds (9.3%, SD 2.0%; p = 0.017). CONCLUSIONS: Almond consumption has limited impact on g
Marchesi J, Allen S, Scott E, et al., 2022, An observational investigation of the faecal microbiota and metabonome of gastrostomy fed children, on blended and formula diets, Gut Microbes, Vol: 14, ISSN: 1949-0976
Gastrostomy fed children traditionally have a Formulae diet (FD), which fulfills nutritional requirements; however, many families are adopting Blended diets (BD), which are what the whole family would eat. We undertook an observational investigation of the colonic microbiota and metabonome in a small group of gastrostomy fed children, who were either on an FD or BD, and compared, where possible to their siblings (17 FD, 28 BD, 19 HS). There was no increase in complications in tube blockage or infection rates, but a significant improvement in the prevalence of bowel problems, a reduction in medication and an increase in quality of life. Metataxonomic analysis showed that the FD group was significantly different to the Sibling group, and that families did not cluster together. Whole sample metabonomics showed no differences between groups; however, univariate analysis of biologically important metabolites did differ. Changing to a BD resulted in no increase in complications or risks, but improved the overall quality of life for the children and families.
Mullish BH, Paizs P, Alexander J, et al., 2022, Intestinal microbiota transplant for recurrent Clostridioides difficile infection restores microbial arylsulfatases and sulfatide degradation: a novel mechanism of efficacy?, UEG Week 2022, Pages: 823-823
Penney N, Yeung K, Garcia Perez I, et al., 2022, Multi-omic phenotyping reveals host-microbe responses to bariatric surgery, glycaemic control and obesity, communications medicine, Vol: 2, Pages: 1-18, ISSN: 2730-664X
Background: Resolution of type 2 diabetes (T2D) is common following bariatric surgery, particularly Roux-en-Y gastric bypass. However, the underlying mechanisms have not been fully elucidated.Methods: To address this we compare the integrated serum, urine and faecal metabolic profiles of participants with obesity +/- T2D (n=80, T2D=42) with participants who underwent Roux-en-Y gastric bypass or sleeve gastrectomy (pre and 3-months post-surgery; n=27), taking diet into account. We co-model these data with shotgun metagenomic profiles of the gut microbiota to provide a comprehensive atlas of host-gut microbe responses to bariatric surgery, weight-loss and glycaemic control at the systems level.Results: Here we show that bariatric surgery reverses several disrupted pathways characteristic of T2D. The differential metabolite set representative of bariatric surgery overlaps with both diabetes (19.3% commonality) and body mass index (18.6% commonality). However, the percentage overlap between diabetes and body mass index is minimal (4.0% commonality), consistent with weight-independent mechanisms of T2D resolution. The gut microbiota is more strongly correlated to body mass index than T2D, although we identify some pathways such as amino acid metabolism that correlate with changes to the gut microbiota and which influence glycaemic control.Conclusion: We identify multi-omic signatures associated with responses to surgery, body mass index, and glycaemic control. Improved understanding of gut microbiota - host co-metabolism may lead to novel therapies for weight-loss or diabetes. However, further experiments are required to provide mechanistic insight into the role of the gut microbiota in host metabolism and establish proof of causality.
Mullish BH, McDonald JAK, Marchesi JR, 2022, Mechanisms of efficacy of intestinal microbiota transplant: do not forget the metabolites, The Lancet Gastroenterology & Hepatology, Vol: 7, Pages: 594-594, ISSN: 2468-1253
Mullish BH, Martinez-Gili L, Chekmeneva E, et al., 2022, Fecal bile acid profiles predict recurrence in patients with primary <i>Clostridioides difficile</i> infection
<jats:label>1.</jats:label><jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Factors that influence recurrence risk in primary <jats:italic>Clostridioides difficile</jats:italic> infection (CDI) are poorly understood, and tools to predict recurrence are lacking. Perturbations in microbial-derived bile acids (BAs) contribute to CDI pathogenesis and may be relevant to primary disease prognosis.</jats:p></jats:sec><jats:sec><jats:title>Aims</jats:title><jats:p>To define stool bile acid profiles and microbial bile-metabolising functionality in primary CDI patients, and explore signatures predicting recurrence.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Weekly stool samples were collected from primary CDI patients from the last day of anti-CDI therapy until recurrence, or through eight weeks post-completion otherwise. Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to profile bile acids, and bacterial bile salt hydrolase (BSH) activity was measured to determine primary BA deconjugation capacity. Multivariate and univariate models were used to define differential BA trajectories in recurrers <jats:italic>versus</jats:italic> non-recurrers, and assess fecal bile acids as predictive markers for recurrence.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Twenty (36%) out of 56 patients (median age 57, 64% male) recurred, with 80% of recurrence occurring within the first nine days post-antibiotic treatment. Principal component analysis (PCA) of stool bile acid profiles demonstrated clustering of samples by recurrence status and post-treatment time point. Longitudinal fecal bile acid trajectories in non-recurrers showed a recovery of secondary bile acids and their derivatives in non-r
Whelan E, Kalliala I, Semertzidou A, et al., 2022, Risk Factors for Ovarian Cancer: An Umbrella Review of the Literature, Cancers, Vol: 14, Pages: 2708-2708
<jats:p>Several non-genetic factors have been associated with ovarian cancer incidence or mortality. To evaluate the strength and validity of the evidence we conducted an umbrella review of the literature that included systematic reviews/meta-analyses that evaluated the link between non-genetic risk factors and ovarian cancer incidence and mortality. We searched PubMed, EMBASE, Cochrane Database of Systematic Reviews and performed a manual screening of references. Evidence was graded into strong, highly suggestive, suggestive or weak based on statistical significance of the random effects summary estimate and the largest study in a meta-analysis, the number of cases, between-study heterogeneity, 95% prediction intervals, small study effects, and presence of excess significance bias. We identified 212 meta-analyses, investigating 55 non-genetic risk factors for ovarian cancer. Risk factors were grouped in eight broad categories: anthropometric indices, dietary intake, physical activity, pre-existing medical conditions, past drug history, biochemical markers, past gynaecological history and smoking. Of the 174 meta-analyses of cohort studies assessing 44 factors, six associations were graded with strong evidence. Greater height (RR per 10 cm 1.16, 95% confidence interval (CI) 1.11–1.20), body mass index (BMI) (RR ≥ 30 kg/m2 versus normal 1.27, 95% CI 1.17–1.38) and three exposures of varying preparations and usage related to hormone replacement therapy (HRT) use increased the risk of developing ovarian cancer. Use of oral contraceptive pill reduced the risk (RR 0.74, 95% CI 0.69–0.80). Refining the significance of genuine risk factors for the development of ovarian cancer may potentially increase awareness in women at risk, aid prevention and early detection.</jats:p>
Webberley TS, Masetti G, Bevan RJ, et al., 2022, The Impact of Probiotic Supplementation on Cognitive, Pathological and Metabolic Markers in a Transgenic Mouse Model of Alzheimer's Disease, FRONTIERS IN NEUROSCIENCE, Vol: 16
- Author Web Link
- Citations: 4
Alexander JL, Mullish BH, Danckert NP, et al., 2022, The gut microbiota and metabolome is associated with diminished COVID-19 vaccine-induced antibody responses in immunosuppressed inflammatory bowel disease patients
<jats:title>Abstract</jats:title> <jats:p>Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. Faecal and serum samples were prospectively collected from infliximab-treated patients with IBD in the CLARITY-IBD study undergoing vaccination against SARS-CoV-2. Antibody responses were measured following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Patients were classified as having responses above or below the geometric mean of the wider CLARITY-IBD cohort. 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-high-performance liquid chromatography mass spectrometry (UHPLC-MS) were performed on faecal samples. Univariate, multivariable and correlation analyses were performed to determine gut microbial and metabolomic predictors of response to vaccination. Forty-three infliximab-treated patients with IBD were recruited (30 Crohn’s disease, 12 ulcerative colitis, 1 IBD-unclassified; 26 with concomitant thiopurine therapy). Eight patients had evidence of prior SARS-CoV-2 infection. Seventeen patients (39.5%) had a serological response below the geometric mean. Gut microbiota diversity was lower in below average responders (p = 0.021). <jats:italic>Bilophila</jats:italic> abundance was associated with better serological response, while <jats:italic>Streptococcus</jats:italic> was associated with poorer response. The faecal metabolome was distinct between above and below average responders (OPLS-DA R<jats:sup>2</jats:sup>X 0.25, R&l
Zhang D, Mullish BH, Wang J, et al., 2022, Identifying transient and stable bacteria- metabolite interactions from longitudinal multi-omics data, Publisher: Research Square
BackgroundUnderstanding the complex relationships between bacteria and metabolites in ecological systems are extremely important in studies of different microbiomes. Longitudinal multi-omics study is adopted to investigate interactions between bacteria and metabolites, by directly associating their longitudinal profiles. Since a bacteria/metabolite may involve in many different biological processes, the longitudinal profile is an average of different interactions. Therefore, direct association could only uncover the strongest interactions.ResultsHere we present a computational approach that can rebuild short- and long-term bacteria-metabolite interactions from longitudinal multi-omics datasets. For this task, we re-analyse data (both microbial sequencing and metabolomic analysis) from an in vitro model of Clostridioides difficile infection and faecal microbiota transplant, a disease state and mode of therapy in which perturbed microbiome-metabolome interactions (and their reversal) are well-established to be pertinent. By analysing such a dataset, we generated both a short-term and a long-term interaction network, which predicted many new interactions. Four new interactions were randomly selected to be validated. In batch culture experiments, we validated two of them: (1) Ruminococcus gnavus and Ruminococcus luti could generate 3-ketocholanic acid (2) Blautia obeum could consume succinate.ConclusionsThe deconvolution of the raw longitudinal signal into short- and long-term trends can help users to gain a deeper understanding of their data. This tool will be useful for high-throughput screening of microbe/metabolite/host interactions from a longitudinal multi-omics setting.
Powles STR, Gallagher KI, Chong LWL, et al., 2022, Effects of bowel preparation on intestinal bacterial associated urine and faecal metabolites and the associated faecal microbiome, BMC Gastroenterology, Vol: 22, Pages: 1-9, ISSN: 1471-230X
BackgroundUrinary and faecal metabolic profiling have been extensively studied in gastrointestinal diseases as potential diagnostic markers, and to enhance our understanding of the intestinal microbiome in the pathogenesis these conditions. The impact of bowel cleansing on the microbiome has been investigated in several studies, but limited to just one study on the faecal metabolome.AimTo compare the effects of bowel cleansing on the composition of the faecal microbiome, and the urine and faecal metabolome.MethodsUrine and faecal samples were obtained from eleven patients undergoing colonoscopy at baseline, and then at day 3 and week 6 after colonoscopy. 16S rRNA gene sequencing was used to analyse changes in the microbiome, and metabonomic analysis was performed using proton nuclear magnetic resonance (1H NMR) spectroscopy.ResultsMicrobiomic analysis demonstrated a reduction in alpha diversity (Shannon index) between samples taken at baseline and three days following bowel cleansing (p = 0.002), and there was no significant difference between samples at baseline and six weeks post colonoscopy. Targeted and non-targeted analysis of urinary and faecal bacterial associated metabolites showed no significant impact following bowel cleansing.ConclusionsBowel cleansing causes a temporary disturbance in bacterial alpha diversity measured in faeces, but no significant changes in the faecal and urine metabolic profiles, suggesting that overall the faecal microbiome and its associated metabolome is resistant to the effects of an induced osmotic diarrhoea.
Blanco JM, Danckert NP, Liu Z, et al., 2022, NEW LINKS BETWEEN PSORIATIC ARTHRITIS AND THE GUT MICROBIOME SUGGEST A STRONGER ROLE OF THE GUT-JOINT AXIS, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S456-S457, ISSN: 0016-5085
Blanco JM, Kragsnaes MS, Liu Z, et al., 2022, IMPACT ON GUT MICROBIAL METABOLITES FROM A 6-MONTH DOUBLE-BLIND RANDOMIZED PLACEBO-CONTROLLED TRIAL OF FECAL MICROBIOTA TRANSPLANTATION FOR ACTIVE PERIPHERAL PSORIATIC ARTHRITIS, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S829-S829, ISSN: 0016-5085
Alexander JL, Mullish BH, Danckert NP, et al., 2022, POOR RESPONSE TO ANTI-SARS-COV-2 VACCINATION IN IMMUNOSUPPRESSED INFLAMMATORY BOWEL DISEASE PATIENTS IS ASSOCIATED WITH ALTERED GUT MICROBIOTA FUNCTION, GASTROENTEROLOGY, Vol: 162, Pages: S653-S653, ISSN: 0016-5085
Ghani R, Blanco JM, Forlano R, et al., 2022, RELATIVE CHANGE OF ENTEROCOCCUS FAECIUM, SELECTED COMMENSAL BACTERIA AND CYTOKINES ARE SEEN IN PATIENTS COLONIZED WITH MULTIDRUG-RESISTANT ORGANISMS WHO UNDERGO INTESTINAL MICROBIOTA TRANSPLANTATION, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S218-S219, ISSN: 0016-5085
Forlano R, Mullish BH, Martinez-Gili L, et al., 2022, FACTORS ASSOCIATED WITH INCREASED GUT PERMEABILITY AND SEVERITY OF LIVER DISEASE IN DIABETIC PATIENTS WITH NAFLD, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S1136-S1136, ISSN: 0016-5085
Ghani R, Mullish BH, Davies FJ, et al., 2022, How to adapt an intestinal microbiota transplantation program to reduce the risk of invasive multidrug-resistant infection, Clinical Microbiology and Infection, Vol: 28, Pages: 502-512, ISSN: 1198-743X
Background:Vulnerable patients with intestinal colonisation of multidrug-resistant organisms (MDROs) are recognised to be at increased risk of invasive MDRO driven infection. Intestinal Microbiota Transplantation (IMT aka FMT) 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 optimising 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) to take into consideration the relative immunosuppressed state of potential recipients. Delivery of IMT occurs 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 two 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 decolonisation as a binary outcome. Repeat IMT is considered case-by-case.Implications:Future research areas should include randomised studies that consider clinical outcomes and cost-effectiveness, and better understa
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