89 results found
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
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
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.
Paizs P, Mullish BH, Alexander JL, et al., 2022, INTESTINAL MICROBIOTA TRANSPLANT FOR RECURRENT CLOSTRIODIOIDES DIFFICILE INFECTION IS ASSOCIATED WITH RESTORATION OF MICROBIAL ARYLSULFATASES AND SULFATIDE DEGRADATION, GASTROENTEROLOGY, Vol: 162, Pages: S649-S649, ISSN: 0016-5085
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, GASTROENTEROLOGY, Vol: 162, Pages: S456-S457, ISSN: 0016-5085
MacIntyre DA, Pruski P, Correia G, et al., 2022, Rapid Assessment of Vaginal Microbiota Host Interactions During Pregnancy and Preterm Birth by Direct On-Swab Desorption Electrospray Ionization Mass Spectrometry, Publisher: SPRINGER HEIDELBERG, Pages: 53-53, ISSN: 1933-7191
Martinez-Gili L, Gordon H, Blad W, et al., 2022, Gut bacteria composition and familiality echo Inflammatory Bowel Disease type and pathological spectrum, 17th Congress of ECCO, Publisher: Oxford University Press, Pages: I601-I602, ISSN: 1873-9946
BackgroundInflammatory bowel disease (IBD) aetiology encompasses genetic and environmental factors. Twin studies provide valuable insights to the familial degree (shared genetics and environment) of observed phenotypes. We characterised the gut bacterial composition of twins with IBD to find taxa associated with disease and estimate their familiality.MethodsFaecal samples were collected from 88 monozygotic (MZ) and dizygotic (DZ) twin pairs concordant or discordant for Crohn’s disease (CD; 26 MZ; 19 DZ) or ulcerative colitis (UC; 16 MZ; 27 DZ). The 16S rRNA gene was sequenced and amplicon sequence variants (ASV) generated. ANCOM software was used to assess differences in IBD vs. non-IBD, stratifying by disease type (CD/UC) and adjusting for age, gender and smoking. Twin pair and zygosity were added as random effects to estimate familiality, defined as percentage of variation due to common environment and genetics. IBD-affected twins were used for differences in disease location or treatment. Participants reporting antibiotic/probiotic treatment within the last 3 months or with a stoma/pouch were not included. In UC, surgery-naive patients were compared to an excluded subset who underwent ileostomy or pouch surgery without any recent antibiotic courses.ResultsDisease concordance in MZ twins was higher in CD (54%) than UC (19%). Alpha diversity was lower in CD, but not UC, and in ileostomy and pouch vs. surgery-naive UC. Principal component analysis showed that CD-affected twins clustered apart from non-IBD ones (Figure 1A). Familiality was lower in CD, with 5% of ASVs having familiality > 50%, compared to 17% in UC (Figure 1B). Two Lachnospirales order ASVs were less abundant in UC, while 15 ASVs from Clostridia, Bacteroidia, Bacilli and Coriobacteriia classes differentiated CD from non-IBD. Firmicutes were higher in CD (β= 0.95; 95%CI [0.34,1.56]), while no phyla changed in UC. Veillonella, Barnesiella, Faecalimonas and Holdemania genera had opposite t
Monaghan TM, Duggal NA, Rosati E, et al., 2021, A multi-factorial observational study on sequential fecal microbiota transplant in patients with medically refractory Clostridioides difficile infection, Cells, Vol: 10, ISSN: 2073-4409
Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI); increasing evidence supports FMT in severe or fulminant Clostridioides difficile 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.
Pruski P, Dos Santos Correia G, Lewis H, et al., 2021, Direct on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth, Nature Communications, Vol: 12, ISSN: 2041-1723
The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.
Allegretti JR, Kelly CR, Grinspan A, et al., 2021, Inflammatory bowel disease outcomes following fecal microbiota transplantation for recurrent C. difficile infection, Inflammatory Bowel Diseases, Vol: 27, Pages: 1371-1378, ISSN: 1078-0998
BackgroundRecurrent 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.MethodsSecondary 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.ResultsFifty 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).ConclusionThis prospective trial assessing FMT in IBD-CDI patients suggests IBD outcomes are better than reported in retrospective studies.
Innes AJ, Mullish BH, Ghani R, et al., 2021, Fecal microbiota transplant mitigates adverse outcomes in patients colonized with multidrug-resistant organisms undergoing allogeneic hematopoietic cell transplantation, Frontiers in Cellular and Infection Microbiology, Vol: 11, Pages: 1-8, ISSN: 2235-2988
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. Weperformed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy forMDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDROgroup), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival wassignificantly higher in the FMT-MDRO group (70% versus 36% p = 0.044). Post-HCT, fewer FMT-MDRO patients required intensivecare (0% versus 46%, P = 0.045) or experienced fever (0.29 versus 0.11 days, P = 0.027). Intestinal MDRO decolonization occurred in25% of FMT-MDRO patients versus 11% non-FMT MDRO patients. Despite the significant difference and statistically comparablepatient/transplant characteristics, as the sample size was small, a matched-pair analysis 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%versus 61.9% respectively, p=0.012), and higher non relapse mortality (NRM; 60.2% versus 16.7% respectively, p=0.009) than theirpaired non-colonized cohort. There was no difference in survival (70% versus 43.4%, p=0.14) or NRM (12.5% versus 31.2%respectively, p=0.24) between the FMT-MDRO group and their paired cohort. Negative outcomes, including mortality associatedwith MDRO colonization, may be ameliorated by pre-HCT FMT, despite lack of intestinal decolonization. Further work is needed toexplore the observed benefit.
Monaghan TM, Biswas RN, Nashine RR, et al., 2021, Multiomics profiling reveals signatures of dysmetabolism in urban populations in central India, Microorganisms, Vol: 9, Pages: 1-21, ISSN: 2076-2607
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 N-glycans and immunoglobulin G Fc N-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.
Miguens Blanco J, Liu Z, Mullish BH, et al., 2021, A Phenomic Characterization of the Gut Microbiota - Associations with Psoriatic Arthritis and Ankylosing Spondylitis, World Microbe Forum
Ghani R, Mullish BH, McDonald JAK, et al., 2021, Disease prevention not decolonization – a model for fecal microbiota transplantation in patients colonized with multidrug-resistant organisms, Clinical Infectious Diseases, Vol: 72, Pages: 1444-1447, ISSN: 1058-4838
Fecal microbiota transplantation (FMT) yields variable intestinal decolonization results for multidrug-resistant organisms (MDROs). This study showed significant reductions in antibiotic duration, bacteremia and length of stay in 20 patients colonized/ infected with MDRO receiving FMT (compared to pre-FMT history, and a matched group not receiving FMT), despite modest decolonization rates.
Mullish BH, Marchesi JR, McDonald JAK, et al., 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, Vol: 13, Pages: 1-9, ISSN: 1949-0976
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.
Ghani R, Mullish B, Innes A, et al., 2021, Faecal microbiota transplant (FMT) prior to allogeneic haematopoietic cell transplantation (HCT) in patients colonised with multidrug-resistant organisms (MDRO) results in improved survival, ECCMID
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
Liu Z, Coales I, Penney N, et al., 2020, A subset of Roux-en-Y Gastric Bypass bacterial consortium colonizes the gut of non-surgical rats without inducing host-microbial metabolic changes, mSystems, Vol: 5, ISSN: 2379-5077
Roux-en-Y gastric bypass (RYGB) is an effective weight loss surgery, resulting in a characteristic increase of fecal Gammaproteobacteria. The contribution of this compositional change to metabolic benefits of RYGB is currently debatable. Therefore, this study employed 16S rRNA gene sequencing and metabolic profiling to monitor the dynamic colonization of the RYGB microbial consortium and their metabolic impact on the host. Eleven Wistar rats received vancomycin and enrofloxacin, followed by fecal microbiota transplantation (FMT) of cecal slurry obtained from either RYGB- or sham-operated rats. Urine and feces from the microbiota recipients (RYGB microbiota recipients [RYGBr], n = 6; sham microbiota recipients [SHAMr], n = 5) were collected pre- and post-antibiotics and 1, 3, 6, 9, and 16 days post-FMT. No significant differences in body weight and food intake were observed between RYGBr and SHAMr. While neither group reached the community richness of that of their donors, by day 6, both groups reached the richness and diversity of that prior to antibiotic treatment. However, the typical signature of RYGB microbiome—increased Enterobacteriaceae—was not replicated in these recipients after two consecutive FMT, suggesting that the environmental changes induced by the anatomical rearrangements of RYGB could be key for sustaining such a consortium. The transplanted bacteria did not induce the same metabolic signature of urine and feces as those previously reported in RYGB-operated rats. Future work is required to explore environmental factors that shape the RYGB microbiota in order to further investigate the metabolic functions of the RYGB microbiota, thereby teasing out the mechanisms of the RYGB surgery.IMPORTANCE Roux-en-Y gastric bypass (RYGB) surgery results in a long-term gut bacterial shift toward Gammaproteobacteria in both patients and rodents. The contribution of this compositional shift, or the RYGB bacterial cons
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
Shenker NS, Perdones-Montero A, Burke A, et al., 2020, Metabolomic and Metataxonomic Fingerprinting of Human Milk Suggests Compositional Stability over a Natural Term of Breastfeeding to 24 Months, NUTRIENTS, Vol: 12
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
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.
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
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
West K, Kanu C, Maric T, et al., 2020, Longitudinal metabolic and gut bacterial profiling of pregnant women with previous bariatric surgery, Gut, Vol: 69, Pages: 1452-1459, ISSN: 0017-5749
Due to the global increase in obesity rates and success of bariatric surgery in weight reduction, an increasing number of women now present pregnant with a previous bariatric procedure. This study investigates the extent of bariatric-associated metabolic and gut microbial alterations during pregnancy and their impact on fetal development.DesignA parallel metabonomic (1H NMR spectroscopy) and gut bacterial (16S rRNA gene amplicon sequencing) profiling approach was used to determine maternal longitudinal phenotypes associated with malabsorptive/mixed (n=25) or restrictive (n=16) procedures, compared to women with similar early pregnancy body mass index but without bariatric surgery (n=70). Metabolic profiles of offspring at birth were also analysed.ResultsPrevious malabsorptive, but not restrictive, procedures induced significant changes in maternal metabolic pathways involving branched-chain and aromatic amino acids with decreased circulation of leucine, isoleucine and isobutyrate, increased excretion of microbial-associated metabolites of protein putrefaction (phenylacetlyglutamine, p-cresol sulfate, indoxyl sulfate and p-hydroxyphenylacetate), and a shift in the gut microbiota. Urinary concentration of phenylacetylglutamine was significantly elevated in malabsorptive patients relative to controls (P=0.001) and was also elevated in urine of neonates born from these mothers (P=0.021). Furthermore, the maternal metabolic changes induced by malabsorptive surgery were associated with reduced maternal insulin resistance and fetal/birth weight.ConclusionMetabolism is altered in pregnant women with a previous malabsorptive bariatric surgery. These alterations may be beneficial for maternal outcomes, but the effect of elevated levels of phenolic and indolic compounds on fetal and infant health should be investigated further.
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