133 results found
Letertre M, Bhatt A, Harvey M, et al., 2022, Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice, Scientific Reports, Vol: 12, ISSN: 2045-2322
The hydrolysis of xenobiotic glucuronides by gut bacterial glucuronidases reactivates previously detoxified compounds resulting in severe gut toxicity for the host. Selective bacterial β-glucuronidase inhibitors can mitigate this toxicity but their impact on wider host metabolic processes has not been studied. To investigate this the inhibitor 4-(8-(piperazin-1-yl)-1,2,3,4-tetrahydro-[1,2,3]triazino[4′,5′:4,5]thieno[2,3-c]isoquinolin-5-yl)morpholine (UNC10201652, Inh 9) was administered to mice to selectively inhibit a narrow range of bacterial β-glucuronidases in the gut. The metabolomic profiles of the intestinal contents, biofluids, and several tissues involved in the enterohepatic circulation were measured and compared to control animals. No biochemical perturbations were observed in the plasma, liver or gall bladder. In contrast, the metabolite profiles of urine, colon contents, feces and gut wall were altered compared to the controls. Changes were largely restricted to compounds derived from gut microbial metabolism. This work establishes that inhibitors targeted towards bacterial β-glucuronidases modulate the functionality of the intestinal microbiota without adversely impacting the host metabolic system.
Farras M, Swann JR, Rowland I, et al., 2022, Impact of Phenol-Enriched Olive Oils on Serum Metabonome and Its Relationship with Cardiometabolic Parameters: A Randomized, Double-Blind, Cross-Over, Controlled Trial, ANTIOXIDANTS, Vol: 11
Penny HA, Domingues RG, Krauss MZ, et al., 2022, Rhythmicity of intestinal IgA responses confers oscillatory commensal microbiota mutualism., Sci Immunol, Vol: 7
Interactions between the mammalian host and commensal microbiota are enforced through a range of immune responses that confer metabolic benefits and promote tissue health and homeostasis. Immunoglobulin A (IgA) responses directly determine the composition of commensal species that colonize the intestinal tract but require substantial metabolic resources to fuel antibody production by tissue-resident plasma cells. Here, we demonstrate that IgA responses are subject to diurnal regulation over the course of a circadian day. Specifically, the magnitude of IgA secretion, as well as the transcriptome of intestinal IgA+ plasma cells, was found to exhibit rhythmicity. Oscillatory IgA responses were found to be entrained by time of feeding and were also found to be in part coordinated by the plasma cell-intrinsic circadian clock via deletion of the master clock gene Arntl. Moreover, reciprocal interactions between the host and microbiota dictated oscillatory dynamics among the commensal microbial community and its associated transcriptional and metabolic activity in an IgA-dependent manner. Together, our findings suggest that circadian networks comprising intestinal IgA, diet, and the microbiota converge to align circadian biology in the intestinal tract and to ensure host-microbial mutualism.
Vaitkute G, Panic G, Alber DG, et al., 2022, Linking gastrointestinal microbiota and metabolome dynamics to clinical outcomes in paediatric haematopoietic stem cell transplantation, MICROBIOME, Vol: 10, ISSN: 2049-2618
Salminen S, Collado MC, Endo A, et al., 2022, The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics (vol 123, pg 1561, 2017), NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, Vol: 19, Pages: 551-551, ISSN: 1759-5045
Caspani G, Green M, Swann JR, et al., 2022, Microbe-Immune Crosstalk: Evidence That T Cells Influence the Development of the Brain Metabolome, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 23
Salminen S, Collado MC, Endo A, et al., 2022, Reply to: Postbiotics - when simplification fails to clarify (Mar, 10.1038/s41575-022-00596-9, 2022), NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, Vol: 19, Pages: 275-275, ISSN: 1759-5045
Kathrani A, Yen S, Swann JR, et al., 2022, The effect of a hydrolyzed protein diet on the fecal microbiota in cats with chronic enteropathy, SCIENTIFIC REPORTS, Vol: 12, ISSN: 2045-2322
Heijtz RD, Gressens P, Swann JR, 2022, Targeting microbial metabolites to treat autism, NATURE MEDICINE, Vol: 28, Pages: 448-450, ISSN: 1078-8956
Shehata E, Parker A, Suzuki T, et al., 2022, Microbiomes in physiology: insights into 21st-century global medical challenges, Publisher: WILEY, Pages: 257-264, ISSN: 0958-0670
Church JA, Rukobo S, Govha M, et al., 2021, Associations between biomarkers of environmental enteric dysfunction and oral rotavirus vaccine immunogenicity in rural Zimbabwean infants, ECLINICALMEDICINE, Vol: 41
Giallourou N, Urbaniak C, Puebla-Barragan S, et al., 2021, Characterizing the breast cancer lipidome and its interaction with the tissue microbiota, Communications Biology, Vol: 4, ISSN: 2399-3642
Breast cancer is the most diagnosed cancer amongst women worldwide. We have previously shown that there is a breast microbiota which differs between women who have breast cancer and those who are disease-free. To better understand the local biochemical perturbations occurring with disease and the potential contribution of the breast microbiome, lipid profiling was performed on non-tumor breast tissue collected from 19 healthy women and 42 with breast cancer. Here we identified unique lipid signatures between the two groups with greater amounts of lysophosphatidylcholines and oxidized cholesteryl esters in the tissue from women with breast cancer and lower amounts of ceramides, diacylglycerols, phosphatidylcholines, and phosphatidylethanolamines. By integrating these lipid signatures with the breast bacterial profiles, we observed that Gammaproteobacteria and those from the class Bacillus, were negatively correlated with ceramides, lipids with antiproliferative properties. In the healthy tissues, diacylglyerols were positively associated with Acinetobacter, Lactococcus, Corynebacterium, Prevotella and Streptococcus. These bacterial groups were found to possess the genetic potential to synthesize these lipids. The cause-effect relationships of these observations and their contribution to disease patho-mechanisms warrants further investigation for a disease afflicting millions of women around the world.
Spitzer SO, Tkacz A, Savignac HM, et al., 2021, Postnatal prebiotic supplementation in rats affects adult anxious behaviour, hippocampus, electrophysiology, metabolomics, and gut microbiota, ISCIENCE, Vol: 24
Osman A, Zuffa S, Walton G, et al., 2021, Post-weaning A1/A2 β-casein milk intake modulates depressive-like behavior, brain μ-opioid receptors, and the metabolome of rats, iScience, Vol: 24, ISSN: 2589-0042
The postnatal period is critical for brain and behavioral development and is sensitive to environmental stimuli, such as nutrition. Prevention of weaning from maternal milk was previously shown to cause depressive-like behavior in rats. Additionally, loss of dietary casein was found to act as a developmental trigger for a population of brain opioid receptors. Here, we explore the effect of exposure to milk containing A1 and A2 β-casein beyond weaning. A1 but not A2 β-casein milk significantly increased stress-induced immobility in rats, concomitant with an increased abundance of Clostridium histolyticum bacterial group in the caecum and colon of A1 β-casein fed animals, brain region-specific alterations of μ-opioid and oxytocin receptors, and modifications in urinary biochemical profiles. Moreover, urinary gut microbial metabolites strongly correlated with altered brain metabolites. These findings suggest that consumption of milk containing A1 β-casein beyond weaning age may affect mood via a possible gut-brain axis mechanism.
Salminen S, Collado MC, Endo A, et al., 2021, Reply to: Postbiotics - when simplification fails to clarify, NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, Vol: 18, Pages: 827-828, ISSN: 1759-5045
DeBoer MD, Platts-Mills JA, Elwood SE, et al., 2021, Effect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural Tanzania: A factorial randomized, double-blind, placebo-controlled trial, PLOS MEDICINE, Vol: 18, ISSN: 1549-1277
Salminen S, Collado MC, Endo A, et al., 2021, The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics., Nat Rev Gastroenterol Hepatol, Vol: 18, Pages: 649-667
In 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of experts specializing in nutrition, microbial physiology, gastroenterology, paediatrics, food science and microbiology to review the definition and scope of postbiotics. The term 'postbiotics' is increasingly found in the scientific literature and on commercial products, yet is inconsistently used and lacks a clear definition. The purpose of this panel was to consider the scientific, commercial and regulatory parameters encompassing this emerging term, propose a useful definition and thereby establish a foundation for future developments. The panel defined a postbiotic as a "preparation of inanimate microorganisms and/or their components that confers a health benefit on the host". Effective postbiotics must contain inactivated microbial cells or cell components, with or without metabolites, that contribute to observed health benefits. The panel also discussed existing evidence of health-promoting effects of postbiotics, potential mechanisms of action, levels of evidence required to meet the stated definition, safety and implications for stakeholders. The panel determined that a definition of postbiotics is useful so that scientists, clinical triallists, industry, regulators and consumers have common ground for future activity in this area. A generally accepted definition will hopefully lead to regulatory clarity and promote innovation and the development of new postbiotic products.
Salminen S, Collado MC, Endo A, et al., 2021, Publisher Correction: The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics, Nature Reviews Gastroenterology & Hepatology, Vol: 18, Pages: 671-671, ISSN: 1759-5045
Salminen S, Collado MC, Endo A, et al., 2021, The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics (May, 10.1038/s41575-021-00481-x, 2021), NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, Vol: 18, Pages: 671-671, ISSN: 1759-5045
Caspani G, Turecki G, Lam R, et al., 2021, Metabolomic signatures associated with depression and predictors of antidepressant response in humans: A CAN-BIND-1 report, Communications Biology, Vol: 4, ISSN: 2399-3642
One of the biggest challenges in treating depression is the heterogeneous and qualitative nature of its clinical presentations. This highlights the need to find quantitative molecular markers to tailor existing treatment strategies to the individual’s biological system. In this study, high-resolution metabolic phenotyping of urine and plasma samples from the CAN-BIND study collected before treatment with two common pharmacological strategies, escitalopram and aripiprazole, was performed. Here we show that a panel of LDL and HDL subfractions were negatively correlated with depression in males. For treatment response, lower baseline concentrations of apolipoprotein A1 and HDL were predictive of escitalopram response in males, while higher baseline concentrations of apolipoprotein A2, HDL and VLDL subfractions were predictive of aripiprazole response in females. These findings support the potential of metabolomics in precision medicine and the possibility of identifying personalized interventions for depression.
Leng J, McNally S, Walton G, et al., 2021, Hay vs haylage: Forage type influences the equine urinary metabonome and faecal microbiota, EQUINE VETERINARY JOURNAL, Vol: 54, Pages: 614-625, ISSN: 0425-1644
Caspani G, Sebok V, Sultana N, et al., 2021, Metabolic phenotyping of opioid and psychostimulant addiction: A novel approach for biomarker discovery and biochemical understanding of the disorder, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 179, Pages: 1578-1606, ISSN: 0007-1188
Guerrant RL, Bolick DT, Swann JR, 2021, Modeling enteropathy or diarrhea with the top bacterial and protozoal pathogens: differential determinants of outcomes, ACS Infectious Diseases, Vol: 7, Pages: 1020-1031, ISSN: 2373-8227
Developing effective therapeutics or preventive interventions for important health threats is greatly enhanced whenever accessible models can enable the assessment of clinically important outcomes. While no non-human model is ever perfect, inexpensive in vivo small animal models in such as mice are often of great help in assessing the relevant efficacy of potential interventions. In addition to acute diarrhea, the long-term growth and developmental effects of enteric infections, with or without overt diarrhea, are increasingly recognized. To address these diverse effects, inexpensive animal models are proving to be very helpful. Herein, we review the major clinical concerns with enteric parasitic and bacterial infections that are extremely common worldwide, especially in vulnerable young children living in impoverished areas, and the recently published murine models of these infections and their outcomes. We find that common dietary deficiencies seen in children in developing areas have striking effects on diarrhea and enteropathy outcomes in mice. However, these effects differ with different pathogens. Specifically, the effects of protein or zinc deficiency differ considerably with different major protozoal and bacterial pathogens, suggesting different pathogenetic pathways and intervention effects. The pathogens reviewed are the seven top parasitic and bacterial pathogens seen in children, namely, Cryptosporidium, Giardia, Campylobacter, Shigella, enterotoxigenic Escherichia coli (ETEC), enteroaggregative E. coli (EAEC), and enteropathogenic E. coli (EPEC).
Mutasa K, Ntozini R, Mbuya MNN, et al., 2021, Biomarkers of environmental enteric dysfunction are not consistently associated with linear growth velocity in rural Zimbabwean infants, The American Journal of Clinical Nutrition, Vol: 113, Pages: 1185-1198, ISSN: 0002-9165
BackgroundChild stunting remains a poorly understood, prevalent public health problem. Environmental enteric dysfunction (EED) is hypothesized to be an important underlying cause.ObjectivesWithin a subgroup of 1169 children enrolled in the SHINE (Sanitation Hygiene Infant Nutrition Efficacy) trial in rural Zimbabwe, followed longitudinally from birth to 18 mo of age, we evaluated associations between the concentration of 11 EED biomarkers and linear growth velocity.MethodsAt infant ages 1, 3, 6, 12, and 18 mo, nurses measured child length and collected stool and blood; the lactulose-mannitol urine test was also conducted at all visits except at 1 mo. Stool neopterin, α-1 antitrypsin, myeloperoxidase, and regenerating gene 1β protein; urinary lactulose and mannitol; and plasma kynurenine, tryptophan, C-reactive protein, insulin-like growth factor-1 (IGF-1), soluble CD14, intestinal fatty acid binding protein, and citrulline were measured. We analyzed the change in relative [∆ length-for-age z score (LAZ)/mo] and absolute (∆ length/mo) growth velocity during 4 age intervals (1–3 mo; 3–6 mo; 6–12 mo; and 12–18 mo) per SD increase in biomarker concentration at the start of each age interval.ResultsIn fully adjusted models, we observed only 3 small, statistically significant associations: kynurenine:tryptophan ratio at 12 mo was associated with decreased mean LAZ velocity during the 12–18 mo interval (−0.015 LAZ/mo; 95% CI: −0.029, −0.001 LAZ/mo); mannitol excretion at 6 mo was associated with increased LAZ velocity during the 6–12 mo interval (0.013 LAZ/mo; 95% CI: 0.001, 0.025 LAZ/mo), and plasma IGF-1 at 1 mo was associated with increased LAZ velocity during the 1–3 mo interval (0.118 LAZ/mo; 95% CI: 0.024, 0.211 LAZ/mo). Results for absolute growth velocity were similar, except IGF-1 was also associated with growth during the 12–18 mo interval. We found no other associations between any EED
Jordi M-P, Wellington A, Lubach G, et al., 2021, Gut microbial and metabolic profiling reveal the lingering effects of infantile iron deficiency unless treated with iron, Molecular Nutrition and Food Research, Vol: 65, ISSN: 1613-4125
ScopeIron deficiency (ID) compromises the health of infants worldwide. Although readily treated with iron, concerns remain about the persistence of some effects. Metabolic and gut microbial consequences of infantile ID were investigated in juvenile monkeys after natural recovery (pID) from iron deficiency or post‐treatment with iron dextran and B vitamins (pID+Fe).Methods and ResultsMetabolomic profiling of urine and plasma is conducted with 1H nuclear magnetic resonance (NMR) spectroscopy. Gut microbiota are characterized from rectal swabs by amplicon sequencing of the 16S rRNA gene. Urinary metabolic profiles of pID monkeys significantly differed from pID+Fe and continuously iron‐sufficient controls (IS) with higher maltose and lower amounts of microbial‐derived metabolites. Persistent differences in energy metabolism are apparent from the plasma metabolic phenotypes with greater reliance on anaerobic glycolysis in pID monkeys. Microbial profiling indicated higher abundances of Methanobrevibacter, Lachnobacterium, and Ruminococcus in pID monkeys and any history of ID resulted in a lower Prevotella abundance compared to the IS controls.ConclusionsLingering metabolic and microbial effects are found after natural recovery from ID. These long‐term biochemical derangements are not present in the pID+Fe animals emphasizing the importance of the early detection and treatment of early‐life ID to ameliorate its chronic metabolic effects.
van der Linde C, Barone M, Turroni S, et al., 2021, An In Vitro Pilot Fermentation Study on the Impact of Chlorella pyrenoidosa on Gut Microbiome Composition and Metabolites in Healthy and Coeliac Subjects, MOLECULES, Vol: 26
Walker JM, Garcet S, Aleman JO, et al., 2021, Obesity and ethnicity alter gene expression in skin (vol 10, 14079, 2021), SCIENTIFIC REPORTS, Vol: 11, ISSN: 2045-2322
Randall D, Alsam A, Kieswich J, et al., 2021, Uremia causes dysbiosis-mediated periodontal disease
<jats:title>Abstract</jats:title> <jats:p>It is presently unclear why there is a high prevalence of periodontal disease (PD) in individuals living with chronic kidney disease (CKD). By employing three different models in rats and mice, we demonstrate that experimental uremia causes periodontal bone loss. Uremia alters the biochemical composition of saliva and induces progressive dysbiosis of the oral microbiota, with microbial samples from uremic animals displaying reduced overall bacterial growth, increased alpha diversity, reduced abundance of key components of the healthy oral microbiota such as Streptococcus and Rothia, and an increase in minor taxa including those from gram-negative phyla Proteobacteria and Bacteroidetes. We show that transfer of oral microbiota from uremic mice induces PD in germ-free animals, whilst co-housing with healthy animals ameliorates the PD phenotype in rats. Thus, we advocate that periodontal disease should be regarded as a bacterially mediated complication of chronic uremia.</jats:p>
Letertre MPM, Myridakis A, Whiley L, et al., 2021, A targeted ultra performance liquid chromatography - Tandem mass spectrometric assay for tyrosine and metabolites in urine and plasma: Application to the effects of antibiotics on mice, JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, Vol: 1164, ISSN: 1570-0232
Whiley L, Chappell KE, D'Hondt E, et al., 2021, Metabolic phenotyping reveals a reduction in the bioavailability of serotonin and kynurenine pathway metabolites in both the urine and serum of individuals living with Alzheimer's disease, Alzheimers Research & Therapy, Vol: 13, Pages: 1-18, ISSN: 1758-9193
BackgroundBoth serotonergic signalling disruption and systemic inflammation have been associated with the pathogenesis of Alzheimer’s disease (AD). The common denominator linking the two is the catabolism of the essential amino acid, tryptophan. Metabolism via tryptophan hydroxylase results in serotonin synthesis, whilst metabolism via indoleamine 2,3-dioxygenase (IDO) results in kynurenine and its downstream derivatives. IDO is reported to be activated in times of host systemic inflammation and therefore is thought to influence both pathways. To investigate metabolic alterations in AD, a large-scale metabolic phenotyping study was conducted on both urine and serum samples collected from a multi-centre clinical cohort, consisting of individuals clinically diagnosed with AD, mild cognitive impairment (MCI) and age-matched controls.MethodsMetabolic phenotyping was applied to both urine (n = 560) and serum (n = 354) from the European-wide AddNeuroMed/Dementia Case Register (DCR) biobank repositories. Metabolite data were subsequently interrogated for inter-group differences; influence of gender and age; comparisons between two subgroups of MCI - versus those who remained cognitively stable at follow-up visits (sMCI); and those who underwent further cognitive decline (cMCI); and the impact of selective serotonin reuptake inhibitor (SSRI) medication on metabolite concentrations.ResultsResults revealed significantly lower metabolite concentrations of tryptophan pathway metabolites in the AD group: serotonin (urine, serum), 5-hydroxyindoleacetic acid (urine), kynurenine (serum), kynurenic acid (urine), tryptophan (urine, serum), xanthurenic acid (urine, serum), and kynurenine/tryptophan ratio (urine). For each listed metabolite, a decreasing trend in concentrations was observed in-line with clinical diagnosis: control > MCI > AD. There were no significant differences in the two MCI subgroups whilst SSRI medication status influenced o
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