Publications
157 results found
Bhatt AP, Arnold JW, Awoniyi M, et al., 2024, Giardia Antagonizes Beneficial Functions of Indigenous and Therapeutic Intestinal Bacteria during Malnutrition., bioRxiv
Undernutrition in children commonly disrupts the structure and function of the small intestinal microbial community, leading to enteropathies, compromised metabolic health, and impaired growth and development. The mechanisms by which diet and microbes mediate the balance between commensal and pathogenic intestinal flora remain elusive. In a murine model of undernutrition, we investigated the direct interactions Giardia lamblia, a prevalent small intestinal pathogen, on indigenous microbiota and specifically on Lactobacillus strains known for their mucosal and growth homeostatic properties. Our research reveals that Giardia colonization shifts the balance of lactic acid bacteria, causing a relative decrease in Lactobacillus spp . and an increase in Bifidobacterium spp . This alteration corresponds with a decrease in multiple indicators of mucosal and nutritional homeostasis. Additionally, protein-deficient conditions coupled with Giardia infection exacerbate the rise of primary bile acids and susceptibility to bile acid-induced intestinal barrier damage. In epithelial cell monolayers, Lactobacillus spp . mitigated bile acid-induced permeability, showing strain-dependent protective effects. In vivo, L. plantarum, either alone or within a Lactobacillus spp consortium, facilitated growth in protein-deficient mice, an effect attenuated by Giardia , despite not inhibiting Lactobacillus colonization. These results highlight Giardia's potential role as a disruptor of probiotic functional activity, underscoring the imperative for further research into the complex interactions between parasites and bacteria under conditions of nutritional deficiency.
McDonnell D, Afolabi PR, Wilding S, et al., 2023, Utilising Pancreatic Exocrine Insufficiency in the Detection of Resectable Pancreatic Ductal Adenocarcinoma., Cancers (Basel), Vol: 15, ISSN: 2072-6694
Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed late, leading to a high mortality rate. Early detection facilitates better treatment options. The aim of this UK-based case-control study was to determine whether two validated tests for pancreatic exocrine insufficiency (PEI), namely, the 13C-mixed triglyceride breath test (13C-MTGBT) and a faecal elastase (FE-1) test, can discriminate between patients with resectable PDAC versus healthy volunteers (HVs) along with a comparison group with chronic pancreatitis (CP). Discrimination between disease states and HVs was tested with receiver operator characteristic (ROC) curves. In total, 59 participants (23 PDAC (16 men), 24 HVs (13 men) and 12 CP (10 men)) were recruited, with a similar age in each population, and a combined median (IQR) age of 66 (57-71). The areas under the ROC curve for discriminating between PDAC and HVs were 0.83 (95% CI: 0.70-0.96) for the 13C-MTGBT, and 0.85 (95% CI: 0.75-0.95) for the FE-1 test. These were similar to CP vs. HV. In conclusion, PEI occurs in resectable PDAC to a similar extent as in CP; further large-scale, prospective studies using these tests in the primary care setting on high-risk groups are warranted.
Kathrani A, Yen S, Hall EJ, et al., 2023, The effects of a hydrolyzed protein diet on the plasma, fecal and urine metabolome in cats with chronic enteropathy., Sci Rep, Vol: 13
Hydrolyzed protein diets are extensively used to treat chronic enteropathy (CE) in cats. However, the biochemical effects of such a diet on feline CE have not been characterized. In this study an untargeted 1H nuclear magnetic resonance spectroscopy-based metabolomic approach was used to compare the urinary, plasma, and fecal metabolic phenotypes of cats with CE to control cats with no gastrointestinal signs recruited at the Royal Veterinary College (RVC). In addition, the biomolecular consequences of a hydrolyzed protein diet in cats with CE was also separately determined in cats recruited from the RVC (n = 16) and the University of Bristol (n = 24) and whether these responses differed between dietary responders and non-responders. Here, plasma metabolites related to energy and amino acid metabolism significantly varied between CE and control cats in the RVC cohort. The hydrolyzed protein diet modulated the urinary metabolome of cats with CE (p = 0.005) in both the RVC and Bristol cohort. In the RVC cohort, the urinary excretion of phenylacetylglutamine, p-cresyl-sulfate, creatinine and taurine at diagnosis was predictive of dietary response (p = 0.025) although this was not observed in the Bristol cohort. Conversely, in the Bristol cohort plasma betaine, glycerol, glutamine and alanine at diagnosis was predictive of outcome (p = 0.001), but these same results were not observed in the RVC cohort. The biochemical signature of feline CE in the RVC cohort was consistent with that identified in human and animal models of inflammatory bowel disease. The hydrolyzed protein diet had the same effect on the urinary metabolome of cats with CE at both sites. However, biomarkers that were predictive of dietary response at diagnosis differed between the 2 sites. This may be due to differences in disease severity, disease heterogeneity, factors unrelated to the disease or small sample size at both sites. As su
Ling C, Versloot CJ, Arvidsson Kvissberg ME, et al., 2023, Rebalancing of mitochondrial homeostasis through an NAD+-SIRT1 pathway preserves intestinal barrier function in severe malnutrition., EBioMedicine, Vol: 96
BACKGROUND: The intestine of children with severe malnutrition (SM) shows structural and functional changes that are linked to increased infection and mortality. SM dysregulates the tryptophan-kynurenine pathway, which may impact processes such as SIRT1- and mTORC1-mediated autophagy and mitochondrial homeostasis. Using a mouse and organoid model of SM, we studied the repercussions of these dysregulations on malnutrition enteropathy and the protective capacity of maintaining autophagy activity and mitochondrial health. METHODS: SM was induced through feeding male weanling C57BL/6 mice a low protein diet (LPD) for 14-days. Mice were either treated with the NAD+-precursor, nicotinamide; an mTORC1-inhibitor, rapamycin; a SIRT1-activator, resveratrol; or SIRT1-inhibitor, EX-527. Malnutrition enteropathy was induced in enteric organoids through amino-acid deprivation. Features of and pathways to malnutrition enteropathy were examined, including paracellular permeability, nutrient absorption, and autophagic, mitochondrial, and reactive-oxygen-species (ROS) abnormalities. FINDINGS: LPD-feeding and ensuing low-tryptophan availability led to villus atrophy, nutrient malabsorption, and intestinal barrier dysfunction. In LPD-fed mice, nicotinamide-supplementation was linked to SIRT1-mediated activation of mitophagy, which reduced damaged mitochondria, and improved intestinal barrier function. Inhibition of mTORC1 reduced intestinal barrier dysfunction and nutrient malabsorption. Findings were validated and extended using an organoid model, demonstrating that resolution of mitochondrial ROS resolved barrier dysfunction. INTERPRETATION: Malnutrition enteropathy arises from a dysregulation of the SIRT1 and mTORC1 pathways, leading to disrupted autophagy, mitochondrial homeostasis, and ROS. Whether nicotinamide-supplementation in children with SM could ameliorate malnutrition enteropathy should be explored in clinical trials. FUNDING: This work was supported by the Bill and Melind
Swann JR, Heijtz RD, Mayneris-Perxachs J, et al., 2023, Characterizing the metabolomic signature of attention-deficit hyperactivity disorder in twins, NEUROPHARMACOLOGY, Vol: 234, ISSN: 0028-3908
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- Citations: 2
Zuffa S, Schimmel P, Gonzalez-Santana A, et al., 2023, Early-life differences in the gut microbiota composition and functionality of infants at elevated likelihood of developing autism spectrum disorder, TRANSLATIONAL PSYCHIATRY, Vol: 13, ISSN: 2158-3188
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- Citations: 1
Warren CA, Shin JH, Bansal EN, et al., 2023, Alanyl-glutamine supplementation for <i>Clostridioides difficile</i> infection treatment (ACT): a double-blind randomised controlled trial study protocol, BMJ OPEN, Vol: 13, ISSN: 2044-6055
Deane CS, Swann JR, 2023, Harnessing metabolomics to better understand exercise-mediated substrate metabolism, EXPERIMENTAL PHYSIOLOGY, Vol: 108, Pages: 797-798, ISSN: 0958-0670
Giallourou N, Arnold J, McQuade ETR, et al., 2023, <i>Giardia</i> hinders growth by disrupting nutrient metabolism independent of inflammatory enteropathy, NATURE COMMUNICATIONS, Vol: 14
Jones HJ, Bourke CD, Swann JR, et al., 2023, Malnourished Microbes: Host-Microbiome Interactions in Child Undernutrition, ANNUAL REVIEW OF NUTRITION, Vol: 43, Pages: 327-353, ISSN: 0199-9885
Hodge SH, Krauss MZ, Kaymak I, et al., 2022, Amino acid availability acts as a metabolic rheostat to determine the magnitude of ILC2 responses, JOURNAL OF EXPERIMENTAL MEDICINE, Vol: 220, ISSN: 0022-1007
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- Citations: 2
Hu G, Ling C, Chi L, et al., 2022, The role of the tryptophan-NAD plus pathway in a mouse model of severe malnutrition induced liver dysfunction, NATURE COMMUNICATIONS, Vol: 13
Smith LE, Chagwena DT, Bourke C, et al., 2022, Child Health, Agriculture and Integrated Nutrition (CHAIN): protocol for a randomised controlled trial of improved infant and young child feeding in rural Zimbabwe, BMJ OPEN, Vol: 12, ISSN: 2044-6055
Marino L, Paulson S, Ashton JJ, et al., 2022, A scoping review: urinary markers of metabolic maturation in infants with CHD and the relationship to growth, CARDIOLOGY IN THE YOUNG, ISSN: 1047-9511
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.
Marino L, Paulson S, Ashton JJ, et al., 2022, A Scoping Review: Urinary Markers of Metabolic Maturation in Preterm Infants and Future Interventions to Improve Growth, NUTRIENTS, Vol: 14
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- Citations: 1
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
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- Citations: 1
Penny HA, Domingues RG, Krauss MZ, et al., 2022, Rhythmicity of intestinal IgA responses confers oscillatory commensal microbiota mutualism, SCIENCE IMMUNOLOGY, Vol: 7, ISSN: 2470-9468
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- Citations: 13
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
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- Citations: 4
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
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- Citations: 2
Leng J, McNally S, Walton G, et al., 2022, Hay vs haylage: Forage type influences the equine urinary metabonome and faecal microbiota, EQUINE VETERINARY JOURNAL, Vol: 54, Pages: 614-625, ISSN: 0425-1644
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- Citations: 1
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
Caspani G, Sebok V, Sultana N, et al., 2022, 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
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- Citations: 10
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
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
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- Citations: 4
Heijtz RD, Gressens P, Swann JR, 2022, Targeting microbial metabolites to treat autism, NATURE MEDICINE, Vol: 28, Pages: 448-450, ISSN: 1078-8956
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
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- Citations: 1
Vatanen T, Sakwinska O, Wilson B, et al., 2022, Transcription shifts in gut bacteria shared between mothers and their infants., Sci Rep, Vol: 12
The infant gut microbiome contains a portion of bacteria that originate from the maternal gut. In the infant gut these bacteria encounter a new metabolic environment that differs from the adult gut, consequently requiring adjustments in their activities. We used pilot community RNA sequencing data (metatranscriptomes) from ten mother-infant dyads participating in the NiPPeR Study to characterize bacterial gene expression shifts following mother-to-infant transmission. Maternally-derived bacterial strains exhibited large scale gene expression shifts following the transmission to the infant gut, with 12,564 activated and 14,844 deactivated gene families. The implicated genes were most numerous and the magnitude shifts greatest in Bacteroides spp. This pilot study demonstrates environment-dependent, strain-specific shifts in gut bacteria function and underscores the importance of metatranscriptomic analysis in microbiome studies.
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
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- Citations: 13
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
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- Citations: 1
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