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Journal articleBrial F, Chilloux J, Nielsen T, et al., 2021,
Human and preclinical studies of the host-gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health.
, Gut, Vol: 70, Pages: 2105-2114, ISSN: 0017-5749OBJECTIVE: Gut microbial products are involved in regulation of host metabolism. In human and experimental studies, we explored the potential role of hippurate, a hepatic phase 2 conjugation product of microbial benzoate, as a marker and mediator of metabolic health. DESIGN: In 271 middle-aged non-diabetic Danish individuals, who were stratified on habitual dietary intake, we applied 1H-nuclear magnetic resonance (NMR) spectroscopy of urine samples and shotgun-sequencing-based metagenomics of the gut microbiome to explore links between the urine level of hippurate, measures of the gut microbiome, dietary fat and markers of metabolic health. In mechanistic experiments with chronic subcutaneous infusion of hippurate to high-fat-diet-fed obese mice, we tested for causality between hippurate and metabolic phenotypes. RESULTS: In the human study, we showed that urine hippurate positively associates with microbial gene richness and functional modules for microbial benzoate biosynthetic pathways, one of which is less prevalent in the Bacteroides 2 enterotype compared with Ruminococcaceae or Prevotella enterotypes. Through dietary stratification, we identify a subset of study participants consuming a diet rich in saturated fat in which urine hippurate concentration, independently of gene richness, accounts for links with metabolic health. In the high-fat-fed mice experiments, we demonstrate causality through chronic infusion of hippurate (20 nmol/day) resulting in improved glucose tolerance and enhanced insulin secretion. CONCLUSION: Our human and experimental studies show that a high urine hippurate concentration is a general marker of metabolic health, and in the context of obesity induced by high-fat diets, hippurate contributes to metabolic improvements, highlighting its potential as a mediator of metabolic health.
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Conference paperBarker GF, Pechlivanis A, Bello AT, et al., 2021,
Aa022 a high-fiber low-fat diet increases fecal levels of lithocholic acid derivative 3-ketocholanic acid
, Digestive Disease Week, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S393-S394, ISSN: 0016-5085 -
Journal articleHoyles L, Mayneris-Perxachs J, Cardellini M, et al., 2021,
Iron status influences non-alcoholic fatty liver disease in obesity through the gut microbiome
, Microbiome, Vol: 9, Pages: 1-18, ISSN: 2049-2618Background: The gut microbiome and iron status are known to play a role in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), although their complex interaction remains unclear.Results: Here, we applied an integrative systems medicine approach (faecal metagenomics, plasma and urine metabolomics, hepatic transcriptomics) in 2 well-characterised human cohorts of subjects with obesity (discovery n = 49 and validation n = 628) and an independent cohort formed by both individuals with and without obesity (n = 130), combined with in vitro and animal models. Serum ferritin levels, as a markers of liver iron stores, were positively associated with liver fat accumulation in parallel with lower gut microbial gene richness, composition and functionality. Specifically, ferritin had strong negative associations with the Pasteurellaceae, Leuconostocaceae and Micrococcaea families. It also had consistent negative associations with several Veillonella, Bifidobacterium and Lactobacillus species, but positive associations with Bacteroides and Prevotella spp. Notably, the ferritin-associated bacterial families had a strong correlation with iron-related liver genes. In addition, several bacterial functions related to iron metabolism (transport, chelation, heme and siderophore biosynthesis) and NAFLD (fatty acid and glutathione biosynthesis) were also associated with the host serum ferritin levels. This iron-related microbiome signature was linked to a transcriptomic and metabolomic signature associated to the degree of liver fat accumulation through hepatic glucose metabolism. In particular, we found a consistent association among serum ferritin, Pasteurellaceae and Micrococcacea families, bacterial functions involved in histidine transport, the host circulating histidine levels and the liver expression of GYS2 and SEC24B. Serum ferritin was also related to bacterial glycine transporters, the host glycine serum levels and the liver expression of glycine transporters. The
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Conference paperMullish BH, Marchesi J, Pass DA, et al., 2021,
DAILY PROBIOTIC USE IS ASSOCIATED WITH A REDUCED RATE OF UPPER RESPIRATORY TRACT SYMPTOMS IN OVERWEIGHT AND OBESE PEOPLE
, Society-for-Surgery-of-the-Alimentary-Tract Annual Meeting at Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S150-S150, ISSN: 0016-5085 -
Conference paperRadhakrishnan ST, Mullish BH, Gallagher K, et al., 2021,
RECTAL SWABS AS A VIABLE ALTERNATIVE TO FECAL SAMPLING FOR THE ANALYSIS OF GUT MICROBIOME FUNCTIONALITY AS WELL AS COMPOSITION
, Society-for-Surgery-of-the-Alimentary-Tract Annual Meeting at Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S733-S733, ISSN: 0016-5085 -
Conference paperMartinez-Gili L, Mullish BH, Correia G, et al., 2021,
A distinctive signature of fecal bile acids and other novel metabolites accompanying recurrence after primary clostridioides difficile infection
, Society for Surgery of the Alimentary Tract Annual Meeting at Digestive Disease Week (DDW), Publisher: Elsevier, Pages: S368-S368, ISSN: 0016-5085 -
Conference paperAllegretti JR, Mullish BH, Marchesi J, et al., 2021,
ASSOCIATION BETWEEN NOVEL METABOLOMIC BIOMARKERS AND C.DIFFICILE RECURRENCE
, Society-for-Surgery-of-the-Alimentary-Tract Annual Meeting at Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S369-S369, ISSN: 0016-5085 -
Conference paperMullish BH, Innes AJ, Ghani R, et al., 2021,
FECAL MICROBIOTA TRANSPLANT PRIOR TO ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANT IN PATIENTS COLONIZED WITH MULTI-DRUG RESISTANT ORGANISMS IS ASSOCIATED WITH IMPROVED SURVIVAL
, Society-for-Surgery-of-the-Alimentary-Tract Annual Meeting at Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S168-S169, ISSN: 0016-5085 -
Journal articleGhani 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: 1058-4838Fecal 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.
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Journal articleMullish BH, Alexander JL, Segal JP, 2021,
Microbiota and faecal microbiota transplant
, Microbiota in Health and Disease, Vol: 3, ISSN: 2704-8845As the range of disease states associated with the gut microbiome expands - and the mechanistic links between the gut microbiome and host physiology further deepens – so interest also grows in microbiome manipulation as medical therapy. In particular, bolstered by its established role in recurrent C. difficile infection (and promising results in other conditions), faecal microbiota transplant (FMT) has remained of growing global focus. This article reviews the key FMT-based studies published between April 2020 - March 2021. While the COVID-19 pandemic was the dominant challenge of the year, important FMT trials of interest were published for patients with a range of different conditions. The emergence of ‘next generation’ microbiome therapeutics offers an additional perspective and new opportunities within the field.
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