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Journal articleAllegretti JR, Mullish BH, Kelly C, et al., 2019, , Lancet, Vol: 394, Pages: 420-431
Developments in high-throughput microbial genomic sequencing and other systems biology techniques have given novel insight into the potential contribution of the gut microbiota to health and disease. As a result, an increasing number of diseases have been characterised by distinctive changes in the composition and functionality of the gut microbiota; however, whether such changes are cause, consequence, or incidental to the disease in question remains largely uncertain. Restoration of the gut microbiota to a premorbid state is a key novel therapeutic approach of interest, and faecal microbiota transplantation-the transfer of prescreened stool from healthy donors into the gastrointestinal tract of patients-is gaining increasing importance in both the clinical and research settings. At present, faecal microbiota transplantation is only recommended in the treatment of recurrent Clostridioides difficile infection, although a large number of trials are ongoing worldwide exploring other potential therapeutic indications.
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Conference paperRiaz Z, Wright M, Atkinson S, et al., 2019,
Malignant and cirrhotic ascites demonstrate a similar microbiome profile
, British Association for the Study of the Liver (BASL) Annual Meeting -
Journal articleAllegretti JA, Kassam Z, Carrellas M, et al., 2019, , American Journal of Gastroenterology, Vol: 114, Pages: 1071-1079, ISSN: 1572-0241
Background: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with no effective medical therapies. A perturbation of the gut microbiota has been described in association with PSC, and fecal microbiota transplantation (FMT) has been reported to restore the microbiome in other disease states. Accordingly, we aimed to evaluate the safety, change in liver enzymes, microbiota and metabolomic profiles in PSC patients after FMT.Methods: Open-label pilot study of PSC patients with concurrent inflammatory bowel disease (IBD) and ALP > 1.5X the upper limit of normal. Participants underwent a single FMT by colonoscopy. Liver enzyme profiles and stool microbiome and metabolomic analysis was conducted at baseline and week 1, 4, 8, 12 and 24 post-FMT. The primaryoutcome was safety and secondary outcomes include a decrease in ALP ≥50% from baseline by week 24 post-FMT, as well as stool microbiota (by 16S rRNA gene profiling) and metabonomic dynamics were assessed.Results. Ten patients underwent FMT. Nine patients had ulcerative colitis and 1 with Crohn’s colitis. The mean baseline ALP was 489 U/L. There were no related adverse events. Overall, 30% (3/10) experienced a ≥50% decrease ALP. The diversity increased in all patients post-FMT, as early as week 1 (p<0.01). Importantly, abundance of engrafter operational taxanomic units (OTUs) in patients post-FMT correlated with decreased ALP (p=0.02).Conclusion: To our knowledge, this first study to demonstrate that FMT in PSC is safe. Additionally, increases in bacterial diversity and engraftment may correlate with an improvement in ALP among PSC patients.
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Journal articleNathwani R, Mullish BH, Kockerling D, et al., 2019, , Gut, Vol: 69, Pages: 726-780, ISSN: 0017-5749
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Conference paperGhani R, Gan C, Mullish BH, et al., 2019, , British Association of Urological Surgeons Annual Scientific Meeting, Publisher: SAGE Publications, Pages: 83-85, ISSN: 2051-4158
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Journal articleAllegretti JR, Kassam Z, Chiang AL, et al., 2019, , Gastroenterology, Vol: 156, Pages: S-129-S-129, ISSN: 0016-5085
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Journal articleAllegretti JR, Hurtado J, Carrellas M, et al., 2019, , Gastroenterology, Vol: 156, Pages: S-2-S-3, ISSN: 0016-5085
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Journal articleChurchward MA, Michaud ER, Blanco JM, et al., 2019, , Gastroenterology, Vol: 156, Pages: S-455-S-455, ISSN: 0016-5085
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Journal articleMcDonald JA, Perez JL, Mullish BH, et al., 2019, , Gastroenterology, Vol: 156, Pages: S-898-S-898, ISSN: 0016-5085
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Journal articleAbdul Rahim MBH, Chilloux J, Martinez-Gili L, et al., 2019, , Acta Diabetologica, Vol: 56, Pages: 493-500, ISSN: 0940-5429
The human gut is a home for more than 100 trillion bacteria, far more than all other microbial populations resident on the body's surface. The human gut microbiome is considered as a microbial organ symbiotically operating within the host. It is a collection of different cell lineages that are capable of communicating with each other and the host and has an ability to undergo self-replication for its repair and maintenance. As the gut microbiota is involved in many host processes including growth and development, an imbalance in its ecological composition may lead to disease and dysfunction in the human. Gut microbial degradation of nutrients produces bioactive metabolites that bind target receptors, activating signalling cascades, and modulating host metabolism. This review covers current findings on the nutritional and pharmacological roles of selective gut microbial metabolites, short-chain fatty acids, methylamines and indoles, as well as discussing nutritional interventions to modulate the microbiome.
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