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Conference paperRouty B, Lenehan J, Daisley B, et al., 2022, , SITC 37th Annual Meeting (SITC 2022) Abstracts, Publisher: BMJ Publishing Group Ltd, Pages: A646-A646
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Conference paperLythgoe M, Mullish B, Frampton A, et al., 2022, , Publisher: BMJ PUBLISHING GROUP, Pages: A659-A659
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Journal articleIaniro G, Mullish BH, Iqbal TH, et al., 2022, , The Lancet Gastroenterology & Hepatology, Vol: 7, Pages: 979-980, ISSN: 2468-1253
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Conference paperMullish BH, Paizs P, Alexander J, et al., 2022, , UEG Week 2022, Pages: 823-823
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Journal articleForlano R, Sivakumar M, Mullish BH, et al., 2022, , International Journal of Molecular Sciences, Vol: 23, Pages: 1-13, ISSN: 1422-0067
Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease, affecting one-third of the population worldwide. Despite many medications being in the pipeline to treat the condition, there is still no pharmaceutical agent licensed to treat the disease. As intestinal bacteria play a crucial role in the pathogenesis and progression of liver damage in patients with NAFLD, it has been suggested that manipulating the microbiome may represent a therapeutical option. In this review, we summarise the latest evidence supporting the manipulation of the intestinal microbiome as a potential therapy for treating liver disease in patients with NAFLD.
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Journal articleMullish BH, McDonald JAK, Marchesi JR, 2022, , The Lancet Gastroenterology & Hepatology, Vol: 7, Pages: 594-594, ISSN: 2468-1253
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Journal articleGhani R, Mullish BH, Davies FJ, et al., 2022, , Clinical Microbiology and Infection, Vol: 28, Pages: 502-512, ISSN: 1198-743X
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Journal articleFromentin S, Forslund SK, Chechi K, et al., 2022, , Nature Medicine, Vol: 28, Pages: 303-+, ISSN: 1078-8956
Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages—acute coronary syndrome, chronic IHD and IHD with heart failure—and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features.
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Journal articleTalmor-Barkan Y, Bar N, Shaul AA, et al., 2022, , NATURE MEDICINE, Vol: 28, Pages: 295-+, ISSN: 1078-8956
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Journal articleForlano R, Mullish BH, Roberts LA, et al., 2022, , International Journal of Molecular Sciences, Vol: 23, ISSN: 1422-0067
Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease worldwide, mirroring the epidemics of obesity and metabolic syndrome. As there are still no licensed medications for treating the disease, there is an ongoing effort to elucidate the pathophysiology and to discover new treatment pathways. An increasing body of evidence has demonstrated a crosstalk between the gut and the liver, which plays a crucial role in the development and progression of liver disease. Among other intestinal factors, gut permeability represents an interesting factor at the interface of the gut–liver axis. In this narrative review, we summarise the evidence from human studies showing the association between increased gut permeability and NAFLD, as well as with type-2 diabetes and obesity. We also discuss the manipulation of the gut permeability as a potential therapeutical target in patients with NAFLD.
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