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• Journal article
  Ghani R, Mullish BH, Davies FJ, Marchesi JRet al., 2022,

  How to adapt an intestinal microbiota transplantation programme to reduce the risk of invasive multidrug-resistant infection

  , Clinical Microbiology and Infection, Vol: 28, Pages: 502-512, ISSN: 1198-743X
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• Journal article
  Fromentin S, Forslund SK, Chechi K, Aron-Wisnewsky J, Chakaroun R, Nielsen T, Tremaroli V, Ji B, Prifti E, Myridakis A, Chilloux J, Andrikopoulos P, Fan Y, Olanipekun MT, Alves R, Adiouch S, Bar N, Talmor-Barkan Y, Belda E, Caesar R, Coelho LP, Falony G, Fellahi S, Galan P, Galleron N, Helft G, Hoyles L, Isnard R, Le Chatelier E, Julienne H, Olsson L, Pedersen HK, Pons N, Quinquis B, Rouault C, Roume H, Salem J-E, Schmidt TSB, Vieira-Silva S, Li P, Zimmermann-Kogadeeva M, Lewinter C, Sondertoft NB, Hansen TH, Gauguier D, Gotze JP, Kober L, Kornowski R, Vestergaard H, Hansen T, Zucker J-D, Hercberg S, Letunic I, Backhed F, Oppert J-M, Nielsen J, Raes J, Bork P, Stumvoll M, Segal E, Clement K, Dumas M-E, Ehrlich SD, Pedersen Oet al., 2022,

  Microbiome and metabolome features of the cardiometabolic disease spectrum

  , 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 article
  Talmor-Barkan Y, Bar N, Shaul AA, Shahaf N, Godneva A, Bussi Y, Lotan-Pompan M, Weinberger A, Shechter A, Chezar-Azerrad C, Arow Z, Hammer Y, Chechi K, Forslund SK, Fromentin S, Dumas M-E, Ehrlich SD, Pedersen O, Kornowski R, Segal Eet al., 2022,

  Metabolomic and microbiome profiling reveals personalized risk factors for coronary artery disease

  , NATURE MEDICINE, Vol: 28, Pages: 295-+, ISSN: 1078-8956
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  • Citations: 131
• Journal article
  Forlano R, Mullish BH, Roberts LA, Thursz MR, Manousou Pet al., 2022,

  The intestinal barrier and its dysfunction in patients with metabolic diseases and non-alcoholic fatty liver disease

  , 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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• Journal article
  Biliński J, Winter K, Jasiński M, Szczęś A, Bilinska N, Mullish BH, Małecka-Panas E, Basak GWet al., 2022,

  Rapid resolution of COVID-19 after faecal microbiota transplantation.

  , Gut, Vol: 71, Pages: 230-232
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• Journal article
  Radhakrishnan ST, Alexander JL, Mullish BH, Gallagher KI, Powell N, Hicks LC, Hart AL, Li JV, Marchesi JR, Williams HRTet al., 2022,

  Systematic review: the association between the gut microbiota and medical therapies in inflammatory bowel disease

  , Alimentary Pharmacology & Therapeutics, Vol: 55, Pages: 26-48, ISSN: 0269-2813

  <jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The gut microbiota has been implicated in the pathogenesis of inflammatory bowel disease (IBD), with <jats:italic>Faecalibacterium prausnitizii</jats:italic> associated with protection, and certain genera (including <jats:italic>Shigella</jats:italic> and <jats:italic>Escherichia</jats:italic>) associated with adverse features. The variability of patient response to medical therapies in IBD is incompletely understood. Given the recognised contribution of the microbiota to treatment efficacy in other conditions, there may be interplay between the gut microbiota, IBD medical therapy and IBD phenotype.</jats:p></jats:sec><jats:sec><jats:title>Aims</jats:title><jats:p>To evaluate the bidirectional relationship between IBD medical therapies and the gut microbiota.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We conducted a systematic search of MEDLINE and EMBASE. All original studies analysing interactions between the gut microbiota and established IBD medical therapies were included.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We screened 1296 records; 19 studies were eligible. There was heterogeneity in terms of sample analysis, treatment protocols, and outcome reporting. Increased baseline α‐diversity was observed in responders versus non‐responders treated with exclusive enteral nutrition (EEN), infliximab, ustekinumab or vedolizumab. Higher baseline <jats:italic>Faecalibacterium</jats:italic> predicted response to infliximab and ustekinumab. A post‐treatment increase in <jats:italic>Faecalibacterium prausnitzii</jats:italic> was noted in responders to aminosalicylates, anti‐TNF medications and ustekinumab; conversely, this speci

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• Journal article
  Forslund SK, Chakaroun R, Zimmermann-Kogadeeva M, Marko L, Aron-Wisnewsky J, Nielsen T, Moitinho-Silva L, Schmidt TSB, Falony G, Vieira-Silva S, Adriouch S, Alves RJ, Assmann K, Bastard J-P, Birkner T, Caesar R, Chilloux J, Coelho LP, Fezeu L, Galleron N, Helft G, Isnard R, Ji B, Kuhn M, Le Chatelier E, Myridakis A, Olsson L, Pons N, Prifti E, Quinquis B, Roume H, Salem J-E, Sokolovska N, Tremaroli V, Valles-Colomer M, Lewinter C, Sondertoft NB, Pedersen HK, Hansen TH, Gotze JP, Kober L, Vestergaard H, Hansen T, Zucker J-D, Hercberg S, Oppert J-M, Letunic I, Nielsen J, Backhed F, Ehrlich SD, Dumas M-E, Raes J, Pedersen O, Clement K, Stumvoll M, Bork Pet al., 2021,

  Combinatorial, additive and dose-dependent drug-microbiome associations

  , Nature, Vol: 600, Pages: 500-505, ISSN: 0028-0836

  During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1,2,3,4,5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.

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• Journal article
  Biliński J, Jasiński M, Tomaszewska A, Lis K, Kacprzyk P, Chmielewska L, KarakulskaPrystupiuk E, Mullish BH, Basak GWet al., 2021,

  Fecal microbiota transplantation with ruxolitinib as a treatment modality for steroid‐refractory/dependent acute, gastrointestinal graft‐versus‐host disease: A case series

  , American Journal of Hematology, Vol: 96, ISSN: 0361-8609
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• Journal article
  Monaghan TM, Duggal NA, Rosati E, Griffin R, Hughes J, Roach B, Yang DY, Wang C, Wong K, Saxinger L, Pučić-Baković M, Vučković F, Klicek F, Lauc G, Tighe P, Mullish BH, Miguens Blanco J, McDonald JAK, Marchesi JR, Xue N, Dottorini T, Acharjee A, Franke A, Wong GK-S, Polytarchou C, Yau TO, Christodoulou N, Hatziapostoulou M, Wang M, Russell LA, Kao DHet al., 2021,

  A multi-factorial observational study on sequential fecal microbiota transplant in patients with medically refractory Clostridioides difficile infection

  , Cells, Vol: 10, ISSN: 2073-4409

  Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI); increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies.

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• Journal article
  Tarazi M, Jamel S, Mullish BH, Markar SR, Hanna GBet al., 2021,

  Impact of gastrointestinal surgery upon the gut microbiome: a systematic review

  , Surgery, Vol: 171, ISSN: 0039-6060

  BackgroundThere is evidence from preclinical models that the gut microbiome may impact outcomes from gastrointestinal surgery, and that surgery may alter the gut microbiome. However, the extent to which gastrointestinal surgery modulates the gut microbiome in clinical practice is currently poorly defined. This systematic review aims to evaluate the changes observed in the gut microbiome after gastrointestinal surgery.MethodsA systematic review and meta-analysis were conducted according to the PRISMA guidelines by screening EMBASE, MEDLINE/PubMed, Web of Science, and CENTRAL for comparative studies meeting the predetermined inclusion criteria. The primary outcome was the difference between pre and postoperative bacterial taxonomic composition and diversity metrics among patients receiving gastrointestinal surgery.ResultsIn total, 33 studies were identified including 6 randomized controlled trials and 27 prospective cohort studies reporting a total of 968 patients. Gastrointestinal surgery was associated with an increase in α diversity and a shift in β diversity postoperatively. Multiple bacterial taxa were identified to consistently trend toward an increase or decrease postoperatively. A difference in microbiota across geographic provenance was also observed. There was a distinct lack of studies showing correlation with clinical outcomes or performing microbiome functional analysis. Furthermore, there was a lack of standardization in sampling, analytical methodology, and reporting.ConclusionThis review highlights changes in bacterial taxa associated with gastrointestinal surgery. There is a need for standardization of microbial analysis methods and reporting of results to allow interstudy comparison. Further adequately powered multicenter studies are required to better assess variation in microbial changes and its potential associations with clinical outcomes.

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