Human liver microbiota modeling strategy at the early onset of fibrosis

BMC Microbiology

Research

Maria Arnoriaga-Rodriguez¹  Jose-Manuel Fernández-Real¹  Herbert Tilg²  Maria Effernberger²  Marina Cardellini³  Massimo Federici³  Jeffrey E. Christensen⁴  Charlotte Thomas⁴  Pascale Loubieres⁴  Matthieu Minty⁴  Vincent Azalbert⁴  Rémy Burcelin⁴  Vincent Blasco-Baque⁴  Camille Champion⁵  Jacques Amar⁶  Jean Michel Loubes⁷  Fabrice Gamboa⁷  Radu M. Neagoe⁸  Daniela T. Sala⁸  Florence Servant⁹  Benjamin Lelouvier⁹ 

[1] Department of Diabetes, Endocrinology and Nutrition, University Hospital of Girona ‘Dr Josep Trueta’, Girona, Spain;Institut d’Investigacio Biomedica de Girona IdibGi, Girona, Spain;CIBER Fisiopatologia de La Obesidad Y Nutricion, Girona, Spain;Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria;Department of Systems Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, 00133, Rome, Italy;Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France;Unité Mixte de Recherche (UMR) 1297, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2: ‘Intestinal Risk FactorsDiabetesDyslipidemia’, Université Paul Sabatier (UPS), F-31432, Toulouse Cedex 4, France;Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France;Unité Mixte de Recherche (UMR) 1297, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2: ‘Intestinal Risk FactorsDiabetesDyslipidemia’, Université Paul Sabatier (UPS), F-31432, Toulouse Cedex 4, France;Institut de Mathématiques de Toulouse, Université Paul Sabatier, Toulouse, France;Institut National de La Santé Et de La Recherche Médicale (INSERM), Toulouse, France;Unité Mixte de Recherche (UMR) 1297, Institut Des Maladies Métaboliques Et Cardiovasculaires (I2MC), Team 2: ‘Intestinal Risk FactorsDiabetesDyslipidemia’, Université Paul Sabatier (UPS), F-31432, Toulouse Cedex 4, France;Therapeutics Department, Rangueil Hospital, Toulouse, France;Institut de Mathématiques de Toulouse, Université Paul Sabatier, Toulouse, France;Second Department of Surgery, Emergency Mureş County Hospital, University of Medicine Pharmacy, Science and Technology “George Emil Palade” Tîrgu Mures, Târgu Mureș, Romania;VAIOMER, 516 Rue Pierre Et Marie Curie, 31670, Labège, France;

关键词: Biomathematics;    Liver diseases;    Metabolic disease;    Microbiota;    Tissue microbiota;   

DOI  :  10.1186/s12866-023-02774-4

 received in 2022-05-05, accepted in 2023-01-13,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundGut microbiota is involved in the development of liver diseases such as fibrosis. We and others identified that selected sets of gut bacterial DNA and bacteria translocate to tissues, notably the liver, to establish a non-infectious tissue microbiota composed of microbial DNA and a low frequency live bacteria. However, the precise set of bacterial DNA, and thereby the corresponding taxa associated with the early stages of fibrosis need to be identified. Furthermore, to overcome the impact of different group size and patient origins we adapted innovative statistical approaches. Liver samples with low liver fibrosis scores (F0, F1, F2), to study the early stages of the disease, were collected from Romania(n = 36), Austria(n = 10), Italy(n = 19), and Spain(n = 17). The 16S rRNA gene was sequenced. We considered the frequency, sparsity, unbalanced sample size between cohorts to identify taxonomic profiles and statistical differences.ResultsMultivariate analyses, including adapted spectral clustering with L1-penalty fair-discriminant strategies, and predicted metagenomics were used to identify that 50% of liver taxa associated with the early stage fibrosis were Enterobacteriaceae, Pseudomonadaceae, Xanthobacteriaceae and Burkholderiaceae. The Flavobacteriaceae and Xanthobacteriaceae discriminated between F0 and F1. Predicted metagenomics analysis identified that the preQ0 biosynthesis and the potential pathways involving glucoryranose and glycogen degradation were negatively associated with liver fibrosis F1-F2 vs F0.ConclusionsWithout demonstrating causality, our results suggest first a role of bacterial translocation to the liver in the progression of fibrosis, notably at the earliest stages. Second, our statistical approach can identify microbial signatures and overcome issues regarding sample size differences, the impact of environment, and sets of analyses.Trial registrationTirguMECCH ROLIVER Prospective Cohort for the Identification of Liver Microbiota, registration 4065/2014. Registered 01 01 2014.

【 授权许可】

CC BY   
© The Author(s) 2023

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