O-5 INTEGRATED ANALYSIS OF ARCHAEAL, FUNGAL AND PROTOZOAN GUT TRANSCRIPTOME IN METABOLIC ASSOCIATED FATTY LIVER DISEASE (MAFLD) IN ARGENTINA

Introduction and Objectives: Fungi, archaea and protozoa are the least known members of the gut microbiome, but they could represent a niche for biomarkers discovery to risk-stratify MAFLD patients. This study aimed to identify gut metatranscriptomic signatures in MAFLD patients from Argentina. Mate...

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Main Authors: Bárbara Suárez, María Florencia Mascardi, Flavia Noelia Mazzini, M. Ruda Vera, Sebastián Marciano, Paola Casciato, Adrián Narvaez, Leila Haddad, Margarita Anders, Federico Orozco, Ana Jesica Tamaroff, Frank Cook, John Gounarides, Susana Gutt, Adrián Gadano, Celia Mén dez García, Martin L. Marro, Alberto Penas Steinhardt, Julieta Trinks
Format: Article
Language:English
Published: Elsevier 2023-03-01
Series:Annals of Hepatology
Online Access:http://www.sciencedirect.com/science/article/pii/S1665268123001199
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author Bárbara Suárez
María Florencia Mascardi
Flavia Noelia Mazzini
M. Ruda Vera
Sebastián Marciano
Paola Casciato
Adrián Narvaez
Leila Haddad
Margarita Anders
Federico Orozco
Ana Jesica Tamaroff
Frank Cook
John Gounarides
Susana Gutt
Adrián Gadano
Celia Mén dez García
Martin L. Marro
Alberto Penas Steinhardt
Julieta Trinks
author_facet Bárbara Suárez
María Florencia Mascardi
Flavia Noelia Mazzini
M. Ruda Vera
Sebastián Marciano
Paola Casciato
Adrián Narvaez
Leila Haddad
Margarita Anders
Federico Orozco
Ana Jesica Tamaroff
Frank Cook
John Gounarides
Susana Gutt
Adrián Gadano
Celia Mén dez García
Martin L. Marro
Alberto Penas Steinhardt
Julieta Trinks
author_sort Bárbara Suárez
collection DOAJ
description Introduction and Objectives: Fungi, archaea and protozoa are the least known members of the gut microbiome, but they could represent a niche for biomarkers discovery to risk-stratify MAFLD patients. This study aimed to identify gut metatranscriptomic signatures in MAFLD patients from Argentina. Materials and Methods: Stool samples, diet, demographic and clinical data were obtained from 33 biopsy-proven MAFLD patients (12 simple steatosis (SS) / 21 steatohepatitis (SH)) and 19 healthy volunteers (HV). PNPLA3 rs738409 SNP was genotyped. RNA-seq was performed in NovaSeq6000®. Data were analyzed with Maaslin2-v1.2.0, bioBakery-v1.8 and DESeq2-v4.1. Results: BMI was higher among MAFLD patients than in HV (q=4.49 × 10−6). The risk GG genotype of PNPLA3-SNP was more prevalent among SH (q=0.0198). In MAFLD patients and in subjects with the GG genotype, differentially expressed genes (DEGs) of fungi, such as Fusarium proliferatum and Candida sorbophila, were up-regulated (q<0.01). After comparing transcript abundance, Saccharomucetaceae was the most active family among MAFLD patients, whereas Aspergillaceae family prevailed in HV. DEGs of methanogenic archaea and protozoa, such as Fonticula alba and Blastocystis spp., were highly expressed in MAFLD and SH after comparing them to HV and SS groups, respectively. The analysis of the functionally active protozoan families revealed that the Blastocystidae and Fonticulidae families were more functionally abundant in MAFLD and SH groups after comparing to HV and SS, respectively (Figure exhibits the statistically significant differences between groups). In subjects with the GG genotype, DEGs of Fonticula alba were up-regulated and those of Blastocystis spp. were less expressed after comparing to those with CC/CG genotypes. In SH, functional profiling of archaeal and fungal DEGs revealed an over-representation of viral capsid assembly and phage shock processes, whereas copper metabolism, peptidoglycan turnover and non-autophagic vacuolization were enriched by protozoan DEGs. Conclusions: The switch in microbiome signatures characteristic of MAFLD onset and progression is achieved through the activity of several community members.
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spelling doaj.art-57c62c97103749109d631284514371a62023-03-23T04:34:31ZengElsevierAnnals of Hepatology1665-26812023-03-0128101015O-5 INTEGRATED ANALYSIS OF ARCHAEAL, FUNGAL AND PROTOZOAN GUT TRANSCRIPTOME IN METABOLIC ASSOCIATED FATTY LIVER DISEASE (MAFLD) IN ARGENTINABárbara Suárez0María Florencia Mascardi1Flavia Noelia Mazzini2M. Ruda Vera3Sebastián Marciano4Paola Casciato5Adrián Narvaez6Leila Haddad7Margarita Anders8Federico Orozco9Ana Jesica Tamaroff10Frank Cook11John Gounarides12Susana Gutt13Adrián Gadano14Celia Mén dez García15Martin L. Marro16Alberto Penas Steinhardt17Julieta Trinks181 Institute of Translational Medicine and Biomedical Engineering (IMTIB) - Conicet University Institute of the Italian Hospital. Buenos Aires Italian Hospital. Buenos Aires, Argentina; National Council for Scientific and Technical Research (CONICET), Buenos Aires, Argentina1 Institute of Translational Medicine and Biomedical Engineering (IMTIB) - Conicet University Institute of the Italian Hospital. Buenos Aires Italian Hospital. Buenos Aires, Argentina; National Council for Scientific and Technical Research (CONICET), Buenos Aires, Argentina1 Institute of Translational Medicine and Biomedical Engineering (IMTIB) - Conicet University Institute of the Italian Hospital. Buenos Aires Italian Hospital. Buenos Aires, ArgentinaBiotherapeutic and Analytical Technologies, Novartis Institutes for Biomedical Research, Cambridge (NIBR), MA, United States of America; Chemical Biology &amp; Therapeutics, NIBR, Cambridge, MA, United States of AmericaLiver Unit of Buenos Aires Italian Hospital. Buenos Aires, ArgentinaNational Council for Scientific and Technical Research (CONICET), Buenos Aires, Argentina; Liver Unit of Buenos Aires Italian Hospital. Buenos Aires, ArgentinaLiver Unit of Buenos Aires Italian Hospital. Buenos Aires, ArgentinaLiver Unit of Buenos Aires Italian Hospital. Buenos Aires, ArgentinaLiver Unit of German Hospital, Buenos Aires, ArgentinaLiver Unit of German Hospital, Buenos Aires, ArgentinaNutrition Department of Buenos Aires Italian Hospital. Buenos Aires, ArgentinaAnalytical Sciences &amp; Imaging Department, NIBR, Cambridge, MA, United States of AmericaAnalytical Sciences &amp; Imaging Department, NIBR, Cambridge, MA, United States of AmericaNutrition Department of Buenos Aires Italian Hospital. Buenos Aires, ArgentinaLiver Unit of Buenos Aires Italian Hospital. Buenos Aires, ArgentinaChemical Biology &amp; Therapeutics, NIBR, Cambridge, MA, United States of America; Chemical Biology &amp; Therapeutics, NIBR, Basel, SwitzerlandCardiovascular and Metabolic Disease Area, NIBR, Cambridge, MA, United States of America; Tectonic Therapeutic, Inc., Watertown, MA, United States of AmericaNational Council for Scientific and Technical Research (CONICET), Buenos Aires, Argentina; National University of de Luján, Basic Sciences Department. Computational Genomics Laboratory, Luján, Buenos Aires, Argentina1 Institute of Translational Medicine and Biomedical Engineering (IMTIB) - Conicet University Institute of the Italian Hospital. Buenos Aires Italian Hospital. Buenos Aires, Argentina; National Council for Scientific and Technical Research (CONICET), Buenos Aires, ArgentinaIntroduction and Objectives: Fungi, archaea and protozoa are the least known members of the gut microbiome, but they could represent a niche for biomarkers discovery to risk-stratify MAFLD patients. This study aimed to identify gut metatranscriptomic signatures in MAFLD patients from Argentina. Materials and Methods: Stool samples, diet, demographic and clinical data were obtained from 33 biopsy-proven MAFLD patients (12 simple steatosis (SS) / 21 steatohepatitis (SH)) and 19 healthy volunteers (HV). PNPLA3 rs738409 SNP was genotyped. RNA-seq was performed in NovaSeq6000®. Data were analyzed with Maaslin2-v1.2.0, bioBakery-v1.8 and DESeq2-v4.1. Results: BMI was higher among MAFLD patients than in HV (q=4.49 × 10−6). The risk GG genotype of PNPLA3-SNP was more prevalent among SH (q=0.0198). In MAFLD patients and in subjects with the GG genotype, differentially expressed genes (DEGs) of fungi, such as Fusarium proliferatum and Candida sorbophila, were up-regulated (q<0.01). After comparing transcript abundance, Saccharomucetaceae was the most active family among MAFLD patients, whereas Aspergillaceae family prevailed in HV. DEGs of methanogenic archaea and protozoa, such as Fonticula alba and Blastocystis spp., were highly expressed in MAFLD and SH after comparing them to HV and SS groups, respectively. The analysis of the functionally active protozoan families revealed that the Blastocystidae and Fonticulidae families were more functionally abundant in MAFLD and SH groups after comparing to HV and SS, respectively (Figure exhibits the statistically significant differences between groups). In subjects with the GG genotype, DEGs of Fonticula alba were up-regulated and those of Blastocystis spp. were less expressed after comparing to those with CC/CG genotypes. In SH, functional profiling of archaeal and fungal DEGs revealed an over-representation of viral capsid assembly and phage shock processes, whereas copper metabolism, peptidoglycan turnover and non-autophagic vacuolization were enriched by protozoan DEGs. Conclusions: The switch in microbiome signatures characteristic of MAFLD onset and progression is achieved through the activity of several community members.http://www.sciencedirect.com/science/article/pii/S1665268123001199
spellingShingle Bárbara Suárez
María Florencia Mascardi
Flavia Noelia Mazzini
M. Ruda Vera
Sebastián Marciano
Paola Casciato
Adrián Narvaez
Leila Haddad
Margarita Anders
Federico Orozco
Ana Jesica Tamaroff
Frank Cook
John Gounarides
Susana Gutt
Adrián Gadano
Celia Mén dez García
Martin L. Marro
Alberto Penas Steinhardt
Julieta Trinks
O-5 INTEGRATED ANALYSIS OF ARCHAEAL, FUNGAL AND PROTOZOAN GUT TRANSCRIPTOME IN METABOLIC ASSOCIATED FATTY LIVER DISEASE (MAFLD) IN ARGENTINA
Annals of Hepatology
title O-5 INTEGRATED ANALYSIS OF ARCHAEAL, FUNGAL AND PROTOZOAN GUT TRANSCRIPTOME IN METABOLIC ASSOCIATED FATTY LIVER DISEASE (MAFLD) IN ARGENTINA
title_full O-5 INTEGRATED ANALYSIS OF ARCHAEAL, FUNGAL AND PROTOZOAN GUT TRANSCRIPTOME IN METABOLIC ASSOCIATED FATTY LIVER DISEASE (MAFLD) IN ARGENTINA
title_fullStr O-5 INTEGRATED ANALYSIS OF ARCHAEAL, FUNGAL AND PROTOZOAN GUT TRANSCRIPTOME IN METABOLIC ASSOCIATED FATTY LIVER DISEASE (MAFLD) IN ARGENTINA
title_full_unstemmed O-5 INTEGRATED ANALYSIS OF ARCHAEAL, FUNGAL AND PROTOZOAN GUT TRANSCRIPTOME IN METABOLIC ASSOCIATED FATTY LIVER DISEASE (MAFLD) IN ARGENTINA
title_short O-5 INTEGRATED ANALYSIS OF ARCHAEAL, FUNGAL AND PROTOZOAN GUT TRANSCRIPTOME IN METABOLIC ASSOCIATED FATTY LIVER DISEASE (MAFLD) IN ARGENTINA
title_sort o 5 integrated analysis of archaeal fungal and protozoan gut transcriptome in metabolic associated fatty liver disease mafld in argentina
url http://www.sciencedirect.com/science/article/pii/S1665268123001199
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