The role of gut microbiota in clinical complications, disease severity, and treatment response in severe alcoholic hepatitis.
Alcohol
Cirrhosis
Dysbiosis
Fecal transplant
Intestinal bacteria
Metabolomics
Metagenomics
Microbiome
Portal hypertension
Journal
Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology
ISSN: 0975-0711
Titre abrégé: Indian J Gastroenterol
Pays: India
ID NLM: 8409436
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
04
04
2020
accepted:
01
02
2021
pubmed:
7
1
2022
medline:
15
4
2022
entrez:
6
1
2022
Statut:
ppublish
Résumé
Dysbiotic gut bacteria engage in the development and progression of severe alcoholic hepatitis (SAH). We aimed to characterize bacterial communities associated with clinical events (CE), identify significant bacteria linked to CE, and define bacterial relationships associated with specific CE and outcomes at baseline and after treatment in SAH. We performed 16-s rRNA sequencing on stool samples (n=38) collected at admission and the last follow-up within 90 days in SAH patients (n=26; 12 corticosteroids; 14 granulocyte colony-stimulating factor, [G-CSF]). Validated pipelines were used to plot bacterial communities, profile functional metabolism, and identify significant taxa and functional metabolites. Conet/NetworkX® was utilized to identify significant non-random patterns of bacterial co-presence and mutual exclusion for clinical events. All the patients were males with median discriminant function (DF) 64, Child-Turcotte-Pugh (CTP) 12, and model for end-stage liver disease (MELD) score 25.5. At admission, 27%, 42%, and 58% had acute kidney injury (AKI), hepatic encephalopathy (HE), and infections respectively; 38.5% died at end of follow-up. Specific bacterial families were associated with HE, sepsis, disease severity, and death. Lachnobacterium and Catenibacterium were associated with HE, and Pediococcus with death after steroid treatment. Change from Enterococcus (promotes AH) to Barnesiella (inhibits E. faecium) was significant after G-CSF. Phenylpropanoid-biosynthesis (innate-immunity) and glycerophospholipid-metabolism (cellular-integrity) pathways in those without infections and the death, respectively, were upregulated. Mutual interactions between Enterococcus cecorum, Acinetobacter schindleri, and Mitsuokella correlated with admission AKI. Specific gut microbiota, their interactions, and metabolites are associated with complications of SAH and treatment outcomes. Microbiota-based precision medicine as adjuvant treatment may be a new therapeutic area.
Sections du résumé
BACKGROUND
Dysbiotic gut bacteria engage in the development and progression of severe alcoholic hepatitis (SAH). We aimed to characterize bacterial communities associated with clinical events (CE), identify significant bacteria linked to CE, and define bacterial relationships associated with specific CE and outcomes at baseline and after treatment in SAH.
METHODS
We performed 16-s rRNA sequencing on stool samples (n=38) collected at admission and the last follow-up within 90 days in SAH patients (n=26; 12 corticosteroids; 14 granulocyte colony-stimulating factor, [G-CSF]). Validated pipelines were used to plot bacterial communities, profile functional metabolism, and identify significant taxa and functional metabolites. Conet/NetworkX® was utilized to identify significant non-random patterns of bacterial co-presence and mutual exclusion for clinical events.
RESULTS
All the patients were males with median discriminant function (DF) 64, Child-Turcotte-Pugh (CTP) 12, and model for end-stage liver disease (MELD) score 25.5. At admission, 27%, 42%, and 58% had acute kidney injury (AKI), hepatic encephalopathy (HE), and infections respectively; 38.5% died at end of follow-up. Specific bacterial families were associated with HE, sepsis, disease severity, and death. Lachnobacterium and Catenibacterium were associated with HE, and Pediococcus with death after steroid treatment. Change from Enterococcus (promotes AH) to Barnesiella (inhibits E. faecium) was significant after G-CSF. Phenylpropanoid-biosynthesis (innate-immunity) and glycerophospholipid-metabolism (cellular-integrity) pathways in those without infections and the death, respectively, were upregulated. Mutual interactions between Enterococcus cecorum, Acinetobacter schindleri, and Mitsuokella correlated with admission AKI.
CONCLUSIONS
Specific gut microbiota, their interactions, and metabolites are associated with complications of SAH and treatment outcomes. Microbiota-based precision medicine as adjuvant treatment may be a new therapeutic area.
Identifiants
pubmed: 34989986
doi: 10.1007/s12664-021-01157-9
pii: 10.1007/s12664-021-01157-9
doi:
Substances chimiques
Granulocyte Colony-Stimulating Factor
143011-72-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
37-51Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021. Indian Society of Gastroenterology.
Références
Seitz HK, Bataller R, Cortez-Pinto H, et al. Alcoholic liver disease. Nat Rev Dis Primers. 2018;4:16.
doi: 10.1038/s41572-018-0014-7
Philips CA, Augustine P, Yerol PK, et al. Modulating the intestinal microbiota: therapeutic opportunities in liver disease. J Clin Transl Hepatol. 2020;8:87–99.
doi: 10.14218/JCTH.2019.00056
Philips CA, Augustine P, Yerol PK, Rajesh S, Mahadevan P. Severe alcoholic hepatitis: current perspectives. Hepat Med. 2019;11:97–108.
doi: 10.2147/HMER.S197933
Llopis M, Cassard AM, Wrzosek L, et al. Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease. Gut. 2016;65:830–9.
doi: 10.1136/gutjnl-2015-310585
Grander C, Adolph TE, Wieser V, et al. Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease. Gut. 2018;67:891–901.
doi: 10.1136/gutjnl-2016-313432
Singal AK, Louvet A, Shah VH, Kamath PS. Grand rounds: alcoholic hepatitis. J Hepatol. 2018;69:534–43.
doi: 10.1016/j.jhep.2018.05.001
Wu WK, Chen CC, Panyod S, et al. Optimization of fecal sample processing for microbiome study - the journey from bathroom to bench. J Formos Med Assoc. 2019;118:545–55.
Philips CA, Phadke N, Ganesan K, Ranade S, Augustine P. Corticosteroids, nutrition, pentoxifylline, or fecal microbiota transplantation for severe alcoholic hepatitis. Indian J Gastroenterol. 2018;37:215–25.
doi: 10.1007/s12664-018-0859-4
Krzywinski M, Schein J, Birol I, et al. Circos: an information aesthetic for comparative genomics. Genome Res. 2009;19:1639–45.
doi: 10.1101/gr.092759.109
Langille MG, Zaneveld J, Caporaso JG, et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol. 2013;31:814–21.
doi: 10.1038/nbt.2676
Segata N, Izard J, Waldron L, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12:R60.
doi: 10.1186/gb-2011-12-6-r60
Lotia S, Montojo J, Dong Y, Bader GD, Pico AR. Cytoscape app store. Bioinformatics. 2013;29:1350–1.
doi: 10.1093/bioinformatics/btt138
Faust K, Raes J. CoNet app: inference of biological association networks using Cytoscape. F1000Res. 2016;5:1519.
doi: 10.12688/f1000research.9050.1
Faust K, Sathirapongsasuti JF, Izard J, et al. Microbial co-occurrence relationships in the human microbiome. PLoS Comput Biol. 2012;8:e1002606.
doi: 10.1371/journal.pcbi.1002606
Hagberg AA, Schult DA, Swart PJ. Exploring network structure, dynamics, and function using NetworkX, in Proceedings of the 7th Python in Science Conference (SciPy2008), Gäel Varoquaux, Travis Vaught, and Jarrod Millman (Eds), (Pasadena, CA USA), pp. 11–15, Aug 2008.
Chen Y, Yang F, Lu H, et al. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology. 2011;54:562–72.
doi: 10.1002/hep.24423
Bajaj JS. Alcohol, liver disease and the gut microbiota. Nat Rev Gastroenterol Hepatol. 2019;16:235–46.
doi: 10.1038/s41575-018-0099-1
Chen Y, Guo J, Qian G, et al. Gut dysbiosis in acute-on-chronic liver failure and its predictive value for mortality. J Gastroenterol Hepatol. 2015;30:1429–37.
doi: 10.1111/jgh.12932
Trebicka J, Bork P, Krag A, Arumugam M. Utilizing the gut microbiome in decompensated cirrhosis and acute-on-chronic liver failure. Nat Rev Gastroenterol Hepatol. 2021;18:167–80.
Smirnova E, Puri P, Muthiah MD, et al. Fecal microbiome distinguishes alcohol consumption from alcoholic hepatitis but does not discriminate disease severity. Hepatology. 2020;72:271–86.
doi: 10.1002/hep.31178
Lang S, Fairfied B, Gao B, et al. Changes in the fecal bacterial microbiota associated with disease severity in alcoholic hepatitis patients. Gut Microbes. 2020;12:1785251.
doi: 10.1080/19490976.2020.1785251
Garcia-Carretero R, Lopez-Lomba M, Carrasco-Fernandez B, Duran-Valle MT. Clinical features and outcomes of fusobacterium species infections in a ten-year follow-up. J Crit Care Med (Targu Mures). 2017;3:141–7.
doi: 10.1515/jccm-2017-0029
Poyer F, Friesenbichler W, Hutter C, et al. Rothia mucilaginosa bacteremia: a 10-year experience of a pediatric tertiary care cancer center. Pediatr Blood Cancer. 2019;66:e27691.
doi: 10.1002/pbc.27691
Eribe ERK, Olsen I. Leptotrichia species in human infections II. J Oral Microbiol. 2017;9:1368848.
doi: 10.1080/20002297.2017.1368848
Naito T, Mulet C, De Castro C, et al. Lipopolysaccharide from crypt-specific core microbiota modulates the colonic epithelial proliferation-to-differentiation balance. mBio. 2017;8:e01680–17.
doi: 10.1128/mBio.01680-17
Louis P, Flint HJ. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol Lett. 2009;294:1–8.
doi: 10.1111/j.1574-6968.2009.01514.x
McGowan S, Sebaihia M, Jones S, et al. Carbapenem antibiotic production in Erwinia carotovora is regulated by CarR, a homologue of the LuxR transcriptional activator. Microbiology. 1995;141:541–50.
doi: 10.1099/13500872-141-3-541
Kageyama A, Benno Y. Catenibacterium mitsuokai gen. nov., sp. nov., a gram-positive anaerobic bacterium isolated from human faeces. Int J Syst Evol Microbiol. 2000;50:1595–9.
doi: 10.1099/00207713-50-4-1595
Hayashi C, Gudino CV, Gibson FC 3rd, Genco CA. Review: Pathogen-induced inflammation at sites distant from oral infection: bacterial persistence and induction of cell-specific innate immune inflammatory pathways. Mol Oral Microbiol. 2010;25:305–16.
doi: 10.1111/j.2041-1014.2010.00582.x
Gosset G. Production of aromatic compounds in bacteria. Curr Opin Biotechnol. 2009;20:651–8.
doi: 10.1016/j.copbio.2009.09.012
Azad MAK, Sarker M, Li T, Yin J. Probiotic species in the modulation of gut microbiota: an overview. Biomed Res Int. 2018;2018:9478630.
pubmed: 29854813
pmcid: 5964481
Bubnov RV, Babenko LP, Lazarenko LM, Mokrozub VV, Spivak MY. Specific properties of probiotic strains: relevance and benefits for the host. EPMA J. 2018;9:205–23.
Arboleya S, Watkins C, Stanton C, Ross RP. Gut Bifidobacteria populations in human health and aging. Front Microbiol. 2016;7:1204.
doi: 10.3389/fmicb.2016.01204
Zhang C, Wang K, Yang L, et al. Lipid metabolism in inflammation-related diseases. Analyst. 2018;143:4526–36.
doi: 10.1039/C8AN01046C
Duan Y, Llorente C, Lang S, et al. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature. 2019;575:505–11.
doi: 10.1038/s41586-019-1742-x
Ubeda C, Bucci V, Caballero S, et al. Intestinal microbiota containing Barnesiella species cures vancomycin-resistant Enterococcus faecium colonization. Infect Immun. 2013;81:965–73.
doi: 10.1128/IAI.01197-12
Jørgensen SF, Macpherson ME, Bjørnetrø T, Pompili M, Gasbarrini A. Rifaximin alters gut microbiota profile but does not affect systemic inflammation - a randomized controlled trial in common variable immunodeficiency. Sci Rep. 2019;9:167.
Ponziani FR, Zocco MA, D'Aversa F, Pompili M, Gasbarrini A. Eubiotic properties of rifaximin: Disruption of the traditional concepts in gut microbiota modulation. World J Gastroenterol. 2017;23:4491–9.
doi: 10.3748/wjg.v23.i25.4491
Francino MP. Antibiotics and the human gut microbiome: dysbioses and accumulation of resistances. Front Microbiol. 2016;6:1543.
doi: 10.3389/fmicb.2015.01543
Palleja A, Mikkelsen KH, Forslund SK, et al. Recovery of gut microbiota of healthy adults following antibiotic exposure. Nat Microbiol. 2018;3:1255–65.
doi: 10.1038/s41564-018-0257-9