Interactions between the gut microbiome, associated metabolites and the manifestation and progression of heart failure with preserved ejection fraction in ZSF1 rats.
Animals
Gastrointestinal Microbiome
Heart Failure
/ physiopathology
Stroke Volume
Methylamines
/ metabolism
Disease Progression
Disease Models, Animal
Male
Ventricular Function, Left
Obesity
/ microbiology
Oxygenases
/ metabolism
Liver
/ metabolism
Biomarkers
/ blood
Feces
/ microbiology
Rats
Intestinal Mucosa
/ metabolism
Bacteria
/ metabolism
Dysbiosis
FMO3
HFpEF
Inflammation
Intestinal barrier
Intestinal microbiome
TMAO
ZSF1-rats
Journal
Cardiovascular diabetology
ISSN: 1475-2840
Titre abrégé: Cardiovasc Diabetol
Pays: England
ID NLM: 101147637
Informations de publication
Date de publication:
14 Aug 2024
14 Aug 2024
Historique:
received:
08
03
2024
accepted:
07
08
2024
medline:
15
8
2024
pubmed:
15
8
2024
entrez:
14
8
2024
Statut:
epublish
Résumé
Heart failure with preserved ejection fraction (HFpEF) is associated with systemic inflammation, obesity, metabolic syndrome, and gut microbiome changes. Increased trimethylamine-N-oxide (TMAO) levels are predictive for mortality in HFpEF. The TMAO precursor trimethylamine (TMA) is synthesized by the intestinal microbiome, crosses the intestinal barrier and is metabolized to TMAO by hepatic flavin-containing monooxygenases (FMO). The intricate interactions of microbiome alterations and TMAO in relation to HFpEF manifestation and progression are analyzed here. Healthy lean (L-ZSF1, n = 12) and obese ZSF1 rats with HFpEF (O-ZSF1, n = 12) were studied. HFpEF was confirmed by transthoracic echocardiography, invasive hemodynamic measurements, and detection of N-terminal pro-brain natriuretic peptide (NT-proBNP). TMAO, carnitine, symmetric dimethylarginine (SDMA), and amino acids were measured using mass-spectrometry. The intestinal epithelial barrier was analyzed by immunohistochemistry, in-vitro impedance measurements and determination of plasma lipopolysaccharide via ELISA. Hepatic FMO3 quantity was determined by Western blot. The fecal microbiome at the age of 8, 13 and 20 weeks was assessed using 16s rRNA amplicon sequencing. Increased levels of TMAO (+ 54%), carnitine (+ 46%) and the cardiac stress marker NT-proBNP (+ 25%) as well as a pronounced amino acid imbalance were observed in obese rats with HFpEF. SDMA levels in O-ZSF1 were comparable to L-ZSF1, indicating stable kidney function. Anatomy and zonula occludens protein density in the intestinal epithelium remained unchanged, but both impedance measurements and increased levels of LPS indicated an impaired epithelial barrier function. FMO3 was decreased (- 20%) in the enlarged, but histologically normal livers of O-ZSF1. Alpha diversity, as indicated by the Shannon diversity index, was comparable at 8 weeks of age, but decreased by 13 weeks of age, when HFpEF manifests in O-ZSF1. Bray-Curtis dissimilarity (Beta-Diversity) was shown to be effective in differentiating L-ZSF1 from O-ZSF1 at 20 weeks of age. Members of the microbial families Lactobacillaceae, Ruminococcaceae, Erysipelotrichaceae and Lachnospiraceae were significantly differentially abundant in O-ZSF1 and L-ZSF1 rats. In the ZSF1 HFpEF rat model, increased dietary intake is associated with alterations in gut microbiome composition and bacterial metabolites, an impaired intestinal barrier, and changes in pro-inflammatory and health-predictive metabolic profiles. HFpEF as well as its most common comorbidities obesity and metabolic syndrome and the alterations described here evolve in parallel and are likely to be interrelated and mutually reinforcing. Dietary adaption may have a positive impact on all entities.
Sections du résumé
BACKGROUND
BACKGROUND
Heart failure with preserved ejection fraction (HFpEF) is associated with systemic inflammation, obesity, metabolic syndrome, and gut microbiome changes. Increased trimethylamine-N-oxide (TMAO) levels are predictive for mortality in HFpEF. The TMAO precursor trimethylamine (TMA) is synthesized by the intestinal microbiome, crosses the intestinal barrier and is metabolized to TMAO by hepatic flavin-containing monooxygenases (FMO). The intricate interactions of microbiome alterations and TMAO in relation to HFpEF manifestation and progression are analyzed here.
METHODS
METHODS
Healthy lean (L-ZSF1, n = 12) and obese ZSF1 rats with HFpEF (O-ZSF1, n = 12) were studied. HFpEF was confirmed by transthoracic echocardiography, invasive hemodynamic measurements, and detection of N-terminal pro-brain natriuretic peptide (NT-proBNP). TMAO, carnitine, symmetric dimethylarginine (SDMA), and amino acids were measured using mass-spectrometry. The intestinal epithelial barrier was analyzed by immunohistochemistry, in-vitro impedance measurements and determination of plasma lipopolysaccharide via ELISA. Hepatic FMO3 quantity was determined by Western blot. The fecal microbiome at the age of 8, 13 and 20 weeks was assessed using 16s rRNA amplicon sequencing.
RESULTS
RESULTS
Increased levels of TMAO (+ 54%), carnitine (+ 46%) and the cardiac stress marker NT-proBNP (+ 25%) as well as a pronounced amino acid imbalance were observed in obese rats with HFpEF. SDMA levels in O-ZSF1 were comparable to L-ZSF1, indicating stable kidney function. Anatomy and zonula occludens protein density in the intestinal epithelium remained unchanged, but both impedance measurements and increased levels of LPS indicated an impaired epithelial barrier function. FMO3 was decreased (- 20%) in the enlarged, but histologically normal livers of O-ZSF1. Alpha diversity, as indicated by the Shannon diversity index, was comparable at 8 weeks of age, but decreased by 13 weeks of age, when HFpEF manifests in O-ZSF1. Bray-Curtis dissimilarity (Beta-Diversity) was shown to be effective in differentiating L-ZSF1 from O-ZSF1 at 20 weeks of age. Members of the microbial families Lactobacillaceae, Ruminococcaceae, Erysipelotrichaceae and Lachnospiraceae were significantly differentially abundant in O-ZSF1 and L-ZSF1 rats.
CONCLUSIONS
CONCLUSIONS
In the ZSF1 HFpEF rat model, increased dietary intake is associated with alterations in gut microbiome composition and bacterial metabolites, an impaired intestinal barrier, and changes in pro-inflammatory and health-predictive metabolic profiles. HFpEF as well as its most common comorbidities obesity and metabolic syndrome and the alterations described here evolve in parallel and are likely to be interrelated and mutually reinforcing. Dietary adaption may have a positive impact on all entities.
Identifiants
pubmed: 39143579
doi: 10.1186/s12933-024-02398-6
pii: 10.1186/s12933-024-02398-6
doi:
Substances chimiques
Methylamines
0
trimethyloxamine
FLD0K1SJ1A
dimethylaniline monooxygenase (N-oxide forming)
EC 1.14.13.8
Oxygenases
EC 1.13.-
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
299Informations de copyright
© 2024. The Author(s).
Références
McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023. https://doi.org/10.1093/eurheartj/ehad195 .
doi: 10.1093/eurheartj/ehad195
pubmed: 37622666
pmcid: 10149529
Reddy YNV, Borlaug BA. Heart failure with preserved ejection fraction. Curr Probl Cardiol. 2016;41:145–88. https://doi.org/10.1016/j.cpcardiol.2015.12.002 .
doi: 10.1016/j.cpcardiol.2015.12.002
pubmed: 26952248
Nassif ME, Windsor SL, Borlaug BA, Kitzman DW, Shah SJ, Tang F, et al. The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial. Nat Med. 2021;27:1954–60. https://doi.org/10.1038/s41591-021-01536-x .
doi: 10.1038/s41591-021-01536-x
pubmed: 34711976
pmcid: 8604725
Dunlay SM, Roger VL, Redfield MM. Epidemiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2017;14:591–602. https://doi.org/10.1038/nrcardio.2017.65 .
doi: 10.1038/nrcardio.2017.65
pubmed: 28492288
Yoo JY, Sniffen S, McGill Percy KC, Pallaval VB, Chidipi B. Gut dysbiosis and immune system in atherosclerotic cardiovascular disease (ACVD). Microorganisms. 2022. https://doi.org/10.3390/microorganisms10010108 .
doi: 10.3390/microorganisms10010108
pubmed: 36296297
pmcid: 9612053
Roh J, Hill JA, Singh A, Valero-Muñoz M, Sam F. Heart failure with preserved ejection fraction: heterogeneous syndrome, diverse preclinical models. Circ Res. 2022;130:1906–25. https://doi.org/10.1161/CIRCRESAHA.122.320257 .
doi: 10.1161/CIRCRESAHA.122.320257
pubmed: 35679364
pmcid: 10035274
Conceição G, Heinonen I, Lourenço AP, Duncker DJ, Falcão-Pires I. Animal models of heart failure with preserved ejection fraction. Neth Heart J. 2016;24:275–86. https://doi.org/10.1007/s12471-016-0815-9 .
doi: 10.1007/s12471-016-0815-9
pubmed: 26936157
pmcid: 4796054
Schauer A, Draskowski R, Jannasch A, Kirchhoff V, Goto K, Männel A, et al. ZSF1 rat as animal model for HFpEF: development of reduced diastolic function and skeletal muscle dysfunction. ESC Heart Fail. 2020;7:2123–34. https://doi.org/10.1002/ehf2.12915 .
doi: 10.1002/ehf2.12915
pubmed: 32710530
pmcid: 7524062
Bilan VP, Salah EM, Bastacky S, Jones HB, Mayers RM, Zinker B, et al. Diabetic nephropathy and long-term treatment effects of rosiglitazone and enalapril in obese ZSF1 rats. J Endocrinol. 2011;210:293–308. https://doi.org/10.1530/JOE-11-0122 .
doi: 10.1530/JOE-11-0122
pubmed: 21680617
Zeisel SH, Warrier M. Trimethylamine N-oxide, the microbiome, and heart and kidney disease. Annu Rev Nutr. 2017;37:157–81. https://doi.org/10.1146/annurev-nutr-071816-064732 .
doi: 10.1146/annurev-nutr-071816-064732
pubmed: 28715991
Al-Rubaye H, Perfetti G, Kaski J-C. The role of microbiota in cardiovascular risk: focus on trimethylamine oxide. Curr Probl Cardiol. 2019;44:182–96. https://doi.org/10.1016/j.cpcardiol.2018.06.005 .
doi: 10.1016/j.cpcardiol.2018.06.005
pubmed: 30482503
Tang WHW, Wang Z, Shrestha K, Borowski AG, Wu Y, Troughton RW, et al. Intestinal microbiota-dependent phosphatidylcholine metabolites, diastolic dysfunction, and adverse clinical outcomes in chronic systolic heart failure. J Card Fail. 2015;21:91–6. https://doi.org/10.1016/j.cardfail.2014.11.006 .
doi: 10.1016/j.cardfail.2014.11.006
pubmed: 25459686
Dong Z, Zheng S, Shen Z, Luo Y, Hai X. Trimethylamine N-oxide is associated with heart failure risk in patients with preserved ejection fraction. Lab Med. 2021;52:346–51. https://doi.org/10.1093/labmed/lmaa075 .
doi: 10.1093/labmed/lmaa075
pubmed: 33135738
Yu W, Jiang Y, Xu H, Zhou Y. The Interaction of Gut Microbiota and Heart failure with preserved ejection fraction: from mechanism to potential therapies. Biomedicines. 2023. https://doi.org/10.3390/biomedicines11020442 .
doi: 10.3390/biomedicines11020442
pubmed: 38275377
pmcid: 10813761
Simó C, García-Cañas V. Dietary bioactive ingredients to modulate the gut microbiota-derived metabolite TMAO. New opportunities for functional food development. Food Funct. 2020;11:6745–76. https://doi.org/10.1039/d0fo01237h .
doi: 10.1039/d0fo01237h
pubmed: 32686802
Kinugasa Y, Nakamura K, Kamitani H, Hirai M, Yanagihara K, Kato M, Yamamoto K. Trimethylamine N-oxide and outcomes in patients hospitalized with acute heart failure and preserved ejection fraction. ESC Heart Fail. 2021;8:2103–10. https://doi.org/10.1002/ehf2.13290 .
doi: 10.1002/ehf2.13290
pubmed: 33734604
pmcid: 8120352
Witkowski M, Weeks TL, Hazen SL. Gut microbiota and cardiovascular disease. Circ Res. 2020;127:553–70. https://doi.org/10.1161/CIRCRESAHA.120.316242 .
doi: 10.1161/CIRCRESAHA.120.316242
pubmed: 32762536
pmcid: 7416843
Peng J, Xiao X, Hu M, Zhang X. Interaction between gut microbiome and cardiovascular disease. Life Sci. 2018;214:153–7. https://doi.org/10.1016/j.lfs.2018.10.063 .
doi: 10.1016/j.lfs.2018.10.063
pubmed: 30385177
Evans M, Dai L, Avesani CM, Kublickiene K, Stenvinkel P. The dietary source of trimethylamine N-oxide and clinical outcomes: an unexpected liaison. Clin Kidney J. 2023;16:1804–12. https://doi.org/10.1093/ckj/sfad095 .
doi: 10.1093/ckj/sfad095
pubmed: 37915930
pmcid: 10616480
Drapala A, Szudzik M, Chabowski D, Mogilnicka I, Jaworska K, Kraszewska K, et al. Heart failure disturbs gut-blood barrier and increases plasma trimethylamine, a toxic bacterial metabolite. Int J Mol Sci. 2020. https://doi.org/10.3390/ijms21176161 .
doi: 10.3390/ijms21176161
pubmed: 32859047
pmcid: 7504565
Goyal S, Tsang DKL, Maisonneuve C, Girardin SE. Sending signals—the microbiota’s contribution to intestinal epithelial homeostasis. Microbes Infect. 2021;23:104774. https://doi.org/10.1016/j.micinf.2020.10.009 .
doi: 10.1016/j.micinf.2020.10.009
pubmed: 33189870
Lewis CV, Taylor WR. Intestinal barrier dysfunction as a therapeutic target for cardiovascular disease. Am J Physiol Heart Circ Physiol. 2020;319:H1227–33. https://doi.org/10.1152/ajpheart.00612.2020 .
doi: 10.1152/ajpheart.00612.2020
pubmed: 32986965
pmcid: 7792706
Kuo W-T, Odenwald MA, Turner JR, Zuo L. Tight junction proteins occludin and ZO-1 as regulators of epithelial proliferation and survival. Ann NY Acad Sci. 2022;1514:21–33. https://doi.org/10.1111/nyas.14798 .
doi: 10.1111/nyas.14798
pubmed: 35580994
Ghosh SS, Wang J, Yannie PJ, Ghosh S. Intestinal barrier dysfunction, LPS translocation, and disease development. J Endocr Soc. 2020;4:bvz039. https://doi.org/10.1210/jendso/bvz039 .
doi: 10.1210/jendso/bvz039
pubmed: 32099951
pmcid: 7033038
Violi F, Castellani V, Menichelli D, Pignatelli P, Pastori D. Gut barrier dysfunction and endotoxemia in heart failure: a dangerous connubium? Am Heart J. 2023;264:40–8. https://doi.org/10.1016/j.ahj.2023.06.002 .
doi: 10.1016/j.ahj.2023.06.002
pubmed: 37301317
Yu Y, Xiong Y, Montani J-P, Yang Z, Ming X-F. En face detection of nitric oxide and superoxide in endothelial layer of intact arteries. J Vis Exp. 2016;108:53718. https://doi.org/10.3791/53718 .
doi: 10.3791/53718
Wang Z, Levison BS, Hazen JE, Donahue L, Li X-M, Hazen SL. Measurement of trimethylamine-N-oxide by stable isotope dilution liquid chromatography tandem mass spectrometry. Anal Biochem. 2014;455:35–40. https://doi.org/10.1016/j.ab.2014.03.016 .
doi: 10.1016/j.ab.2014.03.016
pubmed: 24704102
pmcid: 4167037
Büttner P, Werner S, Baskal S, Tsikas D, Adams V, Lurz P, et al. Arginine metabolism and nitric oxide turnover in the ZSF1 animal model for heart failure with preserved ejection fraction. Sci Rep. 2021;11:20684. https://doi.org/10.1038/s41598-021-00216-7 .
doi: 10.1038/s41598-021-00216-7
pubmed: 34667218
pmcid: 8526609
Ernst FG, Shetty S, Borman T, Braccia DJ, Huang R, Corrada Bravo H, Lahti L. Microbiome @ Git Hub. https://microbiome.github.io/ . Accessed 6 Mar 2024.
McMurdie PJ, Holmes S. Phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE. 2013;8:e61217. https://doi.org/10.1371/journal.pone.0061217 .
doi: 10.1371/journal.pone.0061217
pubmed: 23630581
pmcid: 3632530
Community. Ecology Package [R package vegan version 2.6-4]: Comprehensive R Archive Network (CRAN).
Love MI, Huber W, Anders S. Moderated estimation of Fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550. https://doi.org/10.1186/s13059-014-0550-8 .
doi: 10.1186/s13059-014-0550-8
pubmed: 25516281
pmcid: 4302049
Create Elegant Data Visualisations. Using the Grammar of Graphics [R package ggplot2 version 3.5.0]: Comprehensive R Archive Network (CRAN).
Streamlined Plot Theme and Plot Annotations for ‘ggplot2’ [R package cowplot version 1.1.3]: Comprehensive R Archive Network (CRAN); 2024.
Baptiste Auguie. Miscellaneous functions for Grid Graphics [R package gridExtra version 2.3]: Comprehensive R Archive Network. CRAN); 2017.
Mishra S, Kass DA. Cellular and molecular pathobiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2021;18:400–23. https://doi.org/10.1038/s41569-020-00480-6 .
doi: 10.1038/s41569-020-00480-6
pubmed: 33432192
pmcid: 8574228
Triposkiadis F, Butler J, Abboud FM, Armstrong PW, Adamopoulos S, Atherton JJ, et al. The continuous heart failure spectrum: moving beyond an ejection fraction classification. Eur Heart J. 2019;40:2155–63. https://doi.org/10.1093/eurheartj/ehz158 .
doi: 10.1093/eurheartj/ehz158
pubmed: 30957868
pmcid: 7963129
Ostadal P, Mlcek M, Gorhan H, Simundic I, Strunina S, Hrachovina M, et al. Electrocardiogram-synchronized pulsatile extracorporeal life support preserves left ventricular function and coronary flow in a porcine model of cardiogenic shock. PLoS ONE. 2018;13:e0196321. https://doi.org/10.1371/journal.pone.0196321 .
doi: 10.1371/journal.pone.0196321
pubmed: 29689088
pmcid: 5915277
Leite S, Oliveira-Pinto J, Tavares-Silva M, Abdellatif M, Fontoura D, Falcão-Pires I, et al. Echocardiography and invasive hemodynamics during stress testing for diagnosis of heart failure with preserved ejection fraction: an experimental study. Am J Physiol Heart Circ Physiol. 2015;308:H1556–63. https://doi.org/10.1152/ajpheart.00076.2015 .
doi: 10.1152/ajpheart.00076.2015
pubmed: 25862827
van Dijk CGM, Oosterhuis NR, Xu YJ, Brandt M, Paulus WJ, van Heerebeek L, et al. Distinct endothelial cell responses in the heart and kidney microvasculature characterize the progression of heart failure with preserved ejection fraction in the obese ZSF1 rat with Cardiorenal metabolic syndrome. Circ Heart Fail. 2016;9:e002760. https://doi.org/10.1161/CIRCHEARTFAILURE.115.002760 .
doi: 10.1161/CIRCHEARTFAILURE.115.002760
pubmed: 27056881
Hills RD, Pontefract BA, Mishcon HR, Black CA, Sutton SC, Theberge CR. Gut microbiome: profound implications for diet and disease. Nutrients. 2019. https://doi.org/10.3390/nu11071613 .
doi: 10.3390/nu11071613
pubmed: 31336992
pmcid: 6682904
Leite S, Cerqueira RJ, Ibarrola J, Fontoura D, Fernández-Celis A, Zannad F, et al. Arterial remodeling and dysfunction in the ZSF1 rat model of heart failure with preserved ejection fraction. Circ Heart Fail. 2019;12:e005596. https://doi.org/10.1161/CIRCHEARTFAILURE.118.005596 .
doi: 10.1161/CIRCHEARTFAILURE.118.005596
pubmed: 31525070
Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19:576–85. https://doi.org/10.1038/nm.3145 .
doi: 10.1038/nm.3145
pubmed: 23563705
pmcid: 3650111
Guo F, Qiu X, Tan Z, Li Z, Ouyang D. Plasma trimethylamine n-oxide is associated with renal function in patients with heart failure with preserved ejection fraction. BMC Cardiovasc Disord. 2020;20:394. https://doi.org/10.1186/s12872-020-01669-w .
doi: 10.1186/s12872-020-01669-w
pubmed: 32859154
pmcid: 7456383
Hamlin DM, Schultze AE, Coyne MJ, McCrann DJ, Mack R, Drake C et al. Evaluation of renal biomarkers, including symmetric dimethylarginine, following gentamicin-induced proximal tubular injury in the rat. Kidney360. 2022;3:341–56. https://doi.org/10.34067/KID.0006542020
doi: 10.34067/KID.0006542020
pubmed: 35373128
Michael H, Szlosek D, Clements C, Mack R. Symmetrical dimethylarginine: evaluating chronic kidney disease in the era of multiple kidney biomarkers. Vet Clin North Am Small Anim Pract. 2022;52:609–29.
doi: 10.1016/j.cvsm.2022.01.003
pubmed: 35379500
Oliva-Damaso E, Oliva-Damaso N, Rodriguez-Esparragon F, Payan J, Baamonde-Laborda E, Gonzalez-Cabrera F, et al. Asymmetric (ADMA) and symmetric (SDMA) dimethylarginines in chronic kidney disease: a clinical approach. Int J Mol Sci. 2019. https://doi.org/10.3390/ijms20153668 .
doi: 10.3390/ijms20153668
pubmed: 31357472
pmcid: 6696355
Li D, Chen H, Mao B, Yang Q, Zhao J, Gu Z, et al. Microbial biogeography and core microbiota of the rat digestive tract. Sci Rep. 2017;8:45840. https://doi.org/10.1038/srep45840 .
doi: 10.1038/srep45840
pubmed: 28374781
Rath S, Rud T, Pieper DH, Vital M. Potential TMA-producing bacteria are ubiquitously found in Mammalia. Front Microbiol. 2019;10:2966. https://doi.org/10.3389/fmicb.2019.02966 .
doi: 10.3389/fmicb.2019.02966
pubmed: 31998260
Ferrell M, Bazeley P, Wang Z, Levison BS, Li XS, Jia X, et al. Fecal microbiome composition does not predict diet-induced TMAO production in healthy adults. J Am Heart Assoc. 2021;10:e021934. https://doi.org/10.1161/JAHA.121.021934 .
doi: 10.1161/JAHA.121.021934
pubmed: 34713713
pmcid: 8751816
Ghosh TS, Valdes AM. Evidence for clinical interventions targeting the gut microbiome in cardiometabolic disease. BMJ. 2023;383:e075180. https://doi.org/10.1136/bmj-2023-075180 .
doi: 10.1136/bmj-2023-075180
pubmed: 37813434
pmcid: 10561016
Tuerhongjiang G, Guo M, Qiao X, Lou B, Wang C, Wu H, et al. Interplay between gut microbiota and amino acid metabolism in Heart failure. Front Cardiovasc Med. 2021;8:752241. https://doi.org/10.3389/fcvm.2021.752241 .
doi: 10.3389/fcvm.2021.752241
pubmed: 34746265
pmcid: 8566708
Luedde M, Winkler T, Heinsen F-A, Rühlemann MC, Spehlmann ME, Bajrovic A, et al. Heart failure is associated with depletion of core intestinal microbiota. ESC Heart Fail. 2017;4:282–90. https://doi.org/10.1002/ehf2.12155 .
doi: 10.1002/ehf2.12155
pubmed: 28772054
pmcid: 5542738
Liu T, Li X, Zhang C, Zhao L, Li X, Yu Y, et al. Lactobacillus and Allobaculum mediates the improvement of vascular endothelial dysfunction during hypertension with TaohongSiwu decoction combined with Dubosiella newyorkensis. Heliyon. 2023;9:e22572. https://doi.org/10.1016/j.heliyon.2023.e22572 .
doi: 10.1016/j.heliyon.2023.e22572
pubmed: 38089998
pmcid: 10711123
Liao P-H, Kuo W-W, Hsieh DJ-Y, Yeh Y-L, Day C-H, Chen Y-H, et al. Heat-killed Lactobacillus reuteri GMNL-263 prevents epididymal fat accumulation and cardiac injury in high-calorie diet-fed rats. Int J Med Sci. 2016;13:569–77. https://doi.org/10.7150/ijms.15597 .
doi: 10.7150/ijms.15597
pubmed: 27499689
pmcid: 4974905
Yang J, Li Y, Wen Z, Liu W, Meng L, Huang H. Oscillospira—a candidate for the next-generation probiotics. Gut Microbes. 2021;13:1987783. https://doi.org/10.1080/19490976.2021.1987783 .
doi: 10.1080/19490976.2021.1987783
pubmed: 34693878
pmcid: 8547878
Wei B, Wang S, Wang Y, Ke S, Jin W, Chen J, et al. Gut microbiota-mediated xanthine metabolism is associated with resistance to high-fat diet-induced obesity. J Nutr Biochem. 2021;88:108533. https://doi.org/10.1016/j.jnutbio.2020.108533 .
doi: 10.1016/j.jnutbio.2020.108533
pubmed: 33250443
Zhu Y, Dong L, Huang L, Shi Z, Dong J, Yao Y, Shen R. Effects of oat β-glucan, oat resistant starch, and the whole oat flour on insulin resistance, inflammation, and gut microbiota in high-fat-diet-induced type 2 diabetic rats. J Funct Foods. 2020;69:103939. https://doi.org/10.1016/j.jff.2020.103939 .
doi: 10.1016/j.jff.2020.103939
Beale AL, O’Donnell JA, Nakai ME, Nanayakkara S, Vizi D, Carter K, et al. The gut microbiome of heart failure with preserved ejection fraction. J Am Heart Assoc. 2021;10:e020654. https://doi.org/10.1161/JAHA.120.020654 .
doi: 10.1161/JAHA.120.020654
pubmed: 34212778
pmcid: 8403331
Simadibrata DM, Auliani S, Widyastuti PA, Wijaya AD, Amin HZ, Muliawan HS, et al. The Gut Microbiota Profile in Heart failure patients: a systematic review. J Gastrointestin Liver Dis. 2023;32:393–401. https://doi.org/10.15403/jgld-4779 .
doi: 10.15403/jgld-4779
pubmed: 37774217
Büttner P, Werner S, Böttner J, Ossmann S, Schwedhelm E, Thiele H. Systemic effects of Homoarginine supplementation on arginine metabolizing enzymes in rats with heart failure with preserved ejection fraction. Int J Mol Sci. 2023. https://doi.org/10.3390/ijms241914782 .
doi: 10.3390/ijms241914782
pubmed: 37834229
pmcid: 10572665
Chen W-S, Wang C-H, Cheng C-W, Liu M-H, Chu C-M, Wu H-P, et al. Elevated plasma phenylalanine predicts mortality in critical patients with heart failure. ESC Heart Fail. 2020;7:2884–93. https://doi.org/10.1002/ehf2.12896 .
doi: 10.1002/ehf2.12896
pubmed: 32618142
pmcid: 7524095
Wang C-H, Cheng M-L, Liu M-H. Simplified plasma essential amino acid-based profiling provides metabolic information and prognostic value additive to traditional risk factors in heart failure. Amino Acids. 2018;50:1739–48. https://doi.org/10.1007/s00726-018-2649-9 .
doi: 10.1007/s00726-018-2649-9
pubmed: 30203393
Teunis CJ, Stroes ESG, Boekholdt SM, Wareham NJ, Murphy AJ, Nieuwdorp M, et al. Tryptophan metabolites and incident cardiovascular disease: the EPIC-Norfolk prospective population study. Atherosclerosis. 2023;387:117344. https://doi.org/10.1016/j.atherosclerosis.2023.117344 .
doi: 10.1016/j.atherosclerosis.2023.117344
pubmed: 37945449
Melhem NJ, Taleb S. Tryptophan: from diet to cardiovascular diseases. Int J Mol Sci. 2021. https://doi.org/10.3390/ijms22189904 .
doi: 10.3390/ijms22189904
pubmed: 34948435
pmcid: 8707880
Sandek A, Bjarnason I, Volk H-D, Crane R, Meddings JB, Niebauer J, et al. Studies on bacterial endotoxin and intestinal absorption function in patients with chronic heart failure. Int J Cardiol. 2012;157:80–5. https://doi.org/10.1016/j.ijcard.2010.12.016 .
doi: 10.1016/j.ijcard.2010.12.016
pubmed: 21190739
Li N, Zhou H, Wu H, Wu Q, Duan M, Deng W, Tang Q. STING-IRF3 contributes to lipopolysaccharide-induced cardiac dysfunction, inflammation, apoptosis and pyroptosis by activating NLRP3. Redox Biol. 2019;24:101215. https://doi.org/10.1016/j.redox.2019.101215 .
doi: 10.1016/j.redox.2019.101215
pubmed: 31121492
pmcid: 6529775
Bowman JD, Surani S, Horseman MA. Endotoxin, toll-like Receptor-4, and atherosclerotic heart disease. Curr Cardiol Rev. 2017;13:86–93. https://doi.org/10.2174/1573403X12666160901145313 .
doi: 10.2174/1573403X12666160901145313
pubmed: 27586023
pmcid: 5452150
Chen S-Y, Rong X-Y, Sun X-Y, Zou Y-R, Zhao C, Wang H-J. A novel trimethylamine oxide-induced model implicates gut microbiota-related mechanisms in frailty. Front Cell Infect Microbiol. 2022;12:803082. https://doi.org/10.3389/fcimb.2022.803082 .
doi: 10.3389/fcimb.2022.803082
pubmed: 35360115
pmcid: 8963486
Gawrys-Kopczynska M, Konop M, Maksymiuk K, Kraszewska K, Derzsi L, Sozanski K, et al. TMAO, a seafood-derived molecule, produces diuresis and reduces mortality in heart failure rats. Elife. 2020. https://doi.org/10.7554/eLife.57028 .
doi: 10.7554/eLife.57028
pubmed: 32510330
pmcid: 7334024
Zhao Y, Wang Z. Impact of trimethylamine N-oxide (TMAO) metaorganismal pathway on cardiovascular disease. J Lab Precis Med. 2020. https://doi.org/10.21037/jlpm.2020.01.01 .
doi: 10.21037/jlpm.2020.01.01
pubmed: 32587943
pmcid: 7316184
Velasquez MT, Ramezani A, Manal A, Raj DS. Trimethylamine N-oxide: the good, the bad and the unknown. Toxins (Basel). 2016. https://doi.org/10.3390/toxins8110326 .
doi: 10.3390/toxins8110326
pubmed: 27834801
Wastyk HC, Fragiadakis GK, Perelman D, Dahan D, Merrill BD, Yu FB, et al. Gut-microbiota-targeted diets modulate human immune status. Cell. 2021;184:4137–e415314. https://doi.org/10.1016/j.cell.2021.06.019 .
doi: 10.1016/j.cell.2021.06.019
pubmed: 34256014
pmcid: 9020749
Jiang S, Shui Y, Cui Y, Tang C, Wang X, Qiu X, et al. Gut microbiota dependent trimethylamine N-oxide aggravates angiotensin II-induced hypertension. Redox Biol. 2021;46:102115. https://doi.org/10.1016/j.redox.2021.102115 .
doi: 10.1016/j.redox.2021.102115
pubmed: 34474396
pmcid: 8408632
Taylor CR, Levenson RM. Quantification of immunohistochemistry–issues concerning methods, utility and semiquantitative assessment II. Histopathology. 2006;49:411–24. https://doi.org/10.1111/j.1365-2559.2006.02513.x .
doi: 10.1111/j.1365-2559.2006.02513.x
pubmed: 16978205