Dysbiosis in early sepsis can be modulated by a multispecies probiotic: a randomised controlled pilot trial
In: Beneficial MicrobesSearch for other papers by V. Stadlbauer in
Current site
Google Scholar
Center for Biomarker Research in Medicine (CBmed), Stiftingtalstrasse 5, 8010 Graz, Austria.
Search for other papers by A. Horvath in
Current site
Google Scholar
Search for other papers by I. Komarova in
Current site
Google Scholar
Center for Biomarker Research in Medicine (CBmed), Stiftingtalstrasse 5, 8010 Graz, Austria.
Search for other papers by B. Schmerboeck in
Current site
Google Scholar
Search for other papers by N. Feldbacher in
Current site
Google Scholar
Search for other papers by I. Klymiuk in
Current site
Google Scholar
Search for other papers by M. Durdevic in
Current site
Google Scholar
Search for other papers by F. Rainer in
Current site
Google Scholar
Search for other papers by A. Blesl in
Current site
Google Scholar
Search for other papers by P. Stiegler in
Current site
Google Scholar
Center for Biomarker Research in Medicine (CBmed), Stiftingtalstrasse 5, 8010 Graz, Austria.
Search for other papers by B. Leber in
Current site
Google Scholar
The gut is hypothesised to play an important role in the development and progression of sepsis. It is however unknown whether the gut microbiome and the gut barrier function is already altered early in sepsis development and whether it is possible to modulate the microbiome in early sepsis. Therefore, a randomised, double blind, placebo-controlled pilot study to examine the alterations of the microbiome and the gut barrier in early sepsis and the influence of a concomitant probiotic intervention on dysbiosis at this early stage of the disease was conducted. Patients with early sepsis, defined as fulfilling the sepsis definition from the 2012 Surviving Sepsis Campaign guidelines but without signs of organ failure, received multispecies probiotic (Winclove 607 based on Omnibiotic® 10 AAD) for 28 days. Gut microbiome composition, function, gut barrier and bacterial translocation were studied. Patients with early sepsis had a significantly lower structural and functional alpha diversity, clustered differently and showed structural alterations on all taxonomic levels. Gut permeability was unaltered but endotoxin, endotoxin binding proteins and peptidoglycans were elevated in early sepsis patients compared to controls. Probiotic intervention successfully increased probiotic strains in stool and led to an improvement of functional diversity. Microbiome composition and function are altered in early sepsis. Probiotic intervention successfully modulates the microbiome and is therefore a promising tool for early intervention in sepsis.
-
Afgan, E., Baker, D., Van den Beek, M., Blankenberg, D., Bouvier, D., Cech, M., Chilton, J., Clements, D., Coraor, N., Eberhard, C., Gruning, B., Guerler, A., Hillman-Jackson, J., Von Kuster, G., Rasche, E., Soranzo, N., Turaga, N., Taylor, J., Nekrutenko, A. and Goecks, J., 2016. The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2016 update. Nucleic Acids Research 44: W3-W10.
'The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2016 update ' () 44 Nucleic Acids Research : W3 -W10.
-
Angus, D.C. and Van der Poll, T., 2013. Severe sepsis and septic shock. New England Journal of Medicine 369: 840-851.
'Severe sepsis and septic shock ' () 369 New England Journal of Medicine : 840 -851.
-
Anonymous, 2007. Opinion of the Scientific Committee on a request from EFSA on the introduction of a Qualified Presumption of Safety (QPS) approach for assessment of selected microorganisms referred to EFSA. EFSA Journal 587: 16.
-
Beloborodova, N.V., Olenin, A.Y. and Pautova, A.K., 2018. Metabolomic findings in sepsis as a damage of host-microbial metabolism integration. Journal of Critical Care 43: 246-255.
'Metabolomic findings in sepsis as a damage of host-microbial metabolism integration ' () 43 Journal of Critical Care : 246 -255.
-
Blaabjerg, S., Artzi, D.M. and Aabenhus, R., 2017. Probiotics for the prevention of antibiotic-associated diarrhea in outpatients – a systematic review and meta-analysis. Antibiotics 6(4): E21.
'Probiotics for the prevention of antibiotic-associated diarrhea in outpatients – a systematic review and meta-analysis ' () 6 Antibiotics : E21.
-
Brandl, K. and Schnabl, B., 2015. Is intestinal inflammation linking dysbiosis to gut barrier dysfunction during liver disease? Expert Review of Gastroenterology and Hepatology 9: 1069-1076.
'Is intestinal inflammation linking dysbiosis to gut barrier dysfunction during liver disease? ' () 9 Expert Review of Gastroenterology and Hepatology : 1069 -1076.
-
Bron, P.A., Kleerebezem, M., Brummer, R.J., Cani, P.D., Mercenier, A., MacDonald, T.T., Garcia-Rodenas, C.L. and Wells, J.M., 2017. Can probiotics modulate human disease by impacting intestinal barrier function? British Journal of Nutrition 117: 93-107.
'Can probiotics modulate human disease by impacting intestinal barrier function? ' () 117 British Journal of Nutrition : 93 -107.
-
Cangemi, R., Pignatelli, P., Carnevale, R., Bartimoccia, S., Nocella, C., Falcone, M., Taliani, G., Violi, F. and SIXTUS Study Group, 2016. Low-grade endotoxemia, gut permeability and platelet activation in community-acquired pneumonia. Journal of Infection 73: 107-114.
'Low-grade endotoxemia, gut permeability and platelet activation in community-acquired pneumonia ' () 73 Journal of Infection : 107 -114.
-
Caporaso, J.G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F.D., Costello, E.K., Fierer, N., Pena, A.G., Goodrich, J.K., Gordon, J.I., Huttley, G.A., Kelley, S.T., Knights, D., Koenig, J.E., Ley, R.E., Lozupone, C.A., McDonald, D., Muegge, B.D., Pirrung, M., Reeder, J., Sevinsky, J.R., Turnbaugh, P.J., Walters, W.A., Widmann, J., Yatsunenko, T., Zaneveld, J. and Knight, R., 2010. QIIME allows analysis of high-throughput community sequencing data. Nature Methods 7: 335-336.
'QIIME allows analysis of high-throughput community sequencing data ' () 7 Nature Methods : 335 -336.
-
Dellinger, R.P., Levy, M.M., Rhodes, A., Annane, D., Gerlach, H., Opal, S.M., Sevransky, J.E., Sprung, C.L., Douglas, I.S., Jaeschke, R., Osborn, T.M., Nunnally, M.E., Townsend, S.R., Reinhart, K., Kleinpell, R.M., Angus, D.C., Deutschman, C.S., Machado, F.R., Rubenfeld, G.D., Webb, S., Beale, R.J., Vincent, J.L., Moreno, R. and Surviving Sepsis Campaign Guidelines Committee including The Pediatric, S., 2013. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Medicine 39: 165-228.
'Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012 ' () 39 Intensive Care Medicine : 165 -228.
-
Earley, Z.M., Akhtar, S., Green, S.J., Naqib, A., Khan, O., Cannon, A.R., Hammer, A.M., Morris, N.L., Li, X., Eberhardt, J.M., Gamelli, R.L., Kennedy, R.H. and Choudhry, M.A., 2015. Burn injury alters the intestinal microbiome and increases gut permeability and bacterial translocation. PLoS ONE 10: e0129996.
'Burn injury alters the intestinal microbiome and increases gut permeability and bacterial translocation ' () 10 PLoS ONE : e0129996.
-
Food and Agriculture Organisation / World Health Organisatino (FAO/WHO), 2001. Joint FAO/WHO expert consultation on evaluation of health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria health and nutritional properties of probiotics. FAO Food and Nutrition Paper 85: 1-50.
-
Goldenberg, J.Z., Yap, C., Lytvyn, L., Lo, C.K., Beardsley, J., Mertz, D. and Johnston, B.C., 2017. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Systematic Reviews 12: CD006095.
'Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children ' () 12 Cochrane Database Systematic Reviews : CD006095.
-
Haak, B.W. and Wiersinga, W.J., 2017. The role of the gut microbiota in sepsis. Lancet Gastroenterology and Hepatology 2: 135-143.
'The role of the gut microbiota in sepsis ' () 2 Lancet Gastroenterology and Hepatology : 135 -143.
-
Heimann, S.M., Vehreschild, J.J., Cornely, O.A., Wisplinghoff, H., Hallek, M., Goldbrunner, R., Bottiger, B.W., Goeser, T., Holscher, A., Baldus, S., Muller, F., Jazmati, N., Wingen, S., Franke, B. and Vehreschild, M.J., 2015. Economic burden of Clostridium difficile associated diarrhoea: a cost-of-illness study from a German tertiary care hospital. Infection 43: 707-714.
'Economic burden of Clostridium difficile associated diarrhoea: a cost-of-illness study from a German tertiary care hospital ' () 43 Infection : 707 -714.
-
Hell, M., Bernhofer, C., Stalzer, P., Kern, J.M. and Claassen, E., 2013. Probiotics in Clostridium difficile infection: reviewing the need for a multistrain probiotic. Beneficial Microbes 4: 39-51.
'Probiotics in Clostridium difficile infection: reviewing the need for a multistrain probiotic ' () 4 Beneficial Microbes : 39 -51.
-
Iapichino, G., Callegari, M.L., Marzorati, S., Cigada, M., Corbella, D., Ferrari, S. and Morelli, L., 2008. Impact of antibiotics on the gut microbiota of critically ill patients. Journal of Medical Microbiology 57: 1007-1014.
'Impact of antibiotics on the gut microbiota of critically ill patients ' () 57 Journal of Medical Microbiology : 1007 -1014.
-
Jonsson, N., Nilsen, T., Gille-Johnson, P., Bell, M., Martling, C.R., Larsson, A. and Martensson, J., 2017. Calprotectin as an early biomarker of bacterial infections in critically ill patients: an exploratory cohort assessment. Critical Care and Resuscitation 19: 205-213.
'Calprotectin as an early biomarker of bacterial infections in critically ill patients: an exploratory cohort assessment ' () 19 Critical Care and Resuscitation : 205 -213.
-
Karczewski, J., Troost, F.J., Konings, I., Dekker, J., Kleerebezem, M., Brummer, R.J. and Wells, J.M., 2010. Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier. American Journal of Physiology Gastrointestinal and Liver Physiology 298: G851-859.
'Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier ' () 298 American Journal of Physiology Gastrointestinal and Liver Physiology : G851 -859.
-
Kitsios, G.D., Morowitz, M.J., Dickson, R.P., Huffnagle, G.B., McVerry, B.J. and Morris, A., 2017. Dysbiosis in the intensive care unit: microbiome science coming to the bedside. Journal of Critical Care 38: 84-91.
'Dysbiosis in the intensive care unit: microbiome science coming to the bedside ' () 38 Journal of Critical Care : 84 -91.
-
Klaus, D.A., Motal, M.C., Burger-Klepp, U., Marschalek, C., Schmidt, E.M., Lebherz-Eichinger, D., Krenn, C.G. and Roth, G.A., 2013. Increased plasma zonulin in patients with sepsis. Biochemia Medica: Casopis Hrvatskoga Drustva Medicinskih Biokemicara 23: 107-111.
'Increased plasma zonulin in patients with sepsis ' () 23 Biochemia Medica: Casopis Hrvatskoga Drustva Medicinskih Biokemicara : 107 -111.
-
Klymiuk, I., Bilgilier, C., Stadlmann, A., Thannesberger, J., Kastner, M.T., Hogenauer, C., Puspok, A., Biowski-Frotz, S., Schrutka-Kolbl, C., Thallinger, G.G. and Steininger, C., 2017. The human gastric microbiome is predicated upon infection with Helicobacter pylori. Frontiers in Microbiology 8: 2508.
'The human gastric microbiome is predicated upon infection with Helicobacter pylori ' () 8 Frontiers in Microbiology : 2508.
-
Koning, C.J., Jonkers, D.M., Stobberingh, E.E., Mulder, L., Rombouts, F.M. and Stockbrugger, R.W., 2008. The effect of a multispecies probiotic on the intestinal microbiota and bowel movements in healthy volunteers taking the antibiotic amoxycillin. American Journal of Gastroenterology 103: 178-189.
'The effect of a multispecies probiotic on the intestinal microbiota and bowel movements in healthy volunteers taking the antibiotic amoxycillin ' () 103 American Journal of Gastroenterology : 178 -189.
-
Lang, F.C., 2010. Use of a multi-species probiotic for the prevention of antibiotic associated diarrhea. Nutrafoods 9: 5.
'Use of a multi-species probiotic for the prevention of antibiotic associated diarrhea ' () 9 Nutrafoods : 5.
-
Langille, M.G., Zaneveld, J., Caporaso, J.G., McDonald, D., Knights, D., Reyes, J.A., Clemente, J.C., Burkepile, D.E., Vega Thurber, R.L., Knight, R., Beiko, R.G. and Huttenhower, C., 2013. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nature Biotechnology 31: 814-821.
'Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences ' () 31 Nature Biotechnology : 814 -821.
-
Lenoir-Wijnkoop, I., Nuijten, M.J., Craig, J. and Butler, C.C., 2014. Nutrition economic evaluation of a probiotic in the prevention of antibiotic-associated diarrhea. Frontiers in Pharmacology 5: 13.
'Nutrition economic evaluation of a probiotic in the prevention of antibiotic-associated diarrhea ' () 5 Frontiers in Pharmacology : 13.
-
Mancabelli, L., Milani, C., Lugli, G.A., Turroni, F., Cocconi, D., Van Sinderen, D. and Ventura, M., 2017. Identification of universal gut microbial biomarkers of common human intestinal diseases by meta-analysis. FEMS Microbiology Ecology 93(12): fix153.
'Identification of universal gut microbial biomarkers of common human intestinal diseases by meta-analysis ' () 93 FEMS Microbiology Ecology : fix153.
-
McDonald, D., Ackermann, G., Khailova, L., Baird, C., Heyland, D., Kozar, R., Lemieux, M., Derenski, K., King, J., Vis-Kampen, C., Knight, R. and Wischmeyer, P.E., 2016. Extreme dysbiosis of the microbiome in critical illness. mSphere 1: e00199-16.
'Extreme dysbiosis of the microbiome in critical illness ' () 1 mSphere : e00199 -16.
-
Mikkelsen, K.H., Frost, M., Bahl, M.I., Licht, T.R., Jensen, U.S., Rosenberg, J., Pedersen, O., Hansen, T., Rehfeld, J.F., Holst, J.J., Vilsboll, T. and Knop, F.K., 2015. Effect of antibiotics on gut microbiota, gut hormones and glucose metabolism. PLoS ONE 10: e0142352.
'Effect of antibiotics on gut microbiota, gut hormones and glucose metabolism ' () 10 PLoS ONE : e0142352.
-
Milani, C., Lugli, G.A., Turroni, F., Mancabelli, L., Duranti, S., Viappiani, A., Mangifesta, M., Segata, N., Van Sinderen, D. and Ventura, M., 2014. Evaluation of bifidobacterial community composition in the human gut by means of a targeted amplicon sequencing (ITS) protocol. FEMS Microbiology Ecology 90: 493-503.
'Evaluation of bifidobacterial community composition in the human gut by means of a targeted amplicon sequencing (ITS) protocol ' () 90 FEMS Microbiology Ecology : 493 -503.
-
Mittal, R. and Coopersmith, C.M., 2014. Redefining the gut as the motor of critical illness. Trends in Molecular Medicine 20: 214-223.
'Redefining the gut as the motor of critical illness ' () 20 Trends in Molecular Medicine : 214 -223.
-
Morrow, L.E. and Wischmeyer, P., 2017. Blurred lines: dysbiosis and probiotics in the ICU. Chest 151: 492-499.
'Blurred lines: dysbiosis and probiotics in the ICU ' () 151 Chest : 492 -499.
-
Rhodes, A., Evans, L.E., Alhazzani, W., Levy, M.M., Antonelli, M., Ferrer, R., Kumar, A., Sevransky, J.E., Sprung, C.L., Nunnally, M.E., Rochwerg, B., Rubenfeld, G.D., Angus, D.C., Annane, D., Beale, R.J., Bellinghan, G.J., Bernard, G.R., Chiche, J.D., Coopersmith, C., De Backer, D.P., French, C.J., Fujishima, S., Gerlach, H., Hidalgo, J.L., Hollenberg, S.M., Jones, A.E., Karnad, D.R., Kleinpell, R.M., Koh, Y., Lisboa, T.C., Machado, F.R., Marini, J.J., Marshall, J.C., Mazuski, J.E., McIntyre, L.A., McLean, A.S., Mehta, S., Moreno, R.P., Myburgh, J., Navalesi, P., Nishida, O., Osborn, T.M., Perner, A., Plunkett, C.M., Ranieri, M., Schorr, C.A., Seckel, M.A., Seymour, C.W., Shieh, L., Shukri, K.A., Simpson, S.Q., Singer, M., Thompson, B.T., Townsend, S.R., Van der Poll, T., Vincent, J.L., Wiersinga, W.J., Zimmerman, J.L. and Dellinger, R.P., 2017. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Medicine 43: 304-377.
'Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016 ' () 43 Intensive Care Medicine : 304 -377.
-
Ross, C.L., Spinler, J.K. and Savidge, T.C., 2016. Structural and functional changes within the gut microbiota and susceptibility to Clostridium difficile infection. Anaerobe 41: 37-43.
'Structural and functional changes within the gut microbiota and susceptibility to Clostridium difficile infection ' () 41 Anaerobe : 37 -43.
-
Shen, N.T., Maw, A., Tmanova, L.L., Pino, A., Ancy, K., Crawford, C.V., Simon, M.S. and Evans, A.T., 2017. Timely use of probiotics in hospitalized adults prevents Clostridium difficile infection: a systematic review with meta-regression analysis. Gastroenterology 152: 1889-1900.
'Timely use of probiotics in hospitalized adults prevents Clostridium difficile infection: a systematic review with meta-regression analysis ' () 152 Gastroenterology : 1889 -1900.
-
Stadlbauer, V., 2015. Immunosuppression and probiotics: are they effective and safe? Beneficial Microbes 6: 823-828.
'Immunosuppression and probiotics: are they effective and safe? ' () 6 Beneficial Microbes : 823 -828.
-
Stiefel, U., Pultz, N.J., Helfand, M.S. and Donskey, C.J., 2004. Increased susceptibility to vancomycin-resistant Enterococcus intestinal colonization persists after completion of anti-anaerobic antibiotic treatment in mice. Infection Control and Hospital Epidemiology 25: 373-379.
'Increased susceptibility to vancomycin-resistant Enterococcus intestinal colonization persists after completion of anti-anaerobic antibiotic treatment in mice ' () 25 Infection Control and Hospital Epidemiology : 373 -379.
-
Van den Nieuwboer, M., Van Hemert, S., Claassen, E. and De Vos, W.M., 2016. Lactobacillus plantarum WCFS1 and its host interaction: a dozen years after the genome. Microbial Biotechnology 9: 452-465.
'Lactobacillus plantarum WCFS1 and its host interaction: a dozen years after the genome ' () 9 Microbial Biotechnology : 452 -465.
-
Vancamelbeke, M. and Vermeire, S., 2017. The intestinal barrier: a fundamental role in health and disease. Expert Review of Gastroenterology and Hepatology 11: 821-834.
'The intestinal barrier: a fundamental role in health and disease ' () 11 Expert Review of Gastroenterology and Hepatology : 821 -834.
-
Videlock, E.J. and Cremonini, F., 2012. Probiotics for antibiotic-associated diarrhea. JAMA 308: 665.
'Probiotics for antibiotic-associated diarrhea ' () 308 JAMA : 665.
-
Yu, L.C., Shih, Y.A., Wu, L.L., Lin, Y.D., Kuo, W.T., Peng, W.H., Lu, K.S., Wei, S.C., Turner, J.R. and Ni, Y.H., 2014. Enteric dysbiosis promotes antibiotic-resistant bacterial infection: systemic dissemination of resistant and commensal bacteria through epithelial transcytosis. American Journal of Physiology – Gastrointestinal and Liver Physiology 307: G824-835.
'Enteric dysbiosis promotes antibiotic-resistant bacterial infection: systemic dissemination of resistant and commensal bacteria through epithelial transcytosis ' () 307 American Journal of Physiology – Gastrointestinal and Liver Physiology : G824 -835.
-
Zakrzewski, M., Proietti, C., Ellis, J.J., Hasan, S., Brion, M.J., Berger, B. and Krause, L., 2017. Calypso: a user-friendly web-server for mining and visualizing microbiome-environment interactions. Bioinformatics 33: 782-783.
'Calypso: a user-friendly web-server for mining and visualizing microbiome-environment interactions ' () 33 Bioinformatics : 782 -783.
Supplementary Materials
| All Time | Past 365 days | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 0 | 0 | 0 |
| Full Text Views | 316 | 250 | 40 |
| PDF Views & Downloads | 358 | 287 | 43 |
Dysbiosis in early sepsis can be modulated by a multispecies probiotic: a randomised controlled pilot trial
In: Beneficial MicrobesSearch for other papers by V. Stadlbauer in
Current site
Google Scholar
PubMed
Center for Biomarker Research in Medicine (CBmed), Stiftingtalstrasse 5, 8010 Graz, Austria.
Search for other papers by A. Horvath in
Current site
Google Scholar
PubMed
Search for other papers by I. Komarova in
Current site
Google Scholar
PubMed
Center for Biomarker Research in Medicine (CBmed), Stiftingtalstrasse 5, 8010 Graz, Austria.
Search for other papers by B. Schmerboeck in
Current site
Google Scholar
PubMed
Search for other papers by N. Feldbacher in
Current site
Google Scholar
PubMed
Search for other papers by I. Klymiuk in
Current site
Google Scholar
PubMed
Search for other papers by M. Durdevic in
Current site
Google Scholar
PubMed
Search for other papers by F. Rainer in
Current site
Google Scholar
PubMed
Search for other papers by A. Blesl in
Current site
Google Scholar
PubMed
Search for other papers by P. Stiegler in
Current site
Google Scholar
PubMed
Center for Biomarker Research in Medicine (CBmed), Stiftingtalstrasse 5, 8010 Graz, Austria.
Search for other papers by B. Leber in
Current site
Google Scholar
PubMed
The gut is hypothesised to play an important role in the development and progression of sepsis. It is however unknown whether the gut microbiome and the gut barrier function is already altered early in sepsis development and whether it is possible to modulate the microbiome in early sepsis. Therefore, a randomised, double blind, placebo-controlled pilot study to examine the alterations of the microbiome and the gut barrier in early sepsis and the influence of a concomitant probiotic intervention on dysbiosis at this early stage of the disease was conducted. Patients with early sepsis, defined as fulfilling the sepsis definition from the 2012 Surviving Sepsis Campaign guidelines but without signs of organ failure, received multispecies probiotic (Winclove 607 based on Omnibiotic® 10 AAD) for 28 days. Gut microbiome composition, function, gut barrier and bacterial translocation were studied. Patients with early sepsis had a significantly lower structural and functional alpha diversity, clustered differently and showed structural alterations on all taxonomic levels. Gut permeability was unaltered but endotoxin, endotoxin binding proteins and peptidoglycans were elevated in early sepsis patients compared to controls. Probiotic intervention successfully increased probiotic strains in stool and led to an improvement of functional diversity. Microbiome composition and function are altered in early sepsis. Probiotic intervention successfully modulates the microbiome and is therefore a promising tool for early intervention in sepsis.
| All Time | Past 365 days | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 0 | 0 | 0 |
| Full Text Views | 316 | 250 | 40 |
| PDF Views & Downloads | 358 | 287 | 43 |
