Blood Microbiome Quantity and the Hyperdynamic Circulation in Decompensated Cirrhotic Patients.
BACKGROUND
Recently, a complex microbiome was comprehensibly characterized in the serum and ascitic fluid of cirrhotic patients. In the current study, we investigated for the first time the induction of inflammatory pathways and Nitric Oxide, as well as the systemic hemodynamics in conjunction with the blood microbiome in a Child-Pugh class B cirrhotic cohort.


RESULTS
We used the Intestinal Infections Microbial DNA qPCR Array to screen for 53 bacterial DNA from the gut in the blood. Assays were designed using the 16S rRNA gene as a target, and PCR amplification primers (based on the Human Microbiome Project) and hydrolysis-probe detection. Eighteen systemic hemodynamic parameters were measured non-invasively by impedance cardiography using the BioZ ICG monitor. The inflammatory response was assessed by measuring blood cytokines, Nitric Oxide RNA arrays, and Nitric Oxide. In the blood of this cirrhotic cohort, we detected 19 of 53 bacterial species tested. The number of bacterial species was markedly increased in the blood of cirrhotic patients compared to control individuals (0.2+/-0.4 vs 3.1+/-2.3; 95% CI: 1.3 to 4.9; P = 0.0030). The total bacterial DNA was also increased in the blood of cirrhotic subjects compared to control subjects (0.2+/- 1.1 vs 41.8+/-132.1; 95% CI: 6.0 to 77.2; P = 0.0022). In the cirrhotic cohort, the Cardiac Output increased by 37% and the Systemic Vascular Resistance decreased by 40% (P< 0.00001 for both compared to control subjects). Systemic Vascular Resistance was inversely correlated to blood bacterial DNA quantity (- 0.621; 95% CI -0.843 to -0.218; P = 0.0060), blood bacterial species number (- 0.593; 95% CI -0.83 to -0.175; P = 0.0095; logistic regression: Chi Square = 5.8877; P = 0.0152), and serum Nitric Oxide (- 0.705; 95% CI -0.881 to -0.355; P = 0.0011). Many members of the Nitric Oxide signaling pathway gene family were increased in cirrhotic subjects.


CONCLUSIONS
Our study identified blood bacterial DNA in ~ 90% of the cirrhotic patients without clinical evidences of infection, and suggests that the quantity of bacterial DNA in blood may stimulate signaling pathways, including Nitric Oxide, that could decrease systemic vascular resistance and increase cardiac output.
Department of Medicine, University of California, San Diego, La Jolla, CA, United States of America.|Veterans Affairs San Diego Healthcare System, San Diego, CA, United States of America.
Daniela
D
Traykova
Department of Medicine, University of California, San Diego, La Jolla, CA, United States of America.|Veterans Affairs San Diego Healthcare System, San Diego, CA, United States of America.
Beacher
B
Schneider
Department of Medicine, University of California, San Diego, La Jolla, CA, United States of America.|Veterans Affairs San Diego Healthcare System, San Diego, CA, United States of America.|Biomedical Sciences Program, University of California, San Diego, La Jolla, CA, United States of America.|Clinical Translational Research Institute, University of California, San Diego, La Jolla, CA, United States of America.
Mario
http://orcid.org/0000-0003-1936-2151
M
Chojkier
Department of Medicine, University of California, San Diego, La Jolla, CA, United States of America.|Veterans Affairs San Diego Healthcare System, San Diego, CA, United States of America.|Biomedical Sciences Program, University of California, San Diego, La Jolla, CA, United States of America.
Martina
http://orcid.org/0000-0002-4979-8063
M
Buck
D000368:Aged; D001419:Bacteria / Q000145:classification / Q000235:genetics; D015415:Biomarkers; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D000069196:Gastrointestinal Microbiome; D005786:Gene Expression Regulation; D006439:Hemodynamics; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D008111:Liver Function Tests; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D054892:Metagenome; D056186:Metagenomics / Q000379:methods; D064307:Microbiota; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018805:Sepsis / Q000209:etiology*
D015415:Biomarkers; D016207:Cytokines; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D009569:Nitric Oxide