Bifidobacterium pseudocatenulatum CECT7765 induces an M2 anti-inflammatory transition in macrophages from patients with cirrhosis.
OBJECTIVE
Patients with cirrhosis show recurrent access of bacterial products into the bloodstream inducing a multi-altered immunological status leading to relevant complications. We aimed at evaluating Bifidobacterium pseudocatenulatum CECT7765 effect on the host's macrophage function.


METHODS
Patients with cirrhosis and ascites were included. Granulocyte-macrophage colony-stimulating factor (GM-CSF) monocyte-derived and ascitic fluid (AF) macrophages were cultured with M-CSF, lipopolysaccharide (LPS) and/or the bifidobacterial strain. Pellets and supernatants were evaluated for gene expression of M1 and M2-related genes and cytokine secretion. Cell surface expression molecules were evaluated by flow cytometry. Kupffer cells from bile duct ligated and CCl4 rats were also evaluated.


RESULTS
Experiments were run on GM-CSF blood-derived and AF macrophages from 10 patients with cirrhosis and 10 healthy donors. Different macrophage morphology was observed by optical microscopy in cells stimulated with bifidobacteria vs. LPS. M2-like expression of CD206, CD163 and CD16 was significantly increased in macrophages after stimulation with the bifidobacterial strain vs. LPS. B. pseudocatenulatum CECT7765 was able to significantly change the cytokine secretion pattern of blood-derived and AF macrophages and Kupffer cells from bile duct ligated and CCl4 cirrhotic rats compared to that induced by LPS. B. pseudocatenulatum CECT7765 was also effective in inducing a phenotype transition and a functional change from an M1- to an M2-related gene expression and cytokine secretion pattern in AF macrophages even after LPS-pretreatment. B. pseudocatenulatum CECT7765 did not reduce AF macrophage bacterial killing capacity.


CONCLUSIONS
B. pseudocatenulatum CECT7765 induces a morphologic, phenotypic and functional transition towards an anti-inflammatory profile in GM-CSF monocyte-derived and AF macrophages from patients with cirrhosis that may help in controlling sustained inflammation in decompensated cirrhosis.
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
Alba
A
Moratalla
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Dpto. Medicina Clínica, Universidad Miguel Hernández, San Juan, Spain.
Esther
E
Caparrós
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
Oriol
O
Juanola
Microbial Ecology, Nutrition & Health Research Group, Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Valencia, Spain.
Kevin
K
Portune
Laboratorio Inmuno-Metabolismo, Hospital Gregorio Marañón, Madrid, Spain.
Amaya
A
Puig-Kröger
Laboratorio Inmuno-Metabolismo, Hospital Gregorio Marañón, Madrid, Spain.
Lizbeth
L
Estrada-Capetillo
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Unidad Hepática, Hospital General Universitario, Alicante, Spain.
Pablo
P
Bellot
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
Isabel
I
Gómez-Hurtado
Dpto. Medicina Clínica, Universidad Miguel Hernández, San Juan, Spain.
Paula
P
Piñero
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Servicio de Farmacología Clínica, Hospital General Universitario, Alicante, Spain.
Pedro
P
Zapater
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
José M
JM
González-Navajas
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates.
José
J
Such
Microbial Ecology, Nutrition & Health Research Group, Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Valencia, Spain.
Yolanda
Y
Sanz
CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Dpto. Medicina Clínica, Universidad Miguel Hernández, San Juan, Spain. Electronic address: frances_rub@gva.es.
Rubén
R
Francés
D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001644:Bifidobacterium; D016764:Cell Polarity; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007728:Kupffer Cells / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides
Bifidobacterium pseudocatenulatum CECT7765; Cirrhosis; Cytokines; Macrophages