title: Macrophages Are Involved in Gut Bacterial Translocation and Reversed by Lactobacillus in Experimental Uremia.
abstract: Uremia causes gut microbiome dysbiosis, which is characterized by a reduction in beneficial bacteria. Intestinal bacterial translocation (BT) contributes to microinflammation in uremia, which is associated with adverse outcomes. Whether macrophages are involved in BT remains unclear.
  
  
  
  We investigated the involvement of macrophages in BT and microinflammation in uremic rats and whether Lactobacillus LB can influence macrophage activity.
  
  
  
  Male Sprague-Dawley rats were randomly divided into three groups: sham, uremia, and uremia + probiotic. Macrophages and GFP-labeled tracer bacteria in intestinal and extraintestinal tissues were observed by fluorescence microscopy. The macrophage ultrastructure was examined by transmission electron microscopy. Immunochemistry was used to analyze the expression of cluster of differentiation 11a (CD11a), inducible nitric oxide synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1). RT-PCR and Western blot were employed to assess the mRNA and protein expression of early growth response gene 1 (EGR1) and toll-like receptor 4 (TLR4).
  
  
  
  In uremic rats, the colocalization of GFP-labeled tracer bacteria and macrophages was visible in intestinal and extraintestinal tissues. Compared with the sham group, the uremic macrophages showed fewer cytoplasmic protrusions and pseudopodia. Administration of Lactobacillus LB restored the protrusions and pseudopodia. Compared with the sham group, the uremia group exhibited macrophages with higher staining intensities for CD11a, iNOS, and ICAM-1, and higher mRNA and protein expression of TLR4 and EGR1.
  
  
  
  Intestinal macrophages in the uremic rats are polarized toward a proinflammatory phenotype, resulting in microinflammation. Macrophages with impaired phagocytic function are associated with BT. Lactobacillus LB reduces BT by enhancing macrophage phagocytosis.
authors.affiliation: School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Lingshuang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Dialysis Department of Nephrology Hospital, First Affiliated Hospital of Medicine School, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: Dialysis Department of Nephrology Hospital, First Affiliated Hospital of Medicine School, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China. j92106@sina.com.
authors.forename: Hongli
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Dialysis Department of Nephrology Hospital, First Affiliated Hospital of Medicine School, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wei
authors.affiliation: School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Liang
authors.affiliation: Dialysis Department of Nephrology Hospital, First Affiliated Hospital of Medicine School, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Dialysis Department of Nephrology Hospital, First Affiliated Hospital of Medicine School, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
authors.forename: Kehui
authors.initials: K
authors.lastname: Shi
authors.affiliation: Dialysis Department of Nephrology Hospital, First Affiliated Hospital of Medicine School, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: He
mesh_terms: D000818:Animals; D018988:Bacterial Translocation / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D040881:CD11a Antigen / Q000235:genetics / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D004731:Endotoxins / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005786:Gene Expression Regulation / Q000502:physiology; D007249:Inflammation / Q000097:blood / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000382:microbiology / Q000473:pathology; D007778:Lactobacillus / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014511:Uremia / Q000473:pathology*
chemical_list: D015415:Biomarkers; D040881:CD11a Antigen; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D004731:Endotoxins; D012333:RNA, Messenger; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D018799:Intercellular Adhesion Molecule-1; D052247:Nitric Oxide Synthase Type II
keywords: Bacterial translocation; Macrophages; Microinflammation; Probiotics; Uremia