Gut Microbiota-Immune System Interactions during Acute Kidney Injury.
Kidney360(2021)
摘要
Distant organ crosstalk during AKI, first studied mechanistically in the lung (1), is now known to play an important role in disease outcomes. The relationship between intestinal microbiota and AKI has also been explored, resulting in exciting findings that are promising for future human therapeutics. In search of ways to reduce kidney T cells by using “cleaner,” germfree (GF) mice, it was unexpectedly found that GF mice not only retained their kidney immune cells, but also had a higher number of natural killer T (NKT) cells and reduced IL-4 levels compared with normal wild-type (WT) mice. Moreover, GF mice subjected to kidney ischemia-reperfusion (IR) injury had increased CD8 T-cell trafficking and inflammatory cytokine mediators compared with normal WT mice (2). Induction of ischemic AKI in GF mice led to a worse course of AKI, in terms of both structure and function. Conventionalizing GF mice with normal mouse stool led to normalizing T-cell and NKT populations, and relative protection from AKI, compared with GF mice (2). It was subsequently observed that early exposure to gut microbiota during development was associated with long-term changes in NKT-cell function in nonrenal tissues, and NKT cells in GF mice had a less mature phenotype with diminished activation capacity upon antigen encounter (3,4). To elucidate whether the effects were bidirectional and AKI led to changes in the gut microbiome, gut microbiota was evaluated in C57BL/6 WT mice after ischemic or nephrotoxic (cisplatin; CP) injury. DNA was isolated from the fecal pellets ( n =4–5 per group) at baseline (D0) and at 3 days (D3) post-IR. The V3–V5 region of the 16S ribosomal RNA gene was amplified using the 357F/926R primer set and sequenced using the Roche/454 platform. IR and CP modified the relative abundance of specific bacterial species belonging to the phyla Actinobacteria, Bacteroidetes, Firmicutes, …
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关键词
acute kidney injury and ICU nephrology,acute kidney injury,basic science,cisplatin,dysbiosis,gastrointestinal microbiome,gut microbiota,immune system,ischemia reperfusion injury,transplantation
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