Abstract: TH-OR06
The Kidney-Gut-Brain Axis in AKI
Session Information
- AKI Mechanisms: Cellular and Organ Cross-Talk
November 02, 2023 | Location: Room 118, Pennsylvania Convention Center
Abstract Time: 05:15 PM - 05:24 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Yang, Jihyun, Kangbuk Samsung Hospital, Jongno-gu, Seoul, Korea (the Republic of)
- Choi, Young Eun, Korea University, Seongbuk-gu, Korea (the Republic of)
- Kim, Sungyeon, Korea University, Seongbuk-gu, Korea (the Republic of)
- Chung, Suk Min, Korea University, Seongbuk-gu, Korea (the Republic of)
- Jang, Yookyung, Korea University, Seongbuk-gu, Korea (the Republic of)
- Yoon Sook, Ko, Korea University, Seongbuk-gu, Korea (the Republic of)
- Hee Young, Lee, Korea University, Seongbuk-gu, Korea (the Republic of)
- Koo, Tai yeon, Korea University, Seongbuk-gu, Korea (the Republic of)
- Oh, Sewon, Korea University, Seongbuk-gu, Korea (the Republic of)
- Kim, Myung-Gyu, Korea University, Seongbuk-gu, Korea (the Republic of)
- Jo, Sang-Kyung, Korea University, Seongbuk-gu, Korea (the Republic of)
Background
Although epidemiological studies suggest that long-term survivors of dialysis requiring AKI had increased risk of dementia, its underlying mechanisms remain uncertain. Based on recent data showing kidney-gut crosstalk mediated by immune modulation in AKI, we hypothesized that gut dysbiosis and aberrant gut immune response might contribute to the cognitive dysfunction following AKI.
Methods
In mouse long-term AKI survival model (1yr after kidney ischemia/reperfusion injury (IRI)), we determined functional and structural alterations of brain, changes in gut microenvironment including dysbiosis and immune cell phenotypes. For better insight about the causal relationship in kidney-gut-brain axis, we also tested the effect of fecal microbiota transfer (FMT) and cohousing (transfer microbiota by coprophage) on kidney and brain in long-term AKI mouse model.
Results
One year after kidney IRI, mice showed abnormal behaviors in open field test compared to age matched sham control. Transcriptosome of hippocampus demonstrated more than 120 differentially regulated genes including those involved in angiogenesis/immune and inflammatory response. We also found structural brain injury including disruption of BBB, neuroinflammation, oxidative stress as well as accumulation of amyloid-b fibrils and hyperphosphorylated tau proteins, suggesting the development of Alzheimer like dementia long after AKI. Gut microbiota structure 1yr after kidney IRI was also clearly distinguished from that of sham control and was associated with increased ratio of Th17/Tregs balance, showing the persistence of gut dysbiosis and aberrant gut mucosal immune response long after AKI. Both cohousing and FMT partially restored the gut mucosal inflammation and this also led to not only decreased kidney fibrosis but also improved cognitive function as well as neuroinflammation and tauopathy.
Conclusion
This is the first animal study that showed that AKI can lead to Alzheimer like neurodegeneration. Gut dysbiosis and aberrant mucosal immune response is thought to contribute to the development of tauopathy/neuroinflammation and congtivie dysfunction long after AKI. Our data provide new insights into “kidney-gut-brain” axis in the field of AKI and suggest that gut might be a new therapeutic target for the prevention of long-term adverse outcomes in AKI patients.