Gut Dysbiosis Is Linked to Hypertension

Hypertension - Tập 65 Số 6 - Trang 1331-1340 - 2015
Tao Yang1, Monica M. Santisteban2, Vermalí Rodríguez3, Eric Li4, Niousha Ahmari5, Jessica Marulanda Carvajal6, Mojgan Zadeh7, Minghao Gong8, Yanfei Qi9, Jasenka Zubcevic10, Bikash Sahay11, Carl J. Pepine12, Mohan K. Raizada13, Mansour Mohamadzadeh14
1Tao Yang From the Department of Infectious Diseases and Pathology, College of Veterinary Medicine (T.Y., M.Z., M.G., B.S., M.M.), Division of Gastroenterology, Hematology and Nutrition, Department of Medicine (T.Y., M.Z., M.G., B.S., M.M.), Department of Physiology and Functional Genomics (M.M.S., V.R., J.M.C., M.K.R.), College of Medicine, Division of Cardiovascular Medicine, Department of Medicine (V.R., Y.Q., C.J.P.), Division of Infectious Diseases and Global Medicine, Department of Medicine (E.L.), and Department of Physiological Sciences, College of Veterinary Medicine (N.A., J.Z.), University of Florida, Gainesville.
2Monica M. Santisteban From the Department of Infectious Diseases and Pathology, College of Veterinary Medicine (T.Y., M.Z., M.G., B.S., M.M.), Division of Gastroenterology, Hematology and Nutrition, Department of Medicine (T.Y., M.Z., M.G., B.S., M.M.), Department of Physiology and Functional Genomics (M.M.S., V.R., J.M.C., M.K.R.), College of Medicine, Division of Cardiovascular Medicine, Department of Medicine (V.R., Y.Q., C.J.P.), Division of Infectious Diseases and Global Medicine, Department of Medicine (E.L.), and Department of Physiological Sciences, College of Veterinary Medicine (N.A., J.Z.), University of Florida, Gainesville.
3Vermali Rodriguez From the Department of Infectious Diseases and Pathology, College of Veterinary Medicine (T.Y., M.Z., M.G., B.S., M.M.), Division of Gastroenterology, Hematology and Nutrition, Department of Medicine (T.Y., M.Z., M.G., B.S., M.M.), Department of Physiology and Functional Genomics (M.M.S., V.R., J.M.C., M.K.R.), College of Medicine, Division of Cardiovascular Medicine, Department of Medicine (V.R., Y.Q., C.J.P.), Division of Infectious Diseases and Global Medicine, Department of Medicine (E.L.), and Department of Physiological Sciences, College of Veterinary Medicine (N.A., J.Z.), University of Florida, Gainesville.
4Eric Li From the Department of Infectious Diseases and Pathology, College of Veterinary Medicine (T.Y., M.Z., M.G., B.S., M.M.), Division of Gastroenterology, Hematology and Nutrition, Department of Medicine (T.Y., M.Z., M.G., B.S., M.M.), Department of Physiology and Functional Genomics (M.M.S., V.R., J.M.C., M.K.R.), College of Medicine, Division of Cardiovascular Medicine, Department of Medicine (V.R., Y.Q., C.J.P.), Division of Infectious Diseases and Global Medicine, Department of Medicine (E.L.), and Department of Physiological Sciences, College of Veterinary Medicine (N.A., J.Z.), University of Florida, Gainesville.
5Niousha Ahmari From the Department of Infectious Diseases and Pathology, College of Veterinary Medicine (T.Y., M.Z., M.G., B.S., M.M.), Division of Gastroenterology, Hematology and Nutrition, Department of Medicine (T.Y., M.Z., M.G., B.S., M.M.), Department of Physiology and Functional Genomics (M.M.S., V.R., J.M.C., M.K.R.), College of Medicine, Division of Cardiovascular Medicine, Department of Medicine (V.R., Y.Q., C.J.P.), Division of Infectious Diseases and Global Medicine, Department of Medicine (E.L.), and Department of Physiological Sciences, College of Veterinary Medicine (N.A., J.Z.), University of Florida, Gainesville.
6Jessica Marulanda Carvajal From the Department of Infectious Diseases and Pathology, College of Veterinary Medicine (T.Y., M.Z., M.G., B.S., M.M.), Division of Gastroenterology, Hematology and Nutrition, Department of Medicine (T.Y., M.Z., M.G., B.S., M.M.), Department of Physiology and Functional Genomics (M.M.S., V.R., J.M.C., M.K.R.), College of Medicine, Division of Cardiovascular Medicine, Department of Medicine (V.R., Y.Q., C.J.P.), Division of Infectious Diseases and Global Medicine, Department of Medicine (E.L.), and Department of Physiological Sciences, College of Veterinary Medicine (N.A., J.Z.), University of Florida, Gainesville.
7Mojgan Zadeh From the Department of Infectious Diseases and Pathology, College of Veterinary Medicine (T.Y., M.Z., M.G., B.S., M.M.), Division of Gastroenterology, Hematology and Nutrition, Department of Medicine (T.Y., M.Z., M.G., B.S., M.M.), Department of Physiology and Functional Genomics (M.M.S., V.R., J.M.C., M.K.R.), College of Medicine, Division of Cardiovascular Medicine, Department of Medicine (V.R., Y.Q., C.J.P.), Division of Infectious Diseases and Global Medicine, Department of Medicine (E.L.), and Department of Physiological Sciences, College of Veterinary Medicine (N.A., J.Z.), University of Florida, Gainesville.
8Minghao Gong From the Department of Infectious Diseases and Pathology, College of Veterinary Medicine (T.Y., M.Z., M.G., B.S., M.M.), Division of Gastroenterology, Hematology and Nutrition, Department of Medicine (T.Y., M.Z., M.G., B.S., M.M.), Department of Physiology and Functional Genomics (M.M.S., V.R., J.M.C., M.K.R.), College of Medicine, Division of Cardiovascular Medicine, Department of Medicine (V.R., Y.Q., C.J.P.), Division of Infectious Diseases and Global Medicine, Department of Medicine (E.L.), and Department of Physiological Sciences, College of Veterinary Medicine (N.A., J.Z.), University of Florida, Gainesville.
9Yanfei Qi From the Department of Infectious Diseases and Pathology, College of Veterinary Medicine (T.Y., M.Z., M.G., B.S., M.M.), Division of Gastroenterology, Hematology and Nutrition, Department of Medicine (T.Y., M.Z., M.G., B.S., M.M.), Department of Physiology and Functional Genomics (M.M.S., V.R., J.M.C., M.K.R.), College of Medicine, Division of Cardiovascular Medicine, Department of Medicine (V.R., Y.Q., C.J.P.), Division of Infectious Diseases and Global Medicine, Department of Medicine (E.L.), and Department of Physiological Sciences, College of Veterinary Medicine (N.A., J.Z.), University of Florida, Gainesville.
10Jasenka Zubcevic From the Department of Infectious Diseases and Pathology, College of Veterinary Medicine (T.Y., M.Z., M.G., B.S., M.M.), Division of Gastroenterology, Hematology and Nutrition, Department of Medicine (T.Y., M.Z., M.G., B.S., M.M.), Department of Physiology and Functional Genomics (M.M.S., V.R., J.M.C., M.K.R.), College of Medicine, Division of Cardiovascular Medicine, Department of Medicine (V.R., Y.Q., C.J.P.), Division of Infectious Diseases and Global Medicine, Department of Medicine (E.L.), and Department of Physiological Sciences, College of Veterinary Medicine (N.A., J.Z.), University of Florida, Gainesville.
11Bikash Sahay From the Department of Infectious Diseases and Pathology, College of Veterinary Medicine (T.Y., M.Z., M.G., B.S., M.M.), Division of Gastroenterology, Hematology and Nutrition, Department of Medicine (T.Y., M.Z., M.G., B.S., M.M.), Department of Physiology and Functional Genomics (M.M.S., V.R., J.M.C., M.K.R.), College of Medicine, Division of Cardiovascular Medicine, Department of Medicine (V.R., Y.Q., C.J.P.), Division of Infectious Diseases and Global Medicine, Department of Medicine (E.L.), and Department of Physiological Sciences, College of Veterinary Medicine (N.A., J.Z.), University of Florida, Gainesville.
12Carl J. Pepine From the Department of Infectious Diseases and Pathology, College of Veterinary Medicine (T.Y., M.Z., M.G., B.S., M.M.), Division of Gastroenterology, Hematology and Nutrition, Department of Medicine (T.Y., M.Z., M.G., B.S., M.M.), Department of Physiology and Functional Genomics (M.M.S., V.R., J.M.C., M.K.R.), College of Medicine, Division of Cardiovascular Medicine, Department of Medicine (V.R., Y.Q., C.J.P.), Division of Infectious Diseases and Global Medicine, Department of Medicine (E.L.), and Department of Physiological Sciences, College of Veterinary Medicine (N.A., J.Z.), University of Florida, Gainesville.
13Mohan K. Raizada From the Department of Infectious Diseases and Pathology, College of Veterinary Medicine (T.Y., M.Z., M.G., B.S., M.M.), Division of Gastroenterology, Hematology and Nutrition, Department of Medicine (T.Y., M.Z., M.G., B.S., M.M.), Department of Physiology and Functional Genomics (M.M.S., V.R., J.M.C., M.K.R.), College of Medicine, Division of Cardiovascular Medicine, Department of Medicine (V.R., Y.Q., C.J.P.), Division of Infectious Diseases and Global Medicine, Department of Medicine (E.L.), and Department of Physiological Sciences, College of Veterinary Medicine (N.A., J.Z.), University of Florida, Gainesville.
14Mansour Mohamadzadeh From the Department of Infectious Diseases and Pathology, College of Veterinary Medicine (T.Y., M.Z., M.G., B.S., M.M.), Division of Gastroenterology, Hematology and Nutrition, Department of Medicine (T.Y., M.Z., M.G., B.S., M.M.), Department of Physiology and Functional Genomics (M.M.S., V.R., J.M.C., M.K.R.), College of Medicine, Division of Cardiovascular Medicine, Department of Medicine (V.R., Y.Q., C.J.P.), Division of Infectious Diseases and Global Medicine, Department of Medicine (E.L.), and Department of Physiological Sciences, College of Veterinary Medicine (N.A., J.Z.), University of Florida, Gainesville.

Tóm tắt

Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. This study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension because genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of 2 rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes/Bacteroidetes ratio. These changes were accompanied by decreases in acetate- and butyrate-producing bacteria. In addition, the microbiota of a small cohort of human hypertensive patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects. Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes/Bacteroidetes ratio. In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota. In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes/Bacteroidetes ratio. These observations demonstrate that high blood pressure is associated with gut microbiota dysbiosis, both in animal and human hypertension. They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension.

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Tài liệu tham khảo

10.1155/2013/230868

10.1161/01.HYP.14.2.177

10.1161/01.HYP.0000103160.35395.9E

Harrison DG. The immune system in hypertension. Trans Am Clin Climatol Assoc. 2014;125:130–38; discussion 138.

10.1007/s12026-014-8548-6

10.1016/B978-0-12-381300-8.00008-3

10.1111/imm.12231

10.1186/1471-2180-9-123

10.1152/physrev.00045.2009

10.1038/pr.2014.173

10.1056/NEJMoa1109400

10.1172/JCI58109

10.1016/j.bpg.2013.03.007

10.1038/nm.2895

10.1038/nature06244

10.1007/978-1-4939-0897-4_14

10.1161/HYPERTENSIONAHA.114.03469

10.1038/nmeth.f.303

10.1111/j.1365-2222.2007.02849.x

10.1136/gutjnl-2011-301476

10.3389/fphys.2012.00496

10.1038/ijo.2011.153

10.2337/db08-1637

10.1038/nature12721

10.1079/BJN20041150

10.2174/15680266113136660160

10.1161/HYPERTENSIONAHA.110.150409

10.1016/j.ajpath.2013.07.009

10.1016/j.cell.2004.07.002

10.1371/journal.pone.0017996

10.1111/1469-0691.12172

10.1128/mBio.00893-14

10.2337/db13-1526

10.1186/1471-2180-13-30

10.1073/pnas.1415174111

10.1186/1471-2164-15-511

10.1155/2013/809128

10.1038/nature11450

10.1046/j.1365-2362.1998.00360.x

10.1093/ajh/hpu117

10.3390/nu3100858

10.1111/bph.13058

10.1371/journal.pone.0035240

10.1186/1868-7083-4-4

10.3748/wjg.v17.i12

10.1016/j.jnutbio.2011.01.007

10.1681/ASN.2014030288

10.1073/pnas.1215927110

10.1111/bph.12139

10.1073/pnas.1219451110

10.1158/1541-7786.692.2.12

10.1016/j.phrs.2010.12.011

10.1016/j.bcp.2011.09.004

10.1016/j.bbrc.2009.09.041

10.1111/j.1747-4949.2006.00023.x

10.1161/HYPERTENSIONAHA.112.199547

10.1096/fasebj.28.1_supplement.875.5

10.4049/jimmunol.1400716